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

Abstract

Provided herein are compounds of Formula (I): (G1-Z1)-L-(G2-Z2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein G1, G2, Z1, Z2, and L are as defined others herein. Also provided herein are methods of making the compounds of formula (I). Also provided herein are methods of inhibiting GYS1 and methods of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 406,683, filed on September 14, 2022, the entire content of which is incorporated herein by reference for all purposes. Background of the Invention

[0004] Pathological accumulation of glycogen is a hallmark of multiple devastating and chronic human diseases. For some of these conditions, the cellular etiology driving this abnormal accumulation has an obvious genetic basis, while for others, the mechanistic drivers are more complex. Nevertheless, over time, elevated glycogen levels lead to altered cellular homeostasis and impaired tissue function. The rate - limiting enzyme in the glycogen synthesis pathway is the protein glycogen synthase (GYS). Humans have two isoforms: GYS1 and GYS2. The former is ubiquitously expressed and abundant in muscle cells, while the latter is expressed only in the liver. The ultimate starting point for glycogen synthesis is the transport of glucose into the cell via the GLUT family of transporters. The conversion of glucose to glycogen follows a well - characterized biochemical conversion pathway, in which GYS covalently links glucose molecules via α1,4 - glycosidic bonds into long branches. The final spherical structure of glycogen results from the action of glycogen branching enzyme (GBE), which introduces α1,6 - linked branch points along the chain. The result of this chain of biochemical events is the production of an energy - dense and highly soluble molecule that can be stored in the cytosol of the cell and rapidly broken down into glucose for energy use when needed. Imbalances in the balance of glycogen synthesis or glycogenolysis lead to abnormal accumulation of cellular glycogen stores. It has long been hypothesized that substrate - reduction therapies targeting the inhibition of glycogen synthase could be effective in treating glycogen storage diseases. Indeed, substrate - reduction therapy drugs have been very successful in modulating the course of 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 object of the present invention is to inhibit glycogen synthase activity, thereby reducing tissue glycogen storage and providing a therapeutic benefit to patients suffering from abnormal cellular glycogen accumulation.

[0005] GYS1 exists in a complex with glycogenin in the form of a homotetramer (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).

[0006] Pompe disease is a rare genetic disorder caused by loss-of-function (LOF) mutations in the lysosomal enzyme α-glucosidase (GAA), leading to pathological accumulation of cellular glycogen. GAA catabolizes lysosomal glycogen, and in its absence, glycogen accumulates in lysosomes. This triggers a series of disease cascades, starting with lysosomal and autophagosome dysfunction and ultimately leading to cell death and muscle atrophy (Young SP, et al. Genetics in Medicine, Vol. 11, No. 11, 2009). In humans, the clinical manifestations of the disease vary in severity, with 1 in 40,000 live births affected (Meena NK, Raben N. Pompe disease: new developments in an old lysosomal storage disorder. Biomolecules, Vol. 10, 2020). Patients with infantile-onset disease are born with cellular lesions and rapidly develop severe impairments, including myopathy, heart defects, organomegaly, and hypotonia. Without treatment, the disease will claim the lives of children within a year. Children with later onset may present with cardiac enlargement, but are characterized by a progressive loss of motor function, skeletal muscle degeneration, and ultimately respiratory failure leading to premature death. Late-onset adult Pompe disease patients exhibit normal cardiac function but develop progressive muscle weakness and respiratory function decline, eventually resulting in failure. The standard treatment for Pompe disease patients currently is enzyme replacement therapy (ERT) with recombinant human GAA. ERT treatment has successfully slowed the disease progression rate, but for most patients, there still remain incredibly unmet needs (Schoser B, et al. The humanistic burden of Pompe disease: are there still unmet needs? A systematic review. BMC Neurology, Vol. 17, 2017). For more than a decade, substrate reduction therapy targeting GYS1 has been thought to be beneficial for the treatment of Pompe disease.In fact, three independent preclinical studies have demonstrated that loss of function (LOF) of the GYS1 gene in a murine model of Pompe disease can effectively reduce tissue glycogen and improve disease outcomes in mice (Douillard-Guilloux G, et al. Modulation of glycogen synthesis by RNA interference: towards a new therapeutic approach for glycogenosis type II. Human Molecular Genetics, Vol. 17, No. 24, 2008; Douillard-Guilloux G, et al. Restoration of muscle functionality 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 can be used as monotherapy or in combination with standard of care enzyme replacement therapy (ERT) to meet the currently unmet needs of Pompe disease patients.

[0007] Pompe disease is just 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. For some glycogen storage diseases (GSDs), specific dietary regimens can effectively control the disease, but for others, there are no clinically approved therapeutic interventions to alter the disease course. Therefore, inhibiting glycogen synthesis while simultaneously reducing tissue glycogen levels may be a viable treatment option for these patients. Cori disease (GSD III) is caused by mutations in glycogen debranching enzyme (GDE) that result in pathologic 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). Although dietary management can effectively improve some aspects of the disease, there is currently no treatment that can prevent the progressive myopathy of GSD III. Adult polyglucosan body disease (APBD) is an adult-onset disorder caused by loss of activity of glycogen branching enzyme (GBE1). GBE deficiency leads to the accumulation of long-chain unbranched glycogen that precipitates in the cytosol, generating polyglucosan bodies that ultimately cause neurological dysfunction in the central and peripheral nervous systems. Genetic deletion of GYS1 in an APBD mouse model rescued the harmful accumulation of glycogen, extended lifespan, and improved 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 very severe adolescent epilepsy characterized by the accumulation of polyglucosan bodies. Genetic crosses between LD mouse models and GYS1 knockout (KO) mice rescued 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).

[0008] Recently, the dependence of clear cell carcinoma on high levels of glycogen has emerged as a new therapeutic target. Ewing's 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 that are histopathologically defined by abnormally high levels of PAS+ cellular glycogen. 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, Nos. 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), elevated GYS1 transcript levels are significantly associated with adverse disease outcomes. In cultured myeloid leukemia cells, lentiviral knockdown of GYS1 effectively inhibits cancer cell growth in vitro and tumorigenesis 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). In a ccRCC cell model, gene knockdown of GYS1 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).

[0009] In preclinical models of Pompe disease, APBD, LD, AML, ccRCC, and NSCLC, both the reduction of GYS1 enzyme activity and the decrease in cellular glycogen storage provide strong evidence of the potential therapeutic benefits of inhibiting glycogen synthesis. The object of the present invention is to inhibit glycogen synthase activity, thereby reducing tissue glycogen storage and providing therapeutic benefits to patients suffering from cellular glycogen accumulation. SUMMARY OF THE INVENTION

[0010] In one aspect, the present invention provides compounds of formula (I):

[0011] (G1-Z1)-L-(G2-Z2) (I),

[0012] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:

[0013] (i) G1 and / or G1-Z1 and (ii) G2 and / or G2-Z2 are each independently a GYS1 inhibitory moiety; and

[0014] L is a linker.

[0015] In one aspect, the present invention provides compounds 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) each independently has formula (I-1) or (I-2):

[0016]

[0017] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:

[0018] Y 2 and Y 3 are each C, or

[0019] Y 2 and Y 3 one of which is N, and Y 2 and Y 3 the other of which is C;

[0020] X 1 and X 2 are each independently H, C 1-6 alkyl or C 1-6 alkoxy;

[0021] X 3 and X 4 are each independently H, halogen, C 1-6 alkyl, C 1-6 alkoxy or a 5-20 membered heteroaryl, wherein X 3 and X4 C of 1-6 The alkyl group is optionally substituted by one or more halogen groups;

[0022] X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl;

[0023] Or

[0024] (1) L 1 does not exist; and

[0025] Q 1 is selected from (i) to (iv):

[0026] (i) Phenyl, wherein the phenyl of Q 1 is substituted by one or more halogen groups, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclic group), C 3-10 cycloalkyl or 5- to 20-membered heteroaryl, wherein

[0027] C 1-6 alkyl is optionally substituted by one or more halogen groups, -NH-C(O)-NH(C 1-6 alkyl), -NH-C(O)-C 1-6 alkyl or -NH-C(O)-C 1-6 alkoxy,

[0028] C 3-10 cycloalkyl is optionally substituted by one or more halogen groups or C 1-6 alkyl, and

[0029] 5- to 20-membered heteroaryl is optionally substituted by one or more C 1-6 alkyl,

[0030] (ii) 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of Q 1 is optionally substituted by one or more oxo groups or C 1-6 alkyl,

[0031] (iii) 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Q 1 is optionally substituted by one or more halogen groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein,

[0032] C1-6 The alkyl group is optionally substituted by one or more halogen groups, and

[0033] C 3-10 The cycloalkyl group is optionally substituted by one or more halogen groups or C 1-6 alkyl group, and

[0034] (iv) C 3-10 cycloalkyl group;

[0035] Or

[0036] (2) L 1 is -CH2-; and

[0037] Q 1 is C 3-10 cycloalkyl group;

[0038] L 2 is -C(O)- or -S(O)2-

[0039] R 1 is H or C 1-6 alkyl group;

[0040] R k is H, halogen group, -OH, -NH2 or -NH-C(O)C 1-6 alkyl group;

[0041] R m is H, -OH or C 1-6 alkyl group;

[0042] R n is H, C 1-6 alkyl group or C 3-10 cycloalkyl group, or R n together with the carbon atom to which it is attached forms C 3-5 cycloalkyl group;

[0043] Or R k together with R m or R n and the atoms to which they are attached forms a cyclopropyl group; and R 2 is selected from (i) to (vii):

[0044] (i) C 1-6 alkyl group, wherein the C 2 of R 1-6 alkyl group is optionally substituted by one or more R a substituents, wherein R a is:

[0045] (a) -OH,

[0046] (b) cyano group,

[0047] (c) C 2-6 Alkynyl

[0048] (d) C 6-20 Aryl, where R a of C 6-20 The aryl is optionally substituted by one or more halogen groups, cyano groups, C 1-6 alkoxy groups or -NH-C(O)-C 1-6 alkyl groups

[0049] (e) 3- to 15-membered heterocyclic group, where R a of the 3- to 15-membered heterocyclic group is optionally substituted by one or more R c substituents, where

[0050] R c is a halogen group, oxo group, C 1-6 alkyl group, C 1-6 alkoxy group, -C(O)-C 1-6 alkyl group or -C(O)-C 1-6 alkoxy group, where

[0051] R c of C 1-6 alkyl group is optionally substituted by one or more halogen groups or C 2-6 alkynyl groups, and

[0052] R c of -C(O)-C 1-6 alkoxy group is optionally substituted by one or more halogen groups

[0053] (f) -N(R c )(R d ), where -N(R c )(R d )'s R c and R d are independently of each other H, C 1-6 alkyl group, -C(O)-C 1-6 alkyl group, -C(O)-C 1-6 alkoxy group, -C(O)-NH2, -C(O)-NH(C 1-6 alkyl group), -C(O)-N(C 1-6 alkyl group)2, -C(O)-(3- to 15-membered heterocyclic group), -CH2-C(O)-NH2, 3- to 15-membered heterocyclic group or 5- to 20-membered heteroaryl group, where

[0054] R c or R d of C 1-6 alkyl group is optionally substituted by one or more -C(O)-NH2 groups

[0055] Rc or R d -C(O)-C of 1-6 The alkyl group is optionally substituted by one or more halogen groups,

[0056] R c or R d The 3- to 15-membered heterocyclic group and 5- to 20-membered heteroaryl group of are each independently optionally substituted by one or more C 1-6 alkyl groups,

[0057] R c or R d -C(O)-(3- to 15-membered heterocyclic group) of is optionally substituted by one or more halogen groups, -C(O)-C 1-6 alkoxy groups or C 1-6 alkyl groups, wherein the C 1-6 alkyl group is optionally substituted by one or more halogen groups, C 1-6 alkoxy groups or C 3-10 cycloalkyl groups, and

[0058] R c or R d -C(O)-N(C 1-6 alkyl)2 of the C 1-6 alkyl groups are each independently optionally substituted by one or more halogen groups or C 6-20 aryl groups,

[0059] (g)-O-R e , wherein R e is C 1-6 alkyl group, C 6-20 aryl group, -C(O)-(3- to 15-membered heterocyclic group), -C(O)-N-(C 1-6 alkyl)2 or 5- to 20-membered heteroaryl group, wherein

[0060] R e of the C 1-6 alkyl group is optionally substituted by one or more C 1-6 alkoxy groups, wherein the C 1-6 alkoxy group is optionally substituted by one or more C 2-6 alkynyl groups,

[0061] R e of the C 6-20 aryl group is optionally substituted by one or more C 1-6 alkyl groups, and

[0062] R e -C(O)-(3- to 15-membered heterocyclic group) of is optionally substituted by one or more C 1-6 alkyl groups, C 1-6 alkoxy groups or -C(O)-C 1-6Alkoxy substitution, wherein said C 1-6 alkyl group is optionally substituted by one or more halogen groups, C 1-6 alkoxy groups or C 3-10 cycloalkyl groups,

[0063] (h)-C(O)-R e , wherein R e is -NH2, -OH or a 3- to 15-membered heterocyclic group, or

[0064] (i)-S(O)2-R f , wherein R f is C 1-6 alkyl or a 3- to 15-membered heterocyclic group,

[0065] (ii)C 3-10 cycloalkyl group, wherein R 2 's C 3-10 cycloalkyl group is optionally substituted by one or more R q groups, wherein R q is a 5- to 20-membered heteroaryl group or C 6-20 aryl group, wherein R q 's C 6-20 aryl group is optionally substituted by one or more C 1-6 alkoxy groups,

[0066] (iii)A 3- to 15-membered heterocyclic group, wherein R 2 's 3- to 15-membered heterocyclic group is optionally substituted by one or more halogen groups, oxo groups, C 1-6 alkyl groups, -C(O)-C 1-6 alkyl groups or 5- to 20-membered heteroaryl groups,

[0067] (iv)A 5- to 20-membered heteroaryl group or -(C 1-4 alkyl group)(5- to 20-membered heteroaryl group), wherein C 1-4 alkyl group is optionally substituted by one or more -OH, halogen groups, -NH2, -NH(C 1-6 alkyl group), -N(C 1-6 alkyl group)2, and wherein the 5- to 20-membered heteroaryl group in the 5- to 20-membered heteroaryl group or -(C 1-4 alkyl group)(5- to 20-membered heteroaryl group) is optionally substituted by one or more R s groups, wherein

[0068] R s is a halogen group, 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, C6-20 Aryl, C 3-10 ycloalkyl, 3- to 15-membered heterocyclic group, 5- to 20-membered heteroaryl or -C(O)-C 1-6 alkoxy, wherein

[0069] R s 's C 1-6 alkyl is optionally substituted by one or more halogen groups, 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 alkoxy, and

[0070] R s 's 3- to 15-membered heterocyclic group is optionally substituted by one or more halogen groups or -C(O)-C 1-6 alkoxy,

[0071] (v)-N(R g )(R h ), wherein R g and R h are independently H or C 1-6 alkyl,

[0072] (vi)-C(O)-R j wherein R j is C 3-10 ycloalkyl, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2 or -NH(5- to 20-membered heteroaryl), and

[0073] (vii)C 6-20 aryl, wherein R 2 's C 6-20 aryl is optionally substituted by one or more 5- to 20-membered heteroaryl or -O-R p wherein R p is a 3- to 15-membered heterocyclic group, wherein R p 's 3- to 15-membered heterocyclic group is optionally substituted by one or more -C(O)-C 1-6 alkyl; and

[0074] wherein (G1-Z1) and (Z2-G2) are each independently substituted by a group that binds to L.

[0075] In one aspect, the present invention provides 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) each independently have formula (I-A):

[0076]

[0077] 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 are as defined elsewhere herein.

[0078] In one aspect, the present disclosure provides 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) each independently has formula (I-B):

[0079]

[0080] 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 are as defined elsewhere herein.

[0081] In one aspect, the present disclosure provides 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) each independently has formula (I-C):

[0082]

[0083] 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 are as defined elsewhere herein.

[0084] In one aspect, the present disclosure provides 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) each independently has formula (I-D):

[0085]

[0086] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X 4 and X 5 and R 2 and R k and R u and R t are as defined elsewhere herein.

[0087] In one aspect, the present disclosure provides 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) each independently has formula (I-D1):

[0088]

[0089] wherein X 4 and X 5 and R 2 and R k and R u and R z are as defined elsewhere herein.

[0090] In one aspect, the present disclosure provides 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) each independently has formula (I-D2):

[0091]

[0092] wherein X 4 and X 5 and R 2 and R k and R t and R u are as defined elsewhere herein.

[0093] In one aspect, the present disclosure provides 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) each independently has formula (I-E):

[0094]

[0095] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 2 and R k and R m are as defined elsewhere herein.

[0096] In one aspect, the present disclosure provides 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) each independently has formula (I-F):

[0097]

[0098] 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 are as defined elsewhere herein.

[0099] In one aspect, the present disclosure provides 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) each independently has formula (I-G):

[0100]

[0101] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein ring A, L 1 、Y 2 、Y 3 、R 2 、R k 、X 1 、X 2 、X 3 、X 4 and X 5 are as defined elsewhere herein.

[0102] In one aspect, the present disclosure provides 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) each independently has formula (I-H):

[0103]

[0104] 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 are as defined elsewhere herein.

[0105] In one aspect, the present disclosure provides a compound of formula (I), wherein the compound is a compound of formula (II):

[0106]

[0107] 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 are as defined elsewhere herein.

[0108] In one aspect, the present disclosure provides a compound of formula (I), wherein the compound is a compound of formula (III):

[0109]

[0110] 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 are as defined elsewhere herein.

[0111] In one aspect, the present disclosure provides a compound of formula (I), wherein the compound is a compound of formula (IV):

[0112]

[0113] 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 as defined elsewhere herein.

[0114] In one aspect, the present disclosure provides a compound of formula (I), wherein the compound is a compound of formula (V):

[0115]

[0116] 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 as defined elsewhere herein.

[0117] In one aspect, the present disclosure provides a pharmaceutical composition comprising (i) 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 (ii) one or more pharmaceutically acceptable excipients.

[0118] In one aspect, the present disclosure provides a method of modulating GYS1 in a cell, 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.

[0119] In one aspect, the present disclosure provides a method of inhibiting GYS1 in a cell, 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.

[0120] In one aspect, the present disclosure provides methods for reducing tissue glycogen storage 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 more selective for GYS1 than for GYS2. In some embodiments, the compound of formula (I) is 500 or 1,000 or 1,500 or 1,700 times more selective for GYS1 than for GYS2.

[0121] In one aspect, the present disclosure provides methods for reducing tissue glycogen storage 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.

[0122] In one aspect, the present disclosure provides methods for 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.

[0123] In one aspect, the present disclosure provides methods for treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof, comprising subjecting the individual to glycogen substrate reduction therapy. In some embodiments, the glycogen substrate reduction therapy comprises administering a compound of formula (I). In some embodiments, the compound of formula (I) is more selective for GYS1 than for GYS2. In some embodiments, the compound of formula (I) is 500 or 1,000 or 1,500 or 1,700 times more selective for GYS1 than for GYS2.

[0124] In one aspect, provided herein are methods 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.

[0125] In one aspect, provided herein are methods of treating a glycogen storage disease, disorder, or condition in an individual in need thereof, comprising subjecting the individual to glycogen substrate reduction therapy. In some embodiments, the glycogen substrate reduction therapy comprises administering a compound of formula (I). In some embodiments, the compound of formula (I) is more selective for GYS1 than for GYS2. In some embodiments, the compound of formula (I) is 500 or 1,000 or 1,500 or 1,700 times more selective for GYS1 than for GYS2.

[0126] In one aspect, provided herein are kits that comprise (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 treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

[0127] In some aspects, provided herein are methods of preparing a compound of formula (I) or any embodiment or variant thereof such as a compound of formula (II), (II-A), (III), (II-A), (IV), (IV-A), (V) or (V-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. BRIEF DESCRIPTION OF THE DRAWINGS

[0128] Figure 1 Depicts the pathway by which loss of function (LoF) of PPP1R3A results in reduced muscle glycogen.

[0129] Figure 2A and 2B Depicts the association between PPP1R3A protein truncating variants (PTVs) and left ventricular ejection fraction (LVEF) (%) and left ventricular wall thickness (mm) in the UK Biobank.

[0130] Figure 2C and2D Depicts the association between the truncated variant (PTV) of the PPP1R3A protein and exercise output (watts) and maximum heart rate (HR) exercise (bpm) in the UK Biobank.

[0131] Figure 2E and 2F Depicts the association between the truncated variant (PTV) of the PPP1R3A protein and PQ interval (ms) and QRS duration (ms) in the UK Biobank.

[0132] Figure 2G and 2H Depicts the association between the truncated variant (PTV) of the PPP1R3A protein and QT interval (ms) and serum glucose (mmol / L) in the UK Biobank. Detailed implementation

[0133] "Individual" refers to a mammal and includes human 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, the individual refers to a human.

[0134] "About" a parameter or value as used herein includes and describes the parameter or value itself. For example, "about X" includes and describes X itself.

[0135] An "at-risk" individual as used herein refers to an individual at risk of developing a certain disease or disorder. An "at-risk" individual may or may not have a detectable disease or disorder and may or may not show a detectable disease prior to the treatment methods described herein. "At risk" means that the individual has one or more so-called risk factors, which are measurable parameters associated with the development of a disease or disorder and are known in the art. An individual having one or more of these risk factors has a higher likelihood of developing a disease or disorder than an individual without these risk factors.

[0136] "Treatment" or "treating" is a method for obtaining a beneficial or desired result (including a clinical result). The beneficial or desired result can include one or more of the following: reducing one or more symptoms caused by a disease or disorder; reducing the extent of a disease or condition; slowing or preventing the development of one or more symptoms associated with a disease or disorder (e.g., stabilizing a disease or disorder, preventing or delaying the worsening or progression of a disease or disorder); and alleviating a disease, e.g., by causing the regression of clinical symptoms (e.g., improving the disease state, enhancing the effect of another drug, delaying the progression of a disease, improving quality of life, and / or extending survival).

[0137] As used herein, "retarding" the development of a disease or disorder means delaying, hindering, slowing, retarding, stabilizing, and / or arresting the development of the disease or disorder. This delay may have different time lengths, depending on the disease history and / or the individual being treated. As will be apparent to those skilled in the art, a sufficient or significant delay may actually encompass prevention, since the individual does not develop the disease or disorder.

[0138] As used herein, the term "therapeutically effective amount" or "effective amount" means an amount sufficient to produce a therapeutic effect when the compounds or pharmaceutically acceptable salts thereof disclosed herein are administered to an individual. As understood in the art, an effective amount may be one or more doses, e.g., a single dose or multiple doses may be required to achieve the desired therapeutic endpoint. "Effective amount" may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be administered in an effective amount if, when combined with one or more other agents, a desired or beneficial result is achieved or attained.

[0139] As used herein, "unit dosage form" means a physically discrete unit suitable as a unit dose, each unit containing a predetermined amount of an active ingredient or compound in a pharmaceutically acceptable carrier.

[0140] As used herein, "pharmaceutically acceptable" means a substance that is not biologically or otherwise undesirable, e.g., the substance may be incorporated into a pharmaceutical composition administered to an individual without causing significant undesirable biological effects.

[0141] As used herein, the term "alkyl" means a saturated monovalent hydrocarbon chain, straight or branched. The alkyl groups used herein have 1-20 carbons (i.e., C 1-20 alkyl), 1-16 carbons (i.e., C 1-16 alkyl), 1-12 carbons (i.e., C 1-12 alkyl), 1-10 carbons (i.e., C 1-10 alkyl), 1-8 carbons (i.e., C 1-8 alkyl), 1-6 carbons (i.e., C 1-6 alkyl), 1-4 carbons (i.e., C 1-4 alkyl), or 1-3 carbons (i.e., C 1-3alkyl). Examples of alkyl 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 carbon atoms is named by a chemical name or a molecular formula, it may include all positional isomers having that number of carbon atoms. For example, "butyl" encompasses n-butyl, sec-butyl, isobutyl, and tert-butyl; "propyl" includes n-propyl and isopropyl. Certain commonly used alternative names may be used, and those of ordinary skill in the art will understand these names. For example, a divalent group, such as a divalent "alkyl", may be referred to as "alkylene".

[0142] As used herein, the term "alkenyl" refers to a branched or unbranched monovalent hydrocarbon chain containing at least one carbon-carbon double bond. The alkenyl used herein has 2 - 20 carbons (i.e., C 2-20 alkenyl), 2 - 16 carbons (i.e., C 2-16 alkenyl), 2 - 12 carbons (i.e., C 2-12 alkenyl), 2 - 10 carbons (i.e., C 2-10 alkenyl), 2 - 8 carbons (i.e., C 2-8 alkenyl), 2 - 6 carbons (i.e., C 2-6 alkenyl), 2 - 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, vinyl, 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 a molecular formula, it may include all positional isomers having that number of carbon atoms. For example, "propenyl" encompasses prop-1-enyl and prop-2-enyl. Certain commonly used alternative names may be used, and those of ordinary skill in the art will understand these names. For example, a divalent group, such as a divalent "alkenyl", may be referred to as "alkenylene".

[0143] As used herein, the term "alkynyl" refers to a branched or unbranched monovalent hydrocarbon chain containing at least one carbon-carbon triple bond. The alkynyl used herein has 2 - 20 carbons (i.e., C 2-20 alkynyl), 2 - 16 carbons (i.e., C 2-16 alkynyl), 2 - 12 carbons (i.e., C 2-12 alkynyl), 2 - 10 carbons (i.e., C 2-10 alkynyl), 2 - 8 carbons (i.e., C 2-8 alkynyl), 2 - 6 carbons (i.e., C 2-6 alkynyl), 2 - 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 naming an alkynyl residue with a specific number of carbon atoms using a chemical name or molecular formula, it may include all positional isomers having that number of carbon atoms. For example, "propynyl" includes prop-1-ynyl and prop-2-ynyl. Certain commonly used alternative names may be used, and those skilled in the art will understand these names. For example, a divalent group, such as divalent "alkynyl", may be referred to as "alkynylene".

[0144] As used herein, the term "alkoxy" refers to an -O-alkyl moiety. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentyloxy, n-hexyloxy, and 1,2-dimethylbutoxy.

[0145] As used herein, the term "aryl" refers to a fully unsaturated carbocyclic moiety. The term "aryl" encompasses monocyclic and polycyclic fused ring moieties. The aryl as used herein encompasses ring moieties containing, for example, 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 aryl). Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, fluorenyl, and anthracenyl.

[0146] As used herein, the term "cycloalkyl" refers to a saturated or partially unsaturated carbocyclic moiety. The term "cycloalkyl" encompasses monocyclic and polycyclic moieties, where the polycyclic moiety may be fused, branched, or spiro. Cycloalkyl includes cycloalkenyl, where the ring moiety contains at least one cyclic double bond. Cycloalkyl includes any polycyclic carbocyclic moiety containing at least one non-aromatic ring, regardless of the point of attachment to the rest of the molecule. The cycloalkyl as used herein includes ring moieties containing, for example, 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 3-5rings of (cycloalkyl). Monocyclic cycloalkyl moieties include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic groups include, for example, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, adamantyl, norbornyl, decahydronaphthyl, 7,7-dimethyl-bicyclo[2.2.1]heptyl, and the like. In addition, cycloalkyl also includes spirocycloalkyl ring moieties, such as spiro[2.5]octyl, spiro[4.5]decyl, or spiro[5.5]undecyl.

[0147] As used herein, the term "halo" refers to atoms occupying Group VIIA of the Periodic Table, including fluorine (fluoro), chlorine (chloro), bromine (bromo), and iodine (iodo).

[0148] As used herein, the term "heteroaryl" refers to an aromatic (fully unsaturated) ring moiety containing one or more cyclic heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heteroaryl" includes monocyclic and polycyclic fused ring moieties. Heteroaryls used herein include, for example, 5 to 20 ring atoms (i.e., 5- to 20-membered heteroaryls), 5 to 16 ring atoms (i.e., 5- to 16-membered heteroaryls), 5 to 12 ring atoms (i.e., 5- to 12-membered heteroaryls), 5 to 10 ring atoms (i.e., 5- to 10-membered heteroaryls), 5 to 8 ring atoms (i.e., 5- to 8-membered heteroaryls), or 5 to 6 ring atoms (i.e., 5- to 6-membered heteroaryls). Any monocyclic or polycyclic aromatic ring moiety containing one or more ring heteroatoms is considered a heteroaryl, regardless of the point of attachment to the rest of the molecule (i.e., the heteroaryl moiety can be attached to the rest of the molecule through any ring carbon or any ring heteroatom of the heteroaryl moiety). Examples of heteroaryls include, but are not limited to, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzofuranyl, benzothiazolyl, benzothiadiazolyl, benzonaphthofuranyl, benzoxazolyl, benzothienyl (benzophenylthio), benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, isoquinolinyl, 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 heteroaromatic rings include, but are not limited to, benzo[d]thiazolyl, quinolinyl, isoquinolinyl, benzo[b]thienyl, indazolyl, benzo[d]imidazolyl, pyrazolo[1,5-a]pyridinyl, and imidazo[1,5-a]pyridinyl, where the heteroaryl can be attached through any ring of the fused system.

[0149] As used herein, the term "heterocyclic group" refers to a saturated or partially unsaturated cyclic moiety that encompasses one or more ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heterocyclic group" includes monocyclic and polycyclic moieties, where the polycyclic moieties can be fused, bridged, or spiro. Any non-aromatic monocyclic or polycyclic moiety containing at least one ring heteroatom is considered a heterocyclic group, regardless of the point of attachment to the rest of the molecule (i.e., the heterocyclic group moiety can be attached to the rest of the molecule through any ring carbon or any ring heteroatom of the heterocyclic group moiety). Additionally, the term heterocyclic group is intended to encompass any polycyclic moiety containing at least one ring heteroatom, where the polycyclic moiety contains at least one non-aromatic ring, regardless of the point of attachment to the rest of the molecule. The heterocyclic groups used herein include, for example, 3 to 20 ring atoms (i.e., 3- to 20-membered heterocyclic groups), 3 to 16 ring atoms (i.e., 3- to 16-membered heterocyclic groups), 3 to 12 ring atoms (i.e., 3- to 12-membered heterocyclic groups), 3 to 10 ring atoms (i.e., 3- to 10-membered heterocyclic groups), 3 to 8 ring atoms (i.e., 3- to 8-membered heterocyclic groups), 3 to 6 ring atoms (i.e., 3- to 6-membered heterocyclic groups), 3 to 5 ring atoms (i.e., 3- to 5-membered heterocyclic groups), 5 to 8 ring atoms (i.e., 5- to 8-membered heterocyclic groups), or 5 to 6 ring atoms (i.e., 5- to 6-membered heterocyclic groups). Examples of heterocyclic groups include, for example, azetidinyl, aziridinyl, benzodioxolyl, benz[b][1,4]dioxanyl, 1,4-benzodioxanyl, benzopyranyl, benzodioxinyl, benzopyrone, benzofuranone, dioxolanyl, dihydropyranyl, pyranyl, thieno[3,2-b]thiophenyl, decahydroisoquinolinyl, furanone, imidazolinyl, imidazolidinyl, indolinyl, indolizinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, oxiranyl, oxetanyl, phenothiazinyl, phenoxazinyl, piperidinyl, piperazinyl, 4-piperidinone, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, trithianyl, tetrahydroquinolinyl, thienyl (i.e., thiophenyl), thiomorpholinyl, thioxomorpholinyl, 1-oxothiomorpholinyl, and 1,1-dioxothiomorpholinyl. Examples of spiro heterocyclic rings include, but are not limited to, bicyclic and tricyclic 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 heterocyclic groups 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 heterocyclic group can be attached through any ring of the fused system. yl, benzodioxolyl, benz[b][1,4]dioxanyl yl, 1,4-benzodioxanyl, benzopyranyl, benzodioxinyl, benzopyrone, benzofuranone, dioxolanyl, dihydropyranyl, pyranyl, thieno[3,2-b]thiophenyl, decahydroisoquinolinyl, furanone, imidazolinyl, imidazolidinyl, indolinyl, indolizinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, oxiranyl, oxetanyl, phenothiazinyl, phenoxazinyl, piperidinyl, piperazinyl, 4-piperidinone, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, trithianyl, tetrahydroquinolinyl, thienyl (i.e., thiophenyl), thiomorpholinyl, thioxomorpholinyl, 1-oxothiomorpholinyl, and 1,1-dioxothiomorpholinyl. Examples of spiro heterocyclic rings include, but are not limited to, bicyclic and tricyclic 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 heterocyclic groups 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 heterocyclic group can be attached through any ring of the fused system.

[0150] As used herein, the term "oxo group" refers to the =O moiety.

[0151] As used herein, the term "optional" or "optionally" means that the subsequent described event or circumstance may or may not occur, and this description includes instances where the event or circumstance occurs and instances where it does not occur. Thus, the term "optionally substituted" means that any one or more (e.g., 1, 2, 1 to 5, 1 to 3, 1 to 2, etc.) hydrogen atoms on a specified atom or moiety or group may or may not be replaced by an atom or moiety or group other than hydrogen. By way of example only and not limitation, the phrase "methyl optionally substituted by one or more chlorine atoms" encompasses the -CH3, -CH2Cl, -CHCl2, and -CCl3 moieties.

[0152] It should be understood that aspects and embodiments described herein as "comprising" include embodiments "consisting of" and "consisting essentially of".

[0153] As used herein, the term "pharmaceutically acceptable salt" of a given compound refers to salts that retain the biological effectiveness and properties of the given compound and that are not biologically or otherwise undesirable. "Pharmaceutically acceptable salts" include, for example, salts formed with inorganic acids and salts formed with organic acids. In addition, if the compounds described herein are obtained as acid addition salts, the free base can be obtained by basifying a solution of the acid salt. Conversely, if the product is a free base, addition salts, particularly pharmaceutically acceptable addition salts, 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 basic compounds. See, for example, Handbook of Pharmaceutical Salts Properties, Selection, and Use, International Union of Pure and Applied Chemistry, John Wiley & Sons (2008), which is 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, aluminum, 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.

[0154] Isotopically labeled forms of the compounds described herein can be prepared. An isotopically labeled compound has the structure described 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 compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, such as, respectively 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, wherein one or more hydrogens are replaced by deuterium or tritium.

[0155] Some of the compounds provided herein can exist in the form of tautomers. Tautomers are in equilibrium with each other. For example, an amide-containing compound can be in equilibrium with an imidic acid tautomer. Regardless of which tautomer is shown and regardless of the nature of the equilibrium between the tautomers, one of ordinary skill in the art understands that the compounds of the present disclosure include 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.

[0156] Also provided herein are prodrugs of the compounds described herein, or pharmaceutically acceptable salts thereof. A prodrug is a compound that can be administered to an individual and releases, in vivo, a compound described herein as the parent drug compound. It should be understood that prodrugs can be prepared by modifying a functional group on the parent drug compound such that the modification is 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.

[0157] The compounds of the present disclosure or their pharmaceutically acceptable salts may include asymmetric centers and, accordingly, may give rise to enantiomers, diastereomers, and other stereoisomeric forms, which, in accordance with absolute stereochemistry, may be defined as (R)- or (S)-amino acids (or (D)- or (L)-amino acids). The present disclosure is intended to embrace all such possible isomers, as well as their racemic and optically pure forms and mixtures of any ratios thereof. The optically active (+) and (−), (R)- and (S)-, or (D)- and (L)-isomers can be prepared using chiral synthons or chiral reagents or can be resolved using conventional techniques such as chromatography and / or fractional crystallization. Conventional techniques for the preparation / separation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of the racemate (or racemate of a salt or derivative) using, for example, chiral high performance liquid chromatography (HPLC) and chiral supercritical fluid chromatography (SFC). When the compounds described herein contain olefinic double bonds or other geometrically asymmetric centers, unless otherwise specified, the present disclosure is intended to embrace both the E geometric isomers and the Z geometric isomers. Similarly, cis and trans are used in their conventional sense to describe relative spatial relationships.

[0158] "Stereoisomers" refer to compounds that are made up of the same atoms bonded by the same bonds but have different three-dimensional structures and are non-interchangeable. The present disclosure contemplates various stereoisomers or mixtures thereof and includes "enantiomers", which refer to two stereoisomers whose structures are non-overlapping mirror images of each other. "Diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other.

[0159] When enantiomers and / or diastereomeric forms of a given structure exist, a flat bond indicates that all stereoisomeric forms of the structure shown are possible, e.g.,

[0160]

[0161] When enantiomers and / or diastereomeric forms of a given structure exist, the presence of a flat bond and an asterisk (*) symbol indicates that the composition consists of at least 90% by weight of a single isomer of unknown stereochemistry, e.g.,

[0162]

[0163] When enantiomers and / or diastereomeric forms of a given structure exist, a wedge or slash bond indicates that the composition consists of at least 90% by weight of a single enantiomer or diastereomer of known stereochemistry, e.g.,

[0164]

[0165] In relevant cases, combinations of the above symbols can be used. Example substances may contain stereocenters with known stereochemistry and stereocenters with unknown stereochemistry, for example,

[0166]

[0167] In relevant cases, combinations of the above symbols can be used. Example substances may contain stereocenters with known stereochemistry and stereocenters with a mixture of isomers, for example,

[0168]

[0169] Compound

[0170] In one aspect, the present invention provides compounds of formula (I):

[0171] (G1-Z1)-L-(G2-Z2) (I),

[0172] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:

[0173] (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.

[0174] 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 selected from the group consisting of a bond or a (C1-C 50 ) alkyl group, wherein

[0175] (C1-C 50 ) alkyl is optionally substituted with one or more deuterium, halogen, (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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl; and

[0176] (C1-C 50 ) one or more C atoms in the alkyl are optionally replaced by 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(Rx ) 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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl group or 5- to 20-membered heteroaryl group substitution;

[0177] wherein,

[0178] each C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl group or 5- to 20-membered heteroaryl group is optionally substituted by one or more deuterium, halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo group (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)Rz , -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 is substituted;

[0179] 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

[0180] Each n is independently 0-2.

[0181] In some embodiments of the compound of formula (I), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, L is optionally substituted by one or more deuterium, halogen, (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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl-substituted (C1-C 50 )alkyl, wherein

[0182] (C1-C 50 )alkyl, one or more C atoms of which are optionally substituted by one or more -C(Rx ) = 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 carbocyclic group, 3 - to 15 - membered heterocyclic group, C6 - C 14 aryl or 5 - to 20 - membered heteroaryl substituted;

[0183] wherein

[0184] each C3 - C 15 carbocyclic group, 3 - to 15 - membered heterocyclic group, C6 - C 14 aryl or 5 - to 20 - membered heteroaryl is optionally substituted by one or more deuterium, halogen, (C1 - C6)alkyl, (C1 - C6)haloalkyl, oxo group (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 substituted;

[0185] 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

[0186] each n is independently 0-2.

[0187] 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 (C1-C 20 )alkyl, wherein

[0188] (C1-C 20 )alkyl is optionally substituted with one or more deuterium, halogen, (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 carbocyclic, 3 to 15 membered heterocyclic, C6-C 14 aryl or 5 to 20 membered heteroaryl; and

[0189] (C1-C 20 )alkyl one or more C atoms of which are optionally replaced 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 carbocyclic, 3 to 15 membered heterocyclic, C6-C 14 aryl or 5 to 20 membered heteroaryl;

[0190] wherein

[0191] Each C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl is optionally substituted with one or more deuterium, halogen, (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 ;

[0192] 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

[0193] each n is independently 0-2.

[0194] In some embodiments of the compound of formula (I), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 )alkyl, wherein (C1-C 20 )alkyl is optionally substituted with one or more deuterium, halogen, (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- to 8-membered heterocyclic group, C6-C 10 substituted by aryl or 5- to 10-membered heteroaryl; and

[0195] (C1-C 20 ) one or more C atoms in the alkyl are optionally replaced by 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- to 8-membered heterocyclic group, C6-C 10 substituted by aryl or 5- to 10-membered heteroaryl;

[0196] wherein

[0197] each C3-C8 cycloalkyl, 3- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more deuterium, halogen, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo group (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 Substituted;

[0198] 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

[0199] each n is independently 0-2.

[0200] In some embodiments of the compound of formula (I), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 )alkyl, wherein (C1-C 20 )alkyl is optionally substituted by one or more deuterium, halogen, (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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl; and

[0201] (C1-C 20 )alkyl, one or more C atoms of which are optionally replaced by 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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl;

[0202] wherein

[0203] each R x and R y is independently H, (C1-C6)alkyl, (C1-C6)haloalkyl or (C1-C6)cycloalkyl; and

[0204] each n is independently 0-2.

[0205] In some embodiments of the compound of formula (I), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 )alkyl, wherein the (C1-C 20 )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 or -N(R x )(R y )-; and

[0206] (one or more C atoms in the (C1-C 20 )alkyl are optionally replaced 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)-, -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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl;

[0207] wherein

[0208] each R x and R y is independently H, (C1-C6)alkyl, (C1-C6)haloalkyl or (C1-C6)cycloalkyl; and

[0209] each n is independently 0-2.

[0210] 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 (C1-C 20 )alkyl, wherein the (C1-C 20 )alkyl is optionally substituted with one or more deuterium, halogen, (C1-C4)alkyl, (C1-C4)haloalkyl, oxo (C=O), -O(C1-C4)alkyl, -O(C1-C4)haloalkyl or -O(C1-C4)cycloalkyl; and

[0211] (one or more C atoms of the (C1-C 20 )alkyl are optionally 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)-, -N(R x )-, 3- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl;

[0212] wherein

[0213] each R x and R y is independently H, (C1-C3)alkyl, (C1-C3)haloalkyl or (C1-C3)cycloalkyl; and

[0214] each n is independently 0-2.

[0215] 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 (C1-C 20 )alkyl, wherein one or more C atoms of the (C1-C 20 )alkyl are optionally 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 )-; wherein

[0216] each R x and R y is independently H, (C1-C3)alkyl, (C1-C3)haloalkyl or (C1-C3)cycloalkyl; and

[0217] each n is independently 0-2.

[0218] 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 (C1-C 20 )alkyl, wherein one or more C atoms of the (C1-C 20 )alkyl are replaced by one or more -O-.

[0219] 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-, wherein m is 1-12.

[0220] 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 alkyl. In some embodiments, the alkyl is C1-C2, C1-C3, C1-C4, C1-C5, C1-C6, C1-C8, C1-C 10 , C1-C 12 , C1-C 15 , C1-C 20 , C1-C 30 , C1-C 40 , or C1-C 50 . In some embodiments, the alkyl is C1-C 50 . In some embodiments, the alkyl is C1-C 40 . In some embodiments, the alkyl is C1-C 30 . In some embodiments, the alkyl is C1-C 20 . In some embodiments, the alkyl is C1-C 15 . In some embodiments, the alkyl is C1-C 12 . In some embodiments, the alkyl is C1-C 10 . In some embodiments, the alkyl is C1-C8. In some embodiments, the alkyl is C1-C6. In some embodiments, the alkyl is C1-C4. In some embodiments, the alkyl is C1-C3. In some embodiments, the alkyl is methyl or ethyl. In some embodiments, the alkyl is methyl. In some embodiments, the alkyl is ethyl. In some embodiments, the alkyl is unbranched. In some embodiments, the alkyl is branched.

[0221] 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, the alkyl of L is optionally substituted with one or more deuterium, halogen, (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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl. In some embodiments, the alkyl is optionally substituted with one or more deuterium, halogen, (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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl.

[0222] 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, the alkyl of L is optionally substituted with one or more deuterium, halogen, (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, the alkyl is optionally substituted with one or more deuterium, halogen, (C1-C4)alkyl, (C1-C4)haloalkyl, oxo (C=O), -O(C1-C4)alkyl, -O(C1-C4)haloalkyl or -O(C1-C4)cycloalkyl.

[0223] 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, one or more C atoms of the alkyl of L are optionally replaced 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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl substitution. In some embodiments, one or more C atoms of the alkyl are optionally replaced by 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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl substitution. In some embodiments, one or more C atoms of the alkyl are optionally replaced by 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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl substitution. In some embodiments, one or more C atoms of the alkyl are optionally replaced by one or more -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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl substitution. In some embodiments, one or more C atoms of the alkyl are optionally replaced by one or more -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 heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl substitution. In some embodiments, one or more C atoms of the alkyl are optionally replaced by 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 )- substitution. In some embodiments, one or more C atoms of the alkyl are optionally replaced by one or more -O- or -N(R x )- substitution. In some embodiments, one or more C atoms of the alkyl are optionally replaced by one or more -O- substitution.

[0224] 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 C3-C of L 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl is optionally substituted by one or more deuterium, halogen, (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 ; wherein

[0225] 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 0-2.

[0226] 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 C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl and 5- to 20-membered heteroaryl is optionally substituted with one or more deuterium, halogen, (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 ; wherein

[0227] 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

[0228] each n is independently 0-2.

[0229] 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 C3-C8 cycloalkyl, 3- to 8-membered heterocyclic group, C6-C 10 aryl, and 5- to 10-membered heteroaryl of L is optionally substituted with one or more deuterium, halogen, (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 ; wherein

[0230] 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

[0231] each n is independently 0-2.

[0232] 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-, where m is 1-25. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is 1-20. In some embodiments, L is -(-O-CH2CH2) m-O-, where m is from 1 to 15. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 10. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 6. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 4. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 3. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 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.

[0233] In some embodiments of the compound of formula (I), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, L is -(-O-CH2CH2) m -O-, where m is from 1 to 25. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 20. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 15. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 10. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 6. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 4. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 1 to 3. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is from 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.

[0234] 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-, where m is 1-25. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is 1-20 and one or more O are replaced by NH. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is 1-15 and one or more O are replaced by NH. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is 1-10 and one or more O are replaced by NH. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is 1-6 and one or more O are replaced by NH. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is 1-4 and one or more O are replaced by NH. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is 1-3 and one or more O are replaced by NH. In some embodiments, L is -(-O-CH2CH2) m -O-, where m is 1-2 and one or more O are replaced by NH. In some embodiments, L is -(-O-CH2CH2)-O-. In some embodiments, m is 1 and one O is replaced by NH. In some embodiments, m is 2 and one O is replaced by NH. In some embodiments, m is 3 and one O is replaced by NH. In some embodiments, m is 4 and one O is replaced by NH. In some embodiments, m is 5. In some embodiments, m is 6 and one O is replaced by NH. In some embodiments, m is 10 and one O is replaced by NH. In some embodiments, m is 11 and one O is replaced by NH. In some embodiments, L is -O-CH2CH2-O-CH2CH2-O-CH2CH2-NH-CH2CH2-O-CH2CH2-O-.

[0235] 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 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 carbocyclene, an optionally substituted heterocyclene, an optionally substituted arylene, an optionally substituted heteroarylene or any combination thereof.

[0236] 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 selected from the group consisting of ethylene glycol, polyethylene glycol (PEG), and PEG derivatives. In some embodiments, the PEG derivative comprises polyethylene glycol (PEG), wherein one or more C atoms of the PEG are substituted with one or more groups, and / or one or more C atoms of the PEG are replaced with one or more groups. In some embodiments, one or more C atoms in the PEG are each independently substituted with one or more deuterium, halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo group (C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(R x )(R y )-, C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl; and / or one or more C atoms in the PEG moiety are each independently replaced 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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl;

[0237] Wherein

[0238] each C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl is optionally substituted by one or more deuterium, halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo group (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 )(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 ;

[0239] each R x 、Rxx , R y , R yy and R z are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl or (C1-C6)cycloalkyl; and

[0240] each n is independently 0-2.

[0241] 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 comprises a polymer.

[0242] 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 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.

[0243] 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 a bond.

[0244] 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 binds at any available position of G1 or Z1, and at any available position of G2 or Z2.

[0245] 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 binds to:

[0246] (i) the Z1 moiety of (G1-Z1); and

[0247] (ii) the Z2 moiety of (G2-Z2).

[0248] 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 binds to:

[0249] (i) the G1 moiety of (G1-Z1); and

[0250] (ii) the G2 moiety of (G2-Z2).

[0251] 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 binds to:

[0252] (i) the Z1 moiety of (G1-Z1); and

[0253] (ii) The G2 portion of (G2-Z2).

[0254] 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 to:

[0255] (i) The G1 portion of (G1-Z1); and

[0256] (ii) The Z2 portion of (G2-Z2).

[0257] 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, when R 2 is unsubstituted methyl, then:

[0258] (1) Q 1 is a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Q 1 is optionally substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2, C 3-10 cycloalkyl or -OH, and wherein Q 1 is not unsubstituted pyridyl, or

[0259] (2) Q 1 is phenyl, wherein the phenyl of Q 1 is substituted with:

[0260] (i) At least one C 3-6 alkyl, wherein the at least one C 3-6 alkyl is optionally substituted with one or more halo groups, or

[0261] (ii) At least one C 3-10 cycloalkyl, wherein the at least one C 3-10 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl, or

[0262] (iii) At least one 5- to 20-membered heteroaryl, wherein the at least one 5- to 20-membered heteroaryl is optionally substituted with one or more C 1-6 alkyl.

[0263] 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, (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-Z2 are the same.

[0264] 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, (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.

[0265] 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, (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.

[0266] 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, the compound of formula (I) has enhanced GYS1 inhibition compared to G1, G1-Z1, G2, and / or G2-Z2. In some embodiments, the compound of formula (I) has enhanced GYS1 inhibition compared to G1. In some embodiments, the compound of formula (I) has enhanced GYS1 inhibition compared to G1-Z1. In some embodiments, the compound of formula (I) has enhanced GYS1 inhibition compared to G2. In some embodiments, the compound of formula (I) has enhanced GYS1 inhibition compared to G2-Z2.

[0267] In some embodiments, (G1-Z1)-L-(G2-Z2) is a bivalent inhibitor with the potential to simultaneously bind two GYS1 monomers within a single tetrameric complex.

[0268] 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, wherein (G1-Z1) and (G2-Z2) each independently has formula (I-1) or (I-2):

[0269]

[0270] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:

[0271] Y 2 and Y 3 are each C, or

[0272] Y 2 and Y 3 one of them is N, and Y 2 and Y 3 the other one is C;

[0273] X 1 and X 2 are each independently H, C 1-6 alkyl or C 1-6 alkoxy;

[0274] X 3 and X 4 are each independently H, halo, C 1-6 alkyl, C 1-6 alkoxy or a 5- to 20-membered heteroaryl, wherein the C 3 of X 4 alkyl is optionally substituted with one or more halo; 1-6

[0275] X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl;

[0276] Or

[0277] (1) L 1 is absent; and

[0278] Q 1 is selected from (i) to (iv):

[0279] (i) Phenyl, wherein the phenyl of Q 1 is substituted with 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 heterocyclic group), C 3-10substituted with a cycloalkyl group or a 5- to 20-membered heteroaryl group, wherein

[0280] C 1-6 the alkyl group is optionally substituted with one or more halogen atoms, -NH-C(O)-NH(C 1-6 alkyl), -NH-C(O)-C 1-6 alkyl or -NH-C(O)-C 1-6 alkoxy group,

[0281] C 3-10 the cycloalkyl group is optionally substituted with one or more halogen atoms or C 1-6 alkyl, and

[0282] the 5- to 20-membered heteroaryl group is optionally substituted with one or more C 1-6 alkyl,

[0283] (ii) a 3- to 15-membered heterocyclic group, wherein Q 1 the 3- to 15-membered heterocyclic group of which is optionally substituted with one or more oxo groups or C 1-6 alkyl,

[0284] (iii) a 5- to 20-membered heteroaryl group, wherein Q 1 the 5- to 20-membered heteroaryl group of which is optionally substituted with one or more halogen atoms, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein,

[0285] C 1-6 the alkyl group is optionally substituted with one or more halogen atoms, and

[0286] C 3-10 the cycloalkyl group is optionally substituted with one or more halogen atoms or C 1-6 alkyl, and

[0287] (iv) C 3-10 cycloalkyl;

[0288] or

[0289] (2) L 1 is -CH2-; and

[0290] Q 1 is C 3-10 cycloalkyl;

[0291] L 2 is -C(O)- or -S(O)2-

[0292] R 1 is H or C 1-6 alkyl;

[0293] R k is H, a halogen group, -OH, -NH2 or -NH-C(O)C 1-6 alkyl;

[0294] R m is H, -OH or C 1-6 alkyl;

[0295] 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 forms C 3-5 cycloalkyl;

[0296] or R k with R m or R n and the atoms to which they are attached together form cyclopropyl; and R 2 is selected from (i) to (vii):

[0297] (i) C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is optionally substituted by one or more R a wherein R a is:

[0298] (a) -OH,

[0299] (b) cyano,

[0300] (c) C 2-6 alkynyl,

[0301] (d) C 6-20 aryl, wherein the C a of R 6-20 aryl is optionally substituted by one or more halogen groups, cyano, C 1-6 alkoxy or -NH-C(O)-C 1-6 alkyl,

[0302] (e) a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R a is optionally substituted by one or more R c wherein

[0303] R c is a halogen group, an oxo group, C 1-6 alkyl, C 1-6 alkoxy, -C(O)-C 1-6 alkyl or -C(O)-C 1-6 alkoxy, wherein

[0304] Rc of C 1-6 alkyl is optionally substituted by one or more halogen groups or C 2-6 alkynyl, and

[0305] R c -C(O)-C 1-6 alkoxy is optionally substituted by one or more halogen groups,

[0306] (f)-N(R c )(R d ), wherein -N(R c )(R d )'s R c and R d are independently 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)2, -C(O)-(3-15 membered heterocyclic group), -CH2-C(O)-NH2, 3-15 membered heterocyclic group or 5-20 membered heteroaryl, wherein

[0307] R c or R d 's C 1-6 alkyl is optionally substituted by one or more -C(O)-NH2,

[0308] R c or R d 's -C(O)-C 1-6 alkyl is optionally substituted by one or more halogen groups,

[0309] R c or R d 's 3-15 membered heterocyclic group and 5-20 membered heteroaryl are independently optionally substituted by one or more C 1-6 alkyl,

[0310] R c or R d 's -C(O)-(3-15 membered heterocyclic group) is optionally substituted by one or more halogen groups, -C(O)-C 1-6 alkoxy or C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted by one or more halogen groups, C 1-6 alkoxy or C 3-10 cycloalkyl, and

[0311] R c or R d-C(O)-N(C 1-6 alkyl)2's C 1-6 alkyls are each independently optionally substituted with one or more halo groups or C 6-20 aryl,

[0312] (g)-O-R e , where R e is C 1-6 alkyl, C 6-20 aryl, -C(O)-(3- to 15-membered heterocyclic group), -C(O)-N-(C 1-6 alkyl)2 or 5- to 20-membered heteroaryl, where

[0313] R e 's C 1-6 alkyl is optionally substituted with one or more C 1-6 alkoxy groups, where the C 1-6 alkoxy group is optionally substituted with one or more C 2-6 alkynyl groups,

[0314] R e 's C 6-20 aryl is optionally substituted with one or more C 1-6 alkyl groups, and

[0315] R e 's -C(O)-(3- to 15-membered heterocyclic group) is optionally substituted with one or more C 1-6 alkyl, C 1-6 alkoxy or -C(O)-C 1-6 alkoxy groups, where the C 1-6 alkyl is optionally substituted with one or more halo groups, C 1-6 alkoxy or C 3-10 cycloalkyl groups,

[0316] (h)-C(O)-R e , where R e is -NH2, -OH or a 3- to 15-membered heterocyclic group, or

[0317] (i)-S(O)2-R f , where R f is C 1-6 alkyl or a 3- to 15-membered heterocyclic group,

[0318] (ii)C 3-10 cycloalkyl, where R 2 's C 3-10 cycloalkyl is optionally substituted with one or more R q substituents, where R q is a 5- to 20-membered heteroaryl or C 6-20 aryl, where R q 's C6-20 The aryl is optionally substituted by one or more C 1-6 alkoxy groups,

[0319] (iii) a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R 2 is optionally substituted by one or more halo groups, oxo groups, C 1-6 alkyl groups, -C(O)-C 1-6 alkyl groups or 5- to 20-membered heteroaryl groups,

[0320] (iv) a 5- to 20-membered heteroaryl group or -(C 1-4 alkyl)(5- to 20-membered heteroaryl group), wherein the C 1-4 alkyl is optionally substituted by one or more -OH, halo groups, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5- to 20-membered heteroaryl group in the 5- to 20-membered heteroaryl group or -(C 1-4 alkyl)(5- to 20-membered heteroaryl group) is optionally substituted by one or more R s substituents, wherein

[0321] R s is a halo group, 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 heterocyclic group, 5- to 20-membered heteroaryl group or -C(O)-C 1-6 alkoxy, wherein

[0322] R s 's C 1-6 alkyl is optionally substituted by one or more halo groups, 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 alkoxy, and

[0323] R s 's 3- to 15-membered heterocyclic group is optionally substituted by one or more halo groups or -C(O)-C 1-6 alkoxy,

[0324] (v) -N(R g )(R h ), wherein R gand R h independently is H or C 1-6 alkyl,

[0325] (vi)-C(O)-R j , wherein R j is C 3-10 cycloalkyl, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2 or -NH(5-20 membered heteroaryl), and

[0326] (vii) C 6-20 aryl, wherein R 2 of C 6-20 aryl is optionally substituted with one or more 5-20 membered heteroaryl or -O-R p , wherein R p is 3-15 membered heterocyclic group, wherein R p of the 3-15 membered heterocyclic group is optionally substituted with one or more -C(O)-C 1-6 alkyl; and

[0327] wherein (G1-Z1) and (Z2-G2) are each independently substituted with a group bound to L.

[0328] In some embodiments of the compounds of formula (I), (I-1) or (I-2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, the group bound to L comprises a carbon, oxygen, nitrogen or sulfur atom. In some embodiments, the group bound to L comprises a carbon atom. In some embodiments, the group bound to L comprises an oxygen atom. In some embodiments, the group bound to L comprises a nitrogen atom. In some embodiments, the group bound to L comprises a sulfur atom.

[0329] In some embodiments of the compounds of formula (I), (I-1) or (I-2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, the group bound 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 bound to L is at R 2 or R n . In some embodiments, the group bound to L is at R 2 . In some embodiments, the group bound to L is at R n .

[0330] In some embodiments of the compounds of formula (I), (I-1) or (I-2), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the group bound to L comprises a reactive site suitable for binding to L. In some embodiments, the group bound to L comprises a thiol group to form a disulfide bond or a thioether bond, an aldehyde group, a ketone group and a hydrazine group to form a hydrazone bond, a carboxyl group and an amino group to form a peptide bond, a carboxyl group and a hydroxyl group to form an ester bond, a sulfonic acid group to form a sulfonamide bond, an alcohol group to form a carbamate bond, and an amine group to form an amide bond, a sulfonamide bond or a carbamate bond.

[0331] In some embodiments of the compounds of formula (I), (I-1) or (I-2) (such as the compounds of formula (II), (III), (IV) or (V)), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, G1 and G2 are each independently a moiety of formula (I-1) represented by or a moiety of formula (I-1) or (I-2) represented by 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 are as defined for the 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 are as defined elsewhere herein for the compounds of formula (I), (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-B), (I-B1), (I-B2), (I-C), (I-D), (I-D1), (I-D2), (I-E), (I-F), (I-G) or (I-H).

[0332] In some embodiments of the compound of formula (I), (I-1) or (I-2) (such as the compound of formula (II), (III), (IV) or (V)), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, G1 and G2 are each independently a moiety of formula (I-1) represented by , or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, G1 and G2 are each independently a moiety of formula (I-2) represented by .

[0333] In some embodiments of the compound of formula (I), (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , where R 2 and L 2 are as defined for the compound of formula (I-1) or (I-2). In some embodiments, R 2 and L 2 are as defined elsewhere herein for the compound of formula (I), (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-B), (I-B1), (I-B2), (I-C), (I-D), (I-D1), (I-D2), (I-E), (I-F), (I-G) or (I-H).

[0334] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , where L 2 is -C(O)- or -S(O) 2- , and R 2 is C 1-3 alkyl, where C 1-3 alkyl or R 2 is optionally substituted with one or more 3- to 10-membered heterocycles, and where the 3- to 10-membered heterocycle is further optionally substituted with one or more oxo groups or C 1-3 alkyl. In some embodiments, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , where L 2 is -C(O)-, and R 2 is C 1-3 alkyl, where C 1-3 alkyl or R 2Optionally substituted by one or more 3- to 10-membered heterocycles, and wherein the 3- to 10-membered heterocycle is further optionally substituted by one or more oxo groups or C 1-3 alkyl groups. In some embodiments, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , wherein L 2 is -S(O)2-, and R 2 is C 1-3 alkyl, wherein the C 1-3 alkyl or R 2 is optionally substituted by one or more 3- to 10-membered heterocycles, and wherein the 3- to 10-membered heterocycle is further optionally substituted by one or more oxo groups or C 1-3 alkyl groups.

[0335] In some embodiments of the compounds of formula (I-1) or (I-2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , wherein L 2 is -C(O)- or -S(O)2-, and R 2 is C 1-3 alkyl. In some embodiments, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , wherein L 2 is -C(O)-, and R 2 is C 1-3 alkyl. In some embodiments, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , wherein L 2 is -S(O)2-, and R 2 is C 1-3 alkyl.

[0336] In some embodiments of the compounds of formula (I-1) or (I-2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , wherein L 2 is -C(O)- or -S(O)2-. In some embodiments, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , wherein L 2 is -C(O)-. In some embodiments, Z1 and Z2 are each independently a moiety of formula (I-1) or (I-2) represented by , wherein L 2 is -S(O)2-.

[0337] 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, R 2 is -C(O)- or -S(O)2-. In some embodiments, L 2 is -C(O)-. In some embodiments, L 2 is -S(O)2-.

[0338] 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 1 is a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Q 1 is optionally substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, and the C 3-10 cycloalkyl is optionally substituted with one or more C 1-6 alkyl or halo groups. In some embodiments, Q 1 is a 5- to 6-membered heteroaryl, wherein the 5- to 6-membered heteroaryl of Q 1 is optionally substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, and the C 3-10 cycloalkyl is optionally substituted with one or more C 1-6 alkyl or halo groups. In some embodiments, Q 1 is pyridyl, wherein the pyridyl of Q 1 is optionally substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, and the C 3-10 cycloalkyl is optionally substituted with one or more C 1-6 alkyl or halo groups. In some embodiments, Q 1 is 2-pyridyl or 3-pyridyl, wherein the 2-pyridyl or 3-pyridyl of Q 1 is optionally substituted with one or more halo groups, C1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 substituted by cycloalkyl, where C 1-6 alkyl is optionally substituted by one or more halogen groups, and C 3-10 cycloalkyl is optionally substituted by one or more C 1-6 alkyl or halogen groups. In some embodiments, Q 1 is 2-pyridyl, where the 2-pyridyl of Q 1 is optionally substituted by one or more halogen groups, C 1-6 alkyl, C 1-6 alkoxy, -NH2 or C 3-10 substituted by cycloalkyl, where C 1-6 alkyl is optionally substituted by one or more halogen groups, and C 3-10 cycloalkyl is optionally substituted by one or more C 1-6 alkyl or halogen groups. In some embodiments, Q 1 is 2-pyridyl, where the 2-pyridyl of Q 1 is optionally substituted by one or more halogen groups, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 substituted by cycloalkyl, where C 1-6 alkyl is optionally substituted by one or more halogen groups, and C 3-10 cycloalkyl is optionally substituted by one or more C 1-6 alkyl or halogen groups. In some embodiments, Q 1 is 2-pyridyl, where the 2-pyridyl of Q 1 is optionally substituted by one or more fluoro groups, chloro groups, methyl groups, isopropyl groups, tert-butyl groups, cyclopropyl groups, cyclobutyl groups or methoxy groups, where the methyl groups are optionally substituted by one or more fluoro groups, and the cyclopropyl groups and cyclobutyl groups are independently optionally substituted by one or more methyl groups or fluoro groups.

[0339] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is selected from the group consisting of:

[0340] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is selected from the group consisting of:

[0341] 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 1 is phenyl, wherein Q 1 of the phenyl is substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclic group), or C 3-10 cycloalkyl, wherein C 1-6 alkyl is optionally substituted with one or more halo groups, and C 3-10 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl. In some embodiments, Q 1 is phenyl, wherein Q 1 of the phenyl is substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, or C 3-10 cycloalkyl, wherein C 1-6 alkyl is optionally substituted with one or more halo groups, and C 3-10 cycloalkyl is optionally substituted with one or more C 1-6 alkyl or halo groups. In some embodiments, Q 1 is phenyl, wherein Q 1 of the phenyl is substituted with one or more fluorine, chlorine, methyl, isopropyl, sec-butyl, tert-butyl, prop-1-en-2-yl, cyclopropyl, or cyclobutyl, wherein methyl, isopropyl, sec-butyl, and tert-butyl are independently optionally substituted with one or more halo groups, and cyclopropyl and cyclobutyl are independently optionally substituted with one or more fluoro groups or methyl.

[0342] 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 1 is phenyl, wherein Q 1 of the phenyl is substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclic group), C 3-10 cycloalkyl, or a 5- to 20-membered heteroaryl, wherein C 1-6 alkyl is optionally substituted with one or more halo groups, -NH-C(O)-NH(C 1-6 alkyl), -NH-C(O)-C 1-6 alkyl, or -NH-C(O)-C 1-6 alkoxy, C3-10 The cycloalkyl group is optionally substituted with one or more halogen groups or C 1-6 alkyl groups, and the 5- to 20-membered heteroaryl group is optionally substituted with one or more C 1-6 alkyl groups.

[0343] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is selected from the group consisting of:

[0344] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is selected from the group consisting of: In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is selected from the group consisting of:

[0345] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of Q 1 is optionally substituted with one or more oxo groups. In some embodiments, Q 1 is

[0346] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is (i) a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of Q 1 is optionally substituted with one or more oxo groups or C 1-6 alkyl groups, (ii) a 5- to 20-membered heteroaryl group, wherein the 5- to 20-membered heteroaryl group of Q 1 is optionally substituted with one or more halogen groups, C 1-6 alkyl groups, C 2-6 alkenyl groups, C 1-6 alkoxy groups, -NH2 or C3-10 Cycloalkyl substituted, wherein C 1-6 alkyl is optionally substituted by one or more halogen groups, and C 3-10 cycloalkyl is optionally substituted by one or more halogen groups or C 1-6 alkyl, or (iii) C 3-10 cycloalkyl.

[0347] 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 1 is a 3- to 15-membered heterocyclic group, wherein Q 1 of the 3- to 15-membered heterocyclic group is optionally substituted by one or more oxo groups or C 1-6 alkyl. In some embodiments, Q 1 is selected from the group consisting of:

[0348] 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 1 is a 5- to 20-membered heteroaryl, wherein Q 1 of the 5- to 20-membered heteroaryl is optionally substituted by one or more halogen groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl substituted, wherein C 1-6 alkyl is optionally substituted by one or more halogen groups, and C 3-10 cycloalkyl is optionally substituted by one or more halogen groups or C 1-6 alkyl. In some embodiments, Q 1 is a 5- to 20-membered heteroaryl, wherein Q 1 of the 5- to 20-membered heteroaryl is optionally substituted by one or more C 1-6 alkyl. In some embodiments, is a 5- to 20-membered heteroaryl, wherein Q 1 of the 5- to 20-membered heteroaryl contains one or more ring Ns. In some embodiments, is a 5- to 20-membered heteroaryl, wherein Q 1 of the 5- to 20-membered heteroaryl contains two ring Ns. In some embodiments, is a 5- to 20-membered heteroaryl, wherein Q 1 of the 5- to 20-membered heteroaryl is monocyclic or bicyclic. In some embodiments, is a 5- to 20-membered heteroaryl, wherein Q 1 of the 5- to 20-membered heteroaryl is monocyclic. In some embodiments, is a 5- to 20-membered heteroaryl, wherein Q 1 of the 5- to 20-membered heteroaryl is bicyclic. In some embodiments, Q1 Selected from the group consisting of:

[0349] 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 1 is C 3-10 cycloalkyl. In some embodiments, Q 1 is C 3-6 cycloalkyl. In some embodiments, Q 1 is cyclopropyl.

[0350] 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, L 1 is absent or is -CH2-. In some embodiments, L 1 is absent. In some embodiments, Y 1 is -CH2-. In some embodiments, L 1 is absent and Q 1 is C 3-10 cycloalkyl. In some embodiments, L 1 is absent and Q 1 is C 3-6 cycloalkyl. In some embodiments, L 1 is absent and Q 1 is cyclopropyl. In some embodiments, L 1 is -CH2- and Q 1 is C 3-10 cycloalkyl. In some embodiments, L 1 is -CH2- and Q 1 is C 3-6 cycloalkyl. In some embodiments, L 1 is -CH2- and Q 1 is cyclopropyl.

[0351] 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, X 1 , X 2 , X 3 , X 4 and X 5 are each H.

[0352] 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, R 1is H or C 1-6 alkyl. In some embodiments, R 1 is H. In some embodiments, R 1 is C 1-3 alkyl. In some embodiments, R 1 is methyl.

[0353] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R k is H, halogen, -OH, -NH2 or -NH-C(O)C 1-6 alkyl. In some embodiments, R k is H. In some embodiments, R k is halogen. In some embodiments, R k is F.

[0354] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R m is H, -OH or C 1-6 alkyl. In some embodiments, R m is H.

[0355] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R n is H, C 1-6 alkyl or C 3-10 cycloalkyl. In some embodiments, R n is H.

[0356] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R m is H, R n is H, and R k is H, halogen, -OH, -NH2 or -NH-C(O)C 1-6 alkyl. In some embodiments, R m is H, R n is H, and R k is halogen, -OH or -NH2. In some embodiments, R m is H, R n is H, and R k is halogen. In some embodiments, R m is H, R n is H, and R k is fluoro.

[0357] 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, R k together with R m or R n and the atoms to which they are attached form cyclopropyl.

[0358] 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, R n together with the carbon atom to which it is attached forms a C 3-5 cycloalkyl. In some embodiments, R n together with the carbon atom to which it is attached forms cyclopropyl.

[0359] 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, R 1 is H.

[0360] 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, R 2 is C 1-6 alkyl, wherein the C 2 alkyl of R 1-6 is optionally substituted with one or more R a substituents. In some embodiments, R 2 is C 1-6 alkyl, wherein the C 2 alkyl of R 1-6 is substituted with one or more R a substituents, wherein R a is -OH or a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of R a is optionally substituted with one or more R b substituents. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a substituents, wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more R b substituents. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a substituents, wherein R ais -OH or a 5- to 10-membered heteroaryl, wherein R a The 5- to 10-membered heteroaryl of 1-6 is optionally substituted with one or more C 1-6 alkyl groups, wherein the C 1-6 alkyl group is optionally substituted with one or more halogen groups, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, -NH-C(O)C 1-6 alkyl or -NH-C(O)-C 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more methyl groups, wherein the methyl group is optionally substituted with one or more fluorine groups.

[0361] In some embodiments of the compounds of formula (I-1) or (I-2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is a 5- to 20-membered heteroaryl or -(C 1-4 alkyl)(5- to 20-membered heteroaryl), wherein the C 1-4 alkyl group is optionally substituted with one or more -OH, halogen groups, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein 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, wherein the C 1-4 alkyl group is optionally substituted with one or more –OH, halogen groups, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5- to 20-membered heteroaryl is optionally substituted with one or more R s . In some embodiments, R 2 is (methyl)(5- to 20-membered heteroaryl), wherein the methyl group is optionally substituted with one or more –OH, halogen groups, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5- to 20-membered heteroaryl is optionally substituted with one or more R s . In some embodiments, R s is a halogen group, C 1-6 alkyl, C 1-6 alkoxy, -NH2, -NH(C1-6 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 heterocyclic group, 5- to 20-membered heteroaryl or -C(O)-C 1-6 alkoxy. In some embodiments, R s of C 1-6 alkyl is optionally substituted with one or more halo groups, 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 alkoxy, and the 3- to 15-membered heterocyclic group of R s is optionally substituted with one or more halo groups or -C(O)-C 1-6 alkoxy.

[0362] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of: In some embodiments of the compound of formula (I), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is

[0363] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of:

[0364] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of: In some embodiments, R 2 is

[0365] 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, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is substituted with one or more R a wherein R a is a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R a is optionally substituted with one or more R c .

[0366] 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, in some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is a 3- to 8-membered heterocyclic group, wherein the 3- to 8-membered heterocyclic group of R a is optionally substituted with one or more R c wherein R c is oxo, C 1-6 alkyl or -C(O)-C 1-6 alkoxy, wherein the C c of R 1-6 alkyl is optionally substituted with one or more halogen groups, and the -C(O)-C c of R 1-6 alkoxy is optionally substituted with one or more halogen groups. In some embodiments, R 2 is selected from the group consisting of:

[0367]

[0368] 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, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -O-R e wherein R e is -C(O)-(3- to 15-membered heterocyclic group), wherein the -C(O)-(3- to 15-membered heterocyclic group) of R e is optionally substituted with one or more C 1-6 alkyl, wherein C1-6 The alkyl group is optionally substituted by one or more halogen groups, C 1-6 alkoxy groups or C 3-10 cycloalkyl groups. In some embodiments, R 2 is selected from the group consisting of:

[0369]

[0370] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted by one or more R a wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and the other of R c and R d is -C(O)-C 1-6 alkyl, -C(O)-N(C 1-6 alkyl)2 or -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is selected from the group consisting of:

[0371] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is ethyl, wherein the ethyl of R 2 is substituted by one or more R a wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and the other of R c and R d is -C(O)-C 1-6 alkyl. In some embodiments, R 2 is

[0372] In some embodiments of the compound of formula (I-1) or (I-2), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, X 1 and X 2 are each independently H, C 1-6 alkyl or C1-6 Alkoxy. In some embodiments, X 1 and X 2 are each H.

[0373] 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, X 3 and X 4 are each independently H, halo, C 1-6 alkyl, C 1-6 alkoxy or a 5- to 20-membered heteroaryl, wherein the C 3 of X 4 alkyl is optionally substituted with one or more halo. 1-6 is optionally substituted with one or more halo.

[0374] 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, X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl. In some embodiments, X 5 is H, C 1-4 alkyl, C 1-3 alkoxy or C 3-6 cycloalkyl. In some embodiments, X 5 is H. In some embodiments, X 5 is isopropyl, n-butyl, isobutyl or tert-butyl.

[0375] 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, X 1 -X 5 are each H, and Q 1 is a 5- to 20-membered heteroaryl optionally substituted with one or more halo, C 1-6 alkyl, -NH2 or C 3-10 cycloalkyl, wherein the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl. In some embodiments, X 1 -X 5 are each H, and Q 1 is a 5- to 6-membered heteroaryl optionally substituted with one or more halo, C 1-6 alkyl, -NH2 or C 3-10 cycloalkyl, wherein the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6Alkyl substitution. In some embodiments, X 1 -X 5 are each H, and Q 1 is a pyridyl group optionally substituted with one or more halo groups, C 1-6 alkyl, -NH2 or C 3-10 cycloalkyl, wherein the C 3-10 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl. In some embodiments, X 1 -X 5 are each H, and Q 1 is a pyridyl group optionally substituted with one or more halo groups, C 1-4 alkyl, -NH2 or C 3-4 cycloalkyl, wherein the C 3-4 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl. In some of the above embodiments, R m is H and R n is H. In some of the above embodiments, R 1 is H.

[0376] In some embodiments of the compounds of formula (I-1) or (I-2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing or (I-2), X 1 -X 5 are each H, and Q 1 is a phenyl group substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclic group) or C 3-10 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, and the C 3-10 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl. In some embodiments, X 1 -X 5 are each H, and Q 1 is a phenyl group substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), -NH-C(O)-(3- to 10-membered heterocyclic group) or C 3-10 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, and the C 3-10 cycloalkyl is optionally substituted with one or more halo groups or C1-6 Alkyl substitution. In some embodiments, X 1 -X 5 are each H, and Q 1 is phenyl substituted with one or more halo groups, C 1-4 alkyl, C 2-4 alkenyl, -NH2, -NH-C(O)-(C 1-4 alkyl), -NH-C(O)-(3- to 10-membered heterocyclic group), or C 3-4 cycloalkyl, wherein the C 1-4 alkyl is optionally substituted with one or more halo groups, and the C 3-4 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl.

[0377] In some embodiments of the compounds of formula (I-1) or (I-2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 1 is H. In some of the above embodiments, R m is H and R n is H. In some of the above embodiments, R k together with R m or R n and the atoms to which they are attached form cyclopropyl.

[0378] In some embodiments of the compound of formula (I-1) or any of its embodiments or variants such as the compounds of formula (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-B), (I-B1), (I-B2), (I-C), (I-D), (I-D1), (I-D2), (I-E), (I-F), (I-G), or (I-H), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, the moiety having a carbon atom R k 、R m 、R n and R 1 represented by has the stereochemical configuration of the formula wherein X 1 、X 2 、X 3 、X 4 、X 5 、Y 2 、Y 3 、R 1 、R k 、R m and R n are as defined elsewhere herein.

[0379] In some embodiments of the compound of formula (I-1) or any of its embodiments or variants such as the compounds of formula (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-B), (I-B1), (I-B2), (I-C), (I-D), (I-D1), (I-D2), (I-E), (I-F), (I-G) or (I-H), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, the moiety having a carbon atom R k 、R m 、R n and R 1 represented by has the stereochemical configuration of the formula wherein X 1 、X 2 、X 3 、X 4 、X 5 、Y 2 、Y 3 、R 1 、R k 、R m and R n are as defined elsewhere herein.

[0380] In some embodiments of the compound of formula (I-1) or any of its embodiments or variants such as the compounds of formula (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-B), (I-B1), (I-B2), (I-C), (I-D), (I-D1), (I-D2), (I-E), (I-F), (I-G) or (I-H), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, the moiety having a carbon atom R k 、R m 、R n and R 1 represented by has the stereochemical configuration of the formula wherein R 1 、R m and R n are each H, and X 1 、X 2 、X 3 、X 4 、X 5 、Y 2 、Y 3 and R k are as defined elsewhere herein.

[0381] In some embodiments of the compound of formula (I-1) or any of its embodiments or variants such as the compounds of formula (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-B), (I-B1), (I-B2), (I-C), (I-D), (I-D1), (I-D2), (I-E), (I-F), (I-G) or (I-H), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, the moiety having a carbon atom R k 、R m 、R n and R 1 represented by has the stereochemical configuration of the formula wherein R 1 、R m and R n are each H, R k is halo or H, and X 1 、X 2 、X 3 、X 4 、X 5 、Y 2 and Y 3 are as defined elsewhere herein. In some embodiments, moiety R k is fluoro.

[0382] In some embodiments of the compound of formula (I-1) or any of its embodiments or variants such as the compounds of formula (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-B), (I-B1), (I-B2), (I-C), (I-D), (I-D1), (I-D2), (I-E), (I-F), (I-G) or (I-H), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, the moiety having a carbon atom R k 、R m 、R n and R 1 represented by has the stereochemical configuration of the formula wherein R 1 、R m and R n are each H, R k is fluoro, and X 1 、X 2 、X 3 、X 4 、X 5, Y 2 and Y 3 as defined elsewhere herein. In some embodiments, Y 2 and Y 3 are each C. In some embodiments, Y 2 and Y 3 one of which is C, and Y 2 and Y 3 the other of which is N.

[0383] In some embodiments, provided herein are compounds of formula (I-1), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts thereof, wherein said compounds are compounds of formula (I-A):

[0384]

[0385] or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein Y 1 is CH or N; R x and R z are independently H, halo, C 1-6 alkyl or -NH2, wherein when Y 1 is CH, the C x or R z alkyl of R 1-6 may optionally be 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 cycloalkyl, wherein the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl.

[0386] In some embodiments of the compounds of formula (I-A), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, R x and R z are independently H, fluoro, chloro or methyl; and R y is (i) isopropyl, (ii) isopropenyl or (iii) C 3-4 cycloalkyl, wherein the C 3-4 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; and R y is (i) isopropyl or (ii) C 3-4 cycloalkyl, wherein the C 3-4The cycloalkyl group is optionally substituted with one or more fluoro groups or methyl groups. In some embodiments, R x is H, a fluoro group, a chloro group or a methyl group; R z is H; and R y is (i) isopropyl or (ii) C 3-4 cycloalkyl, wherein C 3-4 cycloalkyl is optionally substituted with one or more fluoro groups or methyl groups.

[0387] In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R x is a fluoro group or a methyl group optionally substituted with one or more fluoro groups; R y is (i) isopropyl, (ii) isopropenyl, or (iii) C 1-6 cycloalkyl optionally substituted with one or more halo groups or C 3-4 alkyl, or (iv) butyl; and R z is a fluoro group or a methyl group; provided that at least one of R x and R z is a halo group, CF2 or CF3.

[0388] In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or a halo group. In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or a fluoro group. In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is a fluoro group.

[0389] In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is optionally substituted with one or more R a substituents. In some embodiments, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is substituted with one or more R a substituents, wherein R a is -OH or a 5-20 membered heteroaryl group, wherein the 5-20 membered heteroaryl group of R a is optionally substituted with one or more R bSubstituted. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more R b Substituted. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo, -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 alkoxy. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more methyls, wherein the methyl is optionally substituted with one or more fluorines.

[0390] In some embodiments of the compound of formula (I-A), or its stereoisomers or tautomers, 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- to 20-membered heteroaryl), wherein the C 1-4 alkyl is optionally substituted with one or more -OH, halo, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5- to 20-membered heteroaryl is optionally substituted with one or more R s Substituted. In some embodiments, R s is 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 6-20Aryl, C 3-10 Cycloalkyl, 3- to 15-membered heterocycloalkyl, 5- to 20-membered heteroaryl, or -C(O)-C 1-6 Alkoxy. In some embodiments, the C s of R 1-6 alkyl is optionally substituted with one or more halo groups, 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 alkoxy, and the 3- to 15-membered heterocycloalkyl of R s is optionally substituted with one or more halo groups or -C(O)-C 1-6 alkoxy.

[0391] In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of:

[0392] In some embodiments, R 2 is

[0393] In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is 3- to 8-membered heterocycloalkyl, wherein the 3- to 8-membered heterocycloalkyl of R a is optionally substituted with one or more R c wherein R c is oxo, C 1-6 alkyl, or -C(O)-C 1-6 alkoxy, wherein the C c of R 1-6 alkyl is optionally substituted with one or more halo groups, and the -C(O)-C c of R 1-6 alkoxy is optionally substituted with one or more halo groups. In some embodiments, R 2 is selected from the group consisting of:

[0394] In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -O-R e wherein R e is -C(O)-(3- to 15-membered heterocyclic group), wherein the -C(O)-(3- to 15-membered heterocyclic group) of R e is optionally substituted with one or more C 1-6 alkyl groups, wherein the C 1-6 alkyl group is optionally substituted with one or more halo groups, C 1-6 alkoxy groups, or C 3-10 cycloalkyl groups. In some embodiments, R 2 is selected from the group consisting of:

[0395]

[0396] In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -N(R c )(R d ) wherein one of R c and R d is H, and the other of R c and R d is -C(O)-C 1-6 alkyl, -C(O)-N(C 1-6 alkyl)2, or -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is selected from the group consisting of:

[0397] In some embodiments of the compound of formula (I-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is ethyl, wherein the ethyl of R 2 is substituted with one or more R a wherein R a is -N(R c )(R d), wherein R c and R d one of which is H, and R c and R d the other of which is -C(O)-C 1-6 alkyl. In some embodiments, R 2 is

[0398] In some embodiments of the compound of formula (I-A), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, Y 1 is CH or N; R x and R z are independently H or halo; R y is C 1-6 alkyl or C 3-10 cycloalkyl; R k is H or halo; and R 2 is selected from (i) to (iii):

[0399] (i) C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is substituted with one or more R a , wherein R a is:

[0400] (a) -OH,

[0401] (b) C 6-20 aryl, wherein the C a of R 6-20 aryl is optionally substituted with one or more halo, cyano, C 1-6 alkoxy or -NH-C(O)-C 1-6 alkyl,

[0402] (c) 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R a is optionally substituted with one or more R c , wherein

[0403] R c is halo, oxo, C 1-6 alkyl, C 1-6 alkoxy, -C(O)-C 1-6 alkyl or -C(O)-C 1-6 alkoxy, wherein

[0404] R c of C 1-6 alkyl is optionally substituted with one or more halo or C 2-6 alkynyl, and

[0405] Rc -C(O)-C 1-6 The alkoxy group is optionally substituted with one or more halogen groups,

[0406] (d) - N(R c )(R d ), wherein R of -N(Rc)(Rd) 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)-NH2, -C(O)-NH(C 1-6 alkyl), -C(O)-N(C 1-6 alkyl)2, -C(O)-(3- to 15-membered heterocyclic group), -CH2-C(O)-NH2, 3- to 15-membered heterocyclic group or 5- to 20-membered heteroaryl, wherein

[0407] R c or R d The C 1-6 alkyl of is optionally substituted with one or more -C(O)-NH2,

[0408] R c or R d The -C(O)-C 1-6 alkyl of is optionally substituted with one or more halogen groups,

[0409] R c or R d The 3- to 15-membered heterocyclic group and 5- to 20-membered heteroaryl of are independently optionally substituted with one or more C 1-6 alkyl,

[0410] R c or R d The -C(O)-(3- to 15-membered heterocyclic group) of is optionally substituted with one or more halogen groups, -C(O)-C 1-6 alkoxy or C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more halogen groups, C 1-6 alkoxy or C 3-10 cycloalkyl, and

[0411] R c or R d The C 1-6 alkyl of -C(O)-N(C 1-6 alkyl)2 are independently optionally substituted with one or more halogen groups or C 6-20 aryl,

[0412] (e) - O - Re , wherein R e is C 1-6 alkyl, C 6-20 aryl, -C(O)-(3-15 membered heterocyclic group), -C(O)-N-(C 1-6 alkyl)2 or 5-20 membered heteroaryl, wherein

[0413] R e 's C 1-6 alkyl is optionally substituted by one or more C 1-6 alkoxy groups, wherein C 1-6 alkoxy is optionally substituted by one or more C 2-6 alkynyl groups,

[0414] R e 's C 6-20 aryl is optionally substituted by one or more C 1-6 alkyl groups, and

[0415] R e 's -C(O)-(3-15 membered heterocyclic group) is optionally substituted by one or more C 1-6 alkyl, C 1-6 alkoxy or -C(O)-C 1-6 alkoxy groups, wherein C 1-6 alkyl is optionally substituted by one or more halogen groups, C 1-6 alkoxy or C 3-10 cycloalkyl groups, or

[0416] (f)-C(O)-R e , wherein -C(O)-R e 's R e is -NH2, -OH or 3-15 membered heterocyclic group,

[0417] (ii) 3-15 membered heterocyclic group, wherein R 2 's 3-15 membered heterocyclic group is optionally substituted by one or more halogen groups, oxo groups, C 1-6 alkyl, -C(O)-C 1-6 alkyl or 5-20 membered heteroaryl groups,

[0418] (iii) 5-20 membered heteroaryl or -(C 1-4 alkyl)(5-20 membered heteroaryl), wherein C 1-4 alkyl is optionally substituted by one or more –OH, halogen groups, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2 groups, and wherein 5-20 membered heteroaryl is optionally substituted by one or more R s substituents, wherein

[0419] Rs is a halogen group, 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, a 3- to 15-membered heterocyclic group, a 5- to 20-membered heteroaryl, or -C(O)-C 1-6 alkoxy, wherein

[0420] R s 's C 1-6 alkyl is optionally substituted with one or more halogen groups, 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 alkoxy, and

[0421] R s 's 3- to 15-membered heterocyclic group is optionally substituted with one or more halogen groups or -C(O)-C 1-6 alkoxy.

[0422] In some embodiments of formula (I-A), Y 1 is CH or N; R x and R z are independently H or a halogen group; R y is C 1-6 alkyl or C 3-10 cycloalkyl; R k is H or a halogen group; R 2 is C 1-6 alkyl, wherein R 2 's C 1-6 alkyl is substituted with one or more R a ; R a is

[0423] (a) -OH,

[0424] (b) an optionally substituted C 1-3 aryl with one or more halogen groups, cyano groups, C 1-3 alkoxy or -NH-C(O)-C 6-10 alkyl, or

[0425] (c) an optionally substituted C 1-6 alkyl, C 1-6 alkoxy, -C(O)-C 1-6alkyl or -C(O)-C 1-6 an alkoxy-substituted 3- to 15-membered heterocyclic group.

[0426] In some embodiments of formula (I-A), Y 1 is CH or N; R x and R z are independently H or halo; R y is C 1-3 alkyl or C 3-5 cycloalkyl; R k is halo; R 2 is C a alkyl substituted with one or more R 1-4 wherein R a is

[0427] (a) -OH,

[0428] (b) an optionally halo-, cyano-, C 1-3 alkoxy- or -NH-C(O)-C 1-3 alkyl-substituted C 6-10 aryl, or

[0429] (c) an optionally halo-, oxo-, C 1-6 alkyl-, C 1-6 alkoxy-, -C(O)-C 1-6 alkyl- or -C(O)-C 1-6 alkoxy-substituted C 3-8 heteroaryl.

[0430] In some embodiments, provided herein are compounds of formula (I-1) or formula (I-A), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts thereof, wherein the compound is a compound of formula (I-A1):

[0431]

[0432] or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein R x and R z are independently H, halo, C 1-6 alkyl or -NH2, wherein C 1-6 alkyl is optionally substituted with one or more halo. In some embodiments, R x is H, halo or C 1-6 alkyl; R y is (i) C 1-6 alkyl, (ii) C 2-6 alkenyl or (ii) C 3-10 cycloalkyl; and R z is H, halo or C1-6 Alkyl. In some embodiments, R z is H. In some embodiments, R x and R z at least one of which is a halogen group.

[0433] In some embodiments of the compound of formula (I-A1), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R x is fluoro or methyl; R y is (i) isopropyl or (ii) C 3-4 cycloalkyl; and R z is fluoro or methyl; provided that at least one of R x and R z is a halogen group.

[0434] In some embodiments of the compound of formula (I-A1), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R x is fluoro or methyl optionally substituted with one or more fluoro groups; R y is (i) isopropyl (ii) C optionally substituted with one or more halogen groups or C 1-6 alkyl-substituted C 3-4 cycloalkyl or (iii) butyl; and R z is fluoro or methyl; provided that at least one of R x and R z is a halogen group, CF2 or CF3.

[0435] In some embodiments of the compound of formula (I-A1), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or a halogen group. In some embodiments of the compound of formula (I-A1), or its stereoisomers or tautomers, 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-A1), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R k is fluoro.

[0436] In some embodiments of the compound of formula (I-A1), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, wherein the C 2 of C 1-6 alkyl of R a is optionally substituted with one or more R 2 substituents. In some embodiments, R 1-6 is C2 C of 1-6 the alkyl group is substituted by one or more R a wherein R a is -OH or a 5-20 membered heteroaryl group, wherein the 5-20 membered heteroaryl group of R a is optionally substituted by one or more R b In some embodiments, R 2 is methyl, wherein the methyl group of R 2 is substituted by one or more R a wherein R a is -OH or a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group of R a is optionally substituted by one or more R b In some embodiments, R 2 is methyl, wherein the methyl group of R 2 is substituted by one or more R a wherein R a is -OH or a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group of R a is optionally substituted by one or more C 1-6 alkyl groups, wherein the C 1-6 alkyl group is optionally substituted by one or more halogen groups, -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 alkoxy. In some embodiments, R 2 is methyl, wherein the methyl group of R 2 is substituted by one or more R a wherein R a is -OH or a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group of R a is optionally substituted by one or more methyl groups, wherein the methyl group is optionally substituted by one or more fluorine groups.

[0437] In some embodiments of the compound of formula (I-A1), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is a 5-20 membered heteroaryl group or -(C 1-4 alkyl)(5-20 membered heteroaryl group), wherein the C 1-4 alkyl group is optionally substituted by one or more -OH, halogen groups, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5-20 membered heteroaryl group is optionally substituted by one or more R s In some embodiments, R sis a halogen group, 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, a 3- to 15-membered heterocyclic group, a 5- to 20-membered heteroaryl group, or -C(O)-C 1-6 alkoxy. In some embodiments, the C s of R 1-6 alkyl is optionally substituted with one or more halogen groups, 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 alkoxy, and the 3- to 15-membered heterocyclic group of R s is optionally substituted with one or more halogen groups or -C(O)-C 1-6 alkoxy.

[0438] In some embodiments of the compound of formula (I-A1), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of: In some embodiments, R 2 is

[0439] In some embodiments of the compound of formula (I-A1), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, in some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is a 3- to 8-membered heterocyclic group, wherein the 3- to 8-membered heterocyclic group of R a is optionally substituted with one or more R c wherein R c is an oxo group, C 1-6 alkyl, or -C(O)-C 1-6 alkoxy, wherein the C c of R 1-6 alkyl is optionally substituted with one or more halogen groups, and the -C(O)-C c of R 1-6 alkoxy is optionally substituted with one or more halogen groups. In some embodiments, R2 For

[0440] 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, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -O-R e wherein R e is -C(O)-(3- to 15-membered heterocyclic group), wherein the -C(O)-(3- to 15-membered heterocyclic group) of R e is optionally substituted with one or more C 1-6 alkyl groups, wherein the C 1-6 alkyl group is optionally substituted with one or more halo groups, C 1-6 alkoxy groups or C 3-10 cycloalkyl groups. In some embodiments, R 2 is

[0441] 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, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and the other of R c and R d is -C(O)-C 1-6 alkyl, -C(O)-N(C 1-6 alkyl)2 or -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is

[0442] 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, wherein the ethyl of R 2 is substituted with one or more R a wherein R a is -N(R c )(R d ), wherein Rc and R d one of which is H, and R c and R d the other of which is -C(O)-C 1-6 alkyl. In some embodiments, R 2 is

[0443] In some embodiments, provided herein are compounds of formula (I-1) or formula (I-A), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein the compound is a compound of formula (I-A2):

[0444]

[0445] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R x is H, halo, C 1-6 alkyl or -NH2, wherein C 1-6 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 cycloalkyl, wherein C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl. In some embodiments, R x is H, halo or C 1-6 alkyl, wherein C 1-6 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 cycloalkyl, wherein C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl. 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 cycloalkyl, wherein C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl.

[0446] 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, wherein the methyl is optionally substituted with one or more fluoro groups; and R y is (i) isopropyl, (ii) isopropenyl, (iii) sec-butyl, (iv) tert-butyl or (v) C 3-4 cycloalkyl, wherein the C 3-4 cycloalkyl is optionally substituted with one or more fluoro groups or methyl groups.

[0447] 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 groups; and R y is (i) isopropyl, (ii) C 1-6 cycloalkyl optionally substituted with one or more halo groups or C 3-4 alkyl, or (iii) butyl.

[0448] 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 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.

[0449] 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, wherein the C 2 alkyl of R 1-6 is optionally substituted with one or more R a substituents. In some embodiments, R 2 is C 1-6 alkyl, wherein the C 2 alkyl of R 1-6 is substituted with one or more R a substituents, wherein R a is -OH or a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of R a is optionally substituted with one or more R b substituents. In some embodiments, R 2is methyl, where R 2 the methyl group is substituted by one or more R a where R a is -OH or a 5- to 10-membered heteroaryl group, where R a the 5- to 10-membered heteroaryl group is optionally substituted by one or more R b In some embodiments, R 2 is methyl, where R 2 the methyl group is substituted by one or more R a where R a is -OH or a 5- to 10-membered heteroaryl group, where R a the 5- to 10-membered heteroaryl group is optionally substituted by one or more C 1-6 alkyl groups, where C 1-6 alkyl groups are optionally substituted by one or more halogen groups, -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 alkoxy groups. In some embodiments, R 2 is methyl, where R 2 the methyl group is substituted by one or more R a where R a is -OH or a 5- to 10-membered heteroaryl group, where R a the 5- to 10-membered heteroaryl group is optionally substituted by one or more methyl groups, where the methyl groups are optionally substituted by one or more fluorine groups.

[0450] In some embodiments of the compound of formula (I-A2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is -(C 1-4 alkyl)(5- to 20-membered heteroaryl), where C 1-4 alkyl is optionally substituted by one or more -OH groups, and where the 5- to 20-membered heteroaryl is optionally substituted by one or more R s In some embodiments, R s is a halogen group, 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 heterocyclic group, 5- to 20-membered heteroaryl or -C(O)-C 1-6 alkoxy. In some embodiments, R s the C of1-6 The alkyl group is optionally substituted by one or more halogen groups, C 1-6 alkoxy groups, -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 alkoxy, and the 3- to 15-membered heterocyclic group of R s is optionally substituted by one or more halogen groups or -C(O)-C 1-6 alkoxy.

[0451] In some embodiments of the compound of formula (I-A2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of: In some embodiments, R 2 is

[0452] In some embodiments of the compound of formula (I-A2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, wherein the methyl group of R 2 is substituted by one or more R a wherein R a is a 3- to 8-membered heterocyclic group, wherein the 3- to 8-membered heterocyclic group of R a is optionally substituted by one or more R c wherein R c is an oxo group, C 1-6 alkyl or -C(O)-C 1-6 alkoxy, wherein the C c alkyl of R 1-6 is optionally substituted by one or more halogen groups, and the -C(O)-C c alkoxy of R 1-6 is optionally substituted by one or more halogen groups. In some embodiments, R 2 is selected from the group consisting of:

[0453] In some embodiments of the compound of formula (I-A2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, wherein the methyl group of R 2 is substituted by one or more R a wherein R a is -O-R e wherein R e-C(O)-(3- to 15-membered heterocyclic group), wherein R e The -C(O)-(3- to 15-membered heterocyclic group) is optionally substituted with one or more C 1-6 alkyl groups, wherein the C 1-6 alkyl group is optionally substituted with one or more halo groups, C 1-6 alkoxy groups or C 3-10 cycloalkyl groups. In some embodiments, R 2 is selected from the group consisting of:

[0454]

[0455] In some embodiments of the compound of formula (I-A2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a groups, wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and the other of R c and R d is -C(O)-C 1-6 alkyl, -C(O)-N(C 1-6 alkyl)2 or -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is selected from the group consisting of:

[0456] In some embodiments of the compound of formula (I-A2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is ethyl, wherein the ethyl of R 2 is substituted with one or more R a groups, wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and the other of R c and R d is -C(O)-C 1-6 alkyl. In some embodiments, R 2 is

[0457] In some embodiments, provided herein are compounds of formula (I-1) or formula (I-A), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein the compound is a compound of formula (I-A3):

[0458]

[0459] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R x is H, halo, C 1-6 alkyl or -NH2, wherein C 1-6 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 cycloalkyl, wherein C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl. In some embodiments, R x is H, halo, C 1-6 alkyl or -NH2; and R y is (i) C 1-6 alkyl, (ii) C 3-10 cycloalkyl, wherein C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl.

[0460] 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, chloro or methyl; and R y is (i) H, (ii) isopropyl or (iii) C 3-4 cycloalkyl, wherein C 3-4 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 cycloalkyl, wherein C 3-4 cycloalkyl is optionally substituted with one or more fluoro or methyl.

[0461] 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, Rk is H or a fluoro group. 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 a fluoro group.

[0462] 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, wherein the C 2 alkyl of R 1-6 is optionally substituted with one or more R a . In some embodiments, R 2 is C 1-6 alkyl, wherein the C 2 alkyl of R 1-6 is substituted with one or more R a , wherein R a is -OH or a 5-20 membered heteroaryl group, wherein the 5-20 membered heteroaryl group of R a is optionally substituted with one or more R b . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group of R a is optionally substituted with one or more R b . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group of R a is optionally substituted with one or more C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, -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 alkoxy. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group of R aThe 5-10 membered heteroaryl is optionally substituted with one or more methyl groups, wherein the methyl groups are optionally substituted with one or more fluoro groups.

[0463] 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 1-4 alkyl)(5-20 membered heteroaryl), wherein the 5-20 membered heteroaryl is optionally substituted with one or more R s substituents. In some embodiments, R s is a halogen group, 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, 3-15 membered heterocyclic group, 5-20 membered heteroaryl or -C(O)-C 1-6 alkoxy. In some embodiments, the C s alkyl of R 1-6 is optionally substituted with one or more halogen groups, 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 alkoxy, and the 3-15 membered heterocyclic group of R s is optionally substituted with one or more halogen groups or -C(O)-C 1-6 alkoxy.

[0464] 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 selected from the group consisting of:

[0465] In some embodiments, R 2 is In some embodiments, R 2 is

[0466] 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, R2 is methyl, where R 2 's methyl group is substituted by one or more R a where R a is a 3- to 8-membered heterocyclic group, where R a 's 3- to 8-membered heterocyclic group is optionally substituted by one or more R c where R c is an oxo group, C 1-6 alkyl or -C(O)-C 1-6 alkoxy, where R c 's C 1-6 alkyl is optionally substituted by one or more halogen groups, and R c 's -C(O)-C 1-6 alkoxy is optionally substituted by one or more halogen groups. In some embodiments, R 2 is

[0467] In some embodiments of the compound of formula (I-A3), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, where R 2 's C 1-6 alkyl is optionally substituted by one or more R a where R a is -O-R e . In some embodiments, R 2 is methyl, where R 2 's methyl group is substituted by one or more R a where R a is -O-R e . In some embodiments, R 2 is methyl, where R 2 's methyl group is substituted by one or more R a where R a is -O-R e where R e is -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is

[0468] In some embodiments of the compound of formula (I-A3), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, where R 2 's methyl group is substituted by one or more R a where R a is -N(Rc )(R d ), wherein one of R c and R d is H, and the other of R c and R d is -C(O)-C 1-6 alkyl, -C(O)-N(C 1-6 alkyl)2 or -C(O)-(3- to 15-membered heterocyclic group), wherein the -C(O)-(3- to 15-membered heterocyclic group) of R c or R d is optionally substituted with one or more halo groups, -C(O)-C 1-6 alkoxy or C 1-6 alkyl, and the C c alkyl of the -C(O)-N(C d alkyl)2 of R 1-6 or R 1-6 is independently optionally substituted with one or more halo groups or C 6-20 aryl. In some embodiments, R 2 is

[0469] In some embodiments of the compound of formula (I-A3), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and the other of R c and R d is a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of R c or R d is independently optionally substituted with one or more C 1-6 alkyl. In some embodiments, R 2 is

[0470] In some embodiments, provided herein are compounds of formula (I-1) or formula (I-A), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein the compound is a compound of formula (I-A4):

[0471]

[0472] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R z is H, a halogen, C 1-6 alkyl or -NH2, and R y is (i) C 1-6 alkyl, (ii) C 2-6 alkenyl, or (iii) C 3-10 cycloalkyl, wherein C 3-10 cycloalkyl is optionally substituted with one or more halogens or C 1-6 alkyl. In some embodiments, R z is H, a halogen or C 1-6 alkyl; and R y is (i) C 1-6 alkyl, (ii) C 2-6 alkenyl or (iii) C 3-10 cycloalkyl, wherein C 3-10 cycloalkyl is optionally substituted with one or more halogens or C 1-6 alkyl. 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 cycloalkyl, wherein C 3-10 cycloalkyl is optionally substituted with one or more halogens or C 1-6 alkyl. 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 z is H or methyl; and R y is (i) isopropyl, or (ii) C 3-4 cycloalkyl.

[0473] 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 a halogen. 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 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.

[0474] 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, wherein R2 C of 1-6 The alkyl group is optionally substituted by one or more R a In some embodiments, R 2 is C 1-6 alkyl, wherein R 2 C of 1-6 alkyl is substituted by one or more R a wherein R a is -OH or a 5- to 20-membered heteroaryl, wherein R a 5- to 20-membered heteroaryl is optionally substituted by one or more R b In some embodiments, R 2 is methyl, wherein R 2 methyl is substituted by one or more R a wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein R a 5- to 10-membered heteroaryl is optionally substituted by one or more R b In some embodiments, R 2 is methyl, wherein R 2 methyl is substituted by one or more R a wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein R a 5- to 10-membered heteroaryl is optionally substituted by one or more C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted by one or more halo groups, -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 alkoxy. In some embodiments, R 2 is methyl, wherein R 2 methyl is substituted by one or more R a wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein R a 5- to 10-membered heteroaryl is optionally substituted by one or more methyl groups, wherein the methyl group is optionally substituted by one or more fluoro groups.

[0475] In some embodiments of the compound of formula (I-A4), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of:

[0476] In some embodiments, R 2 is

[0477] 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, wherein the C 2 alkyl of R 1-6 is substituted with one or more R a , wherein R a is a 3- to 15-membered heterocyclic group, and the 3- to 15-membered heterocyclic group of R a is optionally substituted with one or more R c . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is a 3- to 15-membered heterocyclic group, and the 3- to 15-membered heterocyclic group of R a is optionally substituted with one or more R c . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is a 3- to 8-membered heterocyclic group, and the 3- to 8-membered heterocyclic group of R a is optionally substituted with one or more R c . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is a 3- to 8-membered heterocyclic group, and the 3- to 8-membered heterocyclic group of R a is optionally substituted with one or more oxo groups or C 1-6 alkyl. In some embodiments, R 2 is

[0478] 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, wherein the C 2 alkyl of R 1-6 is optionally substituted with one or more R a , wherein R a is -O-R e . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R ais replaced, where R a is -O-R e . In some embodiments, R 2 is methyl, where the methyl of R 2 is replaced by one or more R a , where R a is -O-R e , where R e is -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is

[0479] 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, where the C 2 of R 1-6 alkyl is optionally replaced by one or more R a , where R a is -N(R c )(R d ). In some embodiments, R 2 is methyl, where the methyl of R 2 is replaced by one or more R a , where R a is -N(R c )(R d ). In some embodiments, R 2 is methyl, where the methyl of R 2 is replaced by one or more R a , where R a is -N(R c )(R d ), where one of R c and R d is H, and the other of R c and R d is -C(O)-N(C 1-6 alkyl)2. In some embodiments, R 2 is

[0480] In some embodiments, provided herein is a compound of formula (I-1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (I-B):

[0481]

[0482] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variant or embodiment thereof, wherein Y 1 is CR x or N; wherein, when the ring bearing R x and R y is phenyl, 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 heterocyclic group), C 3-10 cycloalkyl or 5- to 20-membered heteroaryl, wherein said C 1-6 alkyl is optionally substituted with 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 alkoxy, and C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl, and said 5- to 20-membered heteroaryl is optionally substituted with one or more C 1-6 alkyl; wherein, when the ring bearing R x and R y is pyridyl, 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 cycloalkyl, wherein said C 1-6 alkyl is optionally substituted with one or more halo, and said C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl.

[0483] In some embodiments of the compound of formula (I-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Y 1 is CH or N; R x is H, halo, C 1-6 alkyl or NH2, wherein when Y 1 is CH, the C x alkyl of R 1-6 may optionally be substituted with one or more halo; and R y is (i) C 1-6 alkyl, (ii) C 2-6 alkenyl, or (iii) C 3-10Cycloalkyl, wherein C 3-10 The cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl groups. In some embodiments, Y 1 is CH or N; R x is H or a halo group; R y is C 1-6 alkyl or C 3-10 cycloalkyl; and R k together with R m or R n and the atoms to which they are attached form cyclopropyl. In some embodiments, Y 1 is CH or N; R x is H or fluoro; R y is (i) isopropyl or (ii) C 3-4 cycloalkyl; and R k together with R m or R n and the atoms to which they are attached form cyclopropyl. In some embodiments, Y 1 is CH or N; R x is H or fluoro; R y is (i) isopropyl or (ii) C 3-4 cycloalkyl; and R k together with R m and the atoms to which they are attached form cyclopropyl. In some embodiments, Y 1 is CH or N; R x is H or fluoro; R y is (i) isopropyl or (ii) C 3-4 cycloalkyl; and R k together with R n and the atoms to which they are attached form cyclopropyl. In some embodiments, Y 1 is CH; R x is H or fluoro; R y is (i) isopropyl or (ii) C 3-4 cycloalkyl; and R k together with R m or R n and the atoms to which they are attached form cyclopropyl. In some embodiments, Y 1 is N; R x is H or fluoro; R y is (i) isopropyl or (ii) C 3-4 cycloalkyl; and R k together with R m or R n and the atoms to which they are attached form cyclopropyl.

[0484] In some embodiments of the compound of formula (I-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, wherein the C 2 alkyl of R 1-6 is optionally substituted with one or more R a . In some embodiments, R 2 is C 1-6 alkyl, wherein the C 2 alkyl of R 1-6 is substituted with one or more R a , wherein R a is -OH or a 5- to 20-membered heteroaryl, and the 5- to 20-membered heteroaryl of R a is optionally substituted with one or more R b . In some embodiments, R 2 is methyl, and the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5- to 10-membered heteroaryl, and the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more R b . In some embodiments, R 2 is methyl, and the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5- to 10-membered heteroaryl, and the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more C 1-6 alkyl, and the C 1-6 alkyl is optionally substituted with one or more halo, -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 alkoxy. In some embodiments, R 2 is methyl, and the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5- to 10-membered heteroaryl, and the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more methyls, and the methyl is optionally substituted with one or more fluorines.

[0485] In some embodiments of the compound of formula (I-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2Selected from the group consisting of:

[0486] In some embodiments, R 2 is

[0487]

[0488] In some embodiments of the compound of formula (I-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is substituted with one or more R a wherein R a is a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R a is optionally substituted with one or more R c In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R a is optionally substituted with one or more R c In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is a 3- to 8-membered heterocyclic group, wherein the 3- to 8-membered heterocyclic group of R a is optionally substituted with one or more R c In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is a 3- to 8-membered heterocyclic group, wherein the 3- to 8-membered heterocyclic group of R a is optionally substituted with one or more oxo groups or C 1-6 alkyl. In some embodiments, R 2 is

[0489] In some embodiments of the compound of formula (I-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6The alkyl group is optionally substituted by one or more R a , where R a is -O-R e . In some embodiments, R 2 is methyl, and the methyl group of R 2 is substituted by one or more R a , where R a is -O-R e . In some embodiments, R 2 is methyl, and the methyl group of R 2 is substituted by one or more R a , where R a is -O-R e , where R e is -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is

[0490] In some embodiments of the compound of formula (I-B), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, and the C 2 alkyl of R 1-6 is optionally substituted by one or more R a , where R a is -N(R c )(R d ). In some embodiments, R 2 is methyl, and the methyl group of R 2 is substituted by one or more R a , where R a is -N(R c )(R d ). In some embodiments, R 2 is methyl, and the methyl group of R 2 is substituted by one or more R a , where R a is -N(R c )(R d ), where one of R c and R d is H, and the other of R c and R d is -C(O)-N(C 1-6 alkyl)2. In some embodiments, R 2 is

[0491] In some embodiments, provided herein are compounds of formula (I-1) or formula (I-B), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein the compound is a compound of formula (I-B1):

[0492]

[0493] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variant or embodiment thereof, wherein Y 1 is CR x or N; wherein when the ring bearing R x and R y is phenyl, 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)-(3-15-membered heterocyclic group), C 3-10 cycloalkyl or 5-20-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with 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 alkoxy, the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl, and the 5-20-membered heteroaryl is optionally substituted with one or more C 1-6 alkyl; wherein when the ring bearing R x and R y is pyridyl, 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 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo, and the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl. In some embodiments, Y 1 is CH or N; R x is H or fluoro; and R y is (i) isopropyl or (ii) C 3-4 cycloalkyl. In some embodiments, Y 1 is CH; R xis H or a fluoro group; and R y is (i) isopropyl or (ii) C 3-4 cycloalkyl. In some embodiments, Y 1 is N; R x is H or a fluoro group; and R y is (i) isopropyl or (ii) C 3-4 cycloalkyl.

[0494] 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, wherein the C 2 of R 1-6 alkyl is optionally substituted with one or more R a groups. In some embodiments, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is substituted with one or more R a groups, wherein R a is -OH or a 5-20 membered heteroaryl group, wherein the 5-20 membered heteroaryl group of R a is optionally substituted with one or more R b groups. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a groups, wherein R a is -OH or a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group of R a is optionally substituted with one or more R b groups. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a groups, wherein R a is -OH or a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group of R a is optionally substituted with one or more C 1-6 alkyl groups, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, -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 alkoxy groups. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a groups, wherein Ra is -OH or a 5- to 10-membered heteroaryl, where R a The 5- to 10-membered heteroaryl is optionally substituted with one or more methyl groups, where the methyl groups are optionally substituted with one or more fluoro groups.

[0495] In some embodiments of the compound of formula (I-B1), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of:

[0496] In some embodiments, R 2 is

[0497] In some embodiments of the compound of formula (I-B1), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, where R 2 the C 1-6 alkyl is substituted with one or more R a where R a is a 3- to 15-membered heterocyclic group, where R a the 3- to 15-membered heterocyclic group is optionally substituted with one or more R c substituents. In some embodiments, R 2 is methyl, where R 2 the methyl is substituted with one or more R a where R a is a 3- to 15-membered heterocyclic group, where R a the 3- to 15-membered heterocyclic group is optionally substituted with one or more R c substituents. In some embodiments, R 2 is methyl, where R 2 the methyl is substituted with one or more R a where R a is a 3- to 8-membered heterocyclic group, where R a the 3- to 8-membered heterocyclic group is optionally substituted with one or more R c substituents. In some embodiments, R 2 is methyl, where R 2 the methyl is substituted with one or more R a where R a is a 3- to 8-membered heterocyclic group, where R a the 3- to 8-membered heterocyclic group is optionally substituted with one or more oxo groups or C 1-6 alkyl substituents. In some embodiments, R 2 is

[0498] 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, wherein the C 2 alkyl of R 1-6 is optionally substituted with one or more R a , wherein R a is -O-R e . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -O-R e . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -O-R e , wherein R e is -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is

[0499] 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, wherein the C 2 alkyl of R 1-6 is optionally substituted with one or more R a , wherein R a is -N(R c )(R d ). In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -N(R c )(R d ). In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and R c and Rd Another one in 1-6 is -C(O)-N(C 2 alkyl)2. In some embodiments, R

[0500] In some embodiments, provided herein are compounds of formula (I-1) or formula (I-B), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein the compound is a compound of formula (I-B2):

[0501]

[0502] or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, or any variants or embodiments thereof, wherein Y 1 is CR x or N; wherein when the ring bearing R x and R y is phenyl, 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)-(3-15-membered heterocyclic group), C 3-10 cycloalkyl or 5-20-membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with 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 alkoxy, the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl, and the 5-20-membered heteroaryl is optionally substituted with one or more C 1-6 alkyl; wherein when the ring bearing R x and R y is pyridyl, 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 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo, and the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 alkyl. In some embodiments, Y 1is CH or N; R x is H or a fluoro group; and R y is (i) isopropyl or (ii) C 3-4 cycloalkyl. In some embodiments, Y 1 is CH; R x is H or a fluoro group; and R y is (i) isopropyl or (ii) C 3-4 cycloalkyl. In some embodiments, Y 1 is N; R x is H or a fluoro group; and R y is (i) isopropyl or (ii) C 3-4 cycloalkyl.

[0503] 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, wherein the C 2 of R 1-6 alkyl is optionally substituted with one or more R a groups. In some embodiments, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is substituted with one or more R a groups, wherein R a is -OH or a 5- to 20-membered heteroaryl group, wherein the 5- to 20-membered heteroaryl group of R a is optionally substituted with one or more R b groups. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a groups, wherein R a is -OH or a 5- to 10-membered heteroaryl group, wherein the 5- to 10-membered heteroaryl group of R a is optionally substituted with one or more R b groups. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a groups, wherein R a is -OH or a 5- to 10-membered heteroaryl group, wherein the 5- to 10-membered heteroaryl group of R a is optionally substituted with one or more C 1-6 alkyl groups, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, -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 is alkoxy-substituted. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -OH or a 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl of R a is optionally substituted with one or more methyl groups, wherein the methyl group is optionally substituted with one or more fluoro groups.

[0504] In some embodiments of the compound of formula (I-B2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of: In some embodiments, R 2 is

[0505] In some embodiments of the compound of formula (I-B2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, wherein the C 2 alkyl of R 1-6 is substituted with one or more R a wherein R a is a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R a is optionally substituted with one or more R c In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R a is optionally substituted with one or more R c In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is a 3- to 8-membered heterocyclic group, wherein the 3- to 8-membered heterocyclic group of R a is optionally substituted with one or more R c In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R ais a 3- to 8-membered heterocyclic group, where R a 's 3- to 8-membered heterocyclic group is optionally substituted with one or more oxo groups or C 1-6 alkyl groups. In some embodiments, R 2 is

[0506] In some embodiments of the compound of formula (I-B2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, where R 2 's C 1-6 alkyl is optionally substituted with one or more R a groups, where R a is -O-R e . In some embodiments, R 2 is methyl, where R 2 's methyl is substituted with one or more R a groups, where R a is -O-R e . In some embodiments, R 2 is methyl, where R 2 's methyl is substituted with one or more R a groups, where R a is -O-R e , where R e is -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is

[0507] In some embodiments of the compound of formula (I-B2), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1-6 alkyl, where R 2 's C 1-6 alkyl is optionally substituted with one or more R a groups, where R a is -N(R c )(R d ). In some embodiments, R 2 is methyl, where R 2 's methyl is substituted with one or more R a groups, where R a is -N(R c )(R d ). In some embodiments, R 2 is methyl, where R 2 's methyl is substituted with one or more R a groups, where Ra is -N(R c )(R d ), where one of R c and R d is H, and the other of R c and R d is -C(O)-N(C 1-6 alkyl)2. In some embodiments, R 2 is

[0508] In some embodiments, provided herein are compounds of formula (I-1), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein the compound is a compound of formula (I-C):

[0509]

[0510] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variant or embodiment thereof, wherein X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl; X 4 is H, halo, C 1-6 alkyl, C 1-6 alkoxy or 5-20 membered heteroaryl; R v is -NH2, -NH-C(O)-(C 1-6 alkyl) or -NH-C(O)-(3-15 membered heterocyclic group); and R w is H, -NH2, -NH-C(O)-(C 1-6 alkyl) or -NH-C(O)-(3-15 membered heterocyclic group). In some embodiments, X 5 is H or C 1-6 alkyl; X 4 is H; R v is -NH2, -NH-C(O)-(C 1-6 alkyl) or -NH-C(O)-(3-15 membered heterocyclic group); and R w is H, -NH2, -NH-C(O)-(C 1-6 alkyl) or -NH-C(O)-(3-15 membered heterocyclic group). In some embodiments, R w is H and R v is -NH-C(O)C 1-6 alkyl. In some embodiments, R w is H and R v is -NH-C(O)CH3.

[0511] In some embodiments, provided herein are compounds of formula (I-1), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein the compound is a compound of formula (I-D):

[0512]

[0513] or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, or any variants or embodiments thereof, wherein X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl; X 4 is H, halo, C 1-6 alkyl, C 1-6 alkoxy or 5- to 20-membered heteroaryl; and R t and R u are independently H, C 1-6 alkoxy or -NH2. In some embodiments, X 5 is C 1-6 alkyl; X 4 is H, halo or C 1-6 alkyl; and R t and R u are independently H or -NH2. In some embodiments, at least one of R t and R u is -NH2. In some embodiments, R t is H and R u is -NH2. In some embodiments, R t is -NH2 and R u is H.

[0514] In some embodiments of the compounds of formula (I-C) or (I-D), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, R k is H or halo. In some embodiments of the compounds of formula (I-C) or (I-D), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, R k is H or fluoro. In some embodiments of the compounds of formula (I-C) or (I-D), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, R k is fluoro.

[0515] In some embodiments, provided herein are compounds of formula (I-1), wherein the compound is a compound of formula (I-D1):

[0516]

[0517] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variant or embodiment thereof, wherein X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl; X 4 is H, halogen, C 1-6 alkyl, C 1-6 alkoxy or a 5- to 20-membered heteroaryl; and R t and R u are independently H, C 1-6 alkoxy or -NH2. In some embodiments, X 5 is C 1-6 alkyl; X 4 is H, halogen or C 1-6 alkyl; and R u and R z are independently H, halogen or –NH2. In some embodiments, at least one of R u and R z is -NH2. In some embodiments, R u is H and R z is -NH2. In some embodiments, R u is -NH2, Rz is H. In some embodiments, at least one of R u and R z is halogen. In some embodiments, R u is H, and R z is fluoro. In some embodiments, R u is fluoro, and R z is H.

[0518] In some embodiments, provided herein are compounds of formula (I-1), wherein the compound is a compound of formula (I-D2):

[0519]

[0520] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variant or embodiment thereof, wherein X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl; X 4 is H, halogen, C 1-6 alkyl, C 1-6 alkoxy or a 5- to 20-membered heteroaryl; wherein X 4 of C1-6 The alkyl group is optionally substituted with one or more halogen groups; and R t and R u are independently H, C 1-6 alkoxy or -NH2. In some embodiments, X 5 is C 1-6 alkyl; X 4 is H, a halogen group or C 1-6 alkyl; and R u and R z are independently H, a halogen group or -NH2. In some embodiments, at least one of R u and R z is -NH2. In some embodiments, R u is H and R z is -NH2. In some embodiments, R u is -NH2, Rz is H. In some embodiments, R u and R z at least one of which is a halogen group. In some embodiments, R u is H, and R z is a fluorine group. In some embodiments, R u is a fluorine group, and R z is H.

[0521] In some embodiments, provided herein are compounds of formula (I-1), wherein the compound is a compound of formula (I-E):

[0522]

[0523] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variant or embodiment thereof, wherein R k and R m are independently H, OH, -NH2 or -NH-C(O)C 1-6 alkyl. In some embodiments, R k is H and R m is H, OH, -NH2 or -NH-C(O)C 1-6 alkyl. 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 Rm is H. In some embodiments, R k is OH, -NH2 or -NH-C(O)CH3, and R m is H.

[0524] In some embodiments, provided herein are compounds of formula (I-1), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein the compound is a compound of formula (I-F):

[0525]

[0526] or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, or any variants or embodiments thereof, wherein Y 1 is CH or N; R x is H, halo, C 1-6 alkyl or -NH2, wherein when Y 1 is CH, the C x alkyl of R 1-6 may optionally be substituted with one or more halo; R y is (i) C 1-6 alkyl, (ii) C 2-6 alkenyl or (iii) C 3-10 cycloalkyl, wherein the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 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 cycloalkyl. In some embodiments, Y 1 is CH or N; R x is H, halo or C 1-6 alkyl; R y is (i) C 1-6 alkyl or (ii) C 3-10 cycloalkyl, wherein the C 3-10 cycloalkyl is optionally substituted with one or more halo or C 1-6 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 cycloalkyl.

[0527] In some embodiments of the compounds of formula (I-F), Y 1 is CH or N; Rx is H, a halogen group or C 1-6 alkyl; R y is (i) C 1-6 alkyl, (ii) C 2-6 alkenyl or (iii) C 3-10 cycloalkyl, where C 3-10 cycloalkyl is optionally substituted by one or more halogen groups or C 1-6 alkyl; R k is H or a halogen group; and R n is H, C 1-6 alkyl or C 3-6 cycloalkyl. In some embodiments, Y 1 is N or CH, R x is H or a halogen group, R y is C 1-6 alkyl or C 3-6 cycloalkyl, R k is H or a halogen group, and R n is C 1-6 alkyl or C 3-6 cycloalkyl. In some embodiments, Y 1 is N or CH, R x is H or a fluorine group, R y is C 1-6 alkyl or C 3-6 cycloalkyl, R k is H or a fluorine group, and R n is C 1-6 alkyl or C 3-6 cycloalkyl. In some embodiments, Y 1 is N or CH, R x is H or a fluorine group, R y is C 1-6 alkyl or C 3-6 cycloalkyl, R k is H or a fluorine group, and R n is C 1-6 alkyl or C 3-6 cycloalkyl. In some embodiments, Y 1 is N or CH, R x is H or a fluorine group, R y is C 1-6 alkyl or C 3-6 cycloalkyl, R k is H, and R n is C 1-6 alkyl or C 3-6 cycloalkyl. In some embodiments, Y 1 is N or CH, R x is H or a fluorine group, R y is C 1-3 alkyl or C3-6 Cycloalkyl, R k is H or a halogen group, and R n is C 1-3 alkyl or C 3-6 cycloalkyl.

[0528] In some embodiments of the compounds of formula (I-C), (I-D), (I-E) or (I-F), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is optionally substituted with one or more R a . In some embodiments, R 2 is C 1-6 alkyl, wherein the C 2 of R 1-6 alkyl is substituted with one or more R a , wherein R a is -OH or a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R a is optionally substituted with one or more R b . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl of R a is optionally substituted with one or more R b . In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl of R a is optionally substituted with one or more C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halogen groups, -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 alkoxy. In some embodiments, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a , wherein R a is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl of R aThe 5- to 10-membered heteroaryl is optionally substituted with one or more methyl groups, wherein the methyl groups are optionally substituted with one or more fluoro groups.

[0529] In some embodiments of the compounds of formula (I-C), (I-D), (I-E) or (I-F), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is selected from the group consisting of: In some embodiments, R 2 is

[0530] In some embodiments of the compounds of formula (I-C), (I-D), (I-E) or (I-F), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is selected from the group consisting of:

[0531] In some embodiments of the compounds of formula (I-C), (I-D), (I-E) or (I-F), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is selected from the group consisting of: In some embodiments, R 2 is

[0532] In some embodiments of the compounds of formula (I-C), (I-D), (I-E) or (I-F), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is

[0533] In some embodiments of the compounds of formula (I-C), (I-D), (I-E) or (I-F), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is a 3- to 8-membered heterocyclic group, wherein the 3- to 8-membered heterocyclic group of R a is optionally substituted with one or more R c wherein R c is oxo, C 1-6 alkyl or -C(O)-C 1-6 alkoxy, wherein Rc C of 1-6 The alkyl is optionally substituted with one or more halogen groups, and R c -C(O)-C of 1-6 The alkoxy is optionally substituted with one or more halogen groups. In some embodiments, R 2 is selected from the group consisting of:

[0534] In some embodiments of the compounds of formula (I-C), (I-D), (I-E) or (I-F), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -O-R e wherein R e is -C(O)-(3- to 15-membered heterocyclic group), wherein the -C(O)-(3- to 15-membered heterocyclic group) of R e is optionally substituted with one or more C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halogen groups, C 1-6 alkoxy or C 3-10 cycloalkyl. In some embodiments, R 2 is selected from the group consisting of:

[0535] In some embodiments of the compounds of formula (I-C), (I-D), (I-E) or (I-F), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and the other of R c and R d is -C(O)-C 1-6 alkyl, -C(O)-N(C 1-6 alkyl)2 or -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is

[0536] In some embodiments, the present disclosure provides compounds of formula (I-1), wherein the compound is a compound of formula (I-G):

[0537]

[0538] 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 heterocyclic group, wherein the 3- to 15-membered heterocyclic group of ring A is optionally substituted with one or more oxo groups, (ii) a 5- to 20-membered heteroaryl group, wherein the 5- to 20-membered heteroaryl group of ring A is optionally substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, and the C 3-10 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl, or (iii) C 3-10 cycloalkyl.

[0539] In some embodiments of the compound of formula (I-G), 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 groups; X 4 is (i) isopropyl (ii) C 1-6 cycloalkyl optionally substituted with one or more halo groups or C 3-4 alkyl or (iii) butyl; and R z is fluoro or methyl; provided that at least one of X 3 and X 4 is a halo group, CF2 or CF3.

[0540] In some embodiments of the compound of formula (I-G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or a halo group. In some embodiments of the compound of formula (I-G), 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-G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is fluoro.

[0541] In some embodiments of the compound of formula (I-G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is a 5-20 membered heteroaryl or -(C 1-4 alkyl)(5-20 membered heteroaryl), wherein C 1-4 alkyl is optionally substituted with one or more -OH, halo, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5-20 membered heteroaryl is optionally substituted with one or more R s substituents. In some embodiments, R s is 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, 3-15 membered heterocyclic group, 5-20 membered heteroaryl or -C(O)-C 1-6 alkoxy. In some embodiments, the C s of R 1-6 alkyl is optionally substituted with 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 alkoxy, and the 3-15 membered heterocyclic group of R s is optionally substituted with one or more halo or -C(O)-C 1-6 alkoxy.

[0542] In some embodiments of the compound of formula (I-G), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is selected from the group consisting of:

[0543]

[0544] In some embodiments of the compound of formula (I-G), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl, wherein the methyl of R 2 is substituted with one or more R a substituents, wherein R a is -N(R c )(R d ), wherein one of R c and R d is H, and R cand R d and the other in d is -C(O)-C 1-6 alkyl, -C(O)-N(C 1-6 alkyl)2 or -C(O)-(3- to 15-membered heterocyclic group). In some embodiments, R 2 is

[0545] In some embodiments of the compound of formula (I-G), 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 heterocyclic group, wherein the 3- to 15-membered heterocyclic group of ring A is optionally substituted with one or more oxo groups or C 1-6 alkyl, (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 groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein C 1-6 alkyl is optionally substituted with one or more halo groups, and C 3-10 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl, or (iii) C 3-10 cycloalkyl.

[0546] In some embodiments of the compound of formula (I-G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of ring A is optionally substituted with one or more oxo groups or C 1-6 alkyl. In some embodiments, ring A is selected from the group consisting of:

[0547] In some embodiments of the compound of formula (I-G), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of ring A is optionally substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein C 1-6 alkyl is optionally substituted with one or more halo groups, and C 3-10 cycloalkyl is optionally substituted with one or more halo groups or C 1-6 alkyl. In some embodiments, ring A is a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of ring A is optionally substituted with one or more C 1-6Alkyl substitution. In some embodiments, ring A is selected from the group consisting of:

[0548] In some embodiments of the compound of formula (I-G), or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, ring A is C 3-10 Cycloalkyl. In some embodiments, ring A is C 3-6 Cycloalkyl. In some embodiments, ring A is cyclopropyl.

[0549] In some embodiments, provided herein is a compound of formula (I-1), wherein the compound is a compound of formula (I-H):

[0550]

[0551] or its stereoisomer or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, or any variant or embodiment thereof, wherein Y 1 is CR x or N; wherein when the ring bearing R x , R y and R z is phenyl, R x , R y and R z are H, halo, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), NH-C(O)-(3-15 membered heterocyclic group), C 3-10 cycloalkyl or 5-20 membered heteroaryl, wherein the C 1-6 alkyl is optionally substituted with 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 alkoxy, C 3-10 cycloalkyl is optionally substituted with one or more halo C 1-6 alkyl, and 5-20 membered heteroaryl is optionally substituted with one or more C 1-6 alkyl; and wherein when the ring bearing R x , R y and R z is pyridyl, 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 C3-10 cycloalkyl, wherein C 1-6 alkyl is optionally substituted with one or more halogen groups, and C 3-10 cycloalkyl is optionally substituted with one or more halogen groups or C 1-6 alkyl.

[0552] In some embodiments, provided herein are compounds of formula (I-1) (such as compounds of formula (I), (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-B), (I-B1), (I-B2), (I-C), (I-D), (I-D1), (I-D2), (I-E), (I-F), (I-G), or (I-H)), or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein R 2 is C 1-6 alkyl, wherein C 2 of R 1-6 alkyl is optionally substituted with one or more R a . In some embodiments, R 2 is C 3-10 cycloalkyl, wherein C 2 of R 3-10 cycloalkyl is optionally substituted with one or more R q . In other embodiments, R 2 is a 3- to 15-membered heterocyclic group, wherein the 3- to 15-membered heterocyclic group of R 2 is optionally substituted with one or more halogen groups, oxo groups, C 1-6 alkyl, -C(O)-C 1-6 alkyl, or a 5- to 20-membered heteroaryl group. In some embodiments, R 2 is a 5- to 20-membered heteroaryl group or -(C 1-4 alkyl)(5- to 20-membered heteroaryl group), wherein C 1-4 alkyl is optionally substituted with one or more –OH, halogen groups, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5- to 20-membered heteroaryl group is optionally substituted with one or more R s . In some embodiments, R 2 is -N(R g )(R h ), wherein R g and R h are independently H or C 1-6 alkyl. In some embodiments, R 2 is -C(O)-R j , wherein R j is C 3-10 cycloalkyl, -NH(C1-6 alkyl), -N(C 1-6 alkyl)2 or -NH(5-20 membered heteroaryl). In some embodiments, R 2 is C 6-20 aryl, wherein R 2 of the C 6-20 aryl is optionally substituted with one or more 5-20 membered heteroaryl or -O-R p wherein R p is a 3-15 membered heterocyclic group, wherein R p of the 3-15 membered heterocyclic group is optionally substituted with one or more -C(O)-C 1-6 alkyl.

[0553] In some embodiments of the compound of formula (I), or any variant or embodiment thereof, or its stereoisomers or tautomers, 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 moieties (G1-Z1) and (G2-Z2) selected from Table 1A are each independently substituted with a group that binds to L. In some embodiments, the moieties (G1-Z1) and (G2-Z2) selected from Table 1A are each independently bound to L. In some embodiments, L binds at any available position. In some embodiments, L binds at the group corresponding to R 2 . In some embodiments, L binds at the group corresponding to R n .

[0554] The compound names included in Table 1A, as well as all intermediate and compound names, were generated using Professional software version 17.1.1.0 or Collaborative Drug Discovery Inc. (CDD) CDD Vault update #3.

[0555] A Knime workflow was created to retrieve structures from an internal ChemAxon compound registry, generate canonical smiles using the RDKitCanon SMILES node, remove stereochemistry using the Chem Axon / Infocom MolConverter node, and name the structures using the ChemAxon / Infocom Naming node. The following represent the versions of the Knime analysis platform and extensions used in the workflow:

[0556] · Knime analysis platform 4.2.2

[0557] ·RDKit Knime Integration 4.0.1.v202006261025 (This extension includes the RDKit CanonSMILES node)

[0558] ·ChemAxon / Infocom Marvin Extensions Feature 4.3.0v202100 (This extension includes the MolConverter node)

[0559] ·ChemAxon / Infocom JChem Extensions Feature 4.3.0v202100 (This extension includes the Naming node)

[0560] Table 1A

[0561]

[0562]

[0563]

[0564]

[0565]

[0566]

[0567]

[0568]

[0569]

[0570]

[0571]

[0572]

[0573]

[0574]

[0575]

[0576]

[0577]

[0578]

[0579]

[0580]

[0581]

[0582]

[0583]

[0584]

[0585]

[0586]

[0587]

[0588]

[0589]

[0590]

[0591]

[0592]

[0593]

[0594]

[0595]

[0596]

[0597]

[0598]

[0599]

[0600]

[0601]

[0602]

[0603]

[0604]

[0605]

[0606]

[0607]

[0608]

[0609]

[0610]

[0611]

[0612]

[0613]

[0614]

[0615]

[0616]

[0617]

[0618]

[0619]

[0620]

[0621]

[0622]

[0623]

[0624]

[0625]

[0626]

[0627]

[0628]

[0629]

[0630]

[0631]

[0632]

[0633]

[0634]

[0635]

[0636]

[0637]

[0638]

[0639]

[0640]

[0641]

[0642]

[0643]

[0644]

[0645]

[0646]

[0647]

[0648]

[0649]

[0650]

[0651]

[0652]

[0653]

[0654]

[0655]

[0656]

[0657]

[0658]

[0659]

[0660]

[0661]

[0662]

[0663]

[0664]

[0665]

[0666]

[0667]

[0668]

[0669]

[0670]

[0671]

[0672]

[0673]

[0674]

[0675]

[0676]

[0677]

[0678]

[0679]

[0680]

[0681]

[0682]

[0683]

[0684]

[0685]

[0686]

[0687]

[0688]

[0689]

[0690]

[0691]

[0692]

[0693]

[0694]

[0695]

[0696] In some embodiments, provided herein are compounds of formula (I), or any variant or embodiment thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a moiety selected from the group consisting of:

[0697] 1-cyclopropanecarbonyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0698] 1-acetyl-4-hydroxy-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0699] 1-acetyl-3-hydroxy-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0700] 1-acetyl-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0701] 1-Acetyl-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[0702] 1-(3-Carbamoyl-2-acetamidopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0703] tert-Butyl N-{2-oxo-2-[2-({phenyl[4-(propan-2-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]ethyl}carbamate;

[0704] 1-(2-Hydroxyacetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0705] 1-(2-Acetamidoacetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0706] 1-Acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[0707] 1-(3-Carbamoylpropanoyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0708] 1-Acetyl-N-[(5-cyclopropylpyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[0709] 2-Acetyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-2-azabicyclo[3.1.0]hexane-3-carboxamide;

[0710] 1-{2-[N-(Carbamoylmethyl)acetamido]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0711] 1-Acetyl-5-methyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0712] 1-[2-(1,3-Oxazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0713] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(4H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[0714] 4-Fluoro-1-{2-[(3-methyloxetan-3-yl)amino]acetyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0715] 4-Acetamido-5-[4-fluoro-2-({phenyl[4-(propan-2-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]-5-oxopentanoic acid;

[0716] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0717] 1-(3-Acetamidopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0718] 4-Fluoro-1-[2-(2-oxopyrrolidin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0719] 4-Fluoro-1-[2-(1,3-oxazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0720] 1-(4-Acetamidobutanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0721] 2-Acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide;

[0722] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-(2-acetamidoacetyl)pyrrolidine-2-carboxamide;

[0723] 3-Acetyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-3-azabicyclo[3.1.0]hexane-2-carboxamide;

[0724] 4-Fluoro-1-[2-(2-oxo-1,3-oxazolidin-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0725] 4-Fluoro-1-[2-(oxetan-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0726] 4-Fluoro-1-[2-(3-oxomorpholin-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0727] 1-Acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-5-methylpyrrolidine-2-carboxamide;

[0728] 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0729] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0730] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-oxomorpholin-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0731] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-4H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[0732] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[3-(1,3-oxazol-2-yl)propanoyl]pyrrolidine-2-carboxamide;

[0733] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0734] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-1,3-oxazolidin-3-yl)acetyl]pyrrolidine-2-carboxamide;

[0735] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0736] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0737] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1,2-oxazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[0738] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0739] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0740] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2H-1,2,3,4-tetrazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0741] 4-Fluoro-1-[2-(1,3,4-oxadiazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0742] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0743] 4-Fluoro-1-{2-[(1,3-oxazol-2-yl)amino]acetyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0744] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-methyl-2-oxoimidazolidin-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0745] 1-[2-(5-Cyclopropyl-1,3,4-oxadiazol-2-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[0746] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}pyrrolidine-2-carboxamide;

[0747] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0748] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[0749] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,4-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide;

[0750] 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0751] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0752] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridazin-3-yloxy)acetyl]pyrrolidine-2-carboxamide;

[0753] 4-Fluoro-1-(1-methyl-5-oxopyrrolidine-2-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0754] 1-[2-(2-Chloro-5-fluorophenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0755] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[4-(pyridin-3-yl)butanoyl]pyrrolidine-2-carboxamide;

[0756] 4-Fluoro-1-(3-oxo-octahydroindazole-6-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0757] 4-Fluoro-1-(2-oxopiperidine-4-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0758] 1-[2-(2-Cyano-4-methoxyphenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0759] 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;

[0760] 4-Fluoro-1-[4-(1H-imidazol-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0761] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrimidin-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0762] 4-Fluoro-1-(4-methylpyrimidine-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0763] 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyridin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0764] 1-[3-(3,5-Dimethyl-1,2-oxazol-4-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0765] 4-Fluoro-1-[2-(3-fluoro-4-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0766] 4-Fluoro-1-(1,3-oxazole-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0767] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[4-(pyridin-4-yl)butanoyl]pyrrolidine-2-carboxamide;

[0768] 1-[(Dimethylcarbamoyl)carbonyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0769] 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;

[0770] 4-Fluoro-1-[2-(1H-imidazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0771] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0772] 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;

[0773] 4-Fluoro-1-[2-(5-fluoropyridin-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0774] 4-Fluoro-1-[2-(5-methyl-1H-indol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0775] 1-[2-(4-acetamidophenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0776] 4-Fluoro-1-[2-(1H-imidazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0777] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyridin-3-yl)propanoyl]pyrrolidine-2-carboxamide;

[0778] 4-Fluoro-1-[2-(4-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0779] 1-[2-(1,5-dimethyl-1H-pyrazol-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0780] 4-Fluoro-1-[3-(2-methylpyridin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0781] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrimidin-2-yl)acetyl]pyrrolidine-2-carboxamide;

[0782] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyrazin-2-yl)propanoyl]pyrrolidine-2-carboxamide;

[0783] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2H-1,2,3-triazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[0784] 1-[3-(2,6-Dimethylpyridin-3-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0785] 1-[2-(1H-1,2,3-Benzotriazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0786] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0787] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yloxy)acetyl]pyrrolidine-2-carboxamide;

[0788] 4-Fluoro-1-[3-(1H-imidazol-5-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0789] 4-Fluoro-1-[3-(5-methyl-1,3,4-thiadiazol-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0790] 1-[3-(3,5-Dimethyl-1H-pyrazol-1-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0791] 1-(3-Cyanopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0792] 1-{2-[(Dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0793] 4-Fluoro-1-[2-(5-methyl-1,2,4-oxadiazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0794] 4-Fluoro-1-[2-(1-methyl-1H-indol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0795] 4-Fluoro-1-[3-(5-methylpyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0796] 1-(2-Ethyl-1,3-oxazole-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0797] 4-Fluoro-1-[2-(2-methyl-1,3-thiazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0798] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide;

[0799] 4-Fluoro-1-[2-methyl-3-(1H-pyrazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0800] 4-Fluoro-1-[3-(1H-indol-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0801] 4-Fluoro-1-[2-methyl-3-(pyridin-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0802] 4-Fluoro-1-[2-(4-fluoro-1H-indol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0803] 4-Fluoro-1-{4-oxo-4H,5H,6H,7H,8H-pyrazolo[1,5-a][1,4]diazepin -2-carbonyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0804] 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;

[0805] 4-Fluoro-1-(6-oxopiperidine-3-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0806] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrrolidine-1-sulfonyl)acetyl]pyrrolidine-2-carboxamide;

[0807] 1-[2-(1,2-Benzoxazol-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0808] 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;

[0809] 1-[2-(1H-1,3-Benzodiazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0810] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-1-yl)propanoyl]pyrrolidine-2-carboxamide;

[0811] 4-Fluoro-1-[3-(3-methoxypyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0812] 4-Fluoro-1-[2-(1H-imidazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0813] 1-[2-(3,5-Dimethyl-1,2-oxazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0814] 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0815] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,3-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide;

[0816] 4-Fluoro-1-[3-(1H-imidazol-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0817] 4-Fluoro-1-[2-(2-methylphenoxy)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0818] 4-Fluoro-1-[2-(3-methyl-1,2-oxazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0819] 4-Fluoro-1-(3-methyloxetane-3-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0820] 1-[2-(4-Chloro-1H-pyrazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0821] 1-(1-Ethyl-1H-pyrazole-5-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0822] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-2-yl)propanoyl]pyrrolidine-2-carboxamide;

[0823] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyrimidin-5-yl)propanoyl]pyrrolidine-2-carboxamide;

[0824] 4-Fluoro-1-(3-methoxy-1-methyl-1H-pyrazole-4-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0825] 4-Fluoro-1-[2-(5-methyl-1,3,4-oxadiazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0826] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-pyrazol-4-yl)propanoyl]pyrrolidine-2-carboxamide;

[0827] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1,3-thiazol-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0828] 4-Fluoro-1-[4-(2-methyl-1H-imidazol-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0829] 4-Fluoro-1-(2-{imidazo[1,2-a]pyridin-3-yl}acetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0830] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyridin-2-yl)propanoyl]pyrrolidine-2-carboxamide;

[0831] 4-Fluoro-1-[2-(3-methyl-1,2,4-oxadiazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0832] 1-[2-(3,5-Dimethyl-1H-pyrazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0833] 4-Fluoro-1-[3-(6-methylpyridin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0834] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-(3-{1H-pyrrolo[2,3-b]pyridin-3-yl}propanoyl)pyrrolidine-2-carboxamide;

[0835] 4-Fluoro-1-(2-oxo-1,3-oxazolidine-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0836] 4-Fluoro-1-[2-(4-methyl-1H-pyrazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0837] 4-Fluoro-1-[3-(1-methyl-1H-pyrazol-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0838] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,4-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0839] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[5-(pyridin-4-yl)-1H-pyrazole-3-carbonyl]pyrrolidine-2-carboxamide;

[0840] 4-Fluoro-1-[3-(2-methylpyridin-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0841] 4-Fluoro-1-(2-hydroxy-3-methylbutanoyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0842] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-(3-{1H-pyrrolo[2,3-b]pyridin-5-yl}propanoyl)pyrrolidine-2-carboxamide;

[0843] 4-Fluoro-1-[4-oxo-4-(pyrrolidin-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0844] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(quinolin-6-yl)acetyl]pyrrolidine-2-carboxamide;

[0845] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0846] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2,2,2-trifluoroacetamido)acetyl]pyrrolidine-2-carboxamide;

[0847] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yloxy)propanoyl]pyrrolidine-2-carboxamide;

[0848] 4-Fluoro-1-[2-(1H-indol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0849] 1-(2-Cyclopropyl-2-oxoacetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0850] 4-Fluoro-1-[2-(5-fluoro-2-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0851] 4-Fluoro-1-[2-(6-methoxypyridin-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0852] 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyridin-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0853] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yl)acetyl]pyrrolidine-2-carboxamide;

[0854] 1-[2-(3,5-Dimethyl-1H-pyrazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0855] 1-[2-(2,5-Dioxoimidazolidin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0856] 1-[2-(2,5-Dimethyl-1,3-thiazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0857] 4-Fluoro-1-[2-methyl-3-(pyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0858] 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyrazin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0859] 4-Fluoro-1-[2-(N-methylacetamido)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0860] 4-Fluoro-1-[2-methyl-2-(pyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0861] 4-Fluoro-1-[2-(2-oxopiperidin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0862] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0863] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,4-triazol-1-yl)benzoyl]pyrrolidine-2-carboxamide;

[0864] 4-Fluoro-1-{[(2-methylpropyl)carbamoyl]carbonyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0865] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)propanoyl]pyrrolidine-2-carboxamide;

[0866] 4-Fluoro-1-(2-oxo-1,2,3,4-tetrahydroquinoline-7-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0867] 4-Fluoro-1-[2-(2-methyl-1,3-thiazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0868] 4-Fluoro-1-[3-(6-oxo-1,6-dihydropyridazin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0869] 4-Fluoro-1-[2-(4-methyl-1H-pyrazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0870] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-2-yl)acetyl]pyrrolidine-2-carboxamide;

[0871] 4-Fluoro-1-[2-(3-methyl-1H-pyrazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0872] 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;

[0873] 1-(2-Acetamidopyridine-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0874] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[0875] 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;

[0876] 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;

[0877] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[0878] 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;

[0879] 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;

[0880] 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;

[0881] 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;

[0882] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-hydroxy-2-methylpropanoyl)pyrrolidine-2-carboxamide;

[0883] 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;

[0884] 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;

[0885] 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;

[0886] 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;

[0887] 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;

[0888] 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;

[0889] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0890] 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;

[0891] 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;

[0892] 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;

[0893] 4-Fluoro-1-[2-(1,2-oxazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0894] 4-Fluoro-1-[2-(1,2-oxazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0895] 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;

[0896] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0897] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[0898] 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;

[0899] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-2-yl)acetyl]pyrrolidine-2-carboxamide;

[0900] 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;

[0901] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-3-yl)acetyl]pyrrolidine-2-carboxamide;

[0902] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrimidin-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0903] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrimidin-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0904] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide;

[0905] 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;

[0906] 1-(2-Cyanoacetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0907] 4-Fluoro-1-(2-methylsulfonylethyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0908] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide;

[0909] 1-(4-Acetylmorpholine-2-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0910] 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;

[0911] 1-[2-(4-Acetyl-2-oxopiperazin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0912] 1-(1-Acetylpiperidine-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0913] 1-(2,3-Dihydroxypropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0914] 1-{8-Acetyl-8-azaspiro[4.5]decane-2-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0915] 4-Fluoro-1-[3-(1H-imidazol-1-yl)-2-methylpropanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0916] 1-{6-Acetyl-6-azaspiro[2.5]octane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0917] 1-(1-Acetyl-3-methylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0918] 4-Fluoro-1-[2-(N-methylacetamido)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0919] 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;

[0920] 1-[1-Acetyl-2-(pyridin-3-yl)pyrrolidine-3-carbonyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0921] 4-Fluoro-1-[5-(methoxymethyl)-1,2-oxazole-4-carbonyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0922] 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;

[0923] 4-Fluoro-1-[2-(1H-1,2,4-triazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0924] 1-{5-Acetyl-5-azaspiro[2.4]heptane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0925] 1-[3-(1-Acetylpyrrolidin-2-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0926] 1-{4-[(1-Acetylazetidin-3-yl)oxy]benzoyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0927] 4-Fluoro-1-[3-methoxy-2-(N-methylacetamido)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0928] 1-[2-(1-Acetylpyrrolidin-2-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0929] 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;

[0930] 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;

[0931] 1-(1-Acetylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0932] 4-Fluoro-1-[2-(3-methyl-1H-pyrazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0933] 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;

[0934] 1-[2-(1-Acetylpiperidin-4-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0935] 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;

[0936] 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;

[0937] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0938] 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;

[0939] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-imidazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0940] 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;

[0941] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1,2-oxazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0942] 1-{2-[(Dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide;

[0943] 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;

[0944] 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;

[0945] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(quinolin-6-yl)acetyl]pyrrolidine-2-carboxamide;

[0946] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide;

[0947] 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(piperazin-1-yl)acetyl]pyrrolidine-2-carboxamide;

[0948] 1-(1-Acetyl-3-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0949] 1-(1-Acetyl-4-methylazepane-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0950] 1-(1-Acetylazepane-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0951] 1-(1-Acetylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0952] 1-(4-acetylmorpholine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0953] 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;

[0954] 1-{2-acetyl-2-azaspiro[4.4]nonane-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0955] 1-{2-acetyl-2-azabicyclo[2.2.2]octane-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0956] 1-[2-(1-acetylpiperidin-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0957] 1-(4-acetyl-1,4-oxazepane-2-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0958] 1-(1-acetyl-4-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0959] 1-(4-acetyl-2-methylmorpholine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0960] 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;

[0961] 1-{3-acetyl-3-azabicyclo[3.1.0]hexane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0962] 1-{2-acetyl-octahydrocyclopenta[c]pyrrole-4-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0963] 1-{8-Acetyl-8-azabicyclo[3.2.1]octane-3-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0964] 1-(1-Acetyl-3-methylazetidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0965] 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;

[0966] 1-{3-Acetyl-3-azabicyclo[3.2.1]octane-8-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0967] 1-(2-Acetyl-octahydro-1H-isoindole-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0968] 1-{7-Acetyl-7-azabicyclo[2.2.1]heptane-2-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0969] 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;

[0970] 1-[2-(1-Acetyl-3-methylazetidine-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0971] 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;

[0972] 1-(1-Acetyl-2-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0973] 4-Fluoro-1-{3-[N-(1-methyl-1H-pyrazol-3-yl)acetamido]propanoyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0974] 1-(1-acetyl-3-fluoroazetidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0975] 1-[2-(1-acetyl-3-methoxyazetidine-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0976] 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;

[0977] 1-(1-acetyl-4-ethylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0978] 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;

[0979] 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[1-(1,3,4-oxadiazol-2-yl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide;

[0980] 2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl N,N-dimethylcarbamate;

[0981] 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide;

[0982] 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[0983] 2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl N,N-dimethylcarbamate;

[0984] 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;

[0985] 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;

[0986] 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;

[0987] 1-{2-[(Dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[0988] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[0989] 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;

[0990] 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0991] 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;

[0992] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-[2-(3,5-dimethyl-1H-pyrazol-4-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide;

[0993] N-{2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}piperazine-1-carboxamide;

[0994] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide;

[0995] 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;

[0996] 1-[2-(4-Acetylpiperazin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[0997] 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;

[0998] 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;

[0999] 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;

[1000] 1-{2-[(Dimethylcarbamoyl)(methyl)amino]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1001] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-oxo-1,3-oxazolidine-5-carbonyl)pyrrolidine-2-carboxamide;

[1002] Piperazine-1-carboxylic acid 2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl ester;

[1003] 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;

[1004] 4-{2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}piperazine-1,4-dicarboxylic acid 1-tert-butyl ester;

[1005] 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;

[1006] 1-[2-(1H-1,3-Benzodiazol-1-yl)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1007] 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;

[1008] 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;

[1009] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridazin-4-yl)acetyl]pyrrolidine-2-carboxamide;

[1010] 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;

[1011] 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;

[1012] 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridazin-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1013] N-[(5-Cyclopropylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1014] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxopiperazin-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1015] N-[2-(2-{[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-methylpiperazine-1-carboxamide;

[1016] N-[2-(2-{[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(2,2,2-trifluoroethyl)piperazine-1-carboxamide;

[1017] 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;

[1018] N-[2-(2-{[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(2-methoxyethyl)piperazine-1-carboxamide;

[1019] 1-{2-[5-(Aminomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[1020] 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;

[1021] 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;

[1022] 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;

[1023] N-[2-(2-{[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(cyclopropylmethyl)piperazine-1-carboxamide;

[1024] 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;

[1025] N-{2-[4-Fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-4-methylpiperazine-1-carboxamide;

[1026] 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;

[1027] 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;

[1028] 4-Fluoro-1-[2-(2-methylquinolin-5-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1029] 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;

[1030] 1-{2-[5-(Aminomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[1031] 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;

[1032] 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;

[1033] 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;

[1034] 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;

[1035] 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;

[1036] 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;

[1037] 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;

[1038] 1-{2-[5-(Acetamidomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide;

[1039] 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;

[1040] 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;

[1041] 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;

[1042] 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;

[1043] 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;

[1044] 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;

[1045] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide;

[1046] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1047] 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;

[1048] 1-[2-(1H-1,2,3-Benzotriazol-1-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[1049] 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;

[1050] 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;

[1051] 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;

[1052] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1053] N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]morpholine-4-carboxamide;

[1054] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1055] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1056] Azetidine-1-carboxylic acid 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl ester;

[1057] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1058] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-2,3-dihydro-1H-indol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1059] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methyl-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1060] 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;

[1061] 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;

[1062] 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;

[1063] 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;

[1064] 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;

[1065] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-1H-imidazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1066] 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;

[1067] 4-(Cyclopropylmethyl)piperazine-1-carboxylic acid 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl ester;

[1068] 4-Methylpiperazine-1-carboxylic acid 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl ester;

[1069] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1070] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{imidazo[1,2-a]pyridin-3-yl}acetyl)pyrrolidine-2-carboxamide;

[1071] 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;

[1072] 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;

[1073] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[(pyrazin-2-yl)amino]acetyl}pyrrolidine-2-carboxamide;

[1074] 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;

[1075] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(2-ethyl-2H-1,2,3-triazol-4-yl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1076] 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;

[1077] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(1-ethyl-1H-1,2,3-triazol-4-yl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1078] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methylquinolin-6-yl)acetyl]pyrrolidine-2-carboxamide;

[1079] 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-(2-methoxyethyl)piperazine-1-carboxylate;

[1080] 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;

[1081] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[methyl(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide;

[1082] N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methylquinolin-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1083] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide;

[1084] 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;

[1085] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[methyl(pyrazin-2-yl)amino]acetyl}pyrrolidine-2-carboxamide;

[1086] 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;

[1087] 4-(2,2,2-Trifluoroethyl)piperazine-1-carboxylic acid 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl ester;

[1088] N-[(5-Cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide;

[1089] 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;

[1090] 1-[2-(1H-1,3-Benzodiazol-1-yl)acetyl]-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[1091] 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;

[1092] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1093] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1094] 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;

[1095] 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;

[1096] 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;

[1097] 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-methylquinolin-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1098] tert-Butyl 2-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-1H-indole-1-carboxylate;

[1099] 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;

[1100] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1101] 1-[2-(carbamoylamino)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1102] 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;

[1103] 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;

[1104] 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;

[1105] 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;

[1106] 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;

[1107] 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;

[1108] 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;

[1109] 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;

[1110] 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;

[1111] 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;

[1112] 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;

[1113] 1-{2-[(Dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1114] 4-Fluoro-1-{2-[(methylcarbamoyl)amino]acetyl}-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1115] 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;

[1116] 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[(methylcarbamoyl)amino]acetyl}pyrrolidine-2-carboxamide;

[1117] 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;

[1118] 1-{2-[(Azetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1119] 1-{2-[(Azetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1120] 4-Fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1121] N-[(5-Cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1122] 1-[2-(carbamoylamino)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1123] 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;

[1124] 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;

[1125] 1-[2-(carbamoylamino)acetyl]-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[1126] 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[1127] N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(methylcarbamoyl)amino]acetyl}pyrrolidine-2-carboxamide;

[1128] 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;

[1129] 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;

[1130] N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide;

[1131] 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;

[1132] N-[(5-Cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1133] 4-Fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1134] 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;

[1135] 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;

[1136] 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;

[1137] 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;

[1138] 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;

[1139] 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;

[1140] 1-{2-[(Dimethylcarbamoyl)amino]propanoyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1141] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1142] N-[(4-Cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{[3-(trifluoromethyl)azetidine-1-carbonyl]amino}acetyl)pyrrolidine-2-carboxamide;

[1143] 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;

[1144] N-[(5-Cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]propanoyl}-4-fluoropyridin-2-carboxamide;

[1145] 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;

[1146] 1-{2-[(dimethylcarbamoyl)amino]propanoyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1147] 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;

[1148] N-[(5-Cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1149] 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;

[1150] 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;

[1151] 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;

[1152] 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide;

[1153] 4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-(2-{[3-(trifluoromethyl)azetidine-1-carbonyl]amino}acetyl)pyrrolidine-2-carboxamide;

[1154] 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;

[1155] 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;

[1156] 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;

[1157] N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1158] 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;

[1159] 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;

[1160] N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1161] 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;

[1162] 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;

[1163] 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;

[1164] 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;

[1165] 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1166] 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;

[1167] 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;

[1168] 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;

[1169] 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;

[1170] N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(1,3-oxazol-2-yl)amino]acetyl}pyrrolidine-2-carboxamide;

[1171] 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;

[1172] 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;

[1173] 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;

[1174] 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;

[1175] N-[(5-Cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1176] 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;

[1177] 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;

[1178] 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;

[1179] 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;

[1180] 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;

[1181] 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;

[1182] 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;

[1183] 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;

[1184] 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide;

[1185] 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide;

[1186] N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1187] 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;

[1188] N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1189] 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;

[1190] 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;

[1191] 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;

[1192] 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;

[1193] 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide;

[1194] 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;

[1195] 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;

[1196] 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;

[1197] 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;

[1198] 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;

[1199] 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;

[1200] 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;

[1201] 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;

[1202] 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;

[1203] N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(6-ethoxy-5-methylpyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide;

[1204] 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;

[1205] 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;

[1206] 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;

[1207] 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;

[1208] 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;

[1209] 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;

[1210] 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;

[1211] N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1212] 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide;

[1213] 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;

[1214] 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;

[1215] 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;

[1216] 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide;

[1217] 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide;

[1218] N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1219] 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;

[1220] 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;

[1221] 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;

[1222] 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;

[1223] 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide;

[1224] N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1225] 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide;

[1226] N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1227] 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;

[1228] N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1229] 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;

[1230] N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1231] N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1,3-oxazol-2-yl]acetyl}pyrrolidine-2-carboxamide;

[1232] 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;

[1233] 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1234] 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;

[1235] azetidine-1-carboxylic acid 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl ester;

[1236] 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1237] 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxopiperazin-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1238] 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1239] 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1240] N-{2-[4-Fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}morpholine-4-carboxamide;

[1241] 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;

[1242] 1-[2-(1H-1,3-Benzodiazol-1-yl)propanoyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1243] 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;

[1244] 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;

[1245] 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;

[1246] 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1247] 1-[2-(2,5-Dioxopiperazin-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1248] 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;

[1249] 1-[2-(1H-1,2,3-Benzotriazol-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1250] 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;

[1251] 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;

[1252] 4-{2-[4-Fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-3-oxopiperazine-1-carboxylic acid 2,2,2-trifluoroethyl ester;

[1253] 4-(2-Methoxyethyl)piperazine-1-carboxylic acid 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl ester;

[1254] 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;

[1255] 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;

[1256] 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide;

[1257] 2-[4-Fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-methylpiperazine-1-carboxylate;

[1258] 2-[4-Fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-(cyclopropylmethyl)piperazine-1-carboxylate;

[1259] 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;

[1260] 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;

[1261] 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide;

[1262] Morpholine-4-carboxamide N-{2-[4-fluoro-2-({[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl};

[1263] 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;

[1264] 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;

[1265] 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;

[1266] 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;

[1267] 1-[2-(1H-1,3-benzodioxol-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide;

[1268] 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;

[1269] 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;

[1270] 4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1271] 4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-1,3-benzodioxol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1272] 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-benzodioxol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1273] 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;

[1274] 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;

[1275] 1-Acetyl-N-[(5-cyclobutylpyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[1276] 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;

[1277] 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;

[1278] 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;

[1279] 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;

[1280] 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;

[1281] 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;

[1282] N-[(5-cyclobutylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1283] N-[(5-tert-butylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1284] 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;

[1285] 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;

[1286] N-[(4-Cyclopropyl-3-fluorophenyl)(1H-pyrazol-5-yl)methyl]-1-(2-acetamidoacetyl)pyrrolidine-2-carboxamide;

[1287] 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;

[1288] 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;

[1289] 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;

[1290] 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;

[1291] 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;

[1292] 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;

[1293] N-[(2-Aminopyridin-3-yl)[3-methyl-4-(propan-2-yl)phenyl]methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide;

[1294] 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;

[1295] 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;

[1296] 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;

[1297] 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;

[1298] 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;

[1299] 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;

[1300] 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;

[1301] 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;

[1302] 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;

[1303] 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;

[1304] 1-Acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide;

[1305] 1-Acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1-methyl-1H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide;

[1306] 1-Acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](2-methyl-2H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide;

[1307] 1-Acetyl-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(1H-indazol-6-yl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[1308] Methyl N-({3-[({4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidin-2-yl}carbamoyl)[6-fluoro-5-(propan-2-yl)pyridin-2-yl]methyl]phenyl}methyl)carbamate;

[1309] 1-Acetyl-N-[(2-methoxyphenyl)[4-(propan-2-yl)phenyl]methyl]pyrrolidine-2-carboxamide;

[1310] 1-Acetyl-N-[(2-methylphenyl)[4-(propan-2-yl)phenyl]methyl]pyrrolidine-2-carboxamide;

[1311] 1-Acetyl-N-[(2-methylphenyl)[5-(propan-2-yl)pyridin-2-yl]methyl]pyrrolidine-2-carboxamide;

[1312] N-[(4-Cyclopropyl-3-fluorophenyl)(2-oxo-2,3-dihydro-1,3-benzoxazol-7-yl)methyl]-1-(2-acetamidoacetyl)pyrrolidine-2-carboxamide;

[1313] 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;

[1314] 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;

[1315] 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;

[1316] 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;

[1317] 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;

[1318] 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;

[1319] 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;

[1320] 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;

[1321] 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;

[1322] 1-Acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](3-methoxyphenyl)methyl}pyrrolidine-2-carboxamide;

[1323] 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;

[1324] 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;

[1325] 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;

[1326] 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;

[1327] 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;

[1328] 1-Acetyl-N-[(4-cyclobutyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide;

[1329] N-{[3,5-difluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1330] N-[(4-cyclopropyl-3,5-difluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1331] 4-Fluoro-N-{[2-methyl-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide;

[1332] N-[(3-chloro-4-cyclopropylphenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1333] N-[(4-cyclopropyl-3-methylphenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1334] 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;

[1335] 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;

[1336] 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;

[1337] 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;

[1338] 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;

[1339] N-[(4-cyclobutyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1340] N-[(4-cyclobutyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide;

[1341] N-{[4-(butan-2-yl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide;

[1342] 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;

[1343] N-{[3-(difluorom...

Claims

1. 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.

2. The compound according to claim 1, 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 a bond or a (C1-C 50 ) alkyl group, wherein (C1-C 50 ) The alkyl group is optionally substituted by one or more deuterium, halogen, (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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl; and (C1-C 50 ) One or more C atoms in the alkyl group are optionally replaced by 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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl; Wherein, Each C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl is optionally substituted with one or more deuterium, halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo group (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 ; 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 - 2.

3. The compound according to claim 2, wherein L is optionally substituted by one or more deuterium, halogen, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo group (C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, -N(R x )(R y )-, C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl-substituted (C1-C 50 ) alkyl; wherein (C1-C 50 )One or more C atoms in the alkyl group are optionally replaced by 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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl; Wherein Each C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl is optionally substituted by one or more deuterium, halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo group (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 ; 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 - 2.

4. The compound according to claim 3, wherein L is (C1-C 20 ) alkyl, wherein (C1-C 20 ) The alkyl group is optionally substituted by one or more deuterium, halogen, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo group (C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, -N(R x )(R y )-, C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl; and (C1-C 20 ) One or more C atoms in the alkyl group are optionally replaced by 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 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl; Wherein Each C3-C 15 carbocyclic group, 3- to 15-membered heterocyclic group, C6-C 14 aryl or 5- to 20-membered heteroaryl is optionally substituted with one or more deuterium, halogen, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo group (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 ; 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 - 2.

5. The compound according to claim 4, wherein (C1-C 20 ) The alkyl group is optionally substituted by one or more deuterium, halogen, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo group (C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, -N(R x )(R y )-, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl; and (C1-C 20 ) One or more C atoms in the alkyl group are optionally replaced by 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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl; Wherein Each C3-C8 cycloalkyl, 3- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more deuterium, halogen, (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 ; 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 - 2.

6. The compound according to claim 5, wherein (C1-C 20 ) The alkyl group is optionally substituted by one or more deuterium, halogen, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo group (C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, -N(R x )(R y )-, C3-C8 cycloalkyl, 3- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl; and (C1-C 20 )One or more C atoms in the alkyl group are optionally replaced by 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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl; Wherein Each R x and R y independently is H, (C1-C6) alkyl, (C1-C6) haloalkyl or (C1-C6) cycloalkyl; and each n is independently 0 - 2.

7. The compound according to claim 6, wherein (C1-C 20 ) The alkyl group is optionally substituted by one or more deuterium, halogen, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo group (C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, or -N(R x )(R y )-; and (C1-C 20 ) One or more C atoms in the alkyl group are optionally replaced by one or more –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- to 8-membered heterocyclic group, C6-C 10 aryl or 5- to 10-membered heteroaryl; Wherein Each R x and R y independently is H, (C1-C6)alkyl, (C1-C6)haloalkyl or (C1-C6)cycloalkyl; and each n is independently 0 - 2.

8. The compound according to claim 7, wherein the (C1-C 20 ) alkyl group is optionally substituted by one or more deuterium, halogen, (C1-C4) alkyl, (C1-C4) haloalkyl, oxo group (C=O), -O(C1-C4) alkyl, -O(C1-C4) haloalkyl or -O(C1-C4) cycloalkyl; and (C1-C 20 ) One or more C atoms of the alkyl group are optionally replaced by one or more -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 heterocyclic group, C6-C 10 aryl or 5-10-membered heteroaryl; Wherein Each R x and R y independently is H, (C1-C3)alkyl, (C1-C3)haloalkyl or (C1-C3)cycloalkyl; and each n is independently 0 - 2.

9. The compound according to claim 8, wherein one or more C atoms of the (C1-C 20 ) alkyl are optionally replaced by 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 )-; wherein Each R x and R y is independently H, (C1-C3)alkyl, (C1-C3)haloalkyl or (C1-C3)cycloalkyl; and each n is independently 0 - 2.

10. The compound according to claim 9, wherein one or more C atoms of the (C1-C 20 ) alkyl group are replaced by one or more -O-.

11. The compound according to claim 10, wherein L is selected from the group consisting of -(-O-CH2CH2) m -O-, where m is 1-12.

12. The compound according to claim 1 or claim 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, 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 carbocyclene, an optionally substituted heterocyclene, an optionally substituted arylene, an optionally substituted heteroarylene, or any combination thereof.

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

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

19. A compound as claimed in any one of claims 1-16 or claim 18, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (i) one of G1 or G1-Z1 and (ii) one of 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. A compound as claimed in any one of claims 1-19, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound of formula (I) has enhanced GYS1 inhibition compared to G1, G1-Z1, G2, and / or G2-Z2.

21. A compound as claimed in any one of claims 1-20, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) each independently has formula (I-1) or (I-2): or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Y 2 and Y 3 each is C, or Y 2 and Y 3 one of them is N, and Y 2 and Y 3 the other one is C; X 1 and X 2 each independently is H, C 1-6 alkyl or C 1-6 alkoxy; X 3 and X 4 each independently is H, a halogen group, C 1-6 alkyl, C 1-6 alkoxy or a 5- to 20-membered heteroaryl group, wherein the C 3 of X 4 alkyl is optionally substituted with one or more halogen groups; 1-6 ​ X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl; or (1)L 1 does not exist; and Q 1 Selected from (i) to (iv): (i) phenyl, wherein Q 1 of the phenyl is substituted with one or more halogen groups, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclic group), C 3-10 cycloalkyl or 5- to 20-membered heteroaryl, wherein C 1-6 The alkyl group is optionally substituted by one or more halogen groups, -NH-C(O)-NH(C 1-6 alkyl), -NH-C(O)-C 1-6 alkyl or -NH-C(O)-C 1-6 alkoxy group, C 3-10 The cycloalkyl group is optionally substituted by one or more halogen groups or C 1-6 alkyl groups, and 5-20 yuan heteroaryl optionally substituted by one or more C 1-6 alkyl groups, (ii) 3- to 15-membered heterocyclic group, wherein Q 1 The 3- to 15-membered heterocyclic group of 1-6 is optionally substituted with one or more oxo groups or C alkyl groups, (iii) 5- to 20-membered heteroaryl, wherein Q 1 The 5- to 20-membered heteroaryl of 1 is optionally substituted by one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein C 1-6 The alkyl group is optionally substituted by one or more halogen groups, and C 3-10 The cycloalkyl group is optionally substituted by one or more halogen groups or C 1-6 alkyl groups, and (iv) C 3-10 Naphthenyl; or (2)L 1 is -CH2-; and Q 1 is C 3-10 cycloalkyl; L 2 is -C(O)- or -S(O)2- R 1 is H or C 1-6 alkyl; R k is H, a halogen group, -OH, -NH2 or -NH-C(O)C 1-6 alkyl; R m is H, -OH or C 1-6 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 forms a C 3-5 cycloalkyl; or R k and R m or R n together with the atoms to which they are attached form a cyclopropyl group; and R 2 Selected from (i) to (vii): (i) C 1-6 alkyl, wherein R 2 of C 1-6 alkyl is optionally substituted by one or more R a wherein R a is: (a) -OH, (b) cyano, (c)C 2-6 alkynyl (d) C 6-20 aryl, wherein R a of C 6-20 aryl is optionally substituted with one or more halo groups, cyano groups, C 1-6 alkoxy groups or -NH-C(O)-C 1-6 alkyl groups, (e) A 3- to 15-membered heterocyclic group, wherein R a the 3- to 15-membered heterocyclic group is optionally substituted with one or more R c wherein R c is a halogen group, an oxo group, C 1-6 alkyl, C 1-6 alkoxy, -C(O)-C 1-6 alkyl or -C(O)-C 1-6 alkoxy, wherein R c C of 1-6 The alkyl is optionally substituted by one or more halogen groups or C 2-6 alkynyl groups, and R c -C(O)-C 1-6 The alkoxy group is optionally substituted with one or more halogen groups, (f)-N(R c )(R d ), wherein R of -N(R c )(R d ) and R c and R d are each independently 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)2, -C(O)-(3- to 15-membered heterocyclic group), -CH2-C(O)-NH2, 3- to 15-membered heterocyclic group or 5- to 20-membered heteroaryl, wherein R c or R d C of 1-6 the alkyl group is optionally substituted with one or more -C(O)-NH2, R c or R d -C(O)-C 1-6 wherein the alkyl group is optionally substituted with one or more halogen groups R c or R d The 3- to 15-membered heterocyclic group and 5- to 20-membered heteroaryl group of which are each independently optionally substituted with one or more C 1-6 alkyl groups, R c or R d -C(O)-(3- to 15-membered heterocyclic group) of R is optionally substituted with one or more halo groups, -C(O)-C 1-6 alkoxy or C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more halo groups, C 1-6 alkoxy or C 3-10 cycloalkyl, and R c or R d -C(O)-N(C 1-6 alkyl)2 of the C 1-6 alkyls are each independently optionally substituted with one or more halo groups or C 6-20 aryl groups, (g)-O-R e , wherein R e is C 1-6 alkyl, C 6-20 aryl, -C(O)-(3-15 membered heterocyclic group), -C(O)-N-(C 1-6 alkyl)2 or 5-20 membered heteroaryl, wherein R e C of 1-6 The alkyl is optionally substituted by one or more C 1-6 alkoxy groups, wherein the C 1-6 alkoxy group is optionally substituted by one or more C 2-6 alkynyl groups, R e of C 6-20 The aryl is optionally substituted by one or more C 1-6 alkyl groups, and R e -C(O)-(3- to 15-membered heterocyclic group) is optionally substituted by one or more C 1-6 alkyl, C 1-6 alkoxy or -C(O)-C 1-6 alkoxy, wherein said C 1-6 alkyl is optionally substituted by one or more halo, C 1-6 alkoxy or C 3-10 cycloalkyl, (h)-C(O)-R e , wherein R e is -NH2, -OH or a 3- to 15-membered heterocyclic group, or (i)-S(O)2-R f , wherein R f is C 1-6 alkyl or a 3- to 15-membered heterocyclic group, (ii) C 3-10 cycloalkyl, wherein R 2 of C 3-10 the cycloalkyl is optionally substituted by one or more R q wherein R q is a 5- to 20-membered heteroaryl or C 6-20 aryl, wherein R q of C 6-20 the aryl is optionally substituted by one or more C 1-6 alkoxy groups, (iii) 3- to 15-membered heterocyclic group, wherein R 2 The 3- to 15-membered heterocyclic group is optionally substituted with one or more halo groups, oxo groups, C 1-6 alkyl, -C(O)-C 1-6 alkyl or 5- to 20-membered heteroaryl, (iv) 5 - 20 membered heteroaryl or -(C 1-4 alkyl)(5 - 20 membered heteroaryl), wherein C 1-4 alkyl is optionally substituted by one or more -OH, halo, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5 - 20 membered heteroaryl in the 5 - 20 membered heteroaryl or -(C 1-4 alkyl)(5 - 20 membered heteroaryl) is optionally substituted by one or more R s substituents, wherein R s is a halogen group, 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, a 3- to 15-membered heterocyclic group, a 5- to 20-membered heteroaryl, or -C(O)-C 1-6 alkoxy, wherein R s C of 1-6 the alkyl is optionally substituted by one or more halogen groups, 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 alkoxy, and R s The 3- to 15-membered heterocyclic group is optionally substituted with one or more halogen groups or -C(O)-C 1-6 alkoxy groups, (v)-N(R g )(R h ), wherein R g and R h are independently H or C 1-6 alkyl (vi)-C(O)-R j , wherein R j is cycloalkyl, -NH(C 3-10 alkyl), -N(C 1-6 alkyl)2 or -NH(5-20 membered heteroaryl), and 1-6 ​ (vii) C 6-20 aryl, wherein R 2 of C 6-20 the aryl is optionally substituted by one or more 5- to 20-membered heteroaryl groups or -O-R p wherein R p is a 3- to 15-membered heterocyclic group, wherein R p the 3- to 15-membered heterocyclic group is optionally substituted by one or more -C(O)-C 1-6 alkyl groups; and wherein (G1-Z1) and (Z2-G2) are each independently substituted with a group bound to L.

22. The compound according to claim 21, wherein when R 2 is unsubstituted methyl, then: (1)Q 1 is a 5- to 20-membered heteroaryl, wherein Q 1 of the 5- to 20-membered heteroaryl is optionally substituted by one or more halogen groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2, C 3-10 cycloalkyl or -OH, and wherein Q 1 is not an unsubstituted pyridyl, or (2)Q 1 is phenyl, wherein Q 1 of the phenyl is substituted with the following: (i) at least one C 3-6 alkyl group, wherein said at least one C 3-6 alkyl group is optionally substituted by one or more halogen groups, or (ii) at least one C 3-10 cycloalkyl group, wherein said at least one C 3-10 cycloalkyl group is optionally substituted by one or more halogen groups or C 1-6 alkyl group, or (iii) At least one 5- to 20-membered heteroaryl, wherein said at least one 5- to 20-membered heteroaryl is optionally substituted by one or more C 1-6 alkyl groups.

23. The compound as claimed in claim 21, wherein the group bound to L comprises a carbon, oxygen, or nitrogen atom.

24. The compound according to claim 21 or claim 22, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein G1 and G2 are each independently a moiety of formula (I-1) represented by or a moiety of formula (I-1) or (I-2) represented by , 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 are as defined for the compounds of formula (I-1) or (I-2), as defined in claim 21.

25. A compound according to any one of claims 21-24, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (Z1) and (Z2) are each independently wherein L 2 and R 2 as defined for the compounds of formula (I-1) or (I-2), as defined in claim 21.

26. The compound according to any one of claims 21-25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the moiety having a carbon atom , R k , R m , R n and R 1 of the moiety represented by has the stereochemical configuration of the following formula:

27. A compound as claimed in any one of claims 1-26, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L is bound to: (i) the Z1 moiety of (G1-Z1); and (ii) the Z2 moiety of (G2-Z2).

28. A compound as claimed in any one of claims 1-26, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L is bound to: (i) the G1 moiety of (G1-Z1); and (ii) the G2 moiety of (G2-Z2).

29. A compound as claimed in any one of claims 1-17 or 19-27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (II):

30. A compound as claimed in any one of claims 1-17 or 19-25 or 27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (III):

31. A compound as claimed in any one of claims 1-16 or 18-26, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (IV):

32. A compound as claimed in any one of claims 1-17 or 19-27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is a compound of formula (V):

33. A compound as claimed in any one of claims 21, 29, 31 or 32, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein for 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 are independent: Y 2 and Y 3 one of them is N, and Y 2 and Y 3 the other one is C; X 1 and X 2 are each independently H; X 3 and X 4 each independently is H or a halogen group; X 5 is C 3-6 cycloalkyl; L 1 Does not exist; Q 1 is phenyl; L 2 is -C(O)-; R 1 is H; R k is a halogen group; R m is H; R n is H; R 2 Selected from (i) to (ii): (i) C 1-3 alkyl, wherein R 2 of C 1-3 alkyl is optionally substituted by one or more R a substituents, wherein R a is a 3- to 10-membered heterocyclic group, wherein R a of the 3- to 10-membered heterocyclic group is optionally substituted by one or more R c substituents, wherein R c is an oxo group or C 1-3 alkyl, or (ii) 5- to 10-membered heteroaryl or -(C 1-3 alkyl)(5- to 10-membered heteroaryl); L is a (C1-C 20 ) alkyl group, wherein (C1-C 20 )One or more C atoms in the alkyl group are optionally replaced by one or more -O-, -N(R x )- or a 3- to 10-membered heterocyclic group; wherein, each 3- to 10-membered heterocyclic group is optionally substituted with one or more (C1-C3) alkyl or oxo groups (C=O); and Each R x is independently H.

34. A compound according to any one of claims 21, 30 or 31, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein for 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: Y 2 and Y 3 one of them is N, and Y 2 and Y 3 the other one is C; X 1 and X 2 are each independently H; X 3 and X 4 each independently is H or a halogen group; X 5 is C 3-6 cycloalkyl; L 1 Does not exist; Q 1 is phenyl; L 2 is -C(O)-; R 2 Selected from (i) to (ii): (i) C 1-3 alkyl, wherein R 2 of C 1-3 alkyl is optionally substituted with one or more R a wherein R a is a 3- to 10-membered heterocyclic group, wherein R a of the 3- to 10-membered heterocyclic group is optionally substituted with one or more R c wherein R c is an oxo group or C 1-3 alkyl, or (ii) 5- to 10-membered heteroaryl or -(C 1-3 alkyl)(5- to 10-membered heteroaryl); L is a (C1-C 20 ) alkyl group, wherein (C1-C 20 )One or more C atoms in the alkyl group are optionally replaced by one or more -O-, -N(R x )- or a 3- to 10-membered heterocyclic group; wherein, Each 3- to 10-membered heterocyclic group is optionally substituted with one or more (C1-C3) alkyl groups or oxo groups (C=O); and Each R x is independently H.

35. The compound according to claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is selected from the group consisting of: or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

36. A method for preparing the compound according to any one of claims 1-17, 19-27 or 29, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the method comprises: Reacting a compound of formula (I-1B): Y 2 and Y 3 each is C, or Y 2 and Y 3 one of them is N, and Y 2 and Y 3 the other one is C; X 1 and X 2 each independently is H, C 1-6 alkyl or C 1-6 alkoxy; X 3 and X 4 each independently is H, a halogen group, C 1-6 alkyl, C 1-6 alkoxy or a 5- to 20-membered heteroaryl group, where the C 3 of X 4 and X 1-6 alkyl is optionally substituted with one or more halogen groups; X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl; or (1)L 1 does not exist; and Q 1 Selected from (i) to (iv): (i) phenyl, wherein Q 1 of the phenyl is substituted by one or more halogen groups, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclic group), C 3-10 cycloalkyl or 5- to 20-membered heteroaryl, wherein C 1-6 The alkyl group is optionally substituted by one or more halogen groups, -NH-C(O)-NH(C 1-6 alkyl), -NH-C(O)-C 1-6 alkyl or -NH-C(O)-C 1-6 alkoxy group, C 3-10 The cycloalkyl group is optionally substituted by one or more halogen groups or C 1-6 alkyl groups, and 5 - 20 membered heteroaryl optionally substituted by one or more C 1-6 alkyl groups, (ii) 3- to 15-membered heterocyclic group, wherein Q 1 The 3- to 15-membered heterocyclic group of 1-6 is optionally substituted with one or more oxo groups or C alkyl groups, (iii) 5- to 20-membered heteroaryl, wherein Q 1 the 5- to 20-membered heteroaryl is optionally substituted with one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein C 1-6 The alkyl group is optionally substituted by one or more halogen groups, and C 3-10 The cycloalkyl group is optionally substituted by one or more halogen groups or C 1-6 alkyl groups, and (iv) C 3-10 Naphthenyl; or (2)L 1 is -CH2-; and Q 1 is C 3-10 cycloalkyl; R 1 is H or C 1-6 alkyl; R k is H, a halogen group, -OH, -NH2 or -NH-C(O)C 1-6 alkyl; R m is H, -OH or C 1-6 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 forms a C 3-5 cycloalkyl; and or R k and R m or R n together with the atoms to which they are attached form cyclopropyl; with a compound of formula (L-1): RG-L 2 -R 2 -L-R 2 -L 2 -RG(L-1) wherein L 2 is -C(O)- or -S(O)2-; R 2 selected from (i) to (vii): (i) C 1-6 alkyl, where R 2 of C 1-6 alkyl is optionally substituted by one or more R a where R a is: (a) -OH, (b) cyano, (c)C 2-6 alkynyl (d) C 6-20 aryl, wherein R a of C 6-20 the aryl is optionally substituted with one or more halo groups, cyano groups, C 1-6 alkoxy groups or -NH-C(O)-C 1-6 alkyl groups, (e) 3- to 15-membered heterocyclic group, wherein R a the 3- to 15-membered heterocyclic group is optionally substituted with one or more R c substituents, wherein R c is a halogen group, an oxo group, C 1-6 alkyl, C 1-6 alkoxy, -C(O)-C 1-6 alkyl or -C(O)-C 1-6 alkoxy, wherein R c C of 1-6 The alkyl is optionally substituted by one or more halogen groups or C 2-6 alkynyl groups, and R c -C(O)-C 1-6 The alkoxy group is optionally substituted by one or more halogen groups, (f)-N(R c )(R d ), wherein R c and R d of -N(R c )(R d ) are each independently 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)2, -C(O)-(3- to 15-membered heterocyclic group), -CH2-C(O)-NH2, 3- to 15-membered heterocyclic group or 5- to 20-membered heteroaryl, wherein R c or R d in which the C 1-6 alkyl group is optionally substituted with one or more -C(O)-NH2, R c or R d -C(O)-C 1-6 The alkyl group is optionally substituted with one or more halogen groups, R c or R d The 3- to 15-membered heterocyclic group and 5- to 20-membered heteroaryl group of which are each independently optionally substituted with one or more C 1-6 alkyl groups R c or R d -C(O)-(3- to 15-membered heterocyclic group) of R is optionally substituted with one or more halo groups, -C(O)-C 1-6 alkoxy or C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, C 1-6 alkoxy or C 3-10 cycloalkyl, and R c or R d -C(O)-N(C 1-6 alkyl)2's C 1-6 alkyls are each independently optionally substituted by one or more halo groups or C 6-20 aryl groups, (g)-O-R e , wherein R e is C 1-6 alkyl, C 6-20 aryl, -C(O)-(3- to 15-membered heterocyclic group), -C(O)-N-(C 1-6 alkyl)2 or 5- to 20-membered heteroaryl, wherein R e C of 1-6 The alkyl is optionally substituted by one or more C 1-6 alkoxy groups, wherein the C 1-6 alkoxy groups are optionally substituted by one or more C 2-6 alkynyl groups, R e C of 6-20 The aryl is optionally substituted by one or more C 1-6 alkyl groups, and R e -C(O)-(3- to 15-membered heterocyclic group) is optionally substituted with one or more C 1-6 alkyl, C 1-6 alkoxy or -C(O)-C 1-6 alkoxy, wherein said C 1-6 alkyl is optionally substituted with one or more halo, C 1-6 alkoxy or C 3-10 cycloalkyl, (h)-C(O)-R e , wherein R e is -NH2, -OH or a 3- to 15-membered heterocyclic group, or (i)-S(O)2-R f wherein R f is C 1-6 alkyl or a 3- to 15-membered heterocyclic group, (ii) C 3-10 Cycloalkyl, where R 2 of C 3-10 the cycloalkyl is optionally substituted by one or more R q where R q is a 5- to 20-membered heteroaryl or C 6-20 aryl, where R q of C 6-20 the aryl is optionally substituted by one or more C 1-6 alkoxy groups, (iii) 3- to 15-membered heterocyclic group, wherein R 2 's 3- to 15-membered heterocyclic group is optionally substituted by one or more halo groups, oxo groups, C 1-6 alkyl, -C(O)-C 1-6 alkyl or 5- to 20-membered heteroaryl, (iv) 5 - 20 membered heteroaryl or -(C 1-4 alkyl)(5 - 20 membered heteroaryl), wherein C 1-4 alkyl is optionally substituted by one or more -OH, halogen, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5 - 20 membered heteroaryl in the 5 - 20 membered heteroaryl or -(C 1-4 alkyl)(5 - 20 membered heteroaryl) is optionally substituted by one or more R s substituents, wherein R s is a halogen group, 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, a 3- to 15-membered heterocyclic group, a 5- to 20-membered heteroaryl or -C(O)-C 1-6 alkoxy, wherein R s of C 1-6 The alkyl is optionally substituted with one or more halogen groups, 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 alkoxy, and R s The 3- to 15-membered heterocyclic group is optionally substituted with one or more halogen groups or -C(O)-C 1-6 alkoxy groups, (v)-N(R g )(R h ), wherein R g and R h are independently H or C 1-6 alkyl (vi)-C(O)-R j , wherein R j is a cycloalkyl group, -NH(C 3-10 alkyl), -N(C 1-6 alkyl)2 or -NH(5-20 membered heteroaryl), and 1-6 ​ (vii) C 6-20 aryl, wherein R 2 of C 6-20 the aryl is optionally substituted with one or more 5- to 20-membered heteroaryl or -O-R p wherein R p is a 3- to 15-membered heterocyclic group, wherein R p the 3- to 15-membered heterocyclic group is optionally substituted with one or more -C(O)-C 1-6 alkyl groups; and each RG is independently a reactive group suitable for linking L-1 to the compound of formula (I-1B); to form the compound according to any one of claims 1-17, 19-27 or 29.

37. A method for preparing the compound according to any one of claims 1-17 or 19-25, 27 or 30, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the method comprises: Reacting a compound of formula (I-2B): wherein, Y 2 and Y 3 each is C, or Y 2 and Y 3 one of them is N, and Y 2 and Y 3 the other one is C; X 1 and X 2 each independently is H, C 1-6 alkyl or C 1-6 alkoxy; X 3 and X 4 each independently is H, a halogen group, C 1-6 alkyl, C 1-6 alkoxy or a 5- to 20-membered heteroaryl group, wherein the C 3 of X 4 and X 1-6 alkyl is optionally substituted by one or more halogen groups; X 5 is H, C 1-6 alkyl, C 1-6 alkoxy or C 3-10 cycloalkyl; or (1)L 1 does not exist; and Q 1 Selected from (i) to (iv): (i) phenyl, wherein Q 1 phenyl of which is substituted by one or more halogen groups, C 1-6 alkyl, C 2-6 alkenyl, -NH2, -NH-C(O)-(C 1-6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclic group), C 3-10 cycloalkyl or 5- to 20-membered heteroaryl, wherein C 1-6 The alkyl group is optionally substituted by one or more halogen groups, -NH-C(O)-NH(C 1-6 alkyl), -NH-C(O)-C 1-6 alkyl or -NH-C(O)-C 1-6 alkoxy group, C 3-10 The cycloalkyl group is optionally substituted by one or more halogen groups or C 1-6 alkyl groups, and 5-20 membered heteroaryl optionally substituted by one or more C 1-6 alkyl groups, (ii) 3- to 15-membered heterocyclic group, wherein Q 1 the 3- to 15-membered heterocyclic group is optionally substituted with one or more oxo groups or C 1-6 alkyl groups, (iii) 5- to 20-membered heteroaryl, wherein Q 1 The 5- to 20-membered heteroaryl is optionally substituted by one or more halo groups, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, -NH2 or C 3-10 cycloalkyl, wherein, C 1-6 The alkyl group is optionally substituted by one or more halogen groups, and C 3-10 The cycloalkyl group is optionally substituted by one or more halogen groups or C 1-6 alkyl groups, and (iv) C 3-10 Naphthenyl; or (2)L 1 is -CH2-; and Q 1 is C 3-10 cycloalkyl; with a compound of formula (L-1): RG-L 2 -R 2 -L-R 2 -L 2 -RG(L-1) wherein L 2 is -C(O)- or -S(O)2-; R 2 Selected from (i) to (vii): (i) C 1-6 alkyl group, where R 2 of C 1-6 alkyl group is optionally substituted by one or more R a where R a is: (a) -OH, (b) cyano, (c)C 2-6 alkynyl (d) C 6-20 aryl, wherein R a of C 6-20 the aryl is optionally substituted with one or more halogen groups, cyano groups, C 1-6 alkoxy groups or -NH-C(O)-C 1-6 alkyl groups, (e) 3- to 15-membered heterocyclic group, wherein R a the 3- to 15-membered heterocyclic group is optionally substituted with one or more R c substituents, wherein R c is a halogen group, an oxo group, C 1-6 alkyl, C 1-6 alkoxy, -C(O)-C 1-6 alkyl or -C(O)-C 1-6 alkoxy, wherein R c C of 1-6 The alkyl is optionally substituted by one or more halogen groups or C 2-6 alkynyl groups, and R c -C(O)-C 1-6 The alkoxy group is optionally substituted by one or more halogen groups, (f)-N(R c )(R d ), wherein R c and R d of -N(R c )(R d ) are each independently 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)2, -C(O)-(3- to 15-membered heterocyclic group), -CH2-C(O)-NH2, 3- to 15-membered heterocyclic group or 5- to 20-membered heteroaryl, wherein R c or R d C of 1-6 the alkyl group is optionally substituted with one or more -C(O)-NH2, R c or R d -C(O)-C 1-6 The alkyl group is optionally substituted with one or more halogen groups, R c or R d The 3- to 15-membered heterocyclic group and 5- to 20-membered heteroaryl group of which are each independently optionally substituted with one or more C 1-6 alkyl groups, R c or R d -C(O)-(3- to 15-membered heterocyclic group) of R or R is optionally substituted with one or more halo groups, -C(O)-C 1-6 alkoxy or C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more halo groups, C 1-6 alkoxy or C 3-10 cycloalkyl, and R c or R d -C(O)-N(C 1-6 alkyl)2's C 1-6 alkyls are each independently optionally substituted by one or more halo groups or C 6-20 aryl groups, (g)-O-R e , wherein R e is C 1-6 alkyl, C 6-20 aryl, -C(O)-(3- to 15-membered heterocyclic group), -C(O)-N-(C 1-6 alkyl)2 or 5- to 20-membered heteroaryl, wherein R e C of 1-6 The alkyl is optionally substituted by one or more C 1-6 alkoxy groups, where the C 1-6 alkoxy groups are optionally substituted by one or more C 2-6 alkynyl groups, R e C of 6-20 The aryl is optionally substituted with one or more C 1-6 alkyl groups, and R e -C(O)-(3- to 15-membered heterocyclic group) is optionally substituted with one or more C 1-6 alkyl, C 1-6 alkoxy or -C(O)-C 1-6 alkoxy, wherein said C 1-6 alkyl is optionally substituted with one or more halo, C 1-6 alkoxy or C 3-10 cycloalkyl, (h)-C(O)-R e , wherein R e is -NH2, -OH or a 3- to 15-membered heterocyclic group, or (i)-S(O)2-R f , wherein R f is C 1-6 alkyl or a 3- to 15-membered heterocyclic group, (ii) C 3-10 cycloalkyl, where R 2 of C 3-10 the cycloalkyl is optionally substituted by one or more R q where R q is a 5- to 20-membered heteroaryl or C 6-20 aryl, where R q of C 6-20 the aryl is optionally substituted by one or more C 1-6 alkoxy groups, (iii) 3- to 15-membered heterocyclic group, wherein R 2 's 3- to 15-membered heterocyclic group is optionally substituted by one or more halo groups, oxo groups, C 1-6 alkyl groups, -C(O)-C 1-6 alkyl groups or 5- to 20-membered heteroaryl groups, (iv) 5 - 20 membered heteroaryl or -(C 1-4 alkyl)(5 - 20 membered heteroaryl), wherein the C 1-4 alkyl is optionally substituted by one or more -OH, halo, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)2, and wherein the 5 - 20 membered heteroaryl in the 5 - 20 membered heteroaryl or -(C 1-4 alkyl)(5 - 20 membered heteroaryl) is optionally substituted by one or more R s substituents, wherein R s is a halogen group, 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, a 3- to 15-membered heterocyclic group, a 5- to 20-membered heteroaryl, or -C(O)-C 1-6 alkoxy, wherein R s of C 1-6 The alkyl group is optionally substituted by one or more halogen groups, C 1-6 alkoxy groups, -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 alkoxy, and R s The 3- to 15-membered heterocyclic group of 1-6 is optionally substituted with one or more halogen groups or -C(O)-C (v)-N(R g )(R h ), wherein R g and R h are independently H or C 1-6 alkyl (vi)-C(O)-R j , wherein R j is a cycloalkyl, -NH(C 3-10 alkyl), -N(C 1-6 alkyl)2 or -NH(5-20 membered heteroaryl), and 1-6 ​ (vii) C 6-20 aryl, wherein R 2 of C 6-20 the aryl is optionally substituted with one or more 5- to 20-membered heteroaryl or -O-R p wherein R p is a 3- to 15-membered heterocyclic group, wherein R p the 3- to 15-membered heterocyclic group is optionally substituted with one or more -C(O)-C 1-6 alkyl; and each RG is independently a reactive group suitable for linking L-1 to the compound of formula (I-1B); and to form the compound according to any one of claims 1-17 or 19-25, 27 or 30.

38. The method according to claim 36 or claim 37, wherein RG is an -OH group.

39. A pharmaceutical composition comprising (i) the compound according to any one of claims 1-35, 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. A method for treating a GYS1-mediated disease, disorder or condition in an individual in need thereof, which comprises administering to the individual an effective amount of the compound according to any one of claims 1-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 39.

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

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

44. The method according to claim 40, wherein the disease, disorder or condition is cancer.

45. The method according to 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. The method according to claim 40, wherein the individual has a GAA mutation.

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

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

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

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

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

53. The kit according to claim 48 or claim 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. The kit according to claim 48, wherein the individual has a GAA mutation.

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

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

57. 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 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 39.

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

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

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

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

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

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

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

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

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

69. The method of any one of claims 56-58, wherein the compound is more selective for GYS1 than for GYS2.

70. The method of claim 69, wherein the selectivity of the compound for GYS1 is 500 or 1,000 or 1,500 or 1,700 times the selectivity for GYS2.

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

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

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

74. A compound as claimed in any one of claims 1 - 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition as claimed in claim 39, for inhibiting GYS1 in cells.

75. A compound as claimed in any one of claims 1 - 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition as claimed in claim 39, for reducing tissue glycogen storage in an individual in need thereof.

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

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

78. Use of a compound as claimed in any one of claims 1 - 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition as claimed in claim 39, in the manufacture of a medicament for modulating GYS1 in cells.

79. Use of a compound as claimed in any one of claims 1 - 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition as claimed in claim 39, in the manufacture of a medicament for inhibiting GYS1 in cells.

80. Use of a compound as claimed in any one of claims 1 - 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition as claimed in claim 39, in the manufacture of a medicament for reducing tissue glycogen storage in an individual in need thereof.

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

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