Glycogen synthase 1 (GYS1) inhibitors and methods of use thereof

Abstract

Provided herein is a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharma- ceutically acceptable salt of any of the foregoing, wherein Y2, Y3, L1, L2, X1, X2, X3, X4, X5, Q1, R1, R2, Rk, Rm, and Rn are as defined elsewhere herein. Also provided herein is a method of preparing a compound of formula (F). Also provided herein is a method of inhibiting GYS1 and treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof. TIFF2024511979000697.tif8184

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 161,347, filed March 15, 2021, and U.S. Provisional Application No. 63 / 266,572, filed January 9, 2022, the contents of which are incorporated herein by reference in their entireties. [Background technology]

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

[0003] Pompe disease is a rare genetic disorder caused by a pathological accumulation of cellular glycogen due to loss-of-function (LOF) mutations in the lysosomal enzyme α-glucosidase (GAA). GAA degrades lysosomal glycogen, and in its absence, glycogen accumulates in lysosomes. This triggers a disease cascade that begins with lysosomal and autophagosome dysfunction, ultimately leading to cell death and muscle atrophy over time (Raben N, et al. Autophagy and mitochondria in Pompe Disease: nothing is so new as what has long been forgotten. American Journal of Medical Genetics, vol. 160, 2012; van der Ploeg AT and Reuser AJJ, Pompe's Disease. Lancet vol. 372, 2008). In humans, the clinical manifestations of the disease range in severity and occur at a prevalence of 1 in 40,000 births (Meena NK, Raben N. Pompe disease: new developments in an old lysosomal storage disorder. Biomolecules, vol. 10, 2020). Infantile-onset patients are born with cellular pathology and rapidly develop severe disorders, including myopathy, cardiac defects, organ enlargement, and hypotension, which, if left untreated, can ultimately claim the child's life within a year. Late-onset children may develop cardiac enlargement but are consistently characterized by progressive loss of motor function, skeletal muscle degeneration, and eventual respiratory failure, leading to early death. Late-onset adult Pompe patients exhibit normal cardiac function but develop progressive muscle weakness and respiratory weakness, followed by respiratory failure. The current standard of care for Pompe patients is enzyme replacement therapy (ERT) with recombinant human GAA.Although ERT treatment has been successful in slowing disease progression, there remains an incredible unmet need in the majority of patients (Schoser B, et al. The humanistic burden of Pompe disease: are there still unmet needs? A systematic review. BMC Neurology, vol. 17, 2017). For over a decade, substrate reduction therapies targeting GYS1 have been hypothesized to be beneficial in the treatment of Pompe disease. Indeed, three separate preclinical studies have demonstrated that genetic LOF of GYS1 in Pompe disease mouse models effectively reduces tissue glycogen and improves disease outcomes in mice (Douillard-Guilloux G, et al. Modulation of glycogen synthesis by RNA interference: toward a new therapeutic approach for glycogenosis type II. Human Molecular Genetics, vol. 17, no. 24, 2008; Douillard-Guilloux G, et al. Restoration of muscle function by genetic suppression of glycogen synthesis in a murine model of Pompe disease. Human Molecular Genetics, vol. 19, no. 4, 2010; Clayton NP, et al. Antisense oligonucleotide-mediated suppression of muscle glycogen synthase 1 synthesis as an approach for substrate reduction therapy of Pompe disease. Molecular Therapy - Nucleic Acids, vol. 3, 2014). Small molecule GYS1 inhibitors may be used to address the current unmet needs of Pompe patients, either as monotherapy or in combination with standard of care ERT.

[0004] Pompe disease is only one of more than a dozen diseases caused by inborn errors of metabolism that result in abnormal accumulation of glycogen in various tissues of the body. While specific dietary treatments effectively manage some glycogen storage diseases (GSDs), for others, there are no clinically approved therapeutic interventions to alter the disease course. Therefore, inhibiting glycogen synthesis and the concomitant reduction of tissue glycogen levels may be a viable treatment option for these patients. Cori's disease, GSD III, is caused by mutations in glycogen debranching enzyme (GDE), which leads to pathological glycogen accumulation in the heart, skeletal muscle, and liver (Kishnani P, et al. Glycogen storage disease type III diagnosis and management guidelines. Genetics in Medicine, vol. 12, no. 7, 2010). While dietary management can be effective in ameliorating disease symptoms, there is currently no treatment to prevent progressive myopathy in GSD III. Adult polyglucosan body disease (APBD) is an adult-onset disorder caused by loss of glycogen branching enzyme (GBE1) activity. GBE deficiency leads to the accumulation of long chains of unbranched glycogen that precipitate in the cytosol, generating polyglucosan bodies, ultimately inducing neurological deficits in both the central and peripheral nervous systems. Genetic deletion of GYS1 in an APBD mouse model rescued the deleterious accumulation of glycogen, improved lifespan, and neuromuscular function (Chown EE, et al. GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease. Annals of Clinical and Translational Neurology, vol. 7, no. 11, 2020). Lafora disease (LD) is a highly debilitating early-onset epilepsy disorder similarly characterized by the accumulation of polyglucasone bodies.Genetic crossing of the LD mouse model with GYS1 knockout (KO) mice resulted in rescue of the disease phenotype (Pedersen B, et al. Inhibiting glycogen synthesis prevents Lafora disease in a mouse model. Annals of Neurology, vol. 74, no. 2, 2013; Varea O, et al. Suppression of glycogen synthesis as a treatment for Lafora disease: establishing the window of opportunity. Neurobiology of Disease, 2020).

[0005] Recently, the dependence of clear cell carcinoma on high levels of glycogen has emerged as a novel therapeutic target. Ewing sarcoma (ES), clear cell renal cell carcinoma (ccRCC), glycogen-rich clear cell carcinoma of the breast (GRCC), acute myeloid leukemia (AML), and non-small cell lung cancer (NSCLC) are all examples of cancers histopathologically defined by abnormally high levels of PAS+ cellular glycogen. Increased GYS1 transcript levels have been significantly correlated with poor disease outcomes in NSCLC (Giatromanolaki A, et al. Expression of enzymes related to glucose metabolism in non-small cell lung cancer and prognosis. Experimental Lung Research, vol. 43, no. 4-5, 2017) and AML (Falantes JF, et al. Overexpression of GYS1, MIF, and MYC is associated with adverse outcome and poor response to azacitidine in myelodysplastic syndromes and acute myeloid leukemia. Clinical Lymphoma, Myeloma & Leukemia, vol. 15, no. 4, 2015). Lentiviral knockdown of GYS1 in cultured myeloid leukemia cells strongly inhibited cancer cell proliferation in vitro and tumor formation in vivo (Bhanot H, et al. Pathological glycogenesis through glycogen synthase I and suppression of excessive AMP kinase activity in myeloid leukemia cells. Leukemia, vol. 29, no. 7, 2015).Genetic knockdown of GYS1 in a ccRCC cell model both inhibits tumor growth in vivo and increases the synthetic lethality of sunitinib (Chen S, et al. GYS1 induces glycogen accumulation and promotes tumor progression via the NF-kB pathway in clear cell renal carcinoma. Theranostics, vol. 10, no. 20, 2020). The reduction in GYS1 enzyme activity and reduction in cellular glycogen stores in preclinical models of Pompe disease, APBD, LD, AML, ccRCC, and NSCLC all provide strong evidence of the potential therapeutic benefit of inhibiting glycogen synthesis. The objective of the present invention is to inhibit glycogen synthase activity, resulting in a reduction in tissue glycogen stores, which will provide therapeutic benefit to patients suffering from the consequences of accumulated cellular glycogen. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Platt FM, Butters TD. Substrate Reduction Therapy. Lysosomal Storage Disorders, Springer US chapter 11, pgs153-168, 2007 [Non-patent document 2] Shemesh E,et al.Enzyme replacement and substrate reduction therapy for Gaucher disease.Cochrane Database of Systematic Reviews,Issue 3,2015 [Non-patent document 3] Raben N,et al.Autophagy and mitochondria in Pump Disease: nothing so new as what has long been forgotten.American Journal oMedical Genetics,vol.160,2012.

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[0007] As used herein, in one aspect, there is provided a compound of formula (I'): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Y2 and Y3 are each C, or one of Y2 and Y3 is N and the other of Y2 and Y3 is C; X1 and X2 are each independently H, C1-6 alkyl, or C1-6 alkoxy; X3 and X4 are each independently H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl, and the C1-6 alkyl of X3 and X4 is optionally substituted with one or more halo; X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; (1) L1 does not exist, and Q1 is (i)~(iv): (i) phenyl, wherein the phenyl in Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), C3-10 cycloalkyl, or 5-20 membered heteroaryl; C1-6 alkyl is optionally substituted with one or more halo, -NH-C(O)-NH(C1-6 alkyl), -NH-C(O)-C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; and phenyl, wherein the 5-20 membered heteroaryl is optionally substituted with one or more C1-6 alkyl; (ii) a 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Q1 is optionally substituted with one or more oxo or C1-6 alkyl; (iii) 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl; C1-6 alkyl optionally substituted with one or more halo, and 5-20 membered heteroaryl, wherein the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; and (iv) C3-10 cycloalkyl; or (2) L1 is -CH2-, and Q1 is C3-10 cycloalkyl, L2 is -C(O)- or -S(O)2-; R1 is H or C1-6 alkyl; Rk is H, halo, —OH, —NH2, or —NH—C(O)C1-6 alkyl; Rm is H, —OH, or C1-6 alkyl; Rn is H, C1-6 alkyl, or C3-10 cycloalkyl, or Rn together with the carbon atom to which it is attached forms a C3-5 cycloalkyl; or Rk together with either Rm or Rn and the atom to which they are attached form cyclopropyl; R2 is (i)~(vii): (i) C1-6 alkyl, wherein the C1-6 alkyl of R2 is optionally substituted with one or more Ra, and Ra is (a) -OH, (b) cyano, (c) C2-6 alkynyl, (d) C6-20 aryl, wherein the C6-20 aryl of Ra is optionally substituted with one or more halo, cyano, C1-6 alkoxy, or —NH—C(O)—C1-6 alkyl; (e) 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Ra is optionally substituted with one or more Rc; Rc is halo, oxo, C1-6 alkyl, C1-6 alkoxy, —C(O)—C1-6 alkyl, or —C(O)—C1-6 alkoxy; The C1-6 alkyl of Rc is optionally substituted with one or more halo or C2-6 alkynyl; and Rc -C(O)-C1-6alkoxy is 3-15 membered heterocyclyl optionally substituted with one or more halo; (f) -N(Rc)(Rd), wherein Rc and Rd of N(Rc)(Rd) are each independently H, C1-6 alkyl, -C(O)-C1-6 alkyl, -C(O)-C1-6 alkoxy, -C(O)-NH2, -C(O)-NH(C1-6 alkyl), -C(O)-N(C1-6 alkyl)2, -C(O)-(3- to 15-membered heterocyclyl), -CH2-C(O)-NH2, 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; the C1-6 alkyl of Rc or Rd is optionally substituted with one or more -C(O)-NH2; the —C(O)—C alkyl of Rc or Rd is optionally substituted with one or more halo; the 3- to 15-membered heterocyclyl and 5- to 20-membered heteroaryl of Rc or Rd is independently optionally substituted with one or more C1-6 alkyl; Rc or Rd -C(O)-(3-15 membered heterocyclyl) is optionally substituted with one or more halo, -C(O)-Ci_6 alkoxy, or Ci_6 alkyl, and the Ci_6 alkyl is optionally substituted with one or more halo, Ci_6 alkoxy, or C3_10 cycloalkyl; and -N(Rc)(Rd), wherein the C1-6 alkyl of -C(O)-N(C1-6 alkyl)2 in Rc or Rd is, independently of each other, optionally substituted with one or more halo or C6-20 aryl; (g) -O-Re, where Re is C alkyl, C aryl, -C(O)-(3-15 membered heterocyclyl), -C(O)-N-(C alkyl), or 5-20 membered heteroaryl; The C1-6 alkyl of Re is optionally substituted with one or more C1-6 alkoxy, and the C1-6 alkoxy is optionally substituted with one or more C2-6 alkynyl; The C6-20 aryl of Re is optionally substituted with one or more C1-6 alkyl; and -O-Re, wherein the -C(O)-(3-15 membered heterocyclyl) of Re is optionally substituted with one or more C1-6 alkyl, C1-6 alkoxy, or -C(O)-C1-6 alkoxy, and the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl; (h) —C(O)—Re, where Re in —C(O)—Re is —NH2, —OH, or 3- to 15-membered heterocyclyl; or (i) -S(O)2-Rf, where Rf is C1-6 alkyl or 3-15 membered heterocyclyl; However, when R2 is unsubstituted methyl, (1) Q1 is a 5- to 20-membered heteroaryl, and the 5- to 20-membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, C3-10 cycloalkyl, or -OH, and Q1 is not unsubstituted pyridyl; or (2) Q1 is phenyl, and the phenyl of Q1 is (i) at least one C3-6 alkyl, wherein at least one C3-6 alkyl is optionally substituted with one or more halo, or (ii) at least one C3-10 cycloalkyl, wherein at least one C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; or (iii) at least one 5-20 membered heteroaryl, wherein at least one 5-20 membered heteroaryl is optionally substituted with one or more C1-6 alkyl; (ii) C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of R2 is optionally substituted with one or more Rq, and Rq is a 5-20 membered heteroaryl or C6-20 aryl, and the C6-20 aryl of Rq is optionally substituted with one or more C1-6 alkoxy; (iii) 3- to 15-membered heterocyclyl, wherein R2 is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo, oxo, C1-6 alkyl, —C(O)—C1-6 alkyl, or 5- to 20-membered heteroaryl; (iv) 5-20 membered heteroaryl or -(Ci-4 alkyl)(5-20 membered heteroaryl), wherein the Ci-4 alkyl is optionally substituted with one or more -OH, halo, -NH, -NH(Ci-6 alkyl), -N(Ci-6 alkyl) and the 5-20 membered heteroaryl is optionally substituted with one or more Rs; Rs is halo, C1-6 alkyl, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)-C1-6 alkyl, C6-20 aryl, C3-10 cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or -C(O)-C1-6 alkoxy; the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; and the 3-15 membered heterocyclyl of Rs is a 5-20 membered heteroaryl or -(Ci_4 alkyl)(5-20 membered heteroaryl) optionally substituted with one or more halo or -C(O)-Ci_6 alkoxy; (v) —N(Rg)(Rh), where Rg and Rh are independently H or C1-6 alkyl; (vi) -C(O)-Rj, where Rj is C3-10 cycloalkyl, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, or -NH(5-20 membered heteroaryl); and (vii) C6-20 aryl, wherein the C6-20 aryl of R2 is optionally substituted with one or more 5-20 membered heteroaryl or -O-Rp, wherein Rp is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of Rp is optionally substituted with one or more -C(O)-C1-6 alkyl.

[0008] As used herein, in one aspect, there is provided a compound of formula (I): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: X1 and X2 are each independently H, C1-6 alkyl, or C1-6 alkoxy; X3 and X4 are each independently H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl; X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; Q1 is (i)~(iii): (i) phenyl, wherein the phenyl in Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), or C3-10 cycloalkyl; C1-6 alkyl optionally substituted with one or more halo, and phenyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; (ii) 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Q1 is optionally substituted with one or more oxo groups; and (iii) 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl; C3-10 cycloalkyl is selected from 5-20 membered heteroaryl optionally substituted with one or more halo or C1-6 alkyl; R1 is H or C1-6 alkyl; Rk is H, halo, —OH, —NH2, or —NH—C(O)C1-6 alkyl; Rm is H, —OH, or C1-6 alkyl; Rn is H, C1-6 alkyl, or C3-10 cycloalkyl; or Rk together with either Rm or Rn and the atom to which they are attached form cyclopropyl; R2 is (i)~(vii): (i) C1-6 alkyl, wherein the C1-6 alkyl of R2 is optionally substituted with one or more Ra, and Ra is (a) -OH, (b) cyano, (c) C2-6 alkynyl, (d) C6-20 aryl, wherein the C6-20 aryl of Ra is optionally substituted with one or more halo, cyano, C1-6 alkoxy, or —NH—C(O)—C1-6 alkyl; (e) 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Ra is optionally substituted with one or more Rb; Rb is halo, C1-6 alkyl, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-10 cycloalkyl, 3-15 membered heterocyclyl, or -C(O)-C1-6 alkoxy; the C1-6 alkyl of Rb is optionally substituted with one or more halo, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —NH—C(O)C1-6 alkyl, or —NH—C(O)—C1-6 alkoxy; and the 3-15 membered heterocyclyl of Rb is a 5-20 membered heteroaryl optionally substituted with one or more halo or -C(O)-C1-6alkoxy; (f) 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Ra is optionally substituted with one or more Rc; Rc is halo, oxo, C1-6 alkyl, C1-6 alkoxy, —C(O)—C1-6 alkyl, or —C(O)—C1-6 alkoxy; The C1-6 alkyl of Rc is optionally substituted with one or more halo or C2-6 alkynyl; and Rc -C(O)-C1-6alkoxy is 3-15 membered heterocyclyl optionally substituted with one or more halo; (g) -N(Rc)(Rd), wherein Rc and Rd are each independently H, C1-6 alkyl, -C(O)-C1-6 alkyl, -C(O)-C1-6 alkoxy, -C(O)-NH2, -C(O)-NH(C1-6 alkyl), -C(O)-N(C1-6 alkyl)2, -C(O)-(3- to 15-membered heterocyclyl), -CH2-C(O)-NH2, 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; the —C(O)—C alkyl of Rc or Rd is optionally substituted with one or more halo; The 3- to 15-membered heterocyclyl and 5- to 20-membered heteroaryl of Rc or Rd are independently optionally substituted with one or more C1-6 alkyl; and -N(Rc)(Rd), wherein -C(O)-(3-15 membered heterocyclyl) of Rc or Rd is optionally substituted with one or more halo, -C(O)-Ci_6 alkoxy, or Ci_6 alkyl, and the Ci_6 alkyl is optionally substituted with one or more halo, Ci_6 alkoxy, or C3_10 cycloalkyl; (h) -O-Re, where Re is C alkyl, C aryl, -C(O)-(3-15 membered heterocyclyl), -C(O)-N-(C alkyl), or 5-20 membered heteroaryl; The C1-6 alkyl of Re is optionally substituted with one or more C1-6 alkoxy, and the C1-6 alkoxy is optionally substituted with one or more C2-6 alkynyl; The C6-20 aryl of Re is optionally substituted with one or more C1-6 alkyl; and -O-Re, wherein the -C(O)-(3-15 membered heterocyclyl) of Re is optionally substituted with one or more C1-6 alkyl, C1-6 alkoxy, or -C(O)-C1-6 alkoxy, and the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl; (i) —C(O)—Re, where Re is —NH, —OH, or 3- to 15-membered heterocyclyl; or (j) -S(O)2-Rf, where Rf is C1-6 alkyl or 3-15 membered heterocyclyl; However, when R2 is unsubstituted methyl, (1) Q1 is a 5- to 20-membered heteroaryl, and the 5- to 20-membered heteroaryl of Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, C3-10 cycloalkyl, or -OH; or (2) C1-6 alkyl, wherein Q1 is phenyl, and the phenyl in Q1 is substituted with at least one C3-6 alkyl or at least one C3-10 cycloalkyl, and at least one C3-6 alkyl is optionally substituted with one or more halo, and at least one C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; (ii) C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of R2 is optionally substituted with one or more Rq, and Rq is a 5-20 membered heteroaryl or C6-20 aryl, and the C6-20 aryl of Rq is optionally substituted with one or more C1-6 alkoxy; (iii) 3- to 15-membered heterocyclyl, wherein R2 is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo, oxo, C1-6 alkyl, —C(O)—C1-6 alkyl, or 5- to 20-membered heteroaryl; (iv) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R2 is optionally substituted with one or more Rs, and Rs is C1-6 alkyl, C1-6 alkoxy, -NH-C(O)-C1-6 alkyl, C6-20 aryl, or 5-20 membered heteroaryl, wherein the C1-6 alkyl of Rs is optionally substituted with one or more C1-6 alkoxy; (v) —N(Rg)(Rh), where Rg and Rh are independently H or C1-6 alkyl; (vi) -C(O)-Rj, where Rj is C3-10 cycloalkyl, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, or -NH(5-20 membered heteroaryl); and (vii) C6-20 aryl, wherein the C6-20 aryl of R2 is optionally substituted with one or more 5-20 membered heteroaryl or -O-Rp, wherein Rp is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of Rp is optionally substituted with one or more -C(O)-C1-6 alkyl.

[0009] As used herein, in one aspect, there is provided a compound of formula (IA): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y, R, Rk, Rx, Ry, and Rz are as defined elsewhere herein. In another variation, Y, R, Rk, Rx, Ry, and Rz of formula (IA) are as defined elsewhere herein for a compound of formula (I') or formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0010] As used herein, in one aspect, there is provided a compound of formula (IB): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y, R, R, R, R, R, R, R, and Ry are as defined elsewhere herein. In another variation, Y, R, R, R, R, R, R, and Ry of formula (IB) are as defined elsewhere herein for a compound of formula (I') or formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0011] As used herein, in one aspect, there is provided a compound of formula (IC): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X, X, R, R, R, R, and R are as defined elsewhere herein. In another variation, X, X, R, R, R, and R of formula (IC) are as defined elsewhere herein for a compound of formula (I') or formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0012] As used herein, in one aspect, there is provided a compound of formula (ID): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X, X, R, R, Ru, and R are as defined elsewhere herein. In another variation, X, X, R, R, Ru, and R of formula (ID) are as defined elsewhere herein for a compound of formula (I') or formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0013] In one embodiment, the compound has the formula (I-D1): [ka] wherein X, X, R, R, Ru, and R of formula (I-D1) are as defined for a compound of formula (I') elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0014] In one embodiment, the compound has the formula (I-D1): [ka] wherein X, X, R, R, R, and Ru of formula (I-D2) are as defined for a compound of formula (I') elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0015] As used herein, in one aspect, there is provided a compound of formula (IE): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R, Rk, and Rm are as defined elsewhere herein. In another variation, R, Rk, and Rm of formula (IE) are as defined elsewhere herein for a compound of formula (I') or formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0016] As used herein, in one aspect, there is provided a compound of formula (IF): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y, R, R, R, R, R, and R are as defined elsewhere herein. In another variation, R, R, and R of formula (IF) are as defined elsewhere herein for a compound of formula (I') or formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0017] Herein, in one aspect, a compound is described having the formula (IG): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein ring A, L1, Y2, Y3, R2, Rk, X1, X2, X3, X4, and X5 are as defined elsewhere herein.

[0018] As used herein, in one aspect, a compound is described having the formula (IH): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y, R, R, R, R, and R are as defined elsewhere herein.

[0019]

[0013] Provided herein, in one aspect, is a pharmaceutical composition comprising: (i) a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.

[0014] Provided herein, in another variation, is a pharmaceutical composition comprising: (i) a compound of formula (I'), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.

[0020] Provided herein, in one aspect, is a method for modulating GYS1 in a cell, the method comprising exposing the cell to (i) a composition comprising an effective amount of a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients. In another variation, provided herein is a method for modulating GYS1 in a cell, the method comprising exposing the cell to (i) a composition comprising an effective amount of a compound of formula (I'), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I'), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0021] Provided herein, in one aspect, is a method of inhibiting GYS1 in a cell, the method comprising exposing the cell to (i) a composition comprising an effective amount of a compound of formula (I), or any 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. In another variation, provided herein is a method for inhibiting GYS1 in a cell, the method comprising exposing the cell to (i) a composition comprising an effective amount of a compound of formula (I'), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I'), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0022] Provided herein, in one aspect, is a method for reducing tissue glycogen stores in an individual in need thereof, comprising administering to the individual an effective amount of (i) a GYS1 inhibitor, or (ii) a pharmaceutical composition comprising a GYS1 inhibitor and one or more pharmaceutically acceptable excipients. In some embodiments, the GYS1 inhibitor is selective for GYS1 over GYS2. In some embodiments, the GYS1 inhibitor is 500-fold, 1,000-fold, 1,500-fold, or 1,700-fold selective for GYS1 over GYS2. In some embodiments, the GYS1 inhibitor is a small molecule.

[0023] Provided herein, in one aspect, is a method of reducing tissue glycogen stores in an individual in need thereof, comprising administering to the individual an effective amount of (i) a composition comprising an effective amount of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients. Provided herein, in another variation, is a method of reducing tissue glycogen stores in an individual in need thereof, comprising administering to the individual an effective amount of (i) a composition comprising an effective amount of a compound of formula (F), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (F), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0024] Provided herein, in one aspect, is a method 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 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.

[0025] In one aspect, provided herein is a method of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof, comprising subjecting the individual to glycogen substrate-reducing therapy. In some embodiments, the glycogen substrate-reducing therapy comprises administering a GYS1 inhibitor. In some embodiments, the GYS1 inhibitor is a small molecule. In some embodiments, the GYS1 inhibitor is selective for GYS1 over GYS2. In some embodiments, the GYS1 inhibitor is 500-fold, 1,000-fold, 1,500-fold, or 1,700-fold selective for GYS1 over GYS2.

[0026] Provided herein, in one aspect, is a method of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to the individual an effective amount of (i) a composition comprising an effective amount of a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients. Provided herein, in another variation, is a method of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to the individual an effective amount of (i) a composition comprising an effective amount of a compound of formula (I'), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I'), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0027] Provided herein, in one aspect, are methods of treating a glycogen storage disease, disorder, or condition in an individual in need thereof, comprising subjecting the individual to glycogen substrate-reducing therapy. In some embodiments, the glycogen substrate-reducing therapy comprises administering a GYS1 inhibitor. In some embodiments, the GYS1 inhibitor is a small molecule. In some embodiments, the GYS1 inhibitor is selective for GYS1 over GYS2. In some embodiments, the GYS1 inhibitor is 500-fold, 1,000-fold, 1,500-fold, or 1,700-fold selective for GYS1 over GYS2.

[0028] In one aspect, provided herein is a kit comprising: (i) a composition comprising an effective amount of a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use thereof in treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof. In another variation, provided herein is a kit comprising: (i) a composition comprising an effective amount of a compound of formula (I'), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising a compound of formula (I'), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use thereof in treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

[0029] Provided herein in some aspects are methods for preparing a compound of Formula (I) or (I'), or any embodiment or variation thereof, e.g., a compound of Formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. [Brief explanation of the drawings]

[0030] [Figure 1] Figure 1 shows the pathway by which PPP1R3A loss of function (LoF) leads to reduced muscle glycogen. [Figure 2A] Figure 1 shows the association between PPP1R3A protein truncating variants (PTV) and left ventricular ejection fraction (LVEF) (%) and left ventricular wall thickness (mm) in UK Biobank. [Figure 2B] Figure 1 shows the association between PPP1R3A protein truncating variants (PTV) and left ventricular ejection fraction (LVEF) (%) and left ventricular wall thickness (mm) in UK Biobank. [Figure 2C] Figure 1 shows the association between PPP1R3A protein truncating variants (PTVs) and exercise power (watts) and maximum heart rate (HR) exercise (bpm) in UK Biobank. [Figure 2D] Figure 1 shows the association between PPP1R3A protein truncating variants (PTVs) and exercise power (watts) and maximum heart rate (HR) exercise (bpm) in UK Biobank. [Figure 2E] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and PQ interval (ms) and QRS duration (ms) in UK Biobank. [Figure 2F] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and PQ interval (ms) and QRS duration (ms) in UK Biobank. [Figure 2G]Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and QT interval (ms) and serum glucose (mmol / L) in UK Biobank. [Figure 2H] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and QT interval (ms) and serum glucose (mmol / L) in UK Biobank. DETAILED DESCRIPTION OF THE INVENTION

[0031] "Individual" refers to mammals, including humans and non-human mammals. Examples of individuals include, but are not limited to, mice, rats, hamsters, guinea pigs, pigs, rabbits, cats, dogs, goats, sheep, cows, and humans. In some embodiments, individual refers to a human.

[0032] As used herein, "about" a parameter or value includes and describes the parameter or value itself. For example, "about X" includes and describes X itself.

[0033] As used herein, an "at risk" individual is an individual who is at risk of developing a disease or condition. An "at risk" individual may or may not have a detectable disease or condition, and may or may not exhibit detectable disease prior to the treatment methods described herein. "At risk" means that an individual has one or more so-called risk factors, which are measurable parameters that correlate with the development of a disease or condition and are known in the art. Individuals who have one or more of these risk factors have a higher likelihood of developing a disease or condition than individuals who do not have these risk factors.

[0034] "Treatment" or "treating" is an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired results may include one or more of the following: reducing one or more symptoms resulting from a disease or condition; reducing the severity of a disease or condition; delaying or preventing the onset of one or more symptoms associated with a disease or condition (e.g., stabilizing a disease or condition, preventing or slowing the worsening or progression of a disease or condition); and alleviating the disease, such as by causing regression of clinical symptoms (e.g., ameliorating a disease state, enhancing the effect of another drug, slowing the progression of a disease, improving quality of life, and / or prolonging survival).

[0035] As used herein, "delaying the onset of a disease or condition" means to postpone, inhibit, slow, decelerate, stabilize, and / or postpone the onset of the disease or condition. This delay can be of varying lengths of time, depending on the disease being treated and / or the medical history of the individual. As will be apparent to one of skill in the art, a sufficient or significant delay can, in fact, encompass prevention, in that the individual does not develop the disease or condition.

[0036] As used herein, the term "therapeutically effective amount" or "effective amount" refers to a sufficient amount of a compound of the present disclosure or a pharmaceutical salt thereof to provide treatment when 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 a desired therapeutic endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents; a single agent may be considered to be administered in an effective amount if, in conjunction with one or more other agents, a desired or beneficial result may be obtained or achieved.

[0037] As used herein, "unit dosage form" refers to physically discrete units suitable as unit dosages, each containing a predetermined amount of active ingredient or compound, which may be in a pharmaceutically acceptable carrier.

[0038] As used herein, "pharmaceutically acceptable" means a material that is not biologically or otherwise undesirable, e.g., the material can be incorporated into a pharmaceutical composition administered to an individual without causing significant undesirable biological effects.

[0039] The term "alkyl," as used herein, refers to an unbranched or branched monovalent saturated hydrocarbon chain. As used herein, alkyl has 1 to 20 carbons (i.e., C alkyl), 1 to 16 carbons (i.e., C alkyl), 1 to 12 carbons (i.e., C alkyl), 1 to 10 carbons (i.e., C alkyl), 1 to 8 carbons (i.e., C alkyl), 1 to 6 carbons (i.e., C alkyl), 1 to 4 carbons (i.e., C alkyl), or 1 to 3 carbons (i.e., C alkyl). Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue having a specific number of carbons is named by a chemical name or molecular formula, all positional isomers having that number of carbon atoms can be included (e.g., "butyl" includes n-butyl, sec-butyl, isobutyl, and tert-butyl, and "propyl" includes n-propyl and isopropyl). Certain commonly used alternative names can be used and will be understood by those skilled in the art. For example, a divalent group, such as a divalent "alkyl" group, can be referred to as an "alkylene."

[0040] As used herein, the term "alkenyl" refers to a branched or unbranched monovalent hydrocarbon chain containing at least one carbon-carbon double bond. As used herein, alkenyl has 2 to 20 carbons (i.e., C2-20 alkenyl), 2 to 16 carbons (i.e., C2-16 alkenyl), 2 to 12 carbons (i.e., C2-12 alkenyl), 2 to 10 carbons (i.e., C2-10 alkenyl), 2 to 8 carbons (i.e., C2-8 alkenyl), 2 to 6 carbons (i.e., C2-6 alkenyl), 2 to 4 carbons (i.e., C2-4 alkenyl), or 2 to 3 carbons (i.e., C2-3 alkenyl). Examples of alkenyl include, but are not limited to, ethenyl, prop-1-enyl, prop-2-enyl-1,2-butadienyl, and 1,3-butadienyl. When an alkenyl residue having a specific number of carbon atoms is named by a chemical name or molecular formula, all positional isomers having that number of carbon atoms can be included (e.g., "propenyl" includes prop-1-enyl and prop-2-enyl). Certain commonly used alternative names can be used and will be understood by those skilled in the art. For example, a divalent group, such as a divalent "alkenyl" group, can be referred to as an "alkenylene."

[0041] As used herein, the term "alkynyl" refers to a branched or unbranched monovalent hydrocarbon chain containing at least one carbon-carbon triple bond. As used herein, alkynyl has 2 to 20 carbons (i.e., C2-20 alkynyl), 2 to 16 carbons (i.e., C2-16 alkynyl), 2 to 12 carbons (i.e., C2-12 alkynyl), 2 to 10 carbons (i.e., C2-10 alkynyl), 2 to 8 carbons (i.e., C2-8 alkynyl), 2 to 6 carbons (i.e., C2-6 alkynyl), 2 to 4 carbons (i.e., C2-4 alkynyl), or 2 to 3 carbons (i.e., C2-3 alkynyl). Examples of alkynyl include, but are not limited to, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, and but-3-ynyl. When an alkynyl residue having a specific number of carbon atoms is named by a chemical name or molecular formula, all positional isomers having that number of carbon atoms are encompassed (e.g., "propynyl" includes propyl-1-ynyl and propyl-2-ynyl). Certain commonly used alternative names may be used and will be understood by those skilled in the art. For example, a divalent group, such as a divalent "alkynyl" group, may be referred to as an "alkynylene."

[0042] The term "alkoxy" as used herein refers to an -O-alkyl moiety. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy.

[0043] The term "aryl," as used herein, refers to a fully unsaturated carbocyclic ring moiety. The term "aryl" encompasses monocyclic and polycyclic fused ring moieties. As used herein, aryl encompasses ring moieties containing, for example, 6 to 20 ring carbon atoms (i.e., C6-20 aryl), 6 to 16 ring carbon atoms (i.e., C6-16 aryl), 6 to 12 ring carbon atoms (i.e., C6-12 aryl), or 6 to 10 ring carbon atoms (i.e., C6-10 aryl). Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, fluorenyl, and anthryl.

[0044] The term "cycloalkyl," as used herein, refers to a saturated or partially unsaturated carbocyclic ring moiety. The term "cycloalkyl" encompasses monocyclic and polycyclic ring moieties, which may be fused, branched, or spiro. Cycloalkyl includes cycloalkenyl groups, where the ring moiety contains at least one cyclic double bond. Cycloalkyl includes any polycyclic carbocyclic ring moiety containing at least one non-aromatic ring, regardless of the point of attachment to the rest of the molecule. As used herein, cycloalkyl includes rings containing, for example, 3 to 20 annular carbon atoms (i.e., C3-20 cycloalkyl), 3 to 16 annular carbon atoms (i.e., C3-16 cycloalkyl), 3 to 12 annular carbon atoms (i.e., C3-12 cycloalkyl), 3 to 10 annular carbon atoms (i.e., C3-10 cycloalkyl), 3 to 8 annular carbon atoms (i.e., C3-8 cycloalkyl), 3 to 6 annular carbon atoms (i.e., C3-6 cycloalkyl), or 3 to 5 annular carbon atoms (i.e., C3-5 cycloalkyl). Monocyclic cycloalkyl ring moieties include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic groups include, for example, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl, norbornyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, etc. Furthermore, cycloalkyl also includes spirocycloalkyl ring moieties, for example, spiro[2.5]octanyl, spiro[4.5]decanyl, or spiro[5.5]undecanyl.

[0045] The term "halo," as used herein, refers to the atoms occupying Group VIIA of the periodic table and includes fluorine (fluoro), chlorine (chloro), bromine (bromo), and iodine (iodine).

[0046] The term "heteroaryl," as used herein, refers to an aromatic (fully unsaturated) ring moiety containing one or more ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heteroaryl" includes both monocyclic and polycyclic fused ring moieties. As used herein, heteroaryl includes, for example, 5 to 20 ring atoms (i.e., 5-20-membered heteroaryl), 5 to 16 ring atoms (i.e., 5-16-membered heteroaryl), 5 to 12 ring atoms (i.e., 5-12-membered heteroaryl), 5 to 10 ring atoms (i.e., 5-10-membered heteroaryl), 5 to 8 ring atoms (i.e., 5-8-membered heteroaryl), or 5 to 6 ring atoms (i.e., 5-6-membered heteroaryl). Any monocyclic or polycyclic aromatic ring moiety containing one or more ring heteroatoms is considered heteroaryl, regardless of the point of attachment to the remainder of the molecule (i.e., the heteroaryl moiety can be attached to the remainder of the molecule through any ring carbon or any ring heteroatom of the heteroaryl moiety). Examples of heteroaryl groups are acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzofuranyl, benzothiazolyl, benzothiadiazolyl, benzonaphthofuranyl, benzoxazolyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, isoquinolyl, isopropyl, ... These include, but are not limited to, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, phenazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, and triazinyl.Examples of fused heteroaryl rings include, but are not limited to, benzo[d]thiazolyl, quinolinyl, isoquinolinyl, benzo[b]thiophenyl, indazolyl, benzo[d]imidazolyl, pyrazolo[1,5-a]pyridinyl, and imidazo[1,5-a]pyridinyl, and the heteroaryl may be attached via either ring of the fused system.

[0047] The term "heterocyclyl," as used herein, refers to a saturated or partially unsaturated cyclic moiety containing one or more ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heterocyclyl" includes both monocyclic and polycyclic ring moieties, which may be fused, bridged, or spiro. Any non-aromatic monocyclic or polycyclic aromatic ring moiety containing at least one ring heteroatom is considered to be heterocyclyl, regardless of the point of attachment to the rest of the molecule (i.e., the heterocyclyl moiety can be attached to the rest of the molecule through any ring carbon or any ring heteroatom of the heterocyclyl moiety). Furthermore, the term heterocyclyl is intended to encompass any polycyclic ring moiety containing at least one ring heteroatom, provided that the polycyclic ring moiety contains at least one non-aromatic ring, regardless of the point of attachment to the rest of the molecule. As used herein, heterocyclyl includes, for example, 3 to 20 ring atoms (i.e., 3-20-membered heterocyclyl), 3 to 16 ring atoms (i.e., 3-16-membered heterocyclyl), 3 to 12 ring atoms (i.e., 3-12-membered heterocyclyl), 3 to 10 ring atoms (i.e., 3-10-membered heterocyclyl), 3 to 8 ring atoms (i.e., 3-8-membered heterocyclyl), 3 to 6 ring atoms (i.e., 3-6-membered heterocyclyl), 3 to 5 ring atoms (i.e., 3-5-membered heterocyclyl), 5 to 8 ring atoms (i.e., 5-8-membered heterocyclyl), or 5 to 6 ring atoms (i.e., 5-6-membered heterocyclyl).Examples of heterocyclyl groups are, for example, azetidinyl, azepinyl, benzodioxolyl, benzo[b][l,4]dioxepinyl, 1,4-benzodioxanyl, benzopyranyl, benzodioxinyl, benzopyranonyl, benzofuranonyl, dioxolanyl, dihydropyranyl, hydropyranyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, furanonyl, imidazolinyl, imidazolidinyl, indolinyl, indolizinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoquinol ... Includes isoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, oxiranyl, oxetanyl, phenothiazinyl, phenoxazinyl, piperidinyl, piperazinyl group, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tetrahydropyranyl, trithianyl, tetrahydroquinolinyl, thiophenyl (i.e., thienyl), thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Examples of spiroheterocyclyl rings include, but are not limited to, bicyclic and tricyclic ring systems such as oxabicyclo[2.2.2]octanyl, 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, and 6-oxa-1-azaspiro[3.3]heptanyl. Examples of fused heterocyclyl rings include, but are not limited to, 1,2,3,4-tetrahydroisoquinolinyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridinyl, indolinyl, and isoindolinyl, where the heterocyclyl may be attached via either ring of the fused system.

[0048] As used herein, the term "oxo" refers to the moiety a=O.

[0049] The terms "optional" and "optionally," as used herein, mean that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not occur. Thus, the term "optionally substituted" infers that any one or more (e.g., 1, 2, 1 to 5, 1 to 3, 1 to 2, etc.) hydrogen atoms at the specified atom, moiety, or group may or may not be replaced by atoms, moieties, or groups other than hydrogen. By way of example, and not limitation, the phrase "methyl optionally substituted with one or more chloro" encompasses the moieties -CH, -CHCl, -CHCl, and -CCl.

[0050] Aspects and embodiments described herein as "comprising" are to be understood to include "consisting of" and "consisting essentially of" embodiments.

[0051] As used herein, the term "pharmaceutically acceptable salt" of a given compound refers to a salt that retains the biological effectiveness and properties of the given compound and is not biologically or otherwise undesirable. "Pharmaceutically acceptable salts" include, for example, salts with inorganic acids and salts with organic acids. Furthermore, if a compound described herein is obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid salt. Conversely, if the product is a free base, an addition salt, particularly a pharmaceutically acceptable addition salt, can be produced by dissolving the free base in a suitable organic solvent and treating the solution with an acid according to conventional procedures for preparing acid addition salts from base compounds. See, for example, "Handbook of Pharmaceutical Salts Properties, Selection, and Use," International Union of Pure and Applied Chemistry, John Wiley & Sons (2008), incorporated herein by reference. Those skilled in the art will recognize various synthetic methods that can be used to prepare non-toxic pharmaceutically acceptable addition salts. Pharmaceutically acceptable acid addition salts can be prepared from inorganic or organic acids. Salts derived from inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Salts derived from organic acids include, for example, acetic acid, propionic acid, gluconic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, trifluoroacetic acid, and the like. Similarly, pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include, by way of example only, sodium, potassium, lithium, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines.Specific examples of suitable amines include, by way of example only, isopropylamine, trimethylamine, diethylamine, tri(isopropyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, and the like.

[0052] Isotopically labeled forms of the compounds described herein can be prepared. Isotopically labeled compounds have the structures described herein except that one or more atoms are replaced by atoms having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, such as 2H, 3H, 11C, 13C, 14C, 13N, 15N, 15O, 17O, 18O, 31P, 32P, 35S, 18F, 36Cl, 123I, and 125I, respectively. In some embodiments, compounds of formula (A) are provided in which one or more hydrogen atoms are replaced by deuterium or tritium.

[0053] Some of the compounds provided herein may exist as tautomers. Tautomers are in equilibrium with each other. By way of example, an amide-containing compound may exist in equilibrium with an imidic acid tautomer. Regardless of which tautomer is shown and the nature of the equilibrium between the tautomers, the compounds of this disclosure will be understood by those skilled in the art to include both the amide and imidic acid tautomers. Thus, for example, an amide-containing compound is understood to include its imidic acid tautomer. Similarly, an imidic acid-containing compound is understood to include its amide tautomer.

[0054] Prodrugs of the compounds disclosed herein or pharmaceutically acceptable salts thereof are also provided herein. Prodrugs are compounds that can be administered to an individual and release the compounds disclosed herein as parent drug compounds in vivo. It should be understood that prodrugs can be prepared by modifying functional groups in the parent drug compound so that the modifications are cleaved in vitro or in vivo to release the parent drug compound. See, for example, Rautio, J., Kumpulainen, H., Heimbach, T. et al. Prodrugs: design and clinical applications. Nat Rev Drug Discov 7, 255-270 (2008), which is incorporated herein by reference.

[0055] The compounds of the present disclosure, or pharmaceutically acceptable salts thereof, may contain asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined in terms of absolute stereochemistry as (R)- or (S)- (or, in the case of amino acids, (D)- or (L)-). The present disclosure is intended to include all such possible isomers, as well as their racemic and optically pure forms, and mixtures thereof, in any proportion. Optically active (+)- and (−), (R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiral synthesizers or chiral reagents or resolved using conventional techniques, for example, chromatography and / or fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of the racemates (or racemates of salts or derivatives) using, for example, chiral high-pressure liquid chromatography (HPLC) and chiral supercritical fluid chromatography (SFC). When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, unless otherwise specified, the present disclosure is intended to include both E and Z geometric isomers. Similarly, cis and trans are used in their conventional sense to describe relative spatial relationships.

[0056] "Stereoisomers" refer to compounds consisting of the same atoms connected by the same bonds but having different three-dimensional structures that are not interchangeable. The present disclosure contemplates various stereoisomers, or mixtures thereof, and includes "enantiomers," which refer to two stereoisomers whose structures are non-superimposable mirror images of each other. "Diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other.

[0057] Where enantiomeric and / or diastereomeric forms of a given structure exist, a planar bond indicates that all stereoisomeric forms of the structure shown may exist, for example: [ka]

[0058] Where enantiomeric and / or diastereomeric forms of a given structure exist, the presence of a planar bond and "*" symbol indicates that the composition consists of at least 90% by weight of a single isomer of unknown stereochemistry, for example, [ka]

[0059] Where enantiomeric and / or diastereomeric forms of a given structure exist, a wedge or hash bond indicates that the composition consists of at least 90% by weight of a single enantiomer or diastereomer of the known stereochemistry, for example, [ka]

[0060] Combinations of the above notations may be used where applicable. Exemplary species may contain stereocenters with known stereochemistry and stereocenters with unknown stereochemistry, such as: [ka]

[0061] Combinations of the above notations may be used where applicable. Exemplary species may contain stereocenters with known stereochemistry and stereocenters with mixtures of isomers, such as: [ka]

[0062] compound As used herein, in one aspect, there is provided a compound of formula (I'): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Y2 and Y3 are each C, or one of Y2 and Y3 is N and the other of Y2 and Y3 is C; X1 and X2 are each independently H, C1-6 alkyl, or C1-6 alkoxy; X3 and X4 are each independently H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl, and the C1-6 alkyl of X3 and X4 is optionally substituted with one or more halo; X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; (1) L1 does not exist, and Q1 is (i)~(iv): (i) phenyl, wherein the phenyl in Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), C3-10 cycloalkyl, or 5-20 membered heteroaryl; C1-6 alkyl is optionally substituted with one or more halo, -NH-C(O)-NH(C1-6 alkyl), -NH-C(O)-C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; and phenyl, wherein the 5-20 membered heteroaryl is optionally substituted with one or more C1-6 alkyl; (ii) a 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Q1 is optionally substituted with one or more oxo or C1-6 alkyl; (iii) 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl; C1-6 alkyl optionally substituted with one or more halo, and 5-20 membered heteroaryl, wherein the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; and (iv) C3-10 cycloalkyl; or (2) L1 is -CH2-, and Q1 is C3-10 cycloalkyl, L2 is -C(O)- or -S(O)2-; R1 is H or C1-6 alkyl; Rk is H, halo, —OH, —NH2, or —NH—C(O)C1-6 alkyl; Rm is H, —OH, or C1-6 alkyl; Rn is H, C1-6 alkyl, or C3-10 cycloalkyl, or Rn together with the carbon atom to which it is attached forms a C3-5 cycloalkyl; or Rk together with either Rm or Rn and the atom to which they are attached form cyclopropyl; R2 is (i)~(vii): (i) C1-6 alkyl, wherein the C1-6 alkyl of R2 is optionally substituted with one or more Ra, and Ra is (a) -OH, (b) cyano, (c) C2-6 alkynyl, (d) C6-20 aryl, wherein the C6-20 aryl of Ra is optionally substituted with one or more halo, cyano, C1-6 alkoxy, or —NH—C(O)—C1-6 alkyl; (e) 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Ra is optionally substituted with one or more Rc; Rc is halo, oxo, C1-6 alkyl, C1-6 alkoxy, —C(O)—C1-6 alkyl, or —C(O)—C1-6 alkoxy; The C1-6 alkyl of Rc is optionally substituted with one or more halo or C2-6 alkynyl; and Rc -C(O)-C1-6alkoxy is 3-15 membered heterocyclyl optionally substituted with one or more halo; (f) -N(Rc)(Rd), wherein Rc and Rd of N(Rc)(Rd) are each independently H, C1-6 alkyl, -C(O)-C1-6 alkyl, -C(O)-C1-6 alkoxy, -C(O)-NH2, -C(O)-NH(C1-6 alkyl), -C(O)-N(C1-6 alkyl)2, -C(O)-(3- to 15-membered heterocyclyl), -CH2-C(O)-NH2, 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; the C1-6 alkyl of Rc or Rd is optionally substituted with one or more -C(O)-NH2; the —C(O)—C alkyl of Rc or Rd is optionally substituted with one or more halo; the 3- to 15-membered heterocyclyl and 5- to 20-membered heteroaryl of Rc or Rd is independently optionally substituted with one or more C1-6 alkyl; Rc or Rd -C(O)-(3-15 membered heterocyclyl) is optionally substituted with one or more halo, -C(O)-Ci_6 alkoxy, or Ci_6 alkyl, and the Ci_6 alkyl is optionally substituted with one or more halo, Ci_6 alkoxy, or C3_10 cycloalkyl; and -N(Rc)(Rd), wherein the C1-6 alkyl of -C(O)-N(C1-6 alkyl)2 in Rc or Rd is, independently of each other, optionally substituted with one or more halo or C6-20 aryl; (g) -O-Re, where Re is C alkyl, C aryl, -C(O)-(3-15 membered heterocyclyl), -C(O)-N-(C alkyl), or 5-20 membered heteroaryl; The C1-6 alkyl of Re is optionally substituted with one or more C1-6 alkoxy, and the C1-6 alkoxy is optionally substituted with one or more C2-6 alkynyl; The C6-20 aryl of Re is optionally substituted with one or more C1-6 alkyl; and -O-Re, wherein the -C(O)-(3-15 membered heterocyclyl) of Re is optionally substituted with one or more C1-6 alkyl, C1-6 alkoxy, or -C(O)-C1-6 alkoxy, and the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl; (h) —C(O)—Re, where Re in —C(O)—Re is —NH2, —OH, or 3- to 15-membered heterocyclyl; or (i) -S(O)2-Rf, where Rf is C1-6 alkyl or 3-15 membered heterocyclyl; However, when R2 is unsubstituted methyl, (1) Q1 is a 5- to 20-membered heteroaryl, and the 5- to 20-membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, C3-10 cycloalkyl, or -OH, and Q1 is not unsubstituted pyridyl; or (2) Q1 is phenyl, and the phenyl of Q1 is (i) at least one C3-6 alkyl, wherein at least one C3-6 alkyl is optionally substituted with one or more halo, or (ii) at least one C3-10 cycloalkyl, wherein at least one C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; or (iii) at least one 5-20 membered heteroaryl, wherein at least one 5-20 membered heteroaryl is optionally substituted with one or more C1-6 alkyl; (ii) C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of R2 is optionally substituted with one or more Rq, and Rq is a 5-20 membered heteroaryl or C6-20 aryl, and the C6-20 aryl of Rq is optionally substituted with one or more C1-6 alkoxy; (iii) 3- to 15-membered heterocyclyl, wherein R2 is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo, oxo, C1-6 alkyl, —C(O)—C1-6 alkyl, or 5- to 20-membered heteroaryl; (iv) 5-20 membered heteroaryl or -(Ci-4 alkyl)(5-20 membered heteroaryl), wherein the Ci-4 alkyl is optionally substituted with one or more -OH, halo, -NH, -NH(Ci-6 alkyl), -N(Ci-6 alkyl) and the 5-20 membered heteroaryl is optionally substituted with one or more Rs; Rs is halo, C1-6 alkyl, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)-C1-6 alkyl, C6-20 aryl, C3-10 cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or -C(O)-C1-6 alkoxy; the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; and the 3-15 membered heterocyclyl of Rs is a 5-20 membered heteroaryl or -(Ci_4 alkyl)(5-20 membered heteroaryl) optionally substituted with one or more halo or -C(O)-Ci_6 alkoxy; (v) —N(Rg)(Rh), where Rg and Rh are independently H or C1-6 alkyl; (vi) -C(O)-Rj, where Rj is C3-10 cycloalkyl, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, or -NH(5-20 membered heteroaryl); and (vii) C6-20 aryl, wherein the C6-20 aryl of R2 is optionally substituted with one or more 5-20 membered heteroaryl or -O-Rp, wherein Rp is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of Rp is optionally substituted with one or more -C(O)-C1-6 alkyl.

[0063] In one embodiment, a compound of formula (I): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: X1 and X2 are each independently H, C1-6 alkyl, or C1-6 alkoxy; X3 and X4 are each independently H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl; X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; Q1 is (i)~(iii): (i) phenyl, wherein the phenyl in Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), or C3-10 cycloalkyl; C1-6 alkyl optionally substituted with one or more halo, and phenyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; (ii) 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Q1 is optionally substituted with one or more oxo groups; and (iii) 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl; C3-10 cycloalkyl is selected from 5-20 membered heteroaryl optionally substituted with one or more halo or C1-6 alkyl; R1 is H or C1-6 alkyl; Rk is H, halo, —OH, —NH2, or —NH—C(O)C1-6 alkyl; Rm is H, —OH, or C1-6 alkyl; Rn is H, C1-6 alkyl, or C3-10 cycloalkyl; or Rk together with either Rm or Rn and the atom to which they are attached form cyclopropyl; R2 is (i)~(vii): (i) C1-6 alkyl, wherein the C1-6 alkyl of R2 is optionally substituted with one or more Ra, and Ra is (a) -OH, (b) cyano, (c) C2-6 alkynyl, (d) C6-20 aryl, wherein the C6-20 aryl of Ra is optionally substituted with one or more halo, cyano, C1-6 alkoxy, or —NH—C(O)—C1-6 alkyl; (e) 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Ra is optionally substituted with one or more Rb; Rb is halo, C1-6 alkyl, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-10 cycloalkyl, 3-15 membered heterocyclyl, or -C(O)-C1-6 alkoxy; the C1-6 alkyl of Rb is optionally substituted with one or more halo, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —NH—C(O)C1-6 alkyl, or —NH—C(O)—C1-6 alkoxy; and the 3-15 membered heterocyclyl of Rb is a 5-20 membered heteroaryl optionally substituted with one or more halo or -C(O)-C1-6alkoxy; (f) 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Ra is optionally substituted with one or more Rc; Rc is halo, oxo, C1-6 alkyl, C1-6 alkoxy, —C(O)—C1-6 alkyl, or —C(O)—C1-6 alkoxy; The C1-6 alkyl of Rc is optionally substituted with one or more halo or C2-6 alkynyl; and Rc -C(O)-C1-6alkoxy is 3-15 membered heterocyclyl optionally substituted with one or more halo; (g) -N(Rc)(Rd), wherein Rc and Rd are each independently H, C1-6 alkyl, -C(O)-C1-6 alkyl, -C(O)-C1-6 alkoxy, -C(O)-NH2, -C(O)-NH(C1-6 alkyl), -C(O)-N(C1-6 alkyl)2, -C(O)-(3- to 15-membered heterocyclyl), -CH2-C(O)-NH2, 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; the —C(O)—C alkyl of Rc or Rd is optionally substituted with one or more halo; The 3- to 15-membered heterocyclyl and 5- to 20-membered heteroaryl of Rc or Rd are independently optionally substituted with one or more C1-6 alkyl; and -N(Rc)(Rd), wherein -C(O)-(3-15 membered heterocyclyl) of Rc or Rd is optionally substituted with one or more halo, -C(O)-Ci_6 alkoxy, or Ci_6 alkyl, and the Ci_6 alkyl is optionally substituted with one or more halo, Ci_6 alkoxy, or C3_10 cycloalkyl; (h) -O-Re, where Re is C alkyl, C aryl, -C(O)-(3-15 membered heterocyclyl), -C(O)-N-(C alkyl), or 5-20 membered heteroaryl; The C1-6 alkyl of Re is optionally substituted with one or more C1-6 alkoxy, and the C1-6 alkoxy is optionally substituted with one or more C2-6 alkynyl; The C6-20 aryl of Re is optionally substituted with one or more C1-6 alkyl; and -O-Re, wherein the -C(O)-(3-15 membered heterocyclyl) of Re is optionally substituted with one or more C1-6 alkyl, C1-6 alkoxy, or -C(O)-C1-6 alkoxy, and the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl; (i) —C(O)—Re, where Re is —NH, —OH, or 3- to 15-membered heterocyclyl; or (j) -S(O)2-Rf, where Rf is C1-6 alkyl or 3-15 membered heterocyclyl; However, when R2 is unsubstituted methyl, (1) Q1 is a 5- to 20-membered heteroaryl, and the 5- to 20-membered heteroaryl of Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, C3-10 cycloalkyl, or -OH; or (2) C1-6 alkyl, wherein Q1 is phenyl, and the phenyl in Q1 is substituted with at least one C3-6 alkyl or at least one C3-10 cycloalkyl, and at least one C3-6 alkyl is optionally substituted with one or more halo, and at least one C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; (ii) C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of R2 is optionally substituted with one or more Rq, and Rq is a 5-20 membered heteroaryl or C6-20 aryl, and the C6-20 aryl of Rq is optionally substituted with one or more C1-6 alkoxy; (iii) 3- to 15-membered heterocyclyl, wherein R2 is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo, oxo, C1-6 alkyl, —C(O)—C1-6 alkyl, or 5- to 20-membered heteroaryl; (iv) 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of R2 is optionally substituted with one or more Rs, and Rs is C1-6 alkyl, C1-6 alkoxy, -NH-C(O)-C1-6 alkyl, C6-20 aryl, or 5-20 membered heteroaryl, wherein the C1-6 alkyl of Rs is optionally substituted with one or more C1-6 alkoxy; (v) —N(Rg)(Rh), where Rg and Rh are independently H or C1-6 alkyl; (vi) -C(O)-Rj, where Rj is C3-10 cycloalkyl, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, or -NH(5-20 membered heteroaryl); and (vii) C6-20 aryl, wherein the C6-20 aryl of R2 is optionally substituted with one or more 5-20 membered heteroaryl or -O-Rp, wherein Rp is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of Rp is optionally substituted with one or more -C(O)-C1-6 alkyl.

[0064] Any embodiment provided herein of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, is also, where applicable, an embodiment of a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0065] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L2 is -C(O) or -S(O)2-. In some embodiments, L2 is -C(O)-. In some embodiments, L2 is -S(O)2-.

[0066] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is pyridinyl, wherein the pyridinyl in Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is 2-pyridinyl or 3-pyridinyl, and the 2-pyridinyl or 3-pyridinyl in Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is 2-pyridinyl, wherein the 2-pyridinyl in Q1 is optionally substituted with one or more halo, C1-6 alkyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is 2-pyridinyl, wherein the 2-pyridinyl in Q1 is optionally substituted with one or more halo, C1-6 alkyl, or C3-10 cycloalkyl, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo.In some embodiments, Q1 is 2-pyridinyl, and the 2-pyridinyl of Q1 is optionally substituted with one or more fluoro, chloro, methyl, isopropyl, tert-butyl, cyclopropyl, or cyclobutyl, and the cyclopropyl and cyclobutyl are independently optionally substituted with one or more methyl or fluoro.

[0067] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is pyridinyl, wherein the pyridinyl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is 2-pyridinyl or 3-pyridinyl, and the 2-pyridinyl or 3-pyridinyl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo.In some embodiments, Q1 is 2-pyridinyl, and the 2-pyridinyl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is 2-pyridinyl, and the 2-pyridinyl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more C1-6 alkyl or halo. In some embodiments, Q1 is 2-pyridinyl, and the 2-pyridinyl of Q1 is optionally substituted with one or more fluoro, chloro, methyl, isopropyl, tert-butyl, cyclopropyl, cyclobutyl, or methoxy, and the methyl is optionally substituted with one or more fluoro, and the cyclopropyl and cyclobutyl are independently optionally substituted with one or more methyl or fluoro.

[0068] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is [ka] is selected from the group consisting of:

[0069] 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, Q1 is: [ka] is selected from the group consisting of:

[0070] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0071] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is phenyl, and the phenyl of Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, —NH2, —NH—C(O)—(C1-6 alkyl), —NH—C(O)—(3-15 membered heterocyclyl), or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Q1 is phenyl, wherein the phenyl of Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Q1 is phenyl, wherein the phenyl of Q1 is substituted with one or more fluoro, chloro, 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, and cyclopropyl and cyclobutyl are independently optionally substituted with one or more fluoro or methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0072] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is phenyl; and the phenyl of Q1 is substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), C3-10 cycloalkyl, or 5-20 membered heteroaryl; the C1-6 alkyl is optionally substituted with one or more halo, -NH-C(O)-NH(C1-6 alkyl), -NH-C(O)-C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; and the 5-20 membered heteroaryl is optionally substituted with one or more C1-6 alkyl.

[0073] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is [ka] is selected from the group consisting of:

[0074] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is [ka] 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, Q1 is selected from the group consisting of: [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0075] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is a 3- to 15-membered heterocyclyl, and the 3- to 15-membered heterocyclyl of Q1 is optionally substituted with one or more oxo. In some embodiments, Q1 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0076] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is (i) a 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Q1 is optionally substituted with one or more oxo, or C1-6 alkyl; (ii) a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; or (iii) a C3-10 cycloalkyl.

[0077] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is a 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Q1 is optionally substituted with one or more oxo, or C1-6 alkyl. [ka] is selected from the group consisting of:

[0078] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of Q1 is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Q1 is a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of Q1 is optionally substituted with one or more C1-6 alkyl. In some embodiments, the 5-20 membered heteroaryl of Q1 contains one or more cyclic N. In some embodiments, the 5-20 membered heteroaryl, wherein Q1 is a 5-20 membered heteroaryl, contains two ring Ns. In some embodiments, the 5-20 membered heteroaryl, wherein Q1 is a 5-20 membered heteroaryl, is a bicyclic monocyclic. In some embodiments, the 5-20 membered heteroaryl, wherein Q1 is a 5-20 membered heteroaryl, is a monocyclic. In some embodiments, the 5-20 membered heteroaryl, wherein Q1 is a bicyclic. In some embodiments, Q1 is [ka] is selected from the group consisting of:

[0079] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q1 is C3-10 cycloalkyl. In some embodiments, Q1 is C3-6 cycloalkyl. In some embodiments, Q1 is cyclopropyl.

[0080] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L1 is absent or -CH2-. In some embodiments, L1 is absent. In some embodiments, L1 is -CH2-. In some embodiments, L1 is absent and Q1 is C3-10 cycloalkyl. In some embodiments, L1 is absent and Q1 is C3-6 cycloalkyl. In some embodiments, L1 is absent and Q1 is cyclopropyl. In some embodiments, L1 is -CH2- and Q1 is C3-10 cycloalkyl. In some embodiments, L1 is -CH2- and Q1 is C3-6 cycloalkyl. In some embodiments, L1 is -CH2- and Q1 is C3-6 cycloalkyl. In some embodiments, L1 is -CH2- and Q1 is cyclopropyl.

[0081] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X1, X2, X3, X4, and X5 are each H. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0082] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1 is H or C1-6 alkyl. In some embodiments, R1 is H. In some embodiments, R1 is C1-3 alkyl. In some embodiments, R1 is methyl.

[0083] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H, halo, -OH, -NH, or -NH-C(O)Ci_6 alkyl. In some embodiments, Rk is H. In some embodiments, Rk is halo. In some embodiments, Rk is F.

[0084] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rm is H, -OH, or C1-6 alkyl. In some embodiments, Rm is H.

[0085] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rn is H, C1-6 alkyl, or C3-10 cycloalkyl. In some embodiments, Rn is H.

[0086] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rm is H, Rn is H, and Rk is H, halo, -OH, -NH, or -NH-C(O)Ci-6 alkyl. In some embodiments, Rm is H, Rn is H, and Rk is halo, -OH, or -NH. In some embodiments, Rm is H, Rn is H, and Rk is halo. In some embodiments, Rm is H, Rn is H, and Rk is fluoro. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0087] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk, together with either Rm or Rn and the atom to which they are attached, forms a cyclopropyl. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0088] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rn, together with the carbon atom to which it is attached, forms a C3-5 cycloalkyl. In some embodiments, Rn, together with the carbon atom to which it is attached, forms a cyclopropyl.

[0089] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R is H. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0090] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. R is -OH or a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R. R is -OH or a 5-10 membered heteroaryl, and the 5-10 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro.

[0091] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is a 5-20 membered heteroaryl or -(Ci-4 alkyl)(5-20 membered heteroaryl), wherein the Ci-4 alkyl is optionally substituted with one or more -OH, halo, -NH2, -NH(Ci-6 alkyl), -N(Ci-6 alkyl)2, and the 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, R2 is a 5-20 membered heteroaryl, wherein the Ci-4 alkyl is optionally substituted with one or more -OH, halo, -NH2, -NH(Ci-6 alkyl), -N(Ci-6 alkyl)2, and the 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, R2 is (methyl)(5-20 membered heteroaryl), wherein methyl is optionally substituted with one or more -OH, halo, -NH2, -NH(Ci-6 alkyl), -N(Ci-6 alkyl)2, and wherein the 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, Rs is halo, Ci-6 alkyl, Ci-6 alkoxy, -NH2, -NH(Ci-6 alkyl), -N(Ci-6 alkyl)2, -NH-C(O)-Ci-6 alkyl, C6-20 aryl, C3-10 cycloalkyl, 3-15 membered heterocyclyl, 5-20 membered heteroaryl, or -C(O)-Ci-6 alkoxy. In some embodiments, the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; and the 3- to 15-membered heterocyclyl of Rs is optionally substituted with one or more halo or -C(O)-C1-6 alkoxy.

[0092] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] 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, R2 is selected from the group consisting of: [ka] is.

[0093] In some embodiments of a compound of Formula (I'), (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] is selected from the group consisting of:

[0094] 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, R2 is [ka] [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0095] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is a 3- to 15-membered heterocyclyl, and the 3- to 15-membered heterocyclyl of Ra is optionally substituted with one or more Rc.

[0096] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl in R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl in R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl in R is optionally substituted with one or more oxo or C1-6 alkyl. In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0097] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more Rc, wherein Rc is oxo, C1-6 alkyl, or -C(O)-C1-6 alkoxy, wherein the C1-6 alkyl in Rc is optionally substituted with one or more halo, and wherein the -C(O)-C1-6 alkoxy in Rc is optionally substituted with one or more halo. In some embodiments, R2 is [ka] is selected from the group consisting of:

[0098] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0099] In some embodiments of a compound of Formula (I'), (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is -O-Re, and Re is -C(O)-(3-15 membered heterocyclyl), wherein the -C(O)-(3-15 membered heterocyclyl) in Re is optionally substituted with one or more C1-6 alkyl, and wherein the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl. In some embodiments, R2 is [ka] is selected from the group consisting of:

[0100] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0101] In some embodiments of a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), wherein one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl, -C(O)-N(Ci-6 alkyl), or -C(O)-(3-15 membered heterocyclyl). In some embodiments, R2 is [ka] is selected from the group consisting of:

[0102] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is ethyl, and the ethyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl. In some embodiments, R2 is [ka] is.

[0103] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X1 and X2 are each independently H, C1-6 alkyl, or C1-6 alkoxy. In some embodiments, X1 and X2 are each H.

[0104] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X3 and X4 are each independently H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl, and the C1-6 alkyl of X3 and X4 is optionally substituted with one or more halo.

[0105] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl. In some embodiments, X5 is H, C1-4 alkyl, C1-3 alkoxy, or C3-6 cycloalkyl. In some embodiments, X5 is H. In some embodiments, X5 is isopropyl, n-butyl, isobutyl, or t-butyl.

[0106] In some embodiments of a compound of Formula (I), X1-X5 are each H and Q1 is a 5-20 membered heteroaryl optionally substituted with one or more halo, C1-6 alkyl, -NH2, or C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, X1-X5 are each H and Q1 is a 5-6 membered heteroaryl optionally substituted with one or more halo, C1-6 alkyl, -NH2, or C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, X1-X5 are each H and Q1 is pyridinyl optionally substituted with one or more halo, C1-6 alkyl, —NH2, or C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, X1-X5 are each H and Q1 is pyridinyl optionally substituted with one or more halo, C1-4 alkyl, —NH2, or C3-4 cycloalkyl, wherein C3-4 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some of the foregoing embodiments, Rm is H and Rn is H. In some of the foregoing embodiments, R1 is H. In some variations, the embodiments provided herein also apply to a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0107] In some embodiments of a compound of Formula (I), X1-X5 are each H and Q1 is phenyl substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), or C3-10 cycloalkyl, wherein C1-6 alkyl is optionally substituted with one or more halo, and C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, X1-X5 are each H and Q1 is phenyl substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-10 membered heterocyclyl), or C3-10 cycloalkyl, wherein C1-6 alkyl is optionally substituted with one or more halo, and C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, X1-X5 are each H and Q1 is phenyl substituted with one or more halo, C1-4 alkyl, C2-4 alkenyl, -NH2, -NH-C(O)-(C1-4 alkyl), -NH-C(O)-(3-10 membered heterocyclyl), or C3-4 cycloalkyl, wherein C1-4 alkyl is optionally substituted with one or more halo, and C3-4 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0108] In some of the foregoing embodiments, R is H. In some of the foregoing embodiments, R is H and R is H. In some of the foregoing embodiments, R, together with either R or R and the atom to which they are attached, forms a cyclopropyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0109] In some embodiments of a compound of Formula (I') or (I), or any embodiment or variation thereof, for example, Formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] , Rk, Rm, Rn, and R1 together with the formula: [ka] wherein X1, X2, X3, X4, X5, Y2, Y3, R1, Rk, Rm, and Rn are as defined elsewhere herein.

[0110] In some embodiments of a compound of Formula (I') or (I), or any embodiment or variation thereof, for example, Formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] , Rk, Rm, Rn, and R1 together with the formula: [ka] wherein R and R are both H, and X, X, X, X, X, Y, Y, R, and R are as defined elsewhere herein.

[0111] In some embodiments of a compound of Formula (I') or (I), or any embodiment or variation thereof, for example, Formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] , Rk, Rm, Rn, and R1 together with the formula: [ka] wherein R, R, and R are each H, and X, X, X, X, X, Y, Y, and R are as defined elsewhere herein.

[0112] In some embodiments of a compound of Formula (I') or (I), or any embodiment or variation thereof, for example, Formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] , Rk, Rm, Rn, and R1 together with the formula: [ka] wherein R, R, and R are each H, R is halo or H, and X, X, X, X, X, Y, and Y are as defined elsewhere herein. In some embodiments, the moiety R is fluoro.

[0113] In some embodiments of a compound of Formula (I') or (I), or any embodiment or variation thereof, for example, Formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] , Rk, Rm, Rn, and R1 together with the formula: [ka] wherein R, R, and R are each H, R is fluoro, and X, X, X, X, X, Y, and Y are as defined elsewhere herein. In some embodiments, Y and Y are each C. In some embodiments, one of Y and Y is C and the other of Y and Y is N.

[0114] As used herein, in some embodiments, the compound has the formula (IA): [ka] or a pharmaceutically acceptable salt of any of the foregoing, wherein Y is CH or N; R and R are independently H, halo, C alkyl, or —NH; when Y is CH, the C alkyl of R or R is optionally substituted with one or more halo; and R is (i) C alkyl, (ii) C alkenyl, or (iii) C cycloalkyl, where the C cycloalkyl is optionally substituted with one or more halo or C alkyl. In some variations, R2, Rk, Rx, Ry, and Rz of formula (I-A1) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; Y1 is CRx or N; and when the ring bearing Rx, Ry, and Rz is phenyl, Rx, Ry, and Rz are H, halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), C3-10 cycloalkyl, or 5-20 membered heteroaryl; and C1-6 alkyl is selected from the group consisting of one or more halo, -NH-C(O)-NH(C1-6 alkyl). , -NH-C(O)-Ci-6 alkyl, or -NH-C(O)-Ci-6 alkoxy; C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; 5-20 membered heteroaryl is optionally substituted with one or more C1-6 alkyl; and when the ring bearing Rx, Ry, and Rz is pyridyl, Rx, Ry, and Rz are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl; C1-6 alkyl is optionally substituted with one or more halo; and C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl.

[0115] In some embodiments of a compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rx and Rz are independently H, fluoro, chloro, or methyl; Ry is (i) isopropyl, (ii) isopropenyl, or (iii) C3-4 cycloalkyl, wherein C3-4 cycloalkyl is optionally substituted with one or more fluoro or methyl. In some embodiments, Rx and Rz are independently H, fluoro, chloro, or methyl; Ry is (i) isopropyl or (ii) C3-4 cycloalkyl, wherein C3-4 cycloalkyl is optionally substituted with one or more fluoro or methyl. In some embodiments, Rx is H, fluoro, chloro, or methyl; Rz is H; and Ry is (i) isopropyl, or (ii) C3-4 cycloalkyl, wherein C3-4 cycloalkyl is optionally substituted with one or more fluoro or methyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0116] In some embodiments of a compound of Formula (I'), (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rx is fluoro or methyl optionally substituted with one or more fluoro; Ry is (i) isopropyl, (ii) isopropenyl, or (iii) C3-4 cycloalkyl optionally substituted with one or more halo or C1-6 alkyl, or (iv) butyl; and Rz is fluoro or methyl, with the proviso that at least one of Rx and Rz is halo, CF2, or CF3.

[0117] In some embodiments of a compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or halo. In some embodiments of a compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or fluoro. In some embodiments of a compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is fluoro. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0118] In some embodiments of a compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. R is -OH or a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R. R is -OH or a 5-10 membered heteroaryl, and the 5-10 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro.

[0119] In some embodiments of a compound of Formula (I'), (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is a 5-20 membered heteroaryl or -(C1-4 alkyl)(5-20 membered heteroaryl), wherein the C1-4 alkyl is optionally substituted with one or more -OH, halo, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, and the 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, Rs is halo, C1-6 alkyl, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)-C1-6 alkyl, C6-20 aryl, C3-10 cycloalkyl, 3-15 membered heterocyclyl, 5-20 membered heteroaryl, or -C(O)-C1-6 alkoxy. In some embodiments, the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy, and the 3-15 membered heterocyclyl of Rs is optionally substituted with one or more halo or -C(O)-C1-6 alkoxy.

[0120] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0121] In some embodiments of the compounds of Formula (I'), (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0122] In some embodiments of a compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0123] In some embodiments of a compound of Formula (I'), (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more Rc, wherein Rc is oxo, C1-6 alkyl, or -C(O)-C1-6 alkoxy, wherein the C1-6 alkyl in Rc is optionally substituted with one or more halo, and wherein the -C(O)-C1-6 alkoxy in Rc is optionally substituted with one or more halo. In some embodiments, R2 is [ka] is selected from the group consisting of:

[0124] In some embodiments of a compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0125] In some embodiments of a compound of Formula (I'), (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is -O-Re, and Re is -C(O)-(3-15 membered heterocyclyl), wherein the -C(O)-(3-15 membered heterocyclyl) in Re is optionally substituted with one or more C1-6 alkyl, and wherein the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl. In some embodiments, R2 is [ka] is selected from the group consisting of:

[0126] In some embodiments of a compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0127] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), wherein one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl, -C(O)-N(Ci-6 alkyl), or -C(O)-(3-15 membered heterocyclyl). In some embodiments, R2 is [ka] is selected from the group consisting of:

[0128] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is ethyl, and the ethyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl. In some embodiments, R2 is [ka] is.

[0129] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Y is CH or N; R and R are independently H or halo; R ​​is C alkyl or C cycloalkyl; R is H or halo; and R is selected from (i)-(iii): (i) C1-6 alkyl, wherein the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is (a) -OH, (b) C6-20 aryl, wherein the C6-20 aryl of Ra is optionally substituted with one or more halo, cyano, C1-6 alkoxy, or —NH—C(O)—C1-6 alkyl; (c) 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of Ra is optionally substituted with one or more Rc; Rc is halo, oxo, C1-6 alkyl, C1-6 alkoxy, —C(O)—C1-6 alkyl, or —C(O)—C1-6 alkoxy; The C1-6 alkyl of Rc is optionally substituted with one or more halo or C2-6 alkynyl; and Rc -C(O)-C1-6alkoxy is 3-15 membered heterocyclyl optionally substituted with one or more halo; (d) -N(Rc)(Rd), wherein Rc and Rd of N(Rc)(Rd) are each independently H, C1-6 alkyl, -C(O)-C1-6 alkyl, -C(O)-C1-6 alkoxy, -C(O)-NH2, -C(O)-NH(C1-6 alkyl), -C(O)-N(C1-6 alkyl)2, -C(O)-(3- to 15-membered heterocyclyl), -CH2-C(O)-NH2, 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; the C1-6 alkyl of Rc or Rd is optionally substituted with one or more -C(O)-NH2; the —C(O)—C alkyl of Rc or Rd is optionally substituted with one or more halo; the 3- to 15-membered heterocyclyl and 5- to 20-membered heteroaryl of Rc or Rd is independently optionally substituted with one or more C1-6 alkyl; Rc or Rd -C(O)-(3-15 membered heterocyclyl) is optionally substituted with one or more halo, -C(O)-Ci_6 alkoxy, or Ci_6 alkyl, and the Ci_6 alkyl is optionally substituted with one or more halo, Ci_6 alkoxy, or C3_10 cycloalkyl; and -N(Rc)(Rd), wherein the C1-6 alkyl of -C(O)-N(C1-6 alkyl)2 in Rc or Rd is, independently of each other, optionally substituted with one or more halo or C6-20 aryl; (e) -O-Re, where Re is C alkyl, C aryl, -C(O)-(3-15 membered heterocyclyl), -C(O)-N-(C alkyl), or 5-20 membered heteroaryl; The C1-6 alkyl of Re is optionally substituted with one or more C1-6 alkoxy, and the C1-6 alkoxy is optionally substituted with one or more C2-6 alkynyl; The C6-20 aryl of Re is optionally substituted with one or more C1-6 alkyl; and -O-Re, in which the -C(O)-(3-15 membered heterocyclyl) of Re is optionally substituted with one or more C1-6 alkyl, C1-6 alkoxy, or -C(O)-C1-6 alkoxy, and the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl; or (f) C1-6 alkyl, which is —C(O)—Re, wherein Re of —C(O)—Re is —NH2, —OH, or 3-15 membered heterocyclyl; (ii) 3- to 15-membered heterocyclyl, wherein R2 is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo, oxo, C1-6 alkyl, —C(O)—C1-6 alkyl, or 5- to 20-membered heteroaryl; (iii) 5-20 membered heteroaryl or -(Ci-4 alkyl)(5-20 membered heteroaryl), wherein the Ci-4 alkyl is optionally substituted with one or more -OH, halo, -NH, -NH(Ci-6 alkyl), -N(Ci-6 alkyl) and the 5-20 membered heteroaryl is optionally substituted with one or more Rs; Rs is halo, C1-6 alkyl, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)-C1-6 alkyl, C6-20 aryl, C3-10 cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or -C(O)-C1-6 alkoxy; the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; and The 3-15 membered heterocyclyl of Rs is a 5-20 membered heteroaryl or -(C1-4 alkyl)(5-20 membered heteroaryl) optionally substituted with one or more halo or -C(O)-C1-6 alkoxy.

[0130] In some embodiments of Formula (IA), Y1 is CH or N; Rx and Rz are independently H or halo; Ry is C1-6 alkyl or C3-10 cycloalkyl; Rk is H or halo; R2 is C1-6 alkyl; and the C1-6 alkyl of R2 is substituted with one or more Ra; and Ra is (a) -OH, (b) C6-10 aryl optionally substituted with one or more halo, cyano, C1-3 alkoxy, or -NH-C(O)-C1-3 alkyl; or (c) 3- to 15-membered heterocyclyl optionally substituted with one or more halo, oxo, C1-6 alkyl, C1-6 alkoxy, -C(O)-C1-6 alkyl, or -C(O)-C1-6 alkoxy.

[0131] In some embodiments of Formula (IA), Y1 is CH or N; Rx and Rz are independently H or halo; Ry is C1-3 alkyl or C3-5 cycloalkyl; Rk is halo; R2 is C1-4 alkyl substituted with one or more Ra; and Ra is (a) -OH, (b) C6-10 aryl optionally substituted with one or more halo, cyano, C1-3 alkoxy, or -NH-C(O)-C1-3 alkyl; or (c) C3-8 heteroaryl optionally substituted with one or more halo, oxo, C1-6 alkyl, C1-6 alkoxy, -C(O)-C1-6 alkyl, or -C(O)-C1-6 alkoxy.

[0132] As used herein, in some embodiments, the compound has the formula (I-A1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Rx and Rz are independently H, halo, C1-6 alkyl, or —NH2, wherein C1-6 alkyl is optionally substituted with one or more halo. In some embodiments, Rx is H, halo, or C1-6 alkyl; Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (ii) C3-10 cycloalkyl; and Rz is H, halo, or C1-6 alkyl. In some embodiments, Rz is H. In some embodiments, at least one of Rx and Rz is halo. In some variations, R2, Rk, Rx, Ry, and Rz of formula (I-A1) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; and Rx, Ry, and Rz are independently H, halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl). In some embodiments, Rx is H, halo, or C1-6 alkyl optionally substituted with one or more halo; Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, (iii) C3-10 cycloalkyl optionally substituted with one or more halo or C1-6 alkyl, or (iv) butyl; and Rz is H, halo, or C1-6 alkyl. In some embodiments, Rz is H.In some embodiments, at least one of Rx and Rz is halo or C1-6 alkyl optionally substituted with one or more halo.

[0133] In some embodiments of a compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rx is fluoro or methyl, Ry is (i) isopropyl or (ii) C3-4 cycloalkyl, and Rz is fluoro or methyl, with the proviso that at least one of Rx and Rz is halo. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0134] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rx is fluoro or methyl optionally substituted with one or more fluoro; Ry is (i) isopropyl, (ii) C3-4 cycloalkyl optionally substituted with one or more halo or C1-6 alkyl, or (iii) butyl; and Rz is fluoro or methyl, with the proviso that at least one of Rx and Rz is halo, CF2, or CF3.

[0135] In some embodiments of a compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or halo. In some embodiments of a compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or fluoro. In some embodiments of a compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is fluoro. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0136] In some embodiments of a compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. R is -OH or a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R. R is -OH or a 5-10 membered heteroaryl, and the 5-10 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro.

[0137] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is a 5-20 membered heteroaryl or -(C1-4 alkyl)(5-20 membered heteroaryl), wherein the C1-4 alkyl is optionally substituted with one or more -OH, halo, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, and the 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, Rs is halo, C1-6 alkyl, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)-C1-6 alkyl, C6-20 aryl, C3-10 cycloalkyl, 3-15 membered heterocyclyl, 5-20 membered heteroaryl, or -C(O)-C1-6 alkoxy. In some embodiments, the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy, and the 3-15 membered heterocyclyl of Rs is optionally substituted with one or more halo or -C(O)-C1-6 alkoxy.

[0138] 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, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0139] In some embodiments of the compounds of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0140] In some embodiments of a compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0141] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more Rc, wherein Rc is oxo, C1-6 alkyl, or -C(O)-C1-6 alkoxy, wherein the C1-6 alkyl in Rc is optionally substituted with one or more halo, and wherein the -C(O)-C1-6 alkoxy in Rc is optionally substituted with one or more halo. In some embodiments, R2 is [ka] is.

[0142] In some embodiments of a compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0143] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is -O-Re, and Re is -C(O)-(3-15 membered heterocyclyl), wherein the -C(O)-(3-15 membered heterocyclyl) in Re is optionally substituted with one or more C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl. In some embodiments, R2 is [ka] is.

[0144] In some embodiments of a compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0145] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), wherein one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl, -C(O)-N(Ci-6 alkyl), or -C(O)-(3-15 membered heterocyclyl). In some embodiments, R2 is [ka] is.

[0146] In some embodiments of a compound of Formula (I'), (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is ethyl, and the ethyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl. In some embodiments, R2 is [ka] is.

[0147] In some embodiments, the compound has formula (I-A2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Rx is H, halo, C1-6 alkyl, or —NH2, wherein C1-6 alkyl is optionally substituted with one or more halo; and Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (iii) C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Rx is H, halo, or C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halo, and Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (iii) C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Rx is H, halo, or C1-6 alkyl, and Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (iii) C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl.In some variations, R, R, R, and R of formula (I-A2) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; and R and R are each independently H, halo, C alkyl, C alkenyl, -NH, -NH-C(O)-(C alkyl), -NH-C(O)-(3-15 membered heterocyclyl), and R is H, halo, or C alkyl optionally substituted with one or more halo or C alkyl; or R is (i) C alkyl, (ii) C cycloalkyl optionally substituted with one or more halo or C alkyl, or (iii) butyl.

[0148] In some embodiments of a compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rx is H, fluoro, chloro, or methyl, wherein methyl is optionally substituted with one or more fluoro, and Ry is (i) isopropyl, (ii) isopropenyl, (iii) sec-butyl, (iv) tert-butyl, or (v) C3-4 cycloalkyl, wherein C3-4 cycloalkyl is optionally substituted with one or more fluoro or methyl. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0149] In some embodiments of a compound of Formula (I'), (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rx is fluoro or methyl optionally substituted with one or more fluoro, and Ry is (i) isopropyl, (ii) C3-4 cycloalkyl optionally substituted with one or more halo or C1-6 alkyl, or (iii) butyl.

[0150] In some embodiments of a compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or halo. In some embodiments of a compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or fluoro. In some embodiments of a compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is fluoro. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0151] In some embodiments of a compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. R is -OH or a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R. R is -OH or a 5-10 membered heteroaryl, and the 5-10 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro.

[0152] In some embodiments of a compound of Formula (I'), (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is -(Ci_4 alkyl)(5-20 membered heteroaryl), wherein Ci_4 alkyl is optionally substituted with one or more -OH, and wherein 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, Rs is halo, Ci_6 alkyl, Ci_6 alkoxy, -NH2, -NH(Ci_6 alkyl), -N(Ci_6 alkyl)2, -NH-C(O)-Ci_6 alkyl, C6_20 aryl, C3_10 cycloalkyl, 3-15 membered heterocyclyl, 5-20 membered heteroaryl, or -C(O)-Ci_6 alkoxy. In some embodiments, the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; and the 3- to 15-membered heterocyclyl of Rs is optionally substituted with one or more halo or -C(O)-C1-6 alkoxy.

[0153] 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, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0154] In some embodiments of the compounds of Formula (I'), (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0155] In some embodiments of a compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0156] In some embodiments of a compound of Formula (I'), (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more Rc, wherein Rc is oxo, C1-6 alkyl, or -C(O)-C1-6 alkoxy, wherein the C1-6 alkyl in Rc is optionally substituted with one or more halo, and wherein the -C(O)-C1-6 alkoxy in Rc is optionally substituted with one or more halo. In some embodiments, R2 is [ka] In some embodiments of a compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some embodiments of a compound of Formula (I'), (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is -O-Re, and Re is -C(O)-(3-15 membered heterocyclyl), wherein the -C(O)-(3-15 membered heterocyclyl) in Re is optionally substituted with one or more C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl. In some embodiments, R2 is [ka] is selected from the group consisting of:

[0157] In some embodiments of a compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In some embodiments of a compound of Formula (I'), (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, and the methyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl, -C(O)-N(Ci-6 alkyl)2, or -C(O)-(3-15 membered heterocyclyl). In some embodiments, R2 is [ka] is selected from the group consisting of:

[0158] In some embodiments of a compound of Formula (I'), (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is ethyl, and the ethyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl. In some embodiments, R2 is [ka] is.

[0159] As used herein, in some embodiments, the compound has the formula (I-A3): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Rx is H, halo, C1-6 alkyl, or —NH2, wherein C1-6 alkyl is optionally substituted with one or more halo; and Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (iii) C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Rx is H, halo, C1-6 alkyl, or -NH2, and Ry is (i) C1-6 alkyl or (ii) C3-10 cycloalkyl, where C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some variations, R2, Rk, Rx, and Ry of formula (I-A3) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, and Rx and Ry are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, where C1-6 alkyl is optionally substituted with one or more halo, and where C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Rx is H, halo, C1-6 alkyl, or -NH2, and Ry is (i) C1-6 alkyl or (ii) C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl.

[0160] In some embodiments of a compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rx is H, fluoro, or methyl; Ry is (i) H, (ii) isopropyl, (iii) tert-butyl, or (iv) C3-4 cycloalkyl, wherein C3-4 cycloalkyl is optionally substituted with one or more fluoro or methyl. In some embodiments, Rx is H, fluoro, or methyl; Ry is (i) isopropyl or (ii) C3-4 cycloalkyl, wherein C3-4 cycloalkyl is optionally substituted with one or more fluoro or methyl. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0161] In some embodiments of a 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 halo. In some embodiments of a 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 fluoro. In some embodiments of a compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is fluoro. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0162] In some embodiments of a compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. In some embodiments, R2 is methyl, and the methyl ... In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0163] In some embodiments of a compound of Formula (I'), (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is -(Ci_4 alkyl)(5-20 membered heteroaryl), wherein the 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, Rs is halo, Ci_6 alkyl, Ci_6 alkoxy, -NH2, -NH(Ci_6 alkyl), -N(Ci_6 alkyl)2, -NH-C(O)-Ci_6 alkyl, C6_20 aryl, C3_10 cycloalkyl, 3-15 membered heterocyclyl, 5-20 membered heteroaryl, or -C(O)-Ci_6 alkoxy. In some embodiments, the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy; and the 3- to 15-membered heterocyclyl of Rs is optionally substituted with one or more halo or -C(O)-C1-6 alkoxy.

[0164] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0165] In some embodiments of the compounds of Formula (I'), (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] [ka] In some embodiments, R2 is selected from the group consisting of: [ka] In some embodiments, R2 is [ka] is.

[0166] In some embodiments of a compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In some variations, the embodiments provided herein also apply to a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0167] In some embodiments of a compound of Formula (I'), (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more Rc, wherein Rc is oxo, C1-6 alkyl, or -C(O)-C1-6 alkoxy, wherein the C1-6 alkyl in Rc is optionally substituted with one or more halo, and wherein the -C(O)-C1-6 alkoxy in Rc is optionally substituted with one or more halo. In some embodiments, R2 is [ka] is.

[0168] In some embodiments of a compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In some embodiments of a compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H and the other of Rc and Rd is -C(O)-N(C1-6 alkyl)2. In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0169] In some embodiments of a compound of Formula (I'), (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, and the methyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl, -C(O)-N(Ci-6 alkyl). In some embodiments, R2 is -C(O)-(3-15 membered heterocyclyl), wherein the -C(O)-(3-15 membered heterocyclyl) of Rc or Rd is optionally substituted with one or more halo, -C(O)-Ci-6 alkoxy, or Ci-6 alkyl, and the Ci-6 alkyl of -C(O)-N(Ci-6 alkyl)2 of Rc or Rd is, independently of each other, optionally substituted with one or more halo or C6-20 aryl. [ka] is.

[0170] In some embodiments of a compound of Formula (I'), (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the R2 methyl is substituted with one or more Ra, and Ra is -N(Rc)(Rd), wherein one of Rc and Rd is H, and the other of Rc and Rd is a 5-20 membered heteroaryl, and wherein the 5-20 membered heteroaryl of Rc or Rd is independently optionally substituted with one or more C1-6 alkyl. In some embodiments, R2 is [ka] is.

[0171] As used herein, in some embodiments, the compound is represented by formula (I-A4): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Rz is H, halo, C1-6 alkyl, or —NH2; and Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (iii) C3-10 cycloalkyl, wherein the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Rz is H, halo, or C1-6 alkyl; and Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (iii) C3-10 cycloalkyl, wherein the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Rz is H or C1-6 alkyl and Ry is (i) C1-6 alkyl or (ii) C3-10 cycloalkyl, wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rz is H or methyl and Ry is (i) isopropyl, or (ii) C3-4 cycloalkyl. In some variations, R2, Rk, Ry, and Rz of formula (I-A4) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; and Ry and Rz are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, wherein C1-6 alkyl is optionally substituted with one or more halo, and wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl.In some embodiments, Rz is H, halo, or C1-6 alkyl, wherein the C1-6 alkyl of Rz is optionally substituted with one or more halo, and Ry is (i) C1-6 alkyl, or (ii) C3-10 cycloalkyl, wherein the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rz is H or methyl, wherein the methyl of Rz is optionally substituted with one or more halo, and Ry is (i) isopropyl, or (ii) C3-4 cycloalkyl.

[0172] In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or halo. In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or fluoro. In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is fluoro. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0173] In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. R is -OH or a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R. R is -OH or a 5-10 membered heteroaryl, and the 5-10 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro.

[0174] 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, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0175] In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0176] In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0177] In some embodiments of a compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0178] As used herein, in some embodiments, the compound has the formula (IB): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y is CH or N; R is H, halo, C alkyl, or —NH; when Y is CH, the C alkyl of R is optionally substituted with one or more halo; R ​​is (i) C alkyl, (ii) C alkenyl, or (iii) C cycloalkyl, where the C cycloalkyl is optionally substituted with one or more halo or C alkyl; and R, together with either R or R and any of the atoms to which they are attached, forms cyclopropyl.In some variations, Y, R, R, R, R, R, R, R, R, R, and R of formula (IB) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; Y is CR or N; and when the ring bearing R and R is phenyl, R and R are each independently H, halo, C alkyl, C alkenyl, -NH, -NH-C(O)-(C alkyl), -NH-C(O)-(3-15 membered heterocyclyl), C cycloalkyl, or 5-20 membered heteroaryl; and C alkyl is selected from the group consisting of one or more halo, -NH-C(O)-NH(C the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; the 5-20 membered heteroaryl is optionally substituted with one or more C1-6 alkyl; and when the ring bearing Rx and Ry is pyridyl, Rx and Ry are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl; the C1-6 alkyl is optionally substituted with one or more halo; and the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl.

[0179] In some embodiments of a compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Y is CH or N; R is H, halo, C alkyl, or NH; when Y is CH, the C alkyl of R is optionally substituted with one or more halo; and R is (i) C alkyl, (ii) C alkenyl, or (iii) C cycloalkyl; the C cycloalkyl is optionally substituted with one or more halo or C alkyl. In some embodiments, Y is CH or N; R is H or halo; R ​​is C alkyl or C cycloalkyl; and R, together with either R or R and the atoms to which they are attached, forms cyclopropyl. In some embodiments, Y1 is CH or N, Rx is H or fluoro, Ry is (i) isopropyl or (ii) C3-4 cycloalkyl, and Rk, together with either Rm or Rn and the atom to which they are attached, form cyclopropyl. In some embodiments, Y1 is CH or N, Rx is H or fluoro, Ry is (i) isopropyl or (ii) C3-4 cycloalkyl, and Rk, together with Rm and the atom to which they are attached, form cyclopropyl. In some embodiments, Y1 is CH or N, Rx is H or fluoro, Ry is (i) isopropyl or (ii) C3-4 cycloalkyl, and Rk, together with Rn and the atom to which they are attached, form cyclopropyl. In some embodiments, Y is CH, R is H or fluoro, R is (i) isopropyl or (ii) C cycloalkyl, and R is taken together with R or R and the atom to which they are attached to form cyclopropyl. In some embodiments, Y is N, R is H or fluoro, R is (i) isopropyl or (ii) C cycloalkyl, and R is taken together with R or R and the atom to which they are attached to form cyclopropyl.In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0180] In some embodiments of a compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. R is -OH or a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R. R is -OH or a 5-10 membered heteroaryl, and the 5-10 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0181] In some embodiments of the compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0182] In some embodiments of a compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0183] In some embodiments of a compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0184] In some embodiments of a compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0185] wherein, in some embodiments, the compound has the formula (I-B1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y1 is CH or N, Rx is H or halo, and Ry is C1-6 alkyl or C3-10 cycloalkyl. In some embodiments, Y1 is CH or N, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl. In some embodiments, Y1 is CH, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl. In some embodiments, Y1 is N, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl. In some embodiments, Y1 is N, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl.In some variations, Y1, R2, Rx, and Ry of formula (I-B1) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; Y1 is CRx or N; and when the ring bearing Rx and Ry is phenyl, Rx and Ry are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), C3-10 cycloalkyl, or 5-20 membered heteroaryl; and C1-6 alkyl may be selected from one or more halo, -NH-C(O)-NH(C1-6 alkyl). wherein Rx and Ry are optionally substituted with one or more halo or C1-6 alkyl; and wherein Rx and Ry are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH, or C3-10 cycloalkyl; wherein Rx is optionally substituted with one or more halo; and wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Y1 is CH or N, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl. In some embodiments, Y is CH, R is H or fluoro, and R is (i) isopropyl or (ii) C cycloalkyl. In some embodiments, Y is N, R is H or fluoro, and R is (i) isopropyl or (ii) C cycloalkyl.

[0186] In some embodiments of a compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. In some embodiments, R2 is methyl, and the methyl ... In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0187] 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, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0188] In some embodiments of a compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0189] In some embodiments of a compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0190] In some embodiments of a compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0191] As used herein, in some embodiments, the compound is represented by formula (I-B2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y1 is CH or N, Rx is H or halo, and Ry is C1-6 alkyl or C3-10 cycloalkyl. In some embodiments, Y1 is CH or N, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl. In some embodiments, Y1 is CH, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl. In some embodiments, Y1 is N, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl. In some embodiments, Y1 is N, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl.In some variations, Y1, R2, Rx, and Ry of formula (I-B2) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; Y1 is CRx or N; and when the ring bearing Rx and Ry is phenyl, Rx and Ry are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, -NH2, -NH-C(O)-(C1-6 alkyl), -NH-C(O)-(3-15 membered heterocyclyl), C3-10 cycloalkyl, or 5-20 membered heteroaryl; and C1-6 alkyl may be selected from one or more halo, -NH-C(O)-NH(C1-6 alkyl). wherein Rx and Ry are optionally substituted with one or more halo or C1-6 alkyl; and wherein Rx and Ry are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH, or C3-10 cycloalkyl; wherein Rx is optionally substituted with one or more halo; and wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, Y1 is CH or N, Rx is H or fluoro, and Ry is (i) isopropyl or (ii) C3-4 cycloalkyl. In some embodiments, Y is CH, R is H or fluoro, and R is (i) isopropyl or (ii) C cycloalkyl. In some embodiments, Y is N, R is H or fluoro, and R is (i) isopropyl or (ii) C cycloalkyl.

[0192] In some embodiments of a compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. R is -OH or a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R. R is -OH or a 5-10 membered heteroaryl, and the 5-10 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0193] 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, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0194] In some embodiments of a compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0195] In some embodiments of a compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0196] In some embodiments of a compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0197] As used herein, in some embodiments, the compound has the formula (IC): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; X4 is H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl; Rv is -NH2, -NH-C(O)-(C1-6 alkyl), or -NH-C(O)-(3-15 membered heterocyclyl); and Rw is H, -NH2, -NH-C(O)-(C1-6 alkyl), or -NH-C(O)-(3-15 membered heterocyclyl). In some embodiments, X5 is H or C1-6 alkyl, X4 is H, Rv is -NH2, -NH-C(O)-(C1-6 alkyl), or -NH-C(O)-(3-15 membered heterocyclyl), and Rw is H, -NH2, -NH-C(O)-(C1-6 alkyl), or -NH-C(O)-(3-15 membered heterocyclyl). In some embodiments, Rw is H and Rv is -NH-C(O)C1-6 alkyl. In some embodiments, Rw is H and Rv is -NH-C(O)CH3. In some variations, R2, Rk, Rw, Rv, X4, and X5 of formula (IC) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; X4 is H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl; Rv is -NH2, -NH-C(O)-(C1-6 alkyl), or -NH-C(O)-(3-15 membered heterocyclyl); and Rw is H, -NH2, -NH-C(O)-(C1-6 alkyl), or -NH-C(O)-(3-15 membered heterocyclyl).In some embodiments, X5 is H or C1-6 alkyl, X4 is H, Rv is -NH2, -NH-C(O)-(C1-6 alkyl), or -NH-C(O)-(3-15 membered heterocyclyl), and Rw is H, -NH2, -NH-C(O)-(C1-6 alkyl), or -NH-C(O)-(3-15 membered heterocyclyl). In some embodiments, Rw is H and Rv is -NH-C(O)C1-6 alkyl. In some embodiments, Rw is H and Rv is -NH-C(O)CH3.

[0198] In some embodiments, the compound has the formula (ID): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; X4 is H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl; and Rt and Ru are independently H, C1-6 alkoxy, or -NH2. In some embodiments, X5 is C1-6 alkyl, X4 is H, halo, or C1-6 alkyl, and Rt and Ru are independently H or -NH2. In some embodiments, at least one of Rt and Ru is -NH2. In some embodiments, Rt is H and Ru is -NH2. In some embodiments, Rt is -NH2 and Ru is H. In some variations, R2, Rk, Rt, Ru, X4, and X5 of Formula (ID) are as defined for a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; X4 is H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl; and Rt and Ru are independently H, C1-6 alkoxy, or -NH2. In some embodiments, X5 is C1-6 alkyl; X4 is H, halo, or C1-6 alkyl; and Rt and Ru are independently H or -NH2. In some embodiments, at least one of Rt and Ru is -NH2. In some embodiments, Rt is H and Ru is -NH2. In some embodiments, Rt is -NH2 and Ru is H.

[0199] In some embodiments of a compound of Formula (IC) or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or halo. In some embodiments of a compound of Formula (IC) or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or fluoro. In some embodiments of a compound of Formula (IC) or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is fluoro. In some variations, the embodiments provided herein also apply to a compound of Formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0200] In some embodiments, the compound has the formula (I-D1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; X4 is H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl; and Rt and Ru are independently H, C1-6 alkoxy, or -NH2. In some embodiments, X5 is C1-6 alkyl, X4 is H, halo, or C1-6 alkyl, and Ru and Rz are independently H, halo, or -NH2. In some embodiments, at least one of Ru and Rz is -NH2. In some embodiments, Ru is H and Rz is -NH2. In some embodiments, Ru is -NH2 and Rz is H. In some embodiments, at least one of Ru and Rz is halo. In some embodiments, Ru is H and Rz is fluoro. In some embodiments, Ru is fluoro and Rz is H.

[0201] In some embodiments, the compound has formula (I-D2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X5 is H, C1-6 alkyl, C1-6 alkoxy, or C3-10 cycloalkyl; X4 is H, halo, C1-6 alkyl, C1-6 alkoxy, or 5-20 membered heteroaryl; the C1-6 alkyl of X4 is optionally substituted with one or more halo; and Rt and Ru are independently H, C1-6 alkoxy, or -NH2. In some embodiments, X5 is C1-6 alkyl, X4 is H, halo, or C1-6 alkyl, and Ru and Rz are independently H, halo, or -NH2. In some embodiments, at least one of Ru and Rz is -NH2. In some embodiments, Ru is H and Rz is -NH2. In some embodiments, Ru is -NH2 and Rz is H. In some embodiments, at least one of Ru and Rz is halo. In some embodiments, Ru is H and Rz is fluoro. In some embodiments, Ru is fluoro and Rz is H.

[0202] In some embodiments, the compound has the formula (IE): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Rk and Rm are independently H, OH, -NH, or -NH-C(O)Ci-6 alkyl. In some embodiments, Rk is H and Rm is H, OH, -NH, or -NH-C(O)Ci-6 alkyl. In some embodiments, Rk is H and Rm is OH. In some embodiments, Rk is H, OH, -NH, or -NH-C(O)Ci-6 alkyl and Rm is H. In some embodiments, Rk is OH, -NH, or -NH-C(O)Ci-6 alkyl and Rm is H. In some embodiments, Rk is OH, -NH, or -NH-C(O)Ci-6 alkyl and Rm is H. In some embodiments, Rk is OH, -NH, or -NH-C(O)CH and Rm is H. In some variations, R2, Rk, and Rm of formula (IE) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, and Rk and Rm are independently H, OH, -NH2, or -NH-C(O)C1-6 alkyl. In some embodiments, Rk is H and Rm is H, OH, -NH2, or -NH-C(O)C1-6 alkyl. In some embodiments, Rk is H and Rm is OH. In some embodiments, Rk is H, OH, -NH2, or -NH-C(O)C1-6 alkyl and Rm is H. In some embodiments, Rk is OH, -NH2, or -NH-C(O)C1-6 alkyl and Rm is H. In some embodiments, Rk is OH, -NH2, or -NH-C(O)CH3, and Rm is H.

[0203] In some embodiments, the compound has the formula (IF): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y1 is CH or N; Rx is H, halo, C1-6 alkyl, or —NH2; when Y1 is CH, the C1-6 alkyl of Rx is optionally substituted with one or more halo; Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (iii) C3-10 cycloalkyl, where the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; Rk is H, halo, —OH, —NH2, or —NH—C(O)C1-6 alkyl; and Rn is H, C1-6 alkyl, or C3-10 cycloalkyl. In some embodiments, Y is CH or N; R is H, halo, or C alkyl; R is (i) C alkyl, (ii) C alkenyl, or (iii) C cycloalkyl, wherein C cycloalkyl is optionally substituted with one or more halo or C alkyl; R is H, halo, —OH, —NH, or —NH—C(O)C alkyl; and R is H, C alkyl, or C cycloalkyl. In some variations, R2, Rk, Rx, Ry, and Rz of formula (IF) are as defined for a compound of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof; Y1 is CH or N; Rx is H, halo, C1-6 alkyl, or -NH2, where if Y1 is CH, the C1-6 alkyl of Rx is optionally substituted with one or more halo; Ry is (i) C1-6 alkyl, (ii) C2-6 alkenyl, or (iii) C3-10 cycloalkyl, where the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; Rk is H, halo, -OH, -NH2, or -NH-C(O)C1-6 alkyl; and Rn is H, C1-6 alkyl, or C3-10 cycloalkyl.In some embodiments, Y is CH or N; R is H, halo, or C alkyl; R is (i) C alkyl, or (ii) C cycloalkyl, where C cycloalkyl is optionally substituted with one or more halo or C alkyl; R is H, halo, —OH, —NH, or —NH—C(O)C alkyl; and R is H, C alkyl, or C cycloalkyl.

[0204] In some embodiments of a compound of Formula (IF), Y is CH or N, R is H, halo, or C alkyl, R is (i) C alkyl, (ii) C alkenyl, or (iii) C cycloalkyl, where C cycloalkyl is optionally substituted with one or more halo or C alkyl, R is H or halo, and R is H, C alkyl, or C cycloalkyl. In some embodiments, Y is N or CH, R is H or halo, R is C alkyl or C cycloalkyl, R is H or halo, and R is C alkyl or C cycloalkyl. In some embodiments, Y1 is N or CH, Rx is H or fluoro, Ry is C1-6 alkyl or C3-6 cycloalkyl, Rk is H or fluoro, and Rn is C1-6 alkyl or C3-6 cycloalkyl. In some embodiments, Y1 is N or CH, Rx is H or fluoro, Ry is C1-6 alkyl or C3-6 cycloalkyl, Rk is H or fluoro, and Rn is C1-6 alkyl or C3-6 cycloalkyl. In some embodiments, Y1 is N or CH, Rx is H or fluoro, Ry is C1-6 alkyl or C3-6 cycloalkyl, Rk is H, and Rn is C1-6 alkyl or C3-6 cycloalkyl. In some embodiments, Y1 is N or CH, Rx is H or fluoro, Ry is C1-3 alkyl or C3-6 cycloalkyl, Rk is H, and Rn is C1-3 alkyl or C3-6 cycloalkyl. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0205] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more R. In some embodiments, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R. R is -OH or a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R. R is -OH or a 5-10 membered heteroaryl, and the 5-10 membered heteroaryl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more C alkyl, wherein the C alkyl is optionally substituted with one or more halo, -NH, -NH(C alkyl), -N(C alkyl) -NH-C(O)C alkyl, or -NH-C(O)-C alkoxy. In some embodiments, R2 is methyl, wherein the methyl in R is substituted with one or more R, wherein R is -OH or a 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl in R is optionally substituted with one or more methyl, wherein the methyl is optionally substituted with one or more fluoro. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0206] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0207] In some embodiments of a compound of Formula (I'), (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] is selected from the group consisting of:

[0208] In some embodiments of a compound of Formula (I'), (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] In some embodiments, R2 is selected from the group consisting of: [ka] is.

[0209] In some embodiments of a compound of Formula (I'), (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] is.

[0210] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R, and R is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R, and R is a 3-8 membered heterocyclyl, and the 3-8 membered heterocyclyl of R is optionally substituted with one or more R. In some embodiments, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more oxo or C1-6 alkyl. [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0211] In some embodiments of a compound of Formula (I'), (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is a 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl in Ra is optionally substituted with one or more Rc, wherein Rc is oxo, C1-6 alkyl, or -C(O)-C1-6 alkoxy, wherein the C1-6 alkyl in Rc is optionally substituted with one or more halo, and wherein the -C(O)-C1-6 alkoxy in Rc is optionally substituted with one or more halo. In some embodiments, R2 is [ka] is selected from the group consisting of:

[0212] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re. In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more Ra, and Ra is -O-Re, and Re is -C(O)-(3- to 15-membered heterocyclyl). In some embodiments, R2 is [ka] is.

[0213] In some embodiments of a compound of Formula (I'), (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, wherein Ra is -O-Re, and Re is -C(O)-(3-15 membered heterocyclyl), wherein the -C(O)-(3-15 membered heterocyclyl) in Re is optionally substituted with one or more C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, C1-6 alkoxy, or C3-10 cycloalkyl. In some embodiments, R2 is [ka] is selected from the group consisting of:

[0214] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd). In some embodiments, R2 is methyl, and the methyl of R2 is substituted with one or more R2, and R2 is -N(Rc)(Rd), and one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-N(C1-6 alkyl). In some embodiments, R2 is [ka] In some variations, the embodiments provided herein also apply to compounds of formula (I'), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof.

[0215] In some embodiments of a compound of Formula (I'), (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), wherein one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl, -C(O)-N(Ci-6 alkyl), or -C(O)-(3-15 membered heterocyclyl). In some embodiments, R2 is [ka] is.

[0216] As used herein, in some embodiments, the compound has the formula (IG): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein ring A is (i) a 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of ring A is optionally substituted with one or more oxo, (ii) a 5- to 20-membered heteroaryl, wherein the 5-20 membered heteroaryl of ring A is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl, or (iii) C3-10 cycloalkyl.

[0217] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X3 is H, fluoro, or methyl optionally substituted with one or more fluoro; X4 is (i) isopropyl, (ii) C3-4 cycloalkyl optionally substituted with one or more halo or C1-6 alkyl, or (iii) butyl; and Rz is fluoro or methyl, with the proviso that at least one of X3 and X4 is halo, CF2, or CF3.

[0218] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or halo. In some embodiments of a compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is H or fluoro. In some embodiments of a compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Rk is fluoro.

[0219] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is a 5-20 membered heteroaryl or -(C1-4 alkyl)(5-20 membered heteroaryl), wherein the C1-4 alkyl is optionally substituted with one or more -OH, halo, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, and the 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, Rs is halo, C1-6 alkyl, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)-C1-6 alkyl, C6-20 aryl, C3-10 cycloalkyl, 3-15 membered heterocyclyl, 5-20 membered heteroaryl, or -C(O)-C1-6 alkoxy. In some embodiments, the C1-6 alkyl of Rs is optionally substituted with one or more halo, C1-6 alkoxy, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, -NH-C(O)C1-6 alkyl, or -NH-C(O)-C1-6 alkoxy, and the 3-15 membered heterocyclyl of Rs is optionally substituted with one or more halo or -C(O)-C1-6 alkoxy.

[0220] In some embodiments of the compounds of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is [ka] is selected from the group consisting of:

[0221] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is methyl, wherein the methyl in R2 is substituted with one or more Ra, and Ra is -N(Rc)(Rd), wherein one of Rc and Rd is H, and the other of Rc and Rd is -C(O)-Ci-6 alkyl, -C(O)-N(Ci-6 alkyl), or -C(O)-(3-15 membered heterocyclyl). In some embodiments, R2 is [ka] is.

[0222] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is (i) a 3-15 membered heterocyclyl, wherein the 3-15 membered heterocyclyl of ring A is optionally substituted with one or more oxo, or C alkyl; (ii) a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of ring A is optionally substituted with one or more halo, C alkyl, C alkenyl, C alkoxy, —NH, or C cycloalkyl, wherein the C alkyl is optionally substituted with one or more halo, and the C cycloalkyl is optionally substituted with one or more halo or C alkyl; or (iii) a C cycloalkyl.

[0223] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of ring A is optionally substituted with one or more oxo, or C1-6 alkyl. In some embodiments, ring A is [ka] is selected from the group consisting of:

[0224] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of ring A is optionally substituted with one or more halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, -NH2, or C3-10 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more halo, and the C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl. In some embodiments, ring A is a 5-20 membered heteroaryl, wherein the 5-20 membered heteroaryl of ring A is optionally substituted with one or more C1-6 alkyl. In some embodiments, ring A is [ka] is selected from the group consisting of:

[0225] In some embodiments of a compound of Formula (I'), (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Ring A is C3-10 cycloalkyl. In some embodiments, Ring A is C3-6 cycloalkyl. In some embodiments, Ring A is cyclopropyl.

[0226] As used herein, in some embodiments, the compound has the formula (IH): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y is CR or N, and when the ring bearing R, R, and R is phenyl, R, R, and R are H, halo, C alkyl, C alkenyl, -NH, -NH-C(O)-(C alkyl), -NH-C(O)-(3-15 membered heterocyclyl), C cycloalkyl, or 5-20 membered heteroaryl, and C alkyl is selected from the group consisting of one or more halo, -NH-C(O)-NH(C alkyl), -NH-C( wherein Rx, Ry, and Rz are optionally substituted with one or more halo, C1-6 alkyl, or —NH—C(O)—C1-6 alkoxy; wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl; wherein 5-20 membered heteroaryl is optionally substituted with one or more C1-6 alkyl; and when the ring bearing Rx, Ry, and Rz is pyridyl, Rx, Ry, and Rz are each independently H, halo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, —NH2, or C3-10 cycloalkyl; wherein C1-6 alkyl is optionally substituted with one or more halo; and wherein C3-10 cycloalkyl is optionally substituted with one or more halo or C1-6 alkyl.

[0227] Provided herein, in some embodiments, is a compound of Formula (I), e.g., a compound of Formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more Rq. In some embodiments, R2 is C3-10 cycloalkyl, and the C3-10 cycloalkyl of R2 is optionally substituted with one or more Rq. In other embodiments, R2 is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of R2 is optionally substituted with one or more halo, oxo, C1-6 alkyl, -C(O)-C1-6 alkyl, or 5-20 membered heteroaryl. In some embodiments, R2 is a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of R2 is optionally substituted with one or more Rs. In some embodiments, R2 is -N(Rg)(Rh), and Rg and Rh are independently H or C1-6 alkyl. In some embodiments, R2 is -C(O)-Rj, and Rj is C3-10 cycloalkyl, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, or -NH(5-20 membered heteroaryl). In some embodiments, R2 is C6-20 aryl, and the C6-20 aryl of R2 is optionally substituted with one or more 5-20 membered heteroaryl or -O(Rp), and Rp is a 3-15 membered heterocyclyl, and the 3-15 membered heterocyclyl of Rp is optionally substituted with one or more -C(O)-C1-6 alkyl.

[0228] Provided herein, in some embodiments, is a compound of Formula (I'), e.g., a compound of Formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2 is C1-6 alkyl, and the C1-6 alkyl of R2 is optionally substituted with one or more Rq. In some embodiments, R2 is C3-10 cycloalkyl, and the C3-10 cycloalkyl of R2 is optionally substituted with one or more Rq. In other embodiments, R2 is a 3-15 membered heterocyclyl, wherein the 3-15 membered heterocyclyl of R2 is optionally substituted with one or more halo, oxo, C1-6 alkyl, -C(O)-C1-6 alkyl, or 5-20 membered heteroaryl. In some embodiments, R2 is a 5-20 membered heteroaryl or -(C1-4 alkyl)(5-20 membered heteroaryl), wherein the C1-4 alkyl is optionally substituted with one or more -OH, halo, -NH2, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, and the 5-20 membered heteroaryl is optionally substituted with one or more Rs. In some embodiments, R2 is -N(Rg)(Rh), wherein Rg and Rh are independently H or C1-6 alkyl. In some embodiments, R2 is -C(O)-Rj, where Rj is C3-10 cycloalkyl, -NH(C1-6 alkyl), -N(C1-6 alkyl), or -NH(5-20 membered heteroaryl). In some embodiments, R2 is C6-20 aryl, where the C6-20 aryl of R2 is optionally substituted with one or more 5-20 membered heteroaryl or -O(Rp), where Rp is 3-15 membered heterocyclyl, where the 3-15 membered heterocyclyl of Rp is optionally substituted with one or more -C(O)-C1-6 alkyl.

[0229] In some embodiments of a compound of Formula (I) or Formula (I'), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from Table 1.

[0230] Compound names contained in Table 1 and for all intermediates and compounds were generated using ChemDraw® Professional software version 17.1.1.0 or Collaborative Drug Discovery Inc. (CDD) CDD Vault update#3.

[0231] A KNIME workflow was created to retrieve structures from the internal ChemAxon Compound Registry, generate canonical smiles using the RDKit Canon SMILES node, remove stereochemistry using the ChemAxon / Infocom MolConverter node, and name the structures using the ChemAxon / Infocom Naming node. The following shows the versions of the KNIME Analytics Platform and extensions used in the workflow: ·Knime Analytics Platform 4.2.2 RDKit KNIME Integration 4.0.1.v202006261025 (This extension includes the RDKit Canon SMILES node) ChemAxon / Infocom Marvin Extensions Feature 4.3.0v202100 (This extension includes the MolConverter node) ChemAxon / Infocom JChem Extensions Feature 4.3.0v202100 (This extension includes the Naming node) [Table 1-1] Table 1-2 Table 1-3 Table 1-4 Table 1-5 Table 1-6 Table 1-7 Table 1-8 Table 1-9 Table 1-10 Table 1-11 Table 1-12 Table 1-13 Table 1-14 Table 1-15 Table 1-16 Table 1-17 Table 1-18 Table 1-19 Table 1-20 Table 1-21 Table 1-22 Table 1-23 Table 1-24 Table 1-25 Table 1-26 Table 1-27 Table 1-28 Table 1-29 Table 1-30 Table 1-31 Table 1-32 Table 1-33 Table 1-34 Table 1-35 Table 1-36 Table 1-37 Table 1-38 Table 1-39 Table 1-40 Table 1-41 Table 1-42 Table 1-43 Table 1-44 Table 1-45 Table 1-46 Table 1-47 Table 1-48 Table 1-49 Table 1-50 Table 1-51 Table 1-52 Table 1-53 Table 1-54 Table 1-55 Table 1-56 Table 1-57 Table 1-58 Table 1-59 Table 1-60 Table 1-61 Table 1-62 Table 1-63 Table 1-64 Table 1-65 Table 1-66

Table 1-67

Table 1-90

Table 1-97

Table 1-100

Table 1-110

Table 1-120

[0232] Provided herein, in some embodiments, is a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from the group consisting of: 1-Cyclopropanecarbonyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-hydroxy-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-3-hydroxy-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-(3-carbamoyl-2-acetamidopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; tert-Butyl N-{2-oxo-2-[2-({phenyl[4-(propan-2-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]ethyl}carbamate; 1-(2-hydroxyacetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-acetamidoacetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 1-(3-carbamoylpropanoyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-[(5-cyclopropylpyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 2-acetyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-2-azabicyclo[3.1.0]hexane-3-carboxamide; 1-{2-[N-(carbamoylmethyl)acetamido]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-5-methyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1,3-oxazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(4H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-{2-[(3-methyloxetan-3-yl)amino]acetyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-acetamido-5-[4-fluoro-2-({phenyl[4-(propan-2-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]-5-oxopentanoic acid; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-(3-acetamidopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxopyrrolidin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,3-oxazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(4-acetamidobutanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 2-acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-(2-acetamidoacetyl)pyrrolidine-2-carboxamide; 3-acetyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-3-azabicyclo[3.1.0]hexane-2-carboxamide; 4-Fluoro-1-[2-(2-oxo-1,3-oxazolidin-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(oxetan-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-oxomorpholin-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-5-methylpyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-oxomorpholin-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-4H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[3-(1,3-oxazol-2-yl)propanoyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-1,3-oxazolidin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1,2-oxazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2H-1,2,3,4-tetrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,3,4-oxadiazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-{2-[(1,3-oxazol-2-yl)amino]acetyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-methyl-2-oxoimidazolidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,4-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridazin-3-yloxy)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(1-methyl-5-oxopyrrolidine-2-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(2-chloro-5-fluorophenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[4-(pyridin-3-yl)butanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-oxo-octahydroindolizine-6-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-oxopiperidine-4-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(2-cyano-4-methoxyphenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridine-8-carbonyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[4-(1H-imidazol-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrimidin-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(4-methylpyrimidine-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyridin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[3-(3,5-dimethyl-1,2-oxazol-4-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-fluoro-4-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(1,3-oxazole-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[4-(pyridin-4-yl)butanoyl]pyrrolidine-2-carboxamide; 1-[(dimethylcarbamoyl)carbonyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1H-imidazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-1-[2-methyl-3-(1H-1,2,4-triazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-fluoropyridin-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1H-indol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(4-acetamidophenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1H-imidazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyridin-3-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1,5-dimethyl-1H-pyrazol-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(2-methylpyridin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrimidin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyrazin-2-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2H-1,2,3-triazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-[3-(2,6-dimethylpyridin-3-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,2,3-benzotriazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yloxy)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-imidazol-5-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(5-methyl-1,3,4-thiadiazol-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[3-(3,5-dimethyl-1H-pyrazol-1-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(3-cyanopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1,2,4-oxadiazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-indol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(5-methylpyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-ethyl-1,3-oxazole-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methyl-1,3-thiazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-3-(1H-pyrazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-indol-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-3-(pyridin-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-fluoro-1H-indol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{4-oxo-4H,5H,6H,7H,8H-pyrazolo[1,5-a][1,4]diazepine-2-carbonyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-{2-[5-(propan-2-yl)-1,2,4-oxadiazol-3-yl]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(6-oxopiperidine-3-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrrolidine-1-sulfonyl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1,2-benzoxazol-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-(2-{[1,2,4]triazolo[1,5-a]pyridin-6-yl}acetyl)pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(3-methoxypyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1H-imidazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-1,2-oxazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,3-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-imidazol-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methylphenoxy)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1,2-oxazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-methyloxetane-3-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(4-chloro-1H-pyrazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-ethyl-1H-pyrazole-5-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-2-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyrimidin-5-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-methoxy-1-methyl-1H-pyrazole-4-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1,3,4-oxadiazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-pyrazol-4-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1,3-thiazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[4-(2-methyl-1H-imidazol-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-{imidazo[1,2-a]pyridin-3-yl}acetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyridin-2-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1,2,4-oxadiazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-1H-pyrazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(6-methylpyridin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-(3-{1H-pyrrolo[2,3-b]pyridin-3-yl}propanoyl)pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-oxo-1,3-oxazolidine-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-1H-pyrazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1-methyl-1H-pyrazol-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,4-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[5-(pyridin-4-yl)-1H-pyrazole-3-carbonyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(2-methylpyridin-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-hydroxy-3-methylbutanoyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-(3-{1H-pyrrolo[2,3-b]pyridin-5-yl}propanoyl)pyrrolidine-2-carboxamide; 4-Fluoro-1-[4-oxo-4-(pyrrolidin-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(quinolin-6-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2,2,2-trifluoroacetamido)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yloxy)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1H-indol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-cyclopropyl-2-oxoacetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-fluoro-2-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(6-methoxypyridin-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyridin-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-1H-pyrazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(2,5-dioxoimidazolidin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(2,5-dimethyl-1,3-thiazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-3-(pyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyrazin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(N-methylacetamido)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-2-(pyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxopiperidin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,4-triazol-1-yl)benzoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-{[(2-methylpropyl)carbamoyl]carbonyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-oxo-1,2,3,4-tetrahydroquinoline-7-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methyl-1,3-thiazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(6-oxo-1,6-dihydropyridazin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-1H-pyrazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1H-pyrazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-acetamidopyridine-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-2-[2-(1H-1,2,3-triazol-5-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide; N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-hydroxy-2-methylpropanoyl)pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3,4-tetrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2H-1,2,3,4-tetrazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-4H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-1,2,3-triazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-1,2,3-triazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,2-oxazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,2-oxazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1H-1,2,4-triazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(5-methyl-1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrimidin-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrimidin-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(4-methyl-2,5-dioxopiperazin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-(2-cyanoacetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-methanesulfonylacetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 1-(4-acetylmorpholine-2-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(4-acetyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(4-acetyl-2-oxopiperazin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetylpiperidine-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2,3-dihydroxypropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{8-acetyl-8-azaspiro[4.5]decane-2-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-imidazol-1-yl)-2-methylpropanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{6-acetyl-6-azaspiro[2.5]octane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-3-methylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(N-methylacetamido)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-5-oxa-2,6-diazaspiro[3.4]oct-6-ene-7-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[1-acetyl-2-(pyridin-3-yl)pyrrolidine-3-carbonyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[5-(methoxymethyl)-1,2-oxazole-4-carbonyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{6-acetyl-5H,6H,7H,8H-pyrido[3,4-b]pyrazine-7-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,4-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 1-{5-acetyl-5-azaspiro[2.4]heptane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[3-(1-acetylpyrrolidin-2-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{4-[(1-acetylazetidin-3-yl)oxy]benzoyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-methoxy-2-(N-methylacetamido)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetylpyrrolidin-2-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{7-acetyl-1-oxa-2,7-diazaspiro[4.4]non-2-ene-3-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{5-acetyl-hexahydro-1H-furo[3,4-c]pyrrole-3a-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1H-pyrazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{5-acetyl-2-oxa-5-azabicyclo[2.2.1]heptane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetylpiperidin-4-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-2-(1H-1,2,4-triazol-5-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-methyl-2-(1,3,4-oxadiazol-2-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-{imidazo[1,2-a]pyridin-3-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-imidazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1,2-oxazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-[2-(1H-1,2,3-triazol-5-yl)acetyl]-4-azaspiro[2.4]heptane-5-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-{[1,2,4]triazolo[1,5-a]pyridin-6-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(quinolin-6-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(piperazin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-(1-acetyl-3-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-4-methylazepane-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetylazepane-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(4-acetylmorpholine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-{2-acetyl-2-azaspiro[3.4]octan-5-yl}acetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-2-azaspiro[4.4]nonane-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-2-azabicyclo[2.2.2]octane-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetylpiperidin-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(4-acetyl-1,4-oxazepane-2-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-4-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(4-acetyl-2-methylmorpholine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{5-acetyl-hexahydro-2H-furo[2,3-c]pyrrole-3-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{3-acetyl-3-azabicyclo[3.1.0]hexane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-octahydrocyclopenta[c]pyrrole-4-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{8-acetyl-8-azabicyclo[3.2.1]octane-3-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-3-methylazetidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{5-acetyl-hexahydro-2H-furo[2,3-c]pyrrole-2-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{3-acetyl-3-azabicyclo[3.2.1]octane-8-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-acetyl-octahydro-1H-isoindole-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{7-acetyl-7-azabicyclo[2.2.1]heptane-2-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-5-oxa-2-azaspiro[3.4]octane-7-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetyl-3-methylazetidin-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-5-oxa-2-azaspiro[3.4]octane-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-2-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{3-[N-(1-methyl-1H-pyrazol-3-yl)acetamido]propanoyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-3-fluoroazetidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetyl-3-methoxyazetidin-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{4-acetyl-hexahydro-2H-furo[3,2-b]pyrrole-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-4-ethylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{7-acetyl-1-oxo-2,7-diazaspiro[4.4]nonane-4-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[1-(1,3,4-oxadiazol-2-yl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide; 2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl N,N-dimethylcarbamate; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl N,N-dimethylcarbamate; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-1,2,3-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; tert-butyl 4-({2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}carbamoyl)piperazine-1-carboxylate; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-[2-(3,5-dimethyl-1H-pyrazol-4-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}piperazine-1-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(4-acetylpiperazin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)(methyl)amino]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-oxo-1,3-oxazolidine-5-carbonyl)pyrrolidine-2-carboxamide; 2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethylpiperazine-1-carboxylate; 1-[2-(3,5-dimethyl-1H-pyrazol-4-yl)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-tert-butyl 4-{2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}piperazine-1,4-dicarboxylate; 1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; tert-butyl N-({5-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-1,3,4-oxadiazol-2-yl}methyl)carbamate; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridazin-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-{2-[5-(trifluoromethyl)-2H-1,2,3,4-tetrazol-2-yl]acetyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridazin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxopiperazin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-methylpiperazine-1-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(2,2,2-trifluoroethyl)piperazine-1-carboxamide; N-{2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-4-(2,2,2-trifluoroethyl)piperazine-1-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(2-methoxyethyl)piperazine-1-carboxamide; 1-{2-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(5-methyl-1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(4-methyl-1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(piperazin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}pyrrolidine-2-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(cyclopropylmethyl)piperazine-1-carboxamide; 4-(cyclopropylmethyl)-N-{2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}piperazine-1-carboxamide; N-{2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-4-methylpiperazine-1-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(4-methyl-1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methylquinolin-5-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; tert-butyl N-[(5-{2-[4-fluoro-2-({phenyl[4-(propan-2-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-1,3,4-oxadiazol-2-yl)methyl]carbamate; 1-{2-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; tert-butyl 4-(5-{2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-1H-1,2,3-triazol-4-yl)piperazine-1-carboxylate; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[5-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]acetyl}pyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-2H-1,2,3,4-tetrazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(acetamidomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(aminomethyl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-{5-[(dimethylamino)methyl]-1H-1,2,3-triazol-1-yl}acetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(piperazin-1-yl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(morpholin-4-yl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; 1-(2-{5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}acetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[5-(trifluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,2,3-benzotriazol-1-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]morpholine-4-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethylazetidine-1-carboxylate; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-2,3-dihydro-1H-indol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methyl-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[5-(acetamidomethyl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-1H-imidazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-(cyclopropylmethyl)piperazine-1-carboxylate; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-methylpiperazine-1-carboxylate; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{imidazo[1,2-a]pyridin-3-yl}acetyl)pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{[1,2,4]triazolo[1,5-a]pyridin-6-yl}acetyl)pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[(pyrazin-2-yl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(piperazin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(2-ethyl-2H-1,2,3-triazol-4-yl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(1-ethyl-1H-1,2,3-triazol-4-yl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methylquinolin-6-yl)acetyl]pyrrolidine-2-carboxamide; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-(2-methoxyethyl)piperazine-1-carboxylate; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[2-oxo-4-(2,2,2-trifluoroethyl)piperazin-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[methyl(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methylquinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[methyl(pyrazin-2-yl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-(2,2,2-trifluoroethyl)piperazine-1-carboxylate; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-methylquinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; tert-butyl 2-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-1H-indole-1-carboxylate, 1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(carbamoylamino)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(2-ethyl-2H-1,2,3-triazol-4-yl)(methyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(1-ethyl-1H-1,2,3-triazol-4-yl)(methyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[3-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propanoyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{2-[(methylcarbamoyl)amino]acetyl}-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[(methylcarbamoyl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-[2-(carbamoylamino)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-1-[3-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propanoyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-[2-(carbamoylamino)acetyl]-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(methylcarbamoyl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]propanoyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{[3-(trifluoromethyl)azetidine-1-carbonyl]amino}acetyl)pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]propanoyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]propanoyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-4-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-2-yl}propanoyl)-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-(2-{[3-(trifluoromethyl)azetidine-1-carbonyl]amino}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; 5-methyl-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[4-(3,3-difluoroazetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(diethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[4-(3,3-difluoroazetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(1,3-oxazol-2-yl)amino]acetyl}pyrrolidine-2-carboxamide; N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(3,3-difluoroazetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(diethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(diethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; and N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide, N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide 1-[2-(1H-1,3-Benzodiazol-1-yl)acetyl]-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(6-oxo-1,6-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(2-oxo-1,2-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(3-ethyl-5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(1-ethyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(1-ethyl-5-methyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(6-ethoxy-5-methylpyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(1-ethyl-5-methyl-2-oxo-1,2-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(1-ethyl-2-oxo-1,2-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(4-ethyl-5-oxo-4,5-dihydropyrazin-2-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1,3-oxazol-2-yl]acetyl}pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(3-oxo-3,4-dihydropyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-oxo-4,5-dihydropyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(4-ethyl-3-oxo-3,4-dihydropyrazin-2-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide 1-[2-(1H-1,3-Benzodiazol-1-yl)acetyl]-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1,3-oxazol-2-yl]acetyl}pyrrolidine-2-carboxamide 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1,3-oxazol-2-yl]acetyl}pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](pyridin-3-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethylazetidine-1-carboxylate 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxopiperazin-1-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide N-{2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}morpholine-4-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-methyl-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide 1-[2-(1H-1,3-benzodiazol-1-yl)propanoyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide 1-[2-(2,5-dioxopiperazin-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)acetyl]pyrrolidine-2-carboxamide 1-[2-(1H-1,2,3-benzotriazol-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-indol-1-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide 2,2,2-Trifluoroethyl 4-{2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-3-oxopiperazine-1-carboxylate 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-(2-methoxyethyl)piperazine-1-carboxylate 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-{2-[2-oxo-4-(2,2,2-trifluoroethyl)piperazin-1-yl]acetyl}pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-methylpiperazine-1-carboxylate 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-(cyclopropylmethyl)piperazine-1-carboxylate 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-(2,2,2-trifluoroethyl)piperazine-1-carboxylate 1-[2-(1H-1,3-benzodiazol-1-yl)propanoyl]-4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide N-{2-[4-fluoro-2-({[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}morpholine-4-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-methyl-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide 1-[2-(1H-1,2,3-benzotriazol-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide tert-Butyl 2-{2-[4-fluoro-2-({[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-1H-indole-1-carboxylate 1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{[4-methyl-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide 1-Acetyl-N-[(5-cyclobutylpyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide 4-Fluoro-N-{[4-methyl-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[4-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-{[4-(difluoromethyl)-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-methyl-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{phenyl[5-(propan-2-yl)-4-(trifluoromethyl)pyridin-2-yl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{[6-methyl-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide N-[(5-cyclobutylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(5-tert-butylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-methoxy-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(2-aminopyridin-3-yl)[3-fluoro-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(4-cyclopropyl-3-fluorophenyl)(1H-pyrazol-5-yl)methyl]-1-(2-acetamidoacetyl)pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](5-fluoropyridin-2-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](5-fluoropyridin-3-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(2-aminopyridin-4-yl)[3-fluoro-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](3-fluoropyridin-4-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(6-aminopyridin-3-yl)[3-fluoro-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(6-aminopyridin-2-yl)[3-fluoro-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(2-aminopyridin-3-yl)[3-methyl-4-(propan-2-yl)phenyl]methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](1H-pyrazol-5-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(2-aminopyridin-3-yl)[3-methyl-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide N-[(2-aminopyridin-3-yl)[3-methyl-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](2-methoxypyridin-3-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](2-methylpyridin-3-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl]({imidazo[1,5-a]pyridin-3-yl})methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl]({imidazo[1,5-a]pyridin-1-yl})methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1H-pyrazol-5-yl)methyl}-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl]({imidazo[1,5-a]pyridin-7-yl})methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1H-indazol-6-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1-methyl-1H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](2-methyl-2H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide 1-Acetyl-N-[(5-cyclopropyl-6-fluoropyridin-...

Claims

1. Formula (IA): 【Chemistry 273】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Y １ is CH or N, R ｘ and R ｚ are independently H, halo, or C １～６ is alkyl, and Y １ When is CH, R ｘ or R ｚ The above C １～６ the alkyl may be optionally substituted with one or more halo; R ｙ However, (i) C １～６ alkyl, or (ii) C ３～１０ cycloalkyl, ３～１０ Cycloalkyl is one or more halo or C １～６ optionally substituted with alkyl; R ｋ is halo, or —OH; R ２ However, (i) to (vii): (i) C １～６ alkyl, and R ２ The above C １～６ The alkyl is one or more R ａ and R ａ but, (a) —OH, (b) cyano, (c) C ２～６ Alkynyl, (d) C ６～２０ Aryl, R ａ The above C ６～２０ The aryl is selected from the group consisting of one or more of halo, cyano, C １～６ Alkoxy, or —NH—C(O)—C １～６ C optionally substituted with alkyl ６～２０ aryl, (e) 3- to 15-membered heterocyclyl, wherein R ａ wherein the 3- to 15-membered heterocyclyl is one or more R ｃ and optionally substituted with R ｃ But, halo, oxo, C １～６ Alkyl, C １～６ Alkoxy, —C(O)—C １～６ Alkyl, or —C(O)—C １～６ is an alkoxy, R ｃ The above C １～６ The alkyl may be one or more halo or C ２～６ optionally substituted with alkynyl, and R ｃ The —C(O)—C １～６ alkoxy is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo; (f) -N(R ｃ ) (R ｄ ) where -N(R ｃ ) (R ｄ ) R ｃ and R ｄ are, independently of each other, H, C １～６ Alkyl, —C(O)—C １～６ Alkyl, —C(O)—C １～６ Alkoxy, —C(O)—NH ２ , -C(O)-NH(C １～６ alkyl), -C(O)-N(C １～６ alkyl) ２ , —C(O)—(3- to 15-membered heterocyclyl), —CH ２ —C(O)—NH ２ , 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; R ｃ Or R ｄ The above C １～６ The alkyl group is one or more —C(O)—NH ２ and optionally substituted with R ｃ Or R ｄ The —C(O)—C １～６ the alkyl is optionally substituted with one or more halo; R ｃ Or R ｄ wherein said 3- to 15-membered heterocyclyl and said 5- to 20-membered heteroaryl independently comprise one or more C １～６ optionally substituted with alkyl; R ｃ Or R ｄ wherein the —C(O)—(3- to 15-membered heterocyclyl) is one or more halo, —C(O)—C １～６ Alkoxy or C １～６ Optionally substituted with alkyl, １～６ The alkyl may be one or more halo, C １～６ Alkoxy or C ３～１０ optionally substituted with cycloalkyl, and R ｃ Or R ｄ The —C(O)—N(C １～６ alkyl) ２ The above C １～６ The alkyl may, independently of each other, be one or more halo or C ６～２０ -N(R ｃ ) (R ｄ ), (g) -O-R ｅ and R ｅ But C １～６ Alkyl, C ６～２０ Aryl, —C(O)—(3- to 15-membered heterocyclyl), —C(O)—N—(C １～６ alkyl) ２ or 5- to 20-membered heteroaryl; R ｅ The above C １～６ The alkyl is one or more C １～６ Optionally substituted with alkoxy, １～６ Alkoxy is one or more C ２～６ optionally substituted with alkynyl; R ｅ The above C ６～２０ The aryl is one or more C １～６ optionally substituted with alkyl, and R ｅ The —C(O)—(3- to 15-membered heterocyclyl) is one or more C １～６ Alkyl, C １～６ Alkoxy or —C(O)—C １～６ Optionally substituted with alkoxy, １～６ The alkyl may be one or more halo, C １～６ Alkoxy or C ３～１０ -O-R optionally substituted with cycloalkyl ｅ , (h)-C(O)-R ｅ and R ｅ But -NH ２ , —OH, or 3- to 15-membered heterocyclyl, —C(O)—R ｅ , or (i) -S(O) ２ -R ｆ and R ｆ But C １～６ alkyl or 3- to 15-membered heterocyclyl, ２ -R ｆ , and (ii) C ３～１０ Cycloalkyl, R ２ The above C ３～１０ Cycloalkyl is one or more R ｑ and R ｑ is 5- to 20-membered heteroaryl or C ６～２０ aryl, and R ｑ The above C ６～２０ The aryl is one or more C １～６ C optionally substituted with alkoxy ３～１０ cycloalkyl, (iii) 3- to 15-membered heterocyclyl, wherein R ２ wherein the 3- to 15-membered heterocyclyl is one or more of halo, oxo, C １～６ Alkyl, —C(O)—C １～６ 3- to 15-membered heterocyclyl optionally substituted with alkyl, or 5- to 20-membered heteroaryl; (iv) 5- to 20-membered heteroaryl or -(C １～４ alkyl)(5- to 20-membered heteroaryl), １～４ The alkyl group may be one or more of -OH, halo, -NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ and said 5-20 membered heteroaryl is optionally substituted with one or more R ｓ and optionally substituted with R ｓ But, Halo, C １～６ Alkyl, C １～６ Alkoxy, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -NH-C(O)-C １～６ Alkyl, C ６～２０ Aryl, C ３～１０ cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C １～６ is an alkoxy, R ｓ The above C １～６ The alkyl may be one or more halo, C １～６ Alkoxy, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -NH-C(O)C １～６ Alkyl, or —NH—C(O)—C １～６ optionally substituted with alkoxy, and R ｓ wherein the 3- to 15-membered heterocyclyl is one or more halo or —C(O)—C １～６ 5-20 membered heteroaryl optionally substituted with alkoxy or -(C １～４ alkyl) (5- to 20-membered heteroaryl), (v) -N(R ｇ ) (R ｈ ) where R ｇ and R ｈ are independently H or C １～６ alkyl, —N(R ｇ ) (R ｈ ), (vi)-C(O)-R ｊ and R ｊ But C ３～１０ Cycloalkyl, —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ or —NH(5-20 membered heteroaryl), —C(O)—R ｊ ,and (vii) C ６～２０ Aryl, R ２ The above C ６～２０ The aryl is one or more 5- to 20-membered heteroaryl or —O—R ｐ and R ｐ is 3- to 15-membered heterocyclyl, and R ｐ The 3- to 15-membered heterocyclyl is one or more —C(O)—C １～６ C optionally substituted with alkyl ６～２０ aryl, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

2. R ｘ is H, fluoro, or methyl; R ｙ is (i) isopropyl, or (ii) C ３～４ cycloalkyl, ３～４ 2. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein cycloalkyl is optionally substituted with one or more fluoro or methyl.

3. R ｋ is halo, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

4. R ２ is a 5- to 20-membered heteroaryl or -(C １～４ alkyl) (5- to 20-membered heteroaryl), １～４ The alkyl group may contain one or more —OH, halo, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ and said 5-20 membered heteroaryl is optionally substituted with one or more R ｓ 10. The compound of claim 1, optionally substituted with:

5. R ２ but, 【Chemistry 274-1】 【Chemistry 274-2】 10. The compound of claim 1 selected from the group consisting of: or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. 【Request Item 6】 【Table 1A-1】 Table 1A-2 Table 1A-3 Table 1A-4 Table 1A-5 Table 1A-6 Table 1A-7 【Table 1A-8】 【Table 1A-9】 【Table 1A-10】 【Table 1A-11】 【Table 1A-12】 【Table 1A-13】 【Table 1A-14】 【Table 1A-15】 【Table 1A-16】 【Table 1A-17】 【Table 1A-18】 【Table 1A-19】 【Table 1A-20】 【Table 1A-21】 【Table 1A-22】 【Table 1A-23】 【Table 1A-24】 【Table 1A-25】 【Table 1A-26】 【Table 1A-27】 【Table 1A-28】 【Table 1A-29】 【Table 1A-30】 【Table 1A-31】 【Table 1A-32】 【Table 1A-33】 【Table 1A-34】 【Table 1A-35】 【Table 1A-36】 【Table 1A-37】 【Table 1A-38】 【Table 1A-39】 【Table 1A-40】 【Table 1A-41】 【Table 1A-42】 【Table 1A-43】 【Table 1A-44】 【Table 1A-45】 【Table 1A-46】 【Table 1A-47】 【Table 1A-48】 【Table 1A-49】 【Table 1A-50】 【Table 1A-51】 【Table 1A-52】 【Table 1A-53】 【Table 1A-54】 【Table 1A-55】 【Table 1A-56】 【Table 1A-57】 Table 1A-58 【Table 1A-59】 【Table 1A-60】 【Table 1A-61】 【Table 1A-62】 【Table 1A-63】 and pharmaceutically acceptable salts of any of the foregoing. or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

7. 10. A pharmaceutical composition comprising: (i) a compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.

8. A kit comprising (i) a compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 7, and (ii) instructions for use thereof in treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

9. The compound has formula (I-A3): 【Chemistry 279】 is a compound of the formula R ｘ is H, halo, or C １～６ alkyl, １～６ 2. The compound of claim 1, wherein alkyl is optionally substituted with one or more halo, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

10. Use of a compound described in claim 1 or 9, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition described in claim 7, in the manufacture of a medicament for treating a GYS1-mediated disease, disorder, or condition in an individual in need of treatment thereof.

11. A composition comprising a compound of claim 1 or 9, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 7, for use in treating a GYS1-mediated disease, disorder, or condition in an individual in need of treatment for such a disease, disorder, or condition.

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