Therapeutic compounds

Abstract

The present disclosure relates to compounds of formula (I) that are IL-17A modulators. The compounds have the structural Formula (I) defined herein. The present disclosure also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with modulation of IL-17A activity.

Description

[0001]THERAPEUTIC COMPOUNDS INTRODUCTION The present disclosure relates to therapeutic compounds. More specifically, the present disclosure relates to compounds that are modulators of IL-17A activity. The present disclosure also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with IL-17A activity. BACKGROUND The interleukin-17 cytokine family consists of six members (termed IL-17A through IL-17F) of which IL-17A (also known as CTLA-8) is the primary effector cytokine of the T-helper-17 (Th17) cell lineage. IL-17A is a variably glycosylated, disulfide linked, homodimeric glycoprotein of 34-38 kDa which shares in the order of 50% homology with its closest family member IL- 17F, both of which can be secreted either as homodimers or the heterodimer IL-17AF [K.F. Geoghegan et al., Protein Expression and Purification 2013, 87, 27-34; J.K. Kolls and A. Lindén / Immunity 2004, 21, 467-476]. Activation of naïve CD4+ T-cells in response to cytokines such as IL-6, transforming growth factor ^ (TGF-^), IL-23, STAT3, and ROR^t leads to their differentiation to TH17 cells and expression of pro-inflammatory mediators such as IL-17A. Furthermore, a variety of cell types from the innate and adaptive immune systems have been identified as sources of IL-17A. These include mast cells, neutrophilic granulocytes, NK cells, NKT cells, CD8+ T cells, ^^ T-cells, macrophages, and type 3-innate lymphoid cells [D.J. Cua and C.M. Tato, Nat Rev Immunol 2010, 10, 479-489; W. Jin and C. Dong, Emerging Microbes & Infections 2013, 2, e60]. Cytokines IL-17A, IL-17F, and IL-17AF bind to common heteromeric receptor complexes IL-17RA and IL-17RC, albeit with different affinities, and although various cell types have been reported to express the IL-17RA subunit, the highest responses to IL-17A come from epithelial cells, endothelial cells, keratinocytes, and fibroblasts [T.A. Moseley et al., Cytokine Growth Factor Reviews. 2003, 14, 155-174; S.L. Gaffen, Nature Rev Immunol 2009, 9, 556-567; R.M. Onishi and S.L. Gaffen, Immunology 2010, 129, 311- 321]. Binding of IL-17A to its receptor activates various signal transduction pathways such as nuclear factor (NF)-^B, phosphoinositide 3-kinase (PI3K), activator protein (AP1), CCAAT / enhancer-binding protein (C / EBP), and mitogen-activated protein kinase (MAPK) leading to pro-inflammatory gene expression and the secretion of various pro-inflammatory cytokines including IL-1^, IL-6, IL-8, TNF^, G-CSF, PGE2, and IFN-^ as well as numerous chemokines and other effectors [S.L. Gaffen, Arthritis Research & Therapy 2004, 6, 240- 247; S.L. Gaffen, Nature Rev Immunol 2009, 9, 556-567; R.M. Onishi and S.L. Gaffen, Immunology 2010, 129, 311-321]. The attraction and activation of cells of the innate immune system to the site of inflammation completes the induction of an inflammatory loop which may also be mediated cooperatively with other cytokines such as TNF^, IFN-^, and IL-1^ [S.L. Gaffen, Arthritis Research & Therapy 2004, 6, 240-247]. These IL-17 mediated biological processes have been implicated in the pathology of many human diseases with an immune component or autoimmune pathology, such as psoriasis, ankylosing spondylitis, axial spondyloarthritis, psoriatic arthritis, eczema, enthesitis-related arthritis, asthma (including severe asthma), chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary fibrosis, ulcerative colitis, Crohn's disease, atopic dermatitis, contact dermatitis, dermatomyositis, myocarditis, uveitis, exophtalmos, autoimmune thyroiditis, Peyronie’s disease, coeliac disease, gall bladder disease, Pilonidal disease, peritonitis, multiple sclerosis, Guillan-Bar Syndrome, irritable bowel syndrome, inflammatory bowel disease, Castleman’s disease, pelvic inflammatory disease, systemic onset juvenille idiopathic arthritis (JIA), rheumatoid arthritis, giant cell arteritis, graft versus host disease, discoid lupus erythematosus, systemic lupus erythematosus, lupus nephritis, vasculitis, insulin dependent diabetes type I, autoimmune diabetes, Necrobiosis Lipoidica Diabeticorum, Pyoderma Gangrenosum, Hidradenitis Suppurativa, Papulopustular Rosacea, Lichen Planus (Solimani et al (2019) Front Immunol. 10:1808), and also in cancer (Bartlett, HS; Million, RP (2015) Nat. Rev. Drug Discovery 14:11-12; Santibanez, JF; Bjelica, S (2018) Recent Pat Anticancer Drug Discov. 13(2):133-144). In addition, due to the emerging role of neuroinflammation in neurodegeneration, IL-17 has also been implicated in the progression of neurodegenerative disorders such as Alzheimer’s disease (Cristiano et al (2019) Br J Pharmacol. 176(18):3544-3557) and Parkinson’s disease (Storelli et al, (2019) Front Neurol.24;10:13). An association between serum levels of IL-17 at the time of admission to the intensive care unit and the development of sepsis has also been observed suggesting increased IL-17 may increase the susceptibility for septic complications and endotoxic shock associated with infection [Ahmed et al., Eur J Trauma Emerg Surg 2018, 44(4):621-626]. Its role in sepsis has also been suggested to extend to patients with sepsis-induced Acute Respiratory Distress Syndrome (ARDS) and acute lung injury [Ding et al., Oncotarget 2017, 8(55):93704-93711]. Recently inhibition of IL-17 has also been suggested to be used to prevent acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) [Pacha, Sallman & Evans., Nat Rev Immunol 2020, 1:1-2]. Pre-clinical studies have demonstrated that IL-17A (as well as IL-17F and IL-17C) is elevated in psoriatic skin [N. J. Wilson et al., Nat Immunol 2007, 8, 950-957; L.C. Zaba et al., J Exp Med 2007, 204, 3183-3194; C. Ortega et al, J Leukocyte Biol 2009, 86, 435- 443; C. Johansen et al., Br J Dermatol 2009, 160, 319-324]. Th17 cells in the peripheral circulation and lesional skin of patients with psoriasis have also been shown to positively correlate with disease severity as measured by the Psoriasis Area and Severity Index (PASI) score [L. Zhang et al., Clin Immunol 2010, 135, 108-117]. Serum IL-17A levels are also significantly correlated with PASI score [H. Takahashi et al., Clin Exp Dermatol 2010, 35, 645-649; S.B. Yilmaz et al. Arch Dermatol Res 2012, 304, 465-469; M. Caproni et al., J Clin Immunol 2009, 29, 210-214]. Animal model studies supported the hypothesis that targeting the IL-17A pathway would be an effective treatment for psoriasis [L. van der Fits et al., J Immunol 2009, 182, 5836-5845; K. El Malki et al., J Investig Dermatol 2013, 133, 441-451; J. Skepner et al., J Immunol 2014, 192, 2564-2575], and clinical results with antibodies to IL-17A or IL-17RA delivered the ultimate validation with excellent efficacy being observed [R.G. Langley et al., N Engl J Med 2014, 371, 326-338; K.B. Gordon et al., N Engl J Med 2016, 375, 345- 356; A.S. Lonnberg et al., Clin Cosmet Investig Dermatol 2014, 7, 251-259; S. Coimbra et al., Core Evid 2014, 9, 89-97; M. Lebwohl et al., N Engl J Med 2015, 373, 1318-1328]. Elevated levels of IL-17A or IL-17F have been reported in a number of other diseases including Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS), Systemic Lupus Erythematosus (SLE), Inflammatory Bowel Disease (IBD), Multiple Sclerosis (MS), bone erosion, intraperitoneal abscesses, allograft rejection, angiogenesis, atherosclerosis, and asthma [e.g., S.L. Gaffen, Arthritis Research & Therapy 2004, 6, 240-247; L.A. Tesmer et al., Immunol Rev 2008, 223, 87-113; US Publ No 20080269467]. The anti-IL-17A therapeutic antibodies Secukinumab and Ixekizumab have shown evidence of positive effects in treating palmoplantar and nail psoriasis; [A. Gottlieb et al., J Am Acad Dermatol 2016, 76, 70-80; A. Menter et al., J Eur Acad Dermatol Venereol 2017, 31, 1686-1692; C. Paul et al., J Eur Acad Dermatol Venereol 2014, 28, 1670-1675]; PsA [P. Mease et al., Ann Rheum Dis 2018, 77, 890-897; P. Nash et al., Lancet 2017, 389, 2317-2327] and AS [K. Pavelka et al., Arthritis Res Ther 2017, 19, 285; A. Deodhar et al., Arthritis Rheumatol 2018, doi:10.1002 / art.40753]. A proof-of-concept study with Secukinumab in MS has also shown encouraging signs of efficacy [E. Havdrova et al., J Neurol 2016, 263, 1287-1295]. IL-17A expression has been shown to be increased in SLE patients and correlated with disease severity [Y. Wang et al., Clin Exp Immunol 2009, 159, 1-10; X.Q. Chen et al., J Clin Immunol 2010, 30, 221-225]. In addition, IL-17A has been associated with ocular surface disorders such as DES [PCT publications WO2009089036, WO2010062858, and WO2011163452; C.S. De Paiva et al., Mucosal Immunol 2009, 2, 243-253] and Th17 cells have been shown to be elevated in active uveitis and scleritis [A. Amadi-Obi et al., Nat Med 2007, 13, 711-718]. IL-17A levels in tears were associated with clinical severity of dry eye in patients with a range of systemic autoimmune or inflammatory diseases including Sjögren’s syndrome, Stevens-Johnson syndrome (SJS), SLE, filamentary keratitis, DES, Meibomian gland dysfunction (MGD), and Graft-versus-Host disease (GVHD) [M.H. Kang et al., J Korean Med Sci 2011, 26, 938-944]. Several studies have demonstrated that IL-17A is overexpressed in patients with a range of cancers including gastric carcinoma, medulloblastoma, multiple myeloma, colorectal carcinoma, Non-Small-Cell Lung Cancer (NSCLC), breast cancer, hepatocellular carcinoma (HCC), and thyroid cancer [X. Meng et al., Turk J Gastroenterol 2018, 29, 45-51; P. Zhou et al., J Int Med Res 2010, 38, 611-619; D. Lemancewicz et al., Med Sci Monit 2012, 18, BR 54-59; S. Le Gouvello et al., Gut 2008, 57, 772-779; B. Pan et al., Sci Rep 2015, 5, 16053; T. Welte and X. H-F. Zhang, Mediators Inflammation 2015, 804347; J-F. Tu et al., Medicine (Baltimore) 2016, 95, e3220; D.F.G. Carvalho et al., Oncol Lett 2017, 13, 1925-1931]. Increased levels of IL-17A have been shown to correlate with poor prognosis in several cancer types including malignant thyroid tumor, breast cancer, pancreatic carcinoma, gastric cancer, NSCLC, colorectal cancer, and head and neck cancer [S. Punt et al., OncoImmunol 2015, 4, e984547; D.F.G. Carvalho et al., Oncol Lett 2017, 13, 1925-1931; W-C. Chen et al., Histopathology 2013, 63, 225-233; C. Xu et al., Biomarkers 2014, 19, 287-290; Y. Yamada et al., J Surg Res 2012, 178, 685-691; S. He et al., Int J Mol Sci 2011, 12, 7424-7437; J-Y. Tseng et al., Clin Cancer Res 2014, 20, 2885-2897; M-H. Lee et al., Oncotarget 2018, 9, 9825-9837]. Taken together, modulation of the IL-17A pathway, in particular modulation of IL- 17A activity through inhibition of its interaction with the receptor IL-17RA, may be considered a target for the treatment of conditions relating to the immune system and inflammation, cancer, and neurodegenerative disorders. WO 2013 / 116682, WO 2014 / 066726, and WO 2018 / 229079 describe classes of chemical compounds that are stated to modulate the activity of IL-17 and to be useful in the treatment of medical conditions, including inflammatory disease. Nevertheless, there is an ongoing need for compounds capable of attenuating IL- 17A activity. SUMMARY In one aspect, the present disclosure provides a compound, or a pharmaceutically acceptable salt thereof as defined herein. In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. In another aspect, the present disclosure relates to a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as defined herein, for use in therapy. In another aspect, the present disclosure relates to a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as defined herein, for use in the treatment of diseases or disorders associated with IL-17A activity. In another aspect, the present disclosure relates to the use of a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of diseases or disorders associated with IL-17A activity. In another aspect, the present disclosure relates to a method of treating a disease or disorder associated with IL-17A activity, said method comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as defined herein. Examples of diseases or disorders associated with IL-17A activity include diseases with an immune component or autoimmune pathology (such as psoriasis, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis), cancer, and neurodegenerative disorders. In another aspect, the present disclosure provides a compound, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as defined herein, for use in the treatment of diseases with an immune component or autoimmune pathology (such as psoriasis, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis), cancer, and neurodegenerative disorders. In another aspect, the present disclosure provides the use of a compound, or a pharmaceutically acceptable salt, in the manufacture of a medicament for use in the treatment of diseases with an immune component or autoimmune pathology (such as psoriasis, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis), cancer, and neurodegenerative disorders. In another aspect, the present disclosure provides a method of treating diseases with an immune component or autoimmune pathology (such as psoriasis, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis), cancer, and neurodegenerative disorders, said method comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as defined herein. The present disclosure further provides a method of synthesising a compound, or a pharmaceutically acceptable salt thereof, as defined herein. In another aspect, the present disclosure provides a compound, or a pharmaceutically acceptable salt thereof, obtainable by, or obtained by, or directly obtained by a method of synthesis as defined herein. In another aspect, the present disclosure provides novel intermediates as defined herein which are suitable for use in any one of the synthetic methods set out herein. Convenient, suitable, and optional features of any one particular aspect of the present disclosure are also convenient, suitable, and optional features of any other aspect. DETAILED DESCRIPTION Definitions Unless otherwise stated, the following terms used in the specification and claims have the following meanings set out below. It is to be appreciated that references to “treating” or “treatment” include prophylaxis as well as the alleviation of established symptoms of a condition. “Treating” or “treatment” of a state, disorder, or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder, or condition developing in a human that may be afflicted with or predisposed to the state, disorder, or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder, or condition, (2) inhibiting the state, disorder, or condition, i.e., arresting, reducing, or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease, i.e., causing regression of the state, disorder, or condition or at least one of its clinical or subclinical symptoms. A “therapeutically effective amount” means the amount of a compound that, when administered to a mammal for treating a disease, is sufficient to effect such treatment for the disease. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity, and the age, weight, etc., of the mammal to be treated. In this specification the term “alkyl” refers to a monovalent saturated aliphatic hydrocarbon group and includes both straight and branched chain alkyl groups. References to individual alkyl groups such as “propyl” are specific for the straight chain version only and references to individual branched chain alkyl groups such as “isopropyl” are specific for the branched chain version only. For example, “C1-6alkyl” includes C1-4alkyl, C1-3alkyl, propyl, isopropyl, and t-butyl. A similar convention applies to other radicals, for example “phenylC1-6alkyl” includes phenylC1-4alkyl, benzyl, 1-phenylethyl, and 2-phenylethyl. An “alkoxy” group is a monovalent group consisting of an alkyl group singly bonded to oxygen and in which the free valency resides on the oxygen atom. The term includes both straight and branched chain alkyl groups singly bonded to oxygen. For example, “C1-3alkoxy” comprises methoxy, ethoxy, and isopropoxy. The term “Cm-n” used as a prefix, refers to any group having m to n carbon atoms. “Cycloalkyl” means a monovalent saturated hydrocarbon group which comprises a ring in which all of the ring atoms are carbon atoms. The cycloalkyl group may contain 3 to 8 carbon atoms and includes bridged and spiro-linked ring structures. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicycle[2.2.2]octane, bicycle[2.1.1]hexane, bicycle[1.1.1]pentane, and bicyclo[2.2.1]heptyl. The term “halo” refers to fluoro, chloro, bromo, or iodo. The term “haloalkyl” or “haloalkoxy” is used herein to refer to an alkyl or alkoxy group respectively in which one or more hydrogen atoms have been replaced by halogen (e.g., fluorine) atoms. Examples of haloalkyl and haloalkoxy groups include fluoroalkyl and fluoroalkoxy groups such as –CHF2, –CH2CF3, or perfluoroalkyl / alkoxy groups such as – CF3, –CF2CF3, or –OCF3. The term “heterocyclyl”, “heterocyclic”, or “heterocycle” means a non-aromatic saturated or partially unsaturated monocyclic, fused, bridged, or spiro bicyclic heterocyclic ring system(s). Monocyclic heterocyclic rings contain from about 3 to 12 (suitably from 3 to 7) ring atoms, with from 1 to 5 (suitably 1, 2, or 3) heteroatoms selected from nitrogen, oxygen, or sulfur in the ring. Bicyclic heterocycles contain from 7 to 17 member atoms, suitably 7 to 12 member atoms, in the ring. Bicyclic heterocyclic(s) rings may be fused, spiro, or bridged ring systems. Examples of heterocyclic groups include cyclic ethers such as oxiranyl, oxetanyl, tetrahydrofuranyl, dioxanyl, and substituted cyclic ethers. Heterocycles containing nitrogen include, for example, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrotriazinyl, tetrahydropyrazolyl, and the like. Typical sulfur containing heterocycles include tetrahydrothienyl, dihydro-1,3-dithiol, tetrahydro-2H-thiopyran, and hexahydrothiepine. Other heterocycles include dihydro-oxathiolyl, tetrahydro-oxazolyl, tetrahydro-oxadiazolyl, tetrahydrodioxazolyl, tetrahydro-oxathiazolyl, hexahydrotriazinyl, tetrahydro-oxazinyl, morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl, octahydrobenzimidazolyl, and octahydrobenzothiazolyl. For heterocycles containing sulfur, the oxidized sulfur heterocycles containing SO or SO2 groups are also included. Examples include the sulfoxide and sulfone forms of tetrahydrothienyl and thiomorpholinyl such as tetrahydrothiene 1,1-dioxide and thiomorpholinyl 1,1-dioxide. A suitable value for a heterocyclyl group which bears 1 or 2 oxo (=O) or thioxo (=S) substituents is, for example, 2-oxopyrrolidinyl, 2-thioxopyrrolidinyl, 2-oxoimidazolidinyl, 2-thioxoimidazolidinyl, 2-oxopiperidinyl, 2,5-dioxopyrrolidinyl, 2,5-dioxoimidazolidinyl, or 2,6-dioxopiperidinyl. Particular heterocyclyl groups are saturated monocyclic 3 to 7 membered heterocyclyls containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, or sulfur, for example azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, tetrahydrothienyl, tetrahydrothienyl 1,1- dioxide, thiomorpholinyl, thiomorpholinyl 1,1-dioxide, piperidinyl, homopiperidinyl, piperazinyl, or homopiperazinyl. Partially unsaturated heterocyclyl rings contain at least one double bond, such as 1 or 2 double bonds. Examples of partially unsaturated heterocyclyl rings include 1,6-dihydropyridinyl, 1,6-dihydropyridazinyl, and 2,3- dihydropyrrolyl. As the skilled person would appreciate, any heterocycle may be linked to another group via any suitable atom, such as via a carbon or nitrogen atom. Suitably, the term “heterocyclyl”, “heterocyclic”, or “heterocycle” will refer to 4, 5, 6, or 7 membered monocyclic rings as defined above. The term “bridged ring systems” means ring systems in which two rings share more than two atoms, see for example Advanced Organic Chemistry, by Jerry March, 4th Edition, Wiley Interscience, pages 131-133, 1992. Examples of bridged heterocyclyl ring systems include, for example azabicyclo[3.1.0]hexane, aza-bicyclo[2.2.1]heptane, 2-oxa- 5-azabicyclo[2.2.1]heptane, aza-bicyclo[2.2.2]octane, aza-bicyclo[3.2.1]octane, and quinuclidine. The term “heteroaryl” or “heteroaromatic” means an aromatic mono-, bi-, or polycyclic ring incorporating one or more (for example 1-4, particularly 1, 2, or 3) heteroatoms selected from nitrogen, oxygen, or sulfur. Typically, the heteroaryl ring will contain up to 3 heteroatoms, more usually up to 2, for example a single heteroatom. In one embodiment, the heteroaryl ring contains at least one ring nitrogen atom. The nitrogen atoms in the heteroaryl rings can be basic, as in the case of an imidazole or pyridine, or essentially non-basic as in the case of an indole or pyrrole nitrogen. In general, the number of basic nitrogen atoms present in the heteroaryl group, including any amino group substituents of the ring, will be less than five. Heteroaryl groups containing nitrogen atoms may be present as the corresponding N-oxides. Particular examples of such heteroaryl groups are pyridine N-oxides. Suitably, the term “heteroaryl” or “heteroaromatic” will refer to 5-or 6- membered monocyclic heteroaryl rings as defined above. Non-limiting examples of heteroaryl groups include oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, oxadiazolyl, tetrazolyl, pyridyl, and pyrimidinyl groups. Non-limiting examples of 5 membered heteroaryl groups include but are not limited to imidazolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, and tetrazolyl groups. Non-limiting examples of 6 membered heteroaryl groups include but are not limited to pyridyl, and pyrimidinyl groups. Abond terminating in a wavey line ” indicates an attachment point.The term “substituted” refers to replacement of a hydrogen atom (-H) in a parent group with an alternative atom or group (the substituent). One or more hydrogen atoms of the parent group may be replaced with one or more substituents in accordance with the normal rules of chemical valency. For example, where two hydrogen atoms are replaced, they may be bound to the same atom of the parent group (to introduce a substituent having a single divalent attachment point) or they may be bound to different atoms of the parent group (to introduce two substituents each having a single monovalent attachment point, or to introduce a single substituent having two monovalent attachment points). A parent group may have one, two, or three substituents. That is, the parent group may be mono-, di-, or tri-substituted. It is understood that where there are multiple substituents, the substituents chosen may be the same or different. Where numerical ranges are given, it is understood that the ranges are inclusive of the endpoints. The phrase “compound of the disclosure” means those compounds which are disclosed herein, both generically and specifically. Compounds of the Disclosure In a first aspect, the present disclosure provides a compound of Formula I, or a pharmaceutically acceptable salt thereof: wherein: R1is 5- or 6-membered heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, and oxo; R2is C1-3alkyl; R3is 5- or 6-membered monocyclic heteroaryl or phenyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from halo, C1-4alkyl, C1-3haloalkyl, C1-3haloalkoxy, and C3-6cycloalkyl; R4is independently selected at each instance from fluoro, chloro, bromo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, and C1-3haloalkoxy; R5is independently selected at each instance from fluoro, chloro and C1-3alkyl; n is 0, 1, 2 or 3; p is 0, 1 or 2. Particular compounds of the disclosure include, for example, compounds where R1, R2, R3, R4, R5, n, and p have any of the meanings defined herein before, or in any of paragraphs (1) to (52) hereinafter. For the avoidance of doubt, the present disclosure encompasses combinations of two or more substituent definitions as described in paragraphs (1) to (52): (1) R1is 5- or 6-membered nitrogen-containing heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, and oxo; (2) R1is a 5-membered heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, and oxo; (3) R1is a 5-membered nitrogen-containing heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, and oxo; (4) R1is a 5-membered nitrogen-containing heterocyclyl, which is saturated and is substituted with one to three substituents independently selected from halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, and oxo; (5) R1is a 5-membered nitrogen-containing heterocyclyl, which is saturated and is substituted with one or two substituents independently selected from halo, C1- 3haloalkyl, and oxo; (6) R1is a 6-membered heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, and oxo; (7) R1is a 6-membered nitrogen-containing heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, and oxo; (8) R1is a 6-membered nitrogen-containing heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3haloalkyl, and oxo; (9) R1is 5- or 6-membered heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3haloalkyl, and oxo; (10) R1is 5- or 6-membered nitrogen-containing heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3haloalkyl, and oxo; (11) R1is 5- or 6-membered heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from fluoro, trifluoromethyl, and oxo; (12) R1is 5- or 6-membered nitrogen-containing heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from fluoro, trifluoromethyl, and oxo; (13) R1is selected from: , wherein is the point of attachment to the rest of the compound of Formula I, and wherein R1is further substituted with one or two substituents independently selected from fluoro, methyl, methoxy, and C1-3fluoroalkyl; (14) R1is selected from: , wherein is the point of attachment to the rest of the compound of Formula I, and wherein R1is further substituted with one or two substituents independently selected from fluoro and trifluoromethyl; (15) R1is selected from: , wherein is the point of attachment to the rest of the compound of Formula I; (16) R1is selected from: , wherein is the point of attachment to the rest of the compound of Formula I; (17) R1is: , wherein is the point of attachment to the rest of the compound of Formula I; (18) R2is methyl, ethyl, n-propyl, or isopropyl; (19) R2is methyl, or ethyl; (20) R2is methyl; (21) R3is 5- or 6-membered nitrogen-containing monocyclic heteroaryl or phenyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from halo, C1-4alkyl, C1-3haloalkyl, C1-3haloalkoxy, and C3-6cycloalkyl; (22) R3is 5- or 6-membered nitrogen-containing monocyclic heteroaryl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from halo, C1-4alkyl, C1-3haloalkyl, C1-3haloalkoxy, and C3-6cycloalkyl; (23) R3is selected from phenyl, pyrazolyl, oxadiazolyl, isoxazolyl, and pyridyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from halo, C1-4alkyl, C1-3haloalkyl, C1-3haloalkoxy, and C3- 6cycloalkyl; (24) R3is 5- or 6-membered monocyclic heteroaryl or phenyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from fluoro, C1-3alkyl, C1-2fluoroalkyl, C1-2fluoroalkoxy, and C3-4cycloalkyl; (25) R3is 5-membered monocyclic heteroaryl or phenyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from fluoro, C1-3alkyl, C1-2fluoroalkyl, C1-2fluoroalkoxy, and C3-4cycloalkyl; (26) R3is selected from phenyl, pyrazolyl, oxadiazolyl, isoxazolyl, and pyridyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from fluoro, C1-3alkyl, C1-2fluoroalkyl, C1-2fluoroalkoxy, and C3-4cycloalkyl; (27) R3is 5- or 6-membered monocyclic heteroaryl or phenyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from fluoro, methyl, ethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethoxy, and cyclopropyl; (28) R3is selected from phenyl, pyrazolyl, oxadiazolyl, isoxazolyl, and pyridyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from fluoro, methyl, ethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethoxy, and cyclopropyl; (29) R3is selected from phenyl, pyrazolyl, oxadiazolyl, and isoxazolyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from fluoro, methyl, ethyl, difluoromethyl, trifluoromethyl, 2,2,2- trifluoroethoxy, and cyclopropyl; (30) R3is selected from phenyl, or one of the following heteroaryl groups: , wherein is the point of attachment to the rest of the compound of Formula I, and wherein R3is unsubstituted or substituted with one or two substituents independently selected from halo, C1-4alkyl, C1-3haloalkyl, C1-3haloalkoxy, and C3-6cycloalkyl; (31) R3is selected from phenyl, or one of the following heteroaryl groups: , wherein is the point of attachment to the rest of the compound of Formula I, and wherein R3is unsubstituted or substituted with one or two substituents independently selected from fluoro, methyl, ethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethoxy, and cyclopropyl; (32) R3is selected from: , wherein is the point of attachment to the rest of the compound of Formula I, and wherein R6is independently selected at each instance from hydrogen, halo, C1-4alkyl, C1-3haloalkyl, C1-3haloalkoxy, and C3-6cycloalkyl; (33) R3is selected from: , wherein is the point of attachment to the rest of the compound of Formula I, and wherein R6is independently selected at each instance from hydrogen, fluoro, methyl, ethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethoxy, and cyclopropyl; (34) R3is selected from: , wherein is the point of attachment to the rest of the compound of Formula I, and wherein R6is independently selected at each instance from hydrogen, fluoro, methyl, ethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethoxy, and cyclopropyl; (35) R3is selected from: , wherein is the point of attachment to the rest of the compound of Formula I; (36) R4is independently selected at each instance from fluoro, chloro, C1-3alkyl, and C1- 3haloalkyl; (37) R4is independently selected at each instance from fluoro, chloro, bromo, methyl, ethyl, and C1-3fluoroalkyl; (38) R4is independently selected at each instance from fluoro, chloro, bromo, methyl, ethyl, methoxy, trifluoromethyl, difluoromethyl, trifluoromethoxy, and difluoromethoxy; (39) R4is independently selected at each instance from fluoro, chloro, bromo, methyl, ethyl, and trifluoromethyl; (40) R4is independently selected at each instance from fluoro, chloro, bromo, methyl, and trifluoromethyl; (41) R4is independently selected at each instance from fluoro, chloro, methyl, and trifluoromethyl; (42) R5is independently selected at each instance from fluoro, chloro, and methyl; (43) R5is independently selected at each instance from fluoro and methyl; (44) n is 0, 1, or 2; (45) n is 1 or 2; (46) n is 0; (47) n is 1; (48) n is 2; (49) R4is independently selected at each instance from fluoro, chloro, bromo, methyl, and trifluoromethyl, and n is 1 or 2; (50) p is 0 or 1; (51) p is 1; (52) p is 0; In one embodiment, R1is as defined in any one of paragraphs (1) to (17) above. In a further embodiment, R1is as defined in any one of paragraphs (13) to (17) above. In one embodiment, R2is as defined in any one of paragraphs (18) to (20) above. In a further embodiment, R2is as defined in paragraph (20) above. In one embodiment, R3is as defined in any one of paragraphs (21) to (35) above. In a further embodiment, R3is as defined in any one of paragraphs (30) to (35) above. In one embodiment, R4is as defined in any one of paragraphs (36) to (41) above. In a further embodiment, R4is as defined in paragraph (41) above. In one embodiment, R5is as defined in any one of paragraphs (42) to (43) above. In a further embodiment, R5is as defined in paragraph (43) above. In one embodiment, n is as defined in any one of paragraphs (44) to (48) above. In a further embodiment, n is as defined in paragraph (45) above. In one embodiment, p is as defined in any one of paragraphs (50) to (52) above. In a further embodiment, p is as defined in paragraph (52) above. In an embodiment, there is provided a compound according to any one of formula IA to IH (sub-formulae of formula I), or a pharmaceutically acceptable salt thereof: and the same preferences apply. In an embodiment, there is provided a compound according to any one of formula IA to IH, or a pharmaceutically acceptable salt thereof, wherein R1is as defined in any one of paragraphs (13) to (17) above; R2is as defined in paragraph (20) above; R3is as defined in any one of paragraphs (30) to (35) above; R4is as defined in paragraph (41) above; n is as defined in paragraph (45) above; and / or p is as defined in paragraph (52) above. Particular compounds of the present disclosure include any one of the following compounds, or a pharmaceutically acceptable salt thereof: N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide; N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; 1-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H-pyrazole-5- carboxamide; 4-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)I;midazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1,2,5-oxadiazole- 3-carboxamide 4-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-3- carboxamide; N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole- 3-carboxamide; N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3-methylisoxazole- 4-carboxamide; 4-ethyl-N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-3- carboxamide; N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; 4-ethyl-N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole- 3-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; 1-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H-pyrazole-5- carboxamide; N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; 4-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1,2,5-oxadiazole-3- carboxamide; 4-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-3- carboxamide; N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole- 3-carboxamide; 3-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-4- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3-ethylisoxazole-4- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3-methylisoxazole- 4-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(2-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; 1-ethyl-N-((S)-1-(2-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole- 3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-methylisoxazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(p-tolyl)ethyl)-4-methylisoxazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(p-tolyl)ethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-1-methyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4-methyl- 1,2,5-oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4- methylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4- ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)-4-(2,2,2-trifluoroethoxy)- 1,2,5-oxadiazole-3-carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)benzamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole-3- carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-cyclopropyl-1,2,5-oxadiazole- 3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; 4-cyclopropyl-N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-1,2,5-oxadiazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4-methylisoxazole- 3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)benzamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-cyclopropyl-1,2,5-oxadiazole- 3-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole-3- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2- yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide; 1-ethyl-N-((S)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole-3- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-4-fluoro-1H-pyrazole-5- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-2-fluorobenzamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-2-fluoro-6-methylbenzamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-3-methylpicolinamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-2-fluoro-6- (trifluoromethyl)benzamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-3-(difluoromethyl)picolinamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4- methylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; 4-cyclopropyl-N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)picolinamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3-carboxamide; or N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)picolinamide. The various functional groups and substituents making up the compounds of the present disclosure are typically chosen such that the molecular weight of the compound does not exceed 1000. More usually, the molecular weight of the compound will be less than 750, for example less than 700, or less than 650, or less than 600. A suitable pharmaceutically acceptable salt of a compound of the disclosure is, for example, an acid-addition salt of a compound of the disclosure which is sufficiently basic, for example, an acid-addition salt with, for example, an inorganic or organic acid, for example hydrochloric, hydrobromic, sulfuric, phosphoric, trifluoroacetic, formic, citric, or maleic acid. In addition a suitable pharmaceutically acceptable salt of a compound of the disclosure which is sufficiently acidic is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium or magnesium salt, an ammonium salt, or a salt with an organic base which affords a physiologically-acceptable cation, for example a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine, or tris-(2-hydroxyethyl)amine. Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers”, and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog (Cahn, Ingold & Prelog, Angewandte Chemie Intl. Edtn (1966) 5(4), 385-415), or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+)- or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. The compounds of this disclosure may possess one or more asymmetric centers. Apart from the stereochemistry as specified in Formula I, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof, at any other asymmetric centers that may be present. The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see discussion in Chapter 4 of “Advanced Organic Chemistry”, 4th edition J. March, John Wiley and Sons, New York, 2001), for example by synthesis from optically active starting materials or by resolution of a racemic form. Some of the compounds of the disclosure may have geometric isomeric centres (E- and Z- isomers). It is to be understood that the present disclosure encompasses all optical, diastereoisomers, and geometric isomers and mixtures thereof. The present disclosure also encompasses compounds of the disclosure as defined herein which comprise one or more isotopic substitutions. For example, H may be in any isotopic form, including1H,2H (D), and3H (T); C may be in any isotopic form including12C,13C, and14C; and O may be in any isotopic form, including16O and18O; and the like. It is also to be understood that certain compounds of the disclosure may exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the disclosure encompasses all such solvated forms. It is also to be understood that certain compounds of the disclosure may exhibit polymorphism, and that the disclosure encompasses all such forms. Compounds of the disclosure may exist in a number of different tautomeric forms and references to compounds of the disclosure include all such forms. For the avoidance of doubt, where a compound can exist in one of several tautomeric forms, and only one is specifically described or shown, all others are nevertheless embraced by compounds of the disclosure. Examples of tautomeric forms include keto-, enol-, and enolate-forms, as in, for example, the following tautomeric pairs: keto / enol (illustrated below), imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, and nitro / aci-nitro. keto enol enolateCompounds of the disclosure containing an amine function may also form N- oxides. A reference herein to a compound of the Formula I that contains an amine function also includes the N-oxide. Where a compound contains several amine functions, one or more than one nitrogen atom may be oxidised to form an N-oxide. Particular examples of N-oxides are the N-oxides of a tertiary amine or a nitrogen atom of a nitrogen-containing heterocycle. N-Oxides can be formed by treatment of the corresponding amine with an oxidizing agent such as hydrogen peroxide or a per-acid (e.g., a peroxycarboxylic acid), see for example Advanced Organic Chemistry, by Jerry March, 4th Edition, Wiley Interscience, pages. More particularly, N-oxides can be made by the procedure of L. W. Deady (Syn. Comm.1977, 7, 509-514), in which the amine compound is reacted with m- chloroperoxybenzoic acid (MCPBA), for example, in an inert solvent such as dichloromethane. The compounds of the disclosure may be administered in the form of a pro-drug which is broken down in the human or animal body to release a compound of the disclosure. A pro-drug may be used to alter the physical properties or the pharmacokinetic properties of a compound of the disclosure. A pro-drug can be formed when the compound of the disclosure contains a suitable group or substituent to which a property-modifying group can be attached. Examples of pro-drugs include in vivo cleavable ester derivatives that may be formed at a carboxy group or a hydroxy group in a compound of the disclosure and in-vivo cleavable amide derivatives that may be formed at a carboxy group or an amino group in a compound of the disclosure. Accordingly, the present disclosure includes those compounds of Formula I as defined hereinbefore when made available by organic synthesis and when made available within the human or animal body by way of cleavage of a pro-drug thereof. Accordingly, the present disclosure includes those compounds of Formula I that are produced by organic synthetic means and also such compounds that are produced in the human or animal body by way of metabolism of a precursor compound, that is a compound of the Formula I may be a synthetically-produced compound or a metabolically-produced compound. Synthesis In the description of the synthetic methods described below and in the referenced synthetic methods that are used to prepare the starting materials, it is to be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment, and workup procedures, can be selected by a person skilled in the art. It is understood by one skilled in the art of organic synthesis that the functionality present on various portions of the molecule must be compatible with the reagents and reaction conditions utilised. Necessary starting materials may be obtained by standard procedures of organic chemistry. The preparation of such starting materials is described in conjunction with the following representative process variants and within the accompanying Examples. Alternatively, necessary starting materials are obtainable by analogous procedures to those illustrated which are within the ordinary skill of an organic chemist. It will be appreciated that during the synthesis of the compounds of the disclosure in the processes defined below, or during the synthesis of certain starting materials, it may be desirable to protect certain substituent groups to prevent their undesired reaction. The skilled chemist will appreciate when such protection is required, and how such protecting groups may be put in place and later removed. For examples of protecting groups see one of the many general texts on the subject, for example, “Protecting groups in Organic Synthesis (3rdEd), John Wiley & Sons, NY (1999)”, T. Greene & P. Wuts. Protecting groups may be removed by any convenient method described in the literature or known to the skilled chemist as appropriate for the removal of the protecting group in question, such methods being chosen so as to effect removal of the protecting group with the minimum disturbance of groups elsewhere in the molecule. Thus, if reactants include, for example, groups such as amino, carboxy, or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein. By way of example, a suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl, ethoxycarbonyl, or tert- butoxycarbonyl group, an arylmethoxycarbonyl group, for example benzyloxycarbonyl, or an aroyl group, for example benzoyl. The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group may be removed by, for example, hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively, an acyl group such as a tert-butoxycarbonyl group may be removed, for example, by treatment with a suitable acid as hydrochloric, sulfuric, or phosphoric acid or trifluoroacetic acid, and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example BF3•OEt2. A suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group which may be removed by treatment with an alkylamine, for example dimethylaminopropylamine, or with hydrazine. The person skilled in the art will recognise that the compounds of the disclosure may be prepared, in known manner, in a variety of ways. Compounds of Formula I can be prepared by the methods given below, by the methods given in the experimental, or by analogous methods. The routes described are merely illustrative of some of the methods that can be employed for the synthesis of compounds of Formula I, and the person skilled in the art will appreciate that the order of the reaction steps is not limited to those described. It will also be appreciated that the assignment of nucleophile and electrophile is not limited to that described herein, and in some cases it may be appropriate for the assignment to be reversed. Different approaches to synthetic chemistry strategy are described in “Organic Synthesis: The Disconnection Approach”, 2ndedition, S. Warren and P. Wyatt (2008). A compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, n and p are as previously defined may be prepared using standard acid activation methods like acid chloride, HOBt, HATU, HBTU, TOTU, EDCI, PyBOP, 1-chloro- N,N,2-trimethyl-1-propenylamine or 1-propanephosphonic acid anhydride under basic conditions, e.g. diisopropylethylamine, triethylamine or the like, or neutral conditions, in aprotic solvents like DMF, DMSO, DCM, acetonitrile, or the like by coupling the activated acid (II) to the amine (III), as shown in Scheme A. Scheme A Compounds of the general formula (III) derived from compounds of the general formula (IV) can be obtained by cleaving the protecting group P, which might be an amino protecting group that is cleaved under specific conditions like BOC with HCl in dioxane or other suitable solvents, with TFA without solvent or in DCM or other suitable solvents, with trimethylsilyl iodide in DCM, like CBZ with catalytic hydrogenation in methanol or ethanol or with trimethylsilyl iodide in DCM, or like FMOC with secondary amines like morpholine in suitable solvents like DMF, dioxane, methanol or ethanol. Using standard amide formation methods as described above compounds of the general formula (IV) can be obtained from compounds of the general formula (VI) and amino acids of the formula (V). The respective substituents in formula (I) to (VI) are as defined previously. Compounds of the general formula (I) can also be prepared using standard acid activation methods like acid chloride, HOBt, HATU, HBTU, TOTU, EDCI, PyBOP, 1-chloro- N,N,2-trimethyl-1-propenylamine or 1-propanephosphonic acid anhydride under basic conditions, e.g. diisopropylethylamine, triethylamine or the like, or neutral conditions, in aprotic solvents like DMF, DMSO, DCM, acetonitrile, or the like by coupling the activated acid (VII) to the amine (VI), as shown in Scheme B. Compounds of the general formula (VII) can be obtained from esters of the general formula (VIII) and alkyl groups Z being preferably methyl or ethyl that are preferably cleaved by lithium, sodium or potassium hydroxide or tert. butyl that is preferably cleaved by HCl in dioxane, TFA, TFA / DCM or TMSI / DCM. Amides of the general formula (VIII) can be obtained by coupling acids of the general formula (II) to amines of the general formula (IX) using methods described above. The respective substituents in formula (I) to (IX) are defined as above. Scheme C The preparation of compounds of the general formula (VI) is illustrated in Scheme C by the preparation of (4S)-1-[1-(2-amino-4-pyridyl)-2-methoxy-ethyl]-4-(trifluoromethyl)- imidazolidin-2-one - formula (VIa). This compound can be obtained by cleavage of the respective protecting group P of compounds of the general formula (Xa) under conditions as described in Scheme A. Compounds of the general formula (Xa) can be obtained by cyclisation of compounds of the general formula (XIa) in the presence of carbonyl donating reagents like CDI, phosgene, triphosgene and the like in an aprotic solvent like THF, dioxane or DMF preferably in the presence of a base like TEA or DIPEA and at temperatures ranging between RT and 80°C, preferably 60-70°C. Compounds of the general formula (XIa) can be synthesised from compounds of the general formula (XIIIa) and (2S)-3,3,3-trifluoropropane-1,2-diamine dihydrochloride (XIIa) by reductive amination in a two-step one-pot procedure. In the first step the imine is formed in protic or aprotic solvents like isopropanol or DCM at temperatures ranging from RT to 40 (DCM) or 80°C (isopropanol) in the presence of a base like TEA or DIPEA especially if the amine is used as a salt like its hydrochloride salt. After imine formation the solvent is removed and the residue is dissolved in protic solvents like methanol or ethanol and an acid like acetic acid is added to adjust the pH around 5. As reducing agents borohydrates are used, preferably sodium cyanoborohydride or sodium triacetoxyborohydride. Temperature ranges between RT and 50°C. Compounds of the general formula (XIIIa) are accessible from 1-(2-chloro- 4-pyridyl)-2-methoxy-ethanone (XIVa) by introduction of an amino or preferably protected amino group using preferably catalytic conditions like Pd(OAc)2and XPhos in the presence of a base like Cs2CO3in dioxane. 1-(2-Chloro-4-pyridyl)-2-methoxy-ethanone (XIVa) is accessible from 2-chloro-4-iodo-pyridine (XVa) after metal-halogen exchange with organic lithium reagents like nBuLi at low temperature like (-78°C) by acylation with derivatives with an activated acyl group like acyl chlorides, cyanides or N,O-dimethylhydroxylamides preferably N,O-dimethylhydroxylamides like N,2-dimethoxy-N-methylacetamide. Scheme D Alternatively, the preparation of compounds of the general formula (VI) is illustrated in Scheme D by the preparation of 1-[1-(2-amino-4-pyridyl)-2-methoxy-ethyl]- 5,5-difluoro-hexahydropyrimidin-2-one - formula (VIb). This compound can be obtained by cleavage of the respective protecting group P of compounds of the general formula (Xb) as described in Scheme A. Compounds of the general formula (Xb) can be prepared as described for compounds of the formula (Xa) from N1-(1-(2-chloropyridin-4-yl)-2- methoxyethyl)-2,2-difluoropropane-1,3-diamine, formula (XIb). The latter can be obtained from N1-(1-(2-chloropyridin-4-yl)-2-methoxyethyl)-2,2-difluoromalonamide (formula (XIIb)) by reduction with a solution of borane in THF. The difluoromaloamide (formula (XIIb)) is accessible from ethyl 3-((1-(2-chloropyridin-4-yl)-2-methoxyethyl)amino)-2,2-difluoro-3- oxopropanoate (formula (XIIIb)) by treatment with a solution of ammonia in methanol. The oxopropanoate (formula (XIIIb)) is obtained by treatment of 1-(2-chloropyridin-4-yl)-2- methoxyethan-1-amine (formula (XIVb)) with diethyl 2,2-difluoromalonate in methanol. The methoxyethan-1-amine (formula (XIVb)) can be accessed from (R)-N-(1-(2-chloropyridin- 4-yl)-2-methoxyethyl)-2-methylpropane-2-sulfinamide (formula (XVb)) by treatment with a solution of HCl in dioxane. Using tributyl(methoxymethyl)stannane and nBuLi in THF the sulfinamide of formula (XVb) is obtained from (R)-N-((2-chloropyridin-4-yl)methylene)-2- methylpropane-2-sulfinamide (formula (XVIb)) which is formed from 2- chloroisonicotinaldehyde (formula (XVIIb)) and (R)-2-methylpropane-2-sulfinamide in DCM in the presence of caesium carbonate. Alternatively, the preparation of compounds of the general formula (VI) is illustrated in Scheme E by the preparation of 3-(1-(2-aminopyridin-4-yl)-2-methoxyethyl)- 5-fluoropyridin-2(1H)-one - formula (VIc). This compound can be obtained from compounds of the general formula (Xc) by cleavage of the respective protecting group P and the methyl group of the methoxy group by a mixture of sodium iodide and trimethylsilyl iodide in acetonitrile at 60°C. Compounds of the general formula (Xc) are accessible from compounds of the general formula (XIc) by reduction with hydrogen in the presence of palladium on carbon in a mixture of methanol and DCM. Compounds of the general formula (XIc) are prepared from compounds of the general formula (XIIc) by reacting the triflate with 5-fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine in the presence of Pd(PPh3)4and sodium bicarbonate in a mixture of DME and water at 100°C. Compounds of the general formula (XIIc) are accessible by treatment of compounds of the general formula (XIIIc) with LiHMDS in THF, followed by a solution of 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide in N,N´-dimethyl- propylene urea and THF. As shown in Scheme F, protected amino acids of the formula (V) or the formula (IX), where ‘P’ and ‘Z’ are suitable protecting groups such as BOC, CBZ, or FMOC (‘P’), or methyl, ethyl, or tert. butyl (‘Z’), may be prepared from commercially available aryl glycines of the formula (XVIII) using standard protecting group chemistry known in the art. Scheme F To obtain diastereomeric pure compounds of the general formula (I) chiral separations are required. Preparative SFC or HPLC or a crystallization method can be used at different stages in the synthetic path. Preferably the separation of diastereomeric mixtures is done by chiral preparative SFC. If feasible diastereomers may also be separated by achiral preparative HPLC. Pharmaceutical Compositions The compounds of the disclosure will normally, but not necessarily, be formulated into pharmaceutical compositions prior to administration to a patient. Therefore, according to a further aspect of the disclosure there is provided a pharmaceutical composition which comprises a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, diluents, or carriers. The pharmaceutical compositions of the disclosure may be prepared and packaged in bulk form wherein a safe and effective amount of a compound of the disclosure can be extracted and then given to the patient such as with powders or syrups. Alternatively, the pharmaceutical compositions of the disclosure may be prepared and packaged in unit dosage form wherein each physically discrete unit contains a safe and effective amount of a compound of the disclosure. When prepared in unit dosage form, the pharmaceutical compositions of the disclosure typically contain from 1 mg to 1000 mg. The compositions of the disclosure may be in a form suitable for oral use (for example as tablets, capsules, caplets, pills, troches, powders, syrups, elixirs, suspensions, solutions, emulsions, sachets, and cachets), for topical use (for example as creams, ointments, lotions, solutions, pastes, sprays, foams, and gels), for transdermal administration (for example via transdermal patches), for administration by inhalation (for example as a dry powders, aerosols, suspensions, and solutions), for administration by insufflation (for example as a finely divided powder), or for parenteral administration (for example as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular, intraperitoneal, or intramuscular dosing, or as a suppository for rectal dosing). As used herein, "pharmaceutically acceptable excipient" means a pharmaceutically acceptable material, composition, or vehicle involved in giving form or consistency to the pharmaceutical composition. Each excipient must be compatible with the other ingredients of the pharmaceutical composition when commingled such that interactions which would substantially reduce the efficacy of the compound of the disclosure when administered to a patient, and interactions which would result in pharmaceutical compositions that are not pharmaceutically acceptable, are avoided. In addition, each excipient must of course be of sufficiently high purity to render it pharmaceutically acceptable. The pharmaceutical compositions of the disclosure are prepared using techniques and methods known to those skilled in the art. Some of the methods commonly used in the art are described in Remington's Pharmaceutical Sciences (Mack Publishing Company). An effective amount of a compound of the present disclosure for use in therapy of proliferative disease is an amount sufficient to symptomatically relieve in a warm- blooded animal, particularly a human, the symptoms of the proliferative disease, to slow the progression of the proliferative disease, or to reduce in patients with symptoms of the proliferative disease the risk of getting worse. The amount of active ingredient that is combined with one or more excipients to produce a single dosage form will necessarily vary depending upon the host treated and the particular route of administration. For example, a formulation intended for oral administration to humans will generally contain, for example, from 0.5 mg to 0.5 g of active agent (more particularly from 0.5 to 100 mg, for example from 1 to 30 mg) compounded with an appropriate and convenient amount of excipients which may vary from about 5 to about 98 percent by weight of the total composition. The size of the dose for therapeutic or prophylactic purposes of a compound of Formula I will naturally vary according to the nature and severity of the conditions, the age and sex of the animal or patient, and the route of administration, according to well-known principles of medicine. In using a compound of the disclosure for therapeutic or prophylactic purposes, it will generally be administered so that a daily dose in the range, for example, from 0.1 mg / kg to 75 mg / kg body weight is received, given if required in divided doses. In general, lower doses will be administered when a parenteral route is employed. Thus, for example, for intravenous or intraperitoneal administration, a dose in the range, for example, from 0.1 mg / kg to 30 mg / kg body weight will generally be used. Similarly, for administration by inhalation, a dose in the range, for example, from 0.05 mg / kg to 25 mg / kg body weight will be used. Oral administration may also be suitable, particularly in tablet form. Typically, unit dosage forms will contain about from 0.5 mg to 0.5 g of a compound of this disclosure. Routes of Administration The compounds of the disclosure or pharmaceutical composition comprising the active compound may be administered to a subject by any convenient route of administration, whether systemically, peripherally or topically (i.e., at the site of desired action). Routes of administration include, but are not limited to, oral (e.g., by ingestion); buccal; sublingual; transdermal (including, e.g., by a patch, plaster, etc.); transmucosal (including, e.g., by a gum, film etc.); intranasal (e.g., by nasal spray); ocular (e.g., by eyedrops); pulmonary (e.g., by inhalation or insufflation therapy using, e.g., via an aerosol, e.g., through the mouth or nose); rectal (e.g., by suppository or enema); vaginal (e.g., by pessary); parenteral (e.g., by injection, including subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, and intrasternal); by implant of a depot or reservoir (e.g., subcutaneously or intramuscularly). Therapeutic Uses and Applications The compounds of the present disclosure have been demonstrated to inhibit the binding of human IL-17A to its receptor, IL-17RA (in an AlphaLISA competition assay as described herein), with binding affinities typically being less than 30 ^M. Therefore, the compounds of Formula I, being potent modulators of human IL-17A activity, are potentially beneficial as therapeutic compounds in the treatment or prevention of human ailments occurring as a result of IL-17A activity. The compounds of the present disclosure, being high affinity binders to human IL-17A and potent modulators of human IL-17A activity, may be beneficial as pharmacological standards for use in the development of new biological tests and in the search for new pharmacological agents. Thus, the compounds of the present disclosure may be useful as radioligands in assays for detecting pharmacologically active compounds. Thus, in one aspect, the present disclosure relates to a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition as defined herein, for use in therapy. In another aspect, the present disclosure relates to a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition as defined herein, for use in the treatment of diseases or disorders mediated by IL-17A activity. In another aspect, the present disclosure relates to the use of a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for use in the treatment of diseases or disorders mediated by IL-17A activity. In another aspect, the present disclosure relates to a method of treating a disease or disorder in which IL-17A activity is implicated, said method comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of the disclosure as defined herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition as defined herein. Examples of particular diseases or disorders that the compounds of Formula I and their pharmaceutically acceptable salts may be used to treat include, but are not limited to, any one of the following: acute lung injury, Alzheimer’s Disease, ankylosing spondylitis, axial spondyloarthritis and other spondyloarthropathies, arthritis, asthma (including severe asthma), atopic dermatitis, autoimmune diabetes, other autoimmune disorders, autoimmune thyroiditis, bone resorption, cancer (both solid tumours (such as melanomas, sarcomas, squamous cell carcinomas, transitional call cancers, and ovarian cancers), and hematologic malignancies; in particular acute myelogenous leukemia, chronic lymphocytic leukemia, gastric cancer, and colon cancer), Castleman’s disease, contact dermatitis, Crohn’s Disease, chronic myelogenous leukemia, chronic obstructive pulmonary disease (COPD), coeliac disease, cystic fibrosis, dermatomyositis, discoid lupus erythematosus, eczema, enthesitis-related arthritis, endotoxic shock associated with infection, exophthalmos, fibrosing disorders including pulmonary fibrosis, gall bladder disease, giant cell arteritis, graft-versus-host disease, hepatoblastomas, hypochlorhydria, immune mediated inflammatory disorders of the central and peripheral nervous system such as multiple sclerosis and Guillain-Barr syndrome, Hidradenitis Suppurativa, inflammatory bowel disease, insulin dependent diabetes type I, intravascular coagulation, irritable bowel syndrome, Lichen Planus, liver fibrosis, lupus nephritis, lyme arthritis, meningoencephalitis, myocarditis, meningoencephalitis, Necrobiosis Lipoidica Diabeticorum, osteoporosis, pancreatitis, Papulopustular Rosacea, Parkinson’s disease, pelvic inflammatory disease, periodontitis, peritonitis, Peyronie’s Disease, Pilonidal disease, psoriasis, psoriatic arthritis (PsA), Pyoderma Gangrenosum, renal fibrosis, rheumatoid arthritis, scleroderma or systemic sclerosis, stroke, surgical adhesions, systemic lupus erythematosus (SLE), systemic onset juvenile idiopathic arthritis (JIA), trauma (surgery), transplant rejection, Type I diabetes, ulcerative colitis, uveitis, and vasculitis. Modulators of IL-17 activity may be administered to inhibit or reduce the severity of ocular inflammatory disorders (WO 2009 / 089036), for example ocular surface inflammatory disorders including Dry Eye Syndrome (DES). Consequently, the compounds in accordance with the present disclosure are useful in the treatment or prevention of an IL-17-mediated ocular inflammatory disorder, for example an IL-17- mediated ocular surface inflammatory disorder including Dry Eye Syndrome. Ocular surface inflammatory disorders include Dry Eye Syndrome, penetrating keratoplasty, corneal transplantation, lamellar or partial thickness transplantation, selective endothelial transplantation, corneal neovascularization, keratoprosthesis surgery, corneal ocular surface inflammatory disorders, conjunctival scarring disorders, ocular autoimmune disorders, Pemphigoid syndrome, Stevens-Johnson syndrome, ocular allergy, severe allergic (atopic) eye disease, conjunctivitis, and microbial keratitis. Particular categories of Dry Eye Syndrome include keratoconjunctivitis sicca (KCS), Sjogren syndrome, Sjogren syndrome-associated keratoconjunctivitis sicca, non-Sjogren syndrome-associated keratoconjunctivitis sicca, keratitis sicca, sicca syndrome, xerophthalmia, tear film disorder, decreased tear production, aqueous tear deficiency (ATD), meibomian gland dysfunction, and evaporative loss. Combination Therapies The compounds of the disclosure may be administered alone as a monotherapy, or they may be administered in combination with one or more additional therapeutic agents. The selection of the one or more additional therapeutic agents will of course vary depending on the disease or condition to be treated and its severity. It is common place to use combination therapies to treat certain medical conditions. According to a particular aspect of the disclosure there is provided a combination suitable for use in the treatment of a disease or condition in which IL-17 activity is implicated, comprising a compound of the disclosure as defined hereinbefore, or a pharmaceutically acceptable salt thereof, and another therapeutic agent. In a further aspect of the disclosure there is provided a compound of the disclosure or a pharmaceutically acceptable salt thereof, in combination with one or more additional therapeutic agents. According to a further aspect of the disclosure there is provided a pharmaceutical composition which comprises a compound of the disclosure, or a pharmaceutically acceptable salt thereof in combination with one or more additional therapeutic agents in association with a pharmaceutically acceptable diluent or carrier. The one or more additional therapeutic agents may comprise a further compound of the present disclosure. Therefore, in an embodiment, there is provided a pharmaceutical composition which comprises two compounds of the disclosure, or pharmaceutically acceptable salts thereof, in association with a pharmaceutically acceptable diluent or carrier. The combinations referred to above may conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical formulations comprising a combination as defined above together with a pharmaceutically acceptable diluent or carrier represent a further aspect of the disclosure. Such combination treatment may be achieved by way of the simultaneous, sequential, or separate dosing of the individual components of the treatment. In one embodiment, the individual compounds will be administered simultaneously in a combined pharmaceutical formulation. Such combination therapies employ the compounds of this disclosure within the dosage range described herein and the other pharmaceutically active agent within approved dosage ranges or the dosage such as described in the relevant publication reference. EXAMPLES General Procedures: Methods for preparing the compounds of this disclosure are illustrated in the following Examples. Starting materials are made according to procedures known in the art or as illustrated herein or are available commercially. Commercial reagents were used without further purification. Where no reaction temperature is included, the reaction was performed at ambient temperature which is typically 17 - 27 °C. A person skilled in the art will appreciate that reaction temperatures, reaction times and reagent quantities may be varied from those stated herein. Where compounds described in the disclosure are characterized by1H NMR spectroscopy, spectra were recorded on Bruker AVANCE II 400 (400 MHz), Bruker AVANCE III HD (400 MHz) Bruker AVANCE NEO (400 MHz), or Bruker AVANCE III (600 MHz) instruments. The instruments were equipped with 5 mm BBI room temperature probe heads. Where no temperature is included, the spectra were recorded at ambient temperature. Chemical shift values are expressed in parts per million (ppm). The following abbreviations are used for the multiplicity of the NMR signals: s=singlet, d=doublet, t=triplet, q=quartet, quin = quintet, m=multiplet, b=broad. Where compounds described in the disclosure are characterized by LCMS data, retention time and molecular weight are determined using the conditions listed below. Method A: For retention time and mass detection, a LC / MS-system from Waters (UPLC / SQD; ionization: electrospray in positive and / or negative mode [ES+ / -]) was used. Detected masses are given in mass per charge [m / z]. Waters ACQUITY UPLC BEH C18, 1.7 µm; 2.1 mm x 50 mm; H2O+0.05 % FA : ACN+0.035 % FA; 98:2 (0 min) to 98:2 (0.2 min) to 2:98 (3.8 min) to 2:98 (4.3 min) to 98:2 (4.5 min), 1 ml / min 55°C; given are the RT in min at 220 nm and the observed m / z mass for the respective UV peak. Method B: For retention time and mass detection, a LC / MS-system from Agilent (LC 1200 Series / MS 6120 quadrupole LC / MS, LC 1260 infinity / MS 6120 quadrupole LC / MS or LC 1260 Infinity II / MSD Infinity Lab) was used. Ionization: electrospray in positive mode (ES+). Detected masses are given in mass per charge [m / z]. Luna C18, 3 µm; 2.0 mm x 10 mm; H2O+0.05 % TFA : ACN; 93:7 (0 min) to 5:95 (1.0 min) to 5:95 (1.45 min), 1.1 ml / min; 30°C; given are the RT in min at 220 nm and the observed m / z mass for the respective UV peak. Method C: For retention time and mass detection, a LC / MS-system from Shimadzu (LCMS-2020; Software: LabSolution Version 5.97SP1) was used. Ionization: electrospray in positive mode (ES+). Detected masses are given in mass per charge [m / z]. Kinetex® EVO C18, 5µm; 2.1 mm x 30 mm; 5 % ACN (0.01875 % TFA) in water (0.0375 % TFA) to 95% ACN in water in 0.60 min, then hold at 95 % ACN for 0.18 min; 2.0 ml / min; T 50°C; given are the RT in min at 220 nm and the observed m / z mass for the respective UV peak. For analytical SFC SHIMADZU LC-30AD sf equipment was used. Silica gel chromatography was performed using CombiFlash® Rf (Teledyne ISCO), Büchi Reveleris® X2, or Biotage Dalton 2000 equipment with pre-packed cartridges. Preparative reversed phase liquid chromatography was performed with a Biotage equipment using C18 columns and a water (0.1 % FA) / ACN gradient. For preparative reversed phase HPLC, an Agilent 1200 preparative HPLC machine, Gilson equipment (GX-271 liquid handler, 331 / 332-pump, UV / VIS-155) or a Waters Autopurification LC Prep System was used. For preparative SFC, Waters SFC150mgm and Waters SFC350 equipment was used. In compounds described as HCl-, TFA- or as another salt, the exact amount of the respective salt is usually not determined unless otherwise noted. Therefore, the amount of the salt can range from as low as 0.01 eq. up to 5.0 eq. depending on the chemical structure (e.g., number of basic centres). Compound names were generated using Perkin Elmer’s ChemDraw®, version 20.1.0.110. Abbreviations: ACN acetonitrile BOC tert-butyloxycarbonyl BOC2O di-tert-butyl dicarbonate CBZ carboxybenzyl CDI carbonyldiimidazole DCM dichloromethane DEA diethylamine DIPEA N,N-diisopropylethylamine DMAP 4-dimethylaminopyridine DME Dimethoxyethane DMF N,N-dimethylformamide DMSO Dimethyl sulfoxide DMSO-d6deuterated dimethyl sulfoxide EA ethyl acetate EDCI 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide EtOH ethanol FC flash chromatography FMOC fluorenylmethoxycarbonyl h hour O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium- HATU hexafluorophosphate 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium HBTU hexafluorophosphate HPLC high-performance liquid chromatography HOBt 1-Hydroxy-1H-benzotriazol hydrate LC / MS liquid chromatography / mass spectrometry IPA 2-propanol m / z mass-to-charge ratio MeOH methanol min minute MTB methyl tert-butyl ether nBuLi n-Butyllithium Pd / C palladium on carbon Pd(dppf)Cl2 [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) PE petroleum ether benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium PyBOP hexafluorophosphate RP reverse phase RT room temperature rt retention time SFC supercritical fluid chromatography T3P 1-propanephosphonic acid anhydride (50 % solution in ethyl acetate) TEA triethylamine TFA trifluoroacetic acid THF tetrahydrofuran TMSI trimethylsilyl iodide O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'- TOTU tetramethyluronium tetrafluoroborate TsOH p-toluenesulfonic acid hydrate Intermediate 1: (S)-1-((S)-1-(2-aminopyridin-4-yl)-2-methoxyethyl)-4- (trifluoromethyl)imidazolidin-2-one To a solution of N,O-dimethylhydroxylamine (100 g) and 2-methoxyacetyl chloride (37.09 g) in DCM (1 L) was added TEA (190 ml) at 0°C. The mixture was stirred at 25°C for 1 h. Then the solution was treated with HCl (1 M) to pH = 2~3. The organic phase was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to yield 82.1 g of the title compound.1H NMR (400 MHz, CDCl3) δ ppm: 4.20 (s, 2H), 3.67 (s, 3H), 3.45 (s, 3H), 3.17 (s, 3H). Step B1: (R,E)-2,2,2-Trifluoro-N-(1-phenylethyl)ethan-1-imine To a solution of (1R)-1-phenylethanamine (68 g) in toluene (600 ml) was added TsOH (580 mg) and 2,2,2-trifluoroethane-1,1-diol (78.14 g). The mixture was stirred at 120°C for 12 h. The reaction mixture was diluter with water (500 ml), extracted with EA (300 ml, 2x), washed with brine (500 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the title compound (110 g) as a yellow oil, which was used in the next step without further purification.1H NMR (400 MHz, CDCl3): δ ppm = 7.70 - 7.61 (m, 1 H), 7.43 - 7.28 (m, 5 H), 4.62 (q, J=6.6 Hz, 1 H), 1.60 (d, J = 6.7 Hz, 3 H). Step B2: (S)-1,1,1-Trifluoro-3-nitro-N-((R)-1-phenylethyl)propan-2-amine A mixture of (R,E)-2,2,2-trifluoro-N-(1-phenylethyl)ethan-1-imine (110 g), nitromethane (166.87 g) and ZrCl4(63.71 g) was stirred at 25°C for 3 h. The reaction mixture was diluted with water (500 ml), extracted with EA (300 ml, 3x), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified several times by flash silica gel chromatography (PE:EA = 1:0 to 20:1) to yield 56.5 g of the title compound.1H NMR (400 MHz, CDCl3): δ ppm = 7.40 - 7.28 (m, 5 H), 4.66 (dd, J=4.5, 12.8 Hz, 1 H), 4.45 (dd, J=7.9, 12.7 Hz, 1 H), 4.09 - 4.01 (m, 1 H), 4.01 - 3.91 (m, 1 H), 1.78 (br d, J=9.7 Hz, 1 H), 1.36 (d, J=6.4 Hz, 3 H) . Step B2: Di-tert-butyl (3,3,3-trifluoropropane-1,2-diyl)(S)-dicarbamate To a solution of (S)-1,1,1-trifluoro-3-nitro-N-((R)-1-phenylethyl)propan-2-amine (46 g) in MeOH (500 ml) was added Pd / C (10 %, 9 g) and Boc2O (84.23 g) under N2 atmosphere. The suspension was degassed and purged with H2for 3 times. The mixture was stirred under H2 (50 psi) at 50°C for 48 h. The reaction mixture was filtered and concentrated under reduced pressure to give the crude, then triturated with PE (100 ml) at 25°C for 30 min to give 40.8 g of the title compound.1H NMR (400 MHz, CDCl3): δ ppm = 5.16 (br d, J=6.4 Hz, 1 H), 4.79 (br s, 1 H), 4.32 (br s, 1 H), 3.56 - 3.36 (m, 2 H), 1.45 (s, 18 H). - To a solution of di-tert-butyl (3,3,3-trifluoropropane-1,2-diyl)(S)-dicarbamate (46 g) in HCl / dioxane (230 ml) and dioxane (230 ml). The mixture was stirred at 25°C for 1 h. The reaction mixture concentrated under reduced pressure to give 28 g of the title compound with (2R)-3,3,3-trifluoropropane-1,2-diamine hydrochloride as impurity. Step B5: (S)-N1,N2-dibenzyl-3,3,3-trifluoropropane-1,2-diamine To a solution of (S)-3,3,3-trifluoropropane-1,2-diamine dihydrochloride (8 g) in ACN (80 ml) was added K2CO3(13.75 g) and benzyl bromide (13.61 g) at 0°C. The mixture was stirred at 25°C for 2 h. The reaction mixture was filtered and concentrated under reduced pressure to give a residue, which was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0 to 8 % EA / PE gradient @ 60 ml / min) to give 8.6 g of a residue which was separated by SFC (column: DAICEL CHIRALPAK IG (250 mm x 50 mm, 10 ^m); mobile phase: [0.1 % NH3.H2O in EtOH]; B %: 30 % - 30 %, 8 min) to yield 6 g of the title compound. Analytical chiral analysis (Chiralpak IG-3, 4.6 mm x 50 mm, 3 µm; CO2 / EtOH (0.05 % DEA); gradient: B in A from 5 to 40 %; flow: 3 ml / min; T: 35°C; back pressure: 100 bar) rt: 1.06 min.1H NMR (400 MHz, CDCl3): δ ppm = 7.37 - 7.27 (m, 10 H), 3.76 (d, J=13.6 Hz, 2 H), 3.53 (d, J=13.6 Hz, 2 H), 3.35 (tquin, J=3.7, 7.1 Hz, 1 H), 2.76 - 2.68 (m, 1 H), 2.66 - 2.57 (m, 1 H). Step B6: (S)-3,3,3-trifluoropropane-1,2-diamine dihydrochloride F NH2F F HCl H2N HCl To a solution of (S)-N1,N2-dibenzyl-3,3,3-trifluoropropane-1,2-diamine (7.47 g) and HCl (12 M, 2.22 ml) in EtOH (75 ml) was added Pd / C (10 %, 2.2 g) under N2. The suspension was degassed and purged with H2for 3 times. The mixture was stirred under H2 (15 psi) at 25°C for 16 h. The reaction mixture was filtered and concentrated under reduced pressure to yield 4.88 g of the title compound.1H NMR (400 MHz, MeOH-d4): δ ppm = 4.62 - 4.48 (m, 1 H), 3.63 - 3.56 (m, 1 H), 3.52 - 3.44 (m, 1 H). Step 1: 1-(2-Chloropyridin-4-yl)-2-methoxyethan-1-one To a solution of 2-chloro-4-iodopyridine (80.93 g) in THF (1 l) was added n-BuLi (2.5 M, 203 ml) at -78°C and the mixture was stirred for 10 min. Then N,2-dimethoxy-N- methylacetamide (Step A1, 45 g) was added at -78°C over 1 h. After stirring the mixture at -78°C for 2 h the reaction mixture was quenched by addition of sat. NHCl4 solution (200 ml) at 0°C, diluted with water (200 ml) and extracted with EA (150 ml, 3x). The combined organic layers were washed with brine (100 ml, 2x), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO2, PE / EA = 1 / 0 to 3 / 1) to yield 20 g of the title compound. LC / MS: m / z = 186.2 [M+H]+; rt: 0.23 min (LC / MS-method C). Step 2: Tert-butyl (4-(2-methoxyacetyl)pyridin-2-yl)carbamate To a solution of 1-(2-chloropyridin-4-yl)-2-methoxyethan-1-one (20 g) and NH2Boc (18.93 g) in dioxane (400 ml) were added Pd(OAc)2 (1.21 g), XPhos (2.57 g) and Cs2CO3 (52.66 g). The mixture was stirred at 90°C for 12 h. Then the reaction mixture was filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO2, PE / EA = 1 / 0 to 3 / 1) to yield 8.1 g of the title compound. Step 3: Tert-butyl (4-(1-(((S)-2-amino-3,3,3-trifluoropropyl)amino)-2-methoxyethyl)pyridin- 2-yl)carbamate To a solution of tert-butyl (4-(2-methoxyacetyl)pyridin-2-yl)carbamate (6 g) and (S)-3,3,3-trifluoropropane-1,2-diamine dihydrochloride (Step B6, 3.17 g) in IPA (140 ml) was added TEA (11.29 ml) in one portion at 85°C and the mixture was stirred for 2 h at 85°C. After stirring for 12 h at 25°C the mixture is concentrated in vacuo and the residue was dissolved in MeOH (140 ml). NaBH3CN (7.93 g) was portion wise added, with gas evolution occurring. The suspension was stirred for 5 min, then AcOH (9.29 ml) was added. The reaction mixture was heated at 40°C with stirring for 25 min. Then the reaction mixture was concentrated, diluted with DCM (100 ml) and stirred rapidly with saturated aqueous NaHCO3 solution (200 ml) at 25°C for 1 h. After the layers were separated, the aqueous phase was extracted with DCM (200 ml, 3x). The combined organic layers were washed with brine (300 ml), dried over anhydrous Na2SO4, filtered and concentrated to yield 10 g of the crude title compound. LC / MS: m / z = 379.3 [M+H]+; rt: 0.24 min (LC / MS-method C). Step 4-P1 and -P2: Tert-butyl (4-((S)-2-methoxy-1-((S)-2-oxo-4-(trifluoromethyl)- imidazolidin-1-yl)ethyl)pyridin-2-yl)carbamate (P1) and tert-butyl (4-((R)-2-methoxy-1- ((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)carbamate (P2) To a solution of tert-butyl (4-(1-(((S)-2-amino-3,3,3-trifluoropropyl)amino)-2- methoxyethyl)pyridin-2-yl)carbamate (10 g) in THF (240 ml) was added CDI (12.86 g). The mixture was stirred at 60°C for 1 h. Then the mixture was diluted with water (150 ml) and extracted with EA (150 ml, 3x). The combined organic layers were washed with citric acid (100 ml, 2x), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO2, PE / EA = 1 / 0 to 0 / 1) to yield 2.5 g of the diastereomeric mixture of title compound. The diastereomers (5.5 g) were separated by preparative SFC (column: Regis (S,S) Whelk-O1 (250 mm x 50 mm, 10 ^m); mobile phase: A: CO2, B: [0.1 % NH3●H2O in MeOH]; B: 25 % - isocratic) to yield 2.8 g of P1 and 2 g of P2. P1: LC / MS: m / z = 405.3 [M+H]+; rt: 0.31 min (LC / MS- method C). P2: LC / MS: m / z = 405.3 [M+H]+; rt: 0.32 min (LC / MS-method C). Analytical SFC data: (Regis, Whelk (50 mm x 4.6 mm, 3.5 µm); A: CO2, B: MeOH (0.05 % DEA)]; B %: 5 %-40 %, flow 3 ml / min, T: 35°C): P1: RT= 1.16 min; P2: RT= 1.27 min. Intermediate 1: (S)-1-((S)-1-(2-Aminopyridin-4-yl)-2-methoxyethyl)-4-(trifluoromethyl)- imidazolidin-2-one hydrochloride To a solution of tert-butyl (4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)carbamate (2.8 g) was added HCl / dioxane (4 M, 10.39 ml). The mixture was stirred at 25°C for 1 h. Then the reaction mixture was filtered and concentrated under reduced pressure to yield 1.9 g of the title compound. Analytical SFC data (Chiralpak IC-3 (50 mm x 4.6 mm, 3 µm); A: CO2, B: MeOH (0.05 % DEA)]; B %: 5 %-40 %, flow 3 ml / min, T: 35°C): RT= 1.56 min. Intermediate 2: (S)-1-(1-(2-Aminopyridin-4-yl)-2-methoxyethyl)-5,5- difluorotetrahydropyrimidin-2(1H)-one To a mixture of N-isopropylpropan-2-amine (53.6 ml) and THF (1000 ml) was added dropwise n-BuLi (2.5 M, 151.7 ml) at -78 °C, which was stirred for 30 minutes at the same temperature. Tributylstannane (100 g) was added dropwise to the reaction mixture at the same temperature, and stirred for 30 minutes at 0 °C. The reaction mixture was cooled to -78 °C, and bromo(methoxy)methane (47.39 g) was added dropwise thereto. The reaction mixture was gradually warmed to 25 °C over 1 h. The reaction mixture was diluted with water (800 ml) and extracted with EA (300 ml). The combined organic layers were washed with brine (800 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO2, PE / EA = 1 / 0 to 3 / 1) to yield 99 g of the title compound.1H NMR (400 MHz, CDCl3) δ: 3.60-3.67 (m, 2 H), 3.22 (s, 3 H), 1.35-1.52 (m, 6 H), 1.23 (m, 6 H), 0.74-0.93 (m, 15 H). Step 2: (R)-N-((2-chloropyridin-4-yl)methylene)-2-methylpropane-2-sulfinamide To a solution of 2-chloroisonicotinaldehyde (60 g) and (R)-2-methylpropane-2- sulfinamide (61.65 g) in DCM (500 ml) was added Cs2CO3(207 g). The mixture was stirred at 40 °C for 12 h. Then the reaction mixture was filtered, H2O (300 ml) was added and the mixture was extracted with DCM (200 ml). The combined organic layers were washed with brine (300 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield 95 g of the title compound, which was used for next step without further purification.1H NMR (400 MHz, CDCl3) δ: 8.50-8.64 (m, 2 H), 7.70-7.82 (m, 1 H), 7.62 (m, 1 H), 1.29 (s, 9 H). Step 3: (R)-N-((S)-1-(2-chloropyridin-4-yl)-2-methoxyethyl)-2-methylpropane-2- sulfinamide and (R)-N-((R)-1-(2-chloropyridin-4-yl)-2-methoxyethyl)-2-methylpropane-2- sulfinamide To a solution of tributyl(methoxymethyl)stannane (Step 1, 95.30 g) in THF (100 ml) was added n-BuLi (2.5 M, 113.75 ml) at -70 °C, stirred for 20 min was added (R)-N- ((2-chloropyridin-4-yl)methylene)-2-methylpropane-2-sulfinamide (58 g) in THF (500 ml) at -70 °C. The mixture was stirred at 25 °C for 1 h. The reaction mixture was quenched with water (500 ml) and extracted with EA (500 ml). The combined organic layers were washed with brine (100 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO2, PE / EA = 10 / 1 to 0 / 1) to give the racemic product that was further purified by prep-HPLC (Phenomenex luna C18 (250 mm x 70 mm, 10 µm); A: water (0.1% formic acid); B: ACN]; gradient: 20 %-50 % B over 22 min). 30 g of (R)-N-((S)-1-(2-chloropyridin-4-yl)-2- methoxyethyl)-2-methylpropane-2-sulfinamide and 7 g of (R)-N-((R)-1-(2-chloropyridin-4- yl)-2-methoxyethyl)-2-methylpropane-2-sulfinamide were obtained.1H NMR (400 MHz, CDCl3): δ 8.38 (d, 1 H), 7.38 (s, 1 H), 7.28 (s, 1 H), 4.50-4.60 (m, 1 H), 4.04-4.12 (m, 1 H), 3.67 (d, 2 H), 3.35 (s, 3 H), 1.23 (s, 9 H). Step 4: (S)-1-(2-Chloropyridin-4-yl)-2-methoxyethan-1-amine To a solution of (R)-N-((S)-1-(2-chloropyridin-4-yl)-2-methoxyethyl)-2- methylpropane-2-sulfinamide (30 g) in DCM (60 ml) was added HCl / dioxane (2 M, 257 ml). The mixture was stirred at 25 °C for 0.2 h. The precipitate was collected by filtration, dried under reduced pressure to give the desired compound. The collected solid was diluted with aqueous saturated Na2CO3solution (100 ml) and extracted with EA (120 ml, 4x), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield 18 g of the title compound, which was used for next step without further purification. -2,2-difluoro-3- To a solution of (S)-1-(2-chloropyridin-4-yl)-2-methoxyethan-1-amine (18 g) and diethyl 2,2-difluoromalonate (75.67 g) in MeOH (300 ml). The mixture was stirred at 25 °C for 48 h. The reaction mixture was concentrated and the residue was purified by column chromatography (SiO2, PE / EA = 0 / 1 to 0 / 1) to yield 20 g of the title compound. -2,2-difluoromalonamide A solution of ethyl (S)-3-((1-(2-chloropyridin-4-yl)-2-methoxyethyl)amino)-2,2- difluoro-3-oxopropanoate (20 g) in NH3 / MeOH (7 M, 250 ml) was stirred at 25 °C for 0.5 h. The reaction mixture was concentrated under reduced pressure to yield 19.3 g of the title compound, which was used for next step without further purification. 1,3-diamine To a solution of (S)-N1-(1-(2-chloropyridin-4-yl)-2-methoxyethyl)-2,2- difluoromalonamide (16 g) in THF (160 ml) was added BH3•THF (1 M, 208 ml) at 0 °C. The mixture was stirred at 60 °C for 1 h. Then the reaction mixture was cooled with an ice bath and quenched with 1 M HCl (30 ml) at 0 °C. The reaction mixture was diluted with aqueous Na2CO3 solution (150 ml) and extracted with EA (100 ml, 2x). The combined organic layers were washed with brine (150 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO2, PE / EA = 10 / 1 to 0 / 1 followed by MeOH:EA = 1:4) to yield 10.5 g of the title compound. To a solution of (S)-N1-(1-(2-Chloropyridin-4-yl)-2-methoxyethyl)-2,2- difluoropropane-1,3-diamine (11 g) in THF (110 ml) was added CDI (31.88 g). The mixture was stirred at 60 °C for 1 h. The reaction mixture was diluted with HCl (1 M, 100 ml) and extracted with EA (100 ml, 3x), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield 12 g of the title compound, which was used for next step without further purification.1H NMR (400 MHz, CDCl3): δ 8.40 (d, 1 H), 7.33 (s, 1 H), 7.22 (d, 1 H), 5.71 (m, 1 H), 5.46 (br s, 1 H), 3.85-3.98 (m, 2 H), 3.61-3.78 (m, 3 H), 3.43-3.50 (m, 3 H), 3.28-3.41 (m, 1 H). Step 9: Tert-butyl (S)-(4-(1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- To a solution of (S)-1-(1-(2-Chloropyridin-4-yl)-2-methoxyethyl)-5,5-difluoro- tetrahydropyrimidin-2(1H)-one (6 g), XPhos (3.74 g) NH2Boc (11.50 g) and Cs2CO3 (12.79 g) in dioxane (70 ml) was added Pd(OAc)2 (881.26 mg). The mixture was stirred at 90 °C for 1 h. The reaction mixture was diluted with water (100 ml) and extracted with EA (100 ml, 2x). The combined organic layers were washed with brine (100 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a crude which was triturated with PE:EA = 1:1 at 25 °C for 10 min to yield 6.5 g of the title compound.1H NMR (400 MHz, DMSO-d6): δ 9.71 (s, 1 H), 8.19 (d, 1 H), 7.73 (s, 1 H), 6.96 (d, 1 H), 6.90 (br s, 1 H), 5.50 (tr, 1 H), 3.80 (d, 2 H), 3.44-3.70 (m, 4 H), 3.32 (s, 3 H), 1.47 (s, 9 H). Intermediate 2: (S)-1-(1-(2-Aminopyridin-4-yl)-2- -5,5-difluoro- -one To a solution of tert-butyl (S)-(4-(1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)carbamate (9 g) was added HCl / dioxane (2 M, 100 ml). The mixture was stirred at 25 °C for 1 h. Then the reaction mixture was diluted with saturated aqueous Na2CO3 solution (100 ml) and extracted with EA (100 ml, 6x), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield 5 g of the title compound, which was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6): δ 8.20 (br s, 2 H), 7.92 (d, 1 H), 7.04 (br s, 1 H), 6.93 (s, 1 H), 6.75 (d, 1 H), 5.38 (tr, 1 H), 3.82 (d, 2 H), 3.45-3.62 (m, 4 H), 3.31 (s, 3 H). Intermediate 3: 3-(1-(2-Aminopyridin-4-yl)-2-methoxyethyl)-5-fluoropyridin-2(1H)-one Step 1: 5-Fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine To a solution of 3-bromo-5-fluoro-2-methoxypyridine (50 g), bis(pinacolato)diboron (73.96 g) and KOAc (71.46 g) in dioxane (600 ml) was added Pd(dppf)Cl2 (10.66 g). The mixture was stirred at 90 °C for 2 h. Then the reaction mixture was diluted with water (300 ml) and extracted with EA (300 ml). The combined organic layers were washed with brine (300 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO2, PE / EA = 0 / 1 to 1 / 1) to yield 55 g of the title compound. Step 2: (E)-1-(2-((Tert-butoxycarbonyl)amino)pyridin-4-yl)-2-methoxyvinyl trifluoromethanesulfonate To a solution of tert-butyl (4-(2-methoxyacetyl)pyridin-2-yl)carbamate (40 g) in THF (400 ml) was added LiHMDS (1 M, 225.32 ml). After stirring for 10 min at -70 °C a mixture of 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (80.49 g) in N,N´-dimethylpropylene urea (200 ml) and THF (100 ml) was added. The mixture was stirred at 25 °C for 1 h. The reaction mixture was diluted with citric acid (1 M, 300 ml) and extracted with EA (200 ml). The combined organic layers were washed with brine (350 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue which was triturated with MTB at 20 °C for 10 min to yield 45 g of the title compound. Step 3: Tert-butyl (E)-(4-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-methoxyvinyl)pyridin-2- yl)carbamate To a solution of (E)-1-(2-((tert-butoxycarbonyl)amino)pyridin-4-yl)-2-methoxyvinyl trifluoromethanesulfonate (34 g) and 5-fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridine (Step 1, 34.56 g) in H2O (100 ml) / DME (400 ml) was added NaHCO3 (21.51 g) and Pd(PPh3)4 (9.86 g). The mixture was stirred at 100 °C for 1.5 h. Then the reaction mixture was diluted with water (300 ml) and extracted with EA (150 ml). The combined organic layers were washed with brine (150 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO2, DCM / EA = 10 / 1 to 1 / 1) to yield 27 g of the title compound.1H NMR (400 MHz, CDCl3): δ 8.42 (br s, 1 H), 8.05-8.19 (m, 1 H), 7.97-8.04 (m, 1 H), 7.87 (br s, 1 H), 7.31-7.42 (m, 1 H), 6.96 (s, 1 H), 6.48 (m, 1 H), 3.81 (s, 3 H), 3.79 (s, 3 H), 1.53 (s, 9 H). Step 4: Tert-butyl (4-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-methoxyethyl)pyridin-2- yl)carbamate To a solution of tert-butyl (E)-(4-(1-(5-fluoro-2-methoxypyridin-3-yl)-2- methoxyvinyl)pyridin-2-yl)carbamate (27 g) in the mixture of MeOH (400 ml) and DCM (150 ml) was added Pd / C (5 g, 10 %) under N2 atmosphere. The suspension was degassed and purged with H2for 3 times. The mixture was stirred under H2(15 Psi) at 45 °C for 12 h. Then the reaction mixture was filtered and concentrated under reduced pressure to yield 24 g of the title compound which was used for next step without further purification. Intermediate 3: 3-(1-(2-Aminopyridin-4-yl)-2-methoxyethyl)-5-fluoropyridin-2(1H)-one To a solution of tert-butyl (4-(1-(5-fluoro-2-methoxypyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)carbamate (24 g) in ACN (300 ml) were added TMSI (17.31 ml) and NaI (19.06 g). The mixture was stirred at 60 °C for 2 h. Then the reaction mixture was concentrated under reduced pressure. The residue was diluted with aqueous Na2CO3 solution (50 ml) and stirred for 10 min. Then the mixture was concentrated under reduced pressure, EA (200 ml) was added and the mixture was stirred for 10 min. Then the mixture was filtered and the filtrate concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO2, DCM / MeOH = 100 / 1 to 5 / 1) to yield 11g of the title compound.1H NMR (400 MHz, DMSO-d6): δ 11.50 (br d, 1H), 7.72-7.84 (m, 1 H), 7.43-7.56 (m, 2 H), 6.38-6.53 (m, 1 H), 6.24-6.35 (m, 1 H), 5.84 (br s, 2 H), 4.19 (tr, 1 H), 3.64-3.88 (m, 2 H), 3.24 (s, 3 H). Intermediate 4: (S)-2-amino-2-(4-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Step 1: Benzyl ((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate To a solution of^(S)-2-(((benzyloxy)carbonyl)amino)-2-(4-fluorophenyl)acetic acid (2.99 g)^in^pyridine (30 ml)^was added^EDCI (3.78 g)^and (S)-1-((S)-1-(2-aminopyridin-4- yl)-2-methoxyethyl)-4-(trifluoromethyl)imidazolidin-2-one hydrochloride (Intermediate 1, 1.5 g) and the mixture was stirred at^RT^for^12h before the mixture was^concentrated under reduced pressure. The crude product was purified by reverse-phase HPLC (column: Phenomenex luna C18 (250 mm x 70 mm, 15 μm); mobile phase: [water(FA)-ACN]; gradient:31%-61% B over 22 min) to afford a residue (1.7 g) that was further purified by SFC (column: DAICEL CHIRALPAK AS (250 mm x 30 mm, 10 ^m); mobile phase: [CO2- MeOH (0.1%NH3H2O)]; B%: 50%, isocratic elution mode^) and the title compound was collected as the second eluting peak (866 mg). LC / MS: m / z =^590.2^[M+H]+; rt: 2.14^min (LC / MS-method A).^ Intermediate 4: (S)-2-amino-2-(4-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide To a solution of benzyl ((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo- 4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (280 mg) in methanol (50 ml) under argon was added Pd / C (51 mg) and the mixture was stirred under a hydrogen atmosphere (balloon) for 4h before the mixture was filtered and concentrated under reduced pressure. This afforded the title compound (210 mg) that was without further purification. LC / MS: m / z =^456.2^[M+H]+; rt: 1.11^min (LC / MS-method A). Intermediate 5: (S)-2-amino-2-(4-fluoro-3-methylphenyl)-N-(4-((S)-2-methoxy-1-((S)- 2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate ^ To a solution of (S)-1-((S)-1-(2-aminopyridin-4-yl)-2-methoxyethyl)-4- (trifluoromethyl)imidazolidin-2-one (Intermediate 1; 700 mg) and 2-((tert- butoxycarbonyl)amino)-2-(4-fluoro-3-methylphenyl)acetic acid (652 mg) in pyridine (7 ml) was added EDCI (1.32 g) and the mixture was stirred at 20°C for 2h before the reaction mixture was diluted with water (30 ml) and the aqueous layer extracted with EA (3 x 50 ml). The combined organic layers were washed with brine (2 x 50 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue that was purified by FC (SiO2, PE / EA =1 / 0 to 0 / 1) to afford 1.0 g of the racemic product as a yellow solid. The diastereomers were separated by SFC (column: DAICEL CHIRALPAK AD (250 mm x 30 mm, 10 ^m); mobile phase: [CO2-ACN / i-PrOH (0.1% NH3H2O)]; B%:60%, isocratic elution mode to give to afford 440 mg of the title compound as the first eluting diastereomer as a yellow solid.LC / MS: m / z =^570.1^[M+H]+; rt: 2.21^min (LC / MS- method A).^ Intermediate 5: (S)-2-amino-2-(4-fluoro-3-methylphenyl)-N-(4-((S)-2-methoxy-1-((S)-2- oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide To a solution tert-butyl ((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1- ((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)- carbamate (84 mg) in dry DCM (2.5 ml) was added TFA (0.23 ml) and the mixture stirred at RT for 3h before Na2CO3solution (10 ml, aq. sat.) was added and the mixture stirred for 10 min. The mixture was extracted with DCM (3 x 10 ml) and the organic phase dried over Na2SO4, filtered and evaporated to dryness. The crude product (60 mg) was used directly in the next step. LC / MS: m / z =^470.2^[M+H]+; rt: 0.97^min (LC / MS-method B).^ Intermediate 6: (S)-2-amino-2-(3,4- 1-((S)-2-oxo- 4- 1- 2- Prepared following the procedure described for Intermediate 5 (Step 1) employing 2-((tert-butoxycarbonyl)amino)-2-(3,4-difluorophenyl)acetic acid (661 mg) afforded the crude product (900 mg) that was separated by SFC (column: DAICEL CHIRALPAK AD (250 mm x 30 mm, 10 ^m); mobile phase: [CO2-ACN / i-PrOH (0.1% NH3H2O)]; B%: 60%, isocratic elution mode to afford the title compound (360 mg, yellow solid) as the first eluting diastereomer. LC / MS: m / z =^574.1^[M+H]+; rt: 2.16^min (LC / MS- method A).^ Intermediate 6: (S)-2-amino-2-(3,4-difluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4-(trifluoromethyl)- imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (60 mg) afforded 45 mg of the title compound that was used directly in the next step. LC / MS: m / z =^474.2^[M+H]+; rt: 0.94^min (LC / MS-method B).^ Intermediate 7: (S)-2-amino-2-(3-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Step 1: benzyl ((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 4 (Step 1) employing (S)-2-(((benzyloxy)carbonyl)amino)-2-(3-fluorophenyl)acetic acid afforded 270 mg of the title compound as the first eluting diastereomer with SFC (column: DAICEL CHIRALPAK AD (250 mm x 30 mm, 10 ^m); mobile phase: [CO2-i-PrOH]; B%: 45%, isocratic elution mode. LC / MS: m / z =^590.2^[M+H]+; rt: 2.16^min (LC / MS-method A). Intermediate 7: (S)-2-amino-2-(3-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 4 employing benzyl ((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4-(trifluoromethyl)imidazolidin- 1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (160 mg) afforded 122 mg of the title compound that was used directly in the next step. LC / MS: m / z =^456.1^[M+H]+; rt: 1.12^min (LC / MS-method A).^ Intermediate 8: (S)-2-amino-2-(3-chlorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Step 1: benzyl ((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate ^ Prepared following the procedure described for Intermediate 4 (Step 1) employing (S)-2-(((benzyloxy)carbonyl)amino)-2-(3-chlorophenyl)acetic acid afforded 275 mg of the title compound as the first eluting diastereomer using SFC (column: DAICEL CHIRALPAK AS (250 mm x 30 mm, 10 ^m); mobile phase: [CO2-ACN / MeOH (0.1% NH3H2O)]; B%: 55%, isocratic elution mode. LC / MS: m / z =^606.3^[M+H]+; rt: 2.27^min (LC / MS-method A).^ Intermediate 8: (S)-2-amino-2-(3-chlorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide To a solution of benzyl ((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo- 4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (20 mg) in TFA (0.7 ml) was added thioanisole (0.2 ml) and the mixture stirred at RT for 20h. Then 10 ml diisopropyl ether was added and the precipitated title compound was filtered off and used directly in the next step. LC / MS: m / z =^472.2^[M+H]+; rt: 0.88^min (LC / MS- method B). Intermediate 9: (S)-2-amino-2-(4-chlorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Step 1: benzyl ((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 4 (Step 1) employing (benzyl (S)-(2-amino-1-(4-chlorophenyl)-2-oxoethyl)carbamate afforded 198 mg of the title compound as the second eluting diastereomer using SFC (column: DAICEL CHIRALPAK AS (250 mm x 30 mm, 10 ^m); mobile phase: [CO2-MeOH / ACN]; B%: 55%, isocratic elution mode. LC / MS: m / z =^606.2^[M+H]+; rt: 2.28^min (LC / MS-method A).^ Intermediate 9: (S)-2-amino-2-(4-chlorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 8 employing 180 mg (S)-2-amino-2-(4-chlorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4-(trifluoromethyl)- imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide afforded 155 mg of the title compound that was used directly in the next step. LC / MS: m / z =^472.1^[M+H]+; rt: 1.27^min (LC / MS- method A). Intermediate 10: (S)-2-amino-2-(3-chloro-4-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)- 2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 5 (Step 1) employing tert-butyl (2-amino-1-(3-chloro-4-fluorophenyl)-2-oxoethyl)carbamate afforded 450 mg of the title compound as the first eluting diastereomer. LC / MS: m / z =^590.0^[M+H]+; rt: 2.26^min (LC / MS-method A). Intermediate 10: (S)-2-amino-2-(3-chloro-4-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2- oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4-(trifluoro- methyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (41 mg) afforded 30 mg of the title compound that was used directly in the next step. LC / MS: m / z =^490.1^[M+H]+; rt: 0.88^min (LC / MS-method B).^ Intermediate 11: (S)-2-amino-2-(2-chlorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Step 1: benzyl ((S)-1-(2-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 4 (Step 1) employing benzyl (S)-(2-amino-1-(2-chlorophenyl)-2-oxoethyl)carbamate afforded 370 mg of the title compound as the last eluting diastereomer with SFC (column: DAICEL CHIRALPAK AS(250 mm x 30 mm,10 ^m); mobile phase: [CO2-ACN / MeOH (0.1% NH3H2O)]; B%: 60%, isocratic elution mode). LC / MS: m / z =^606.3^[M+H]+; rt: 2.22^min (LC / MS-method A).^ Intermediate 11: (S)-2-amino-2-(2-chlorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 8 employing 180 mg benzyl ((S)-1-(2-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4-(trifluoromethyl)- imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate afforded 160 mg of the title compound that was used directly in the next step. LC / MS: m / z =^472.1^[M+H]+; rt: 1.14^min (LC / MS-method A). Intermediate 12: (S)-2-amino-2-(2-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Step 1: benzyl ((S)-1-(2-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 4 (Step 1) employing benzyl (2-amino-1-(2-fluorophenyl)-2-oxoethyl)carbamate afforded 342 mg of the title compound as the first eluting diastereomer with SFC (column: DAICEL CHIRALCEL OX (250 mm x 30 mm, 10 ^m); mobile phase: [CO2-MeOH]; B%: 40%, isocratic elution mode). LC / MS: m / z =^590.2^[M+H]+; rt: 2.14^min (LC / MS-method A).^ Intermediate 12: (S)-2-amino-2-(2-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 4 employing benzyl ((S)-1-(2-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4-(trifluoromethyl)imidazolidin- 1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (200 mg) afforded 154 mg of the title compound that was used directly in the next step. LC / MS: m / z =^456.2^[M+H]+; rt: 1.10^min (LC / MS-method A). To a solution of (S)-1-(1-(2-aminopyridin-4-yl)-2-methoxyethyl)-5,5- difluorotetrahydropyrimidin-2(1H)-one (Intermediate 2; 400 mg) and tert-butyl (S)-(2- amino-1-(3-chlorophenyl)-2-oxoethyl)carbamate (599 mg) ^in DCM (5 ml)^was added pyridine (0.339 ml)^and EDCI (402 mg) and the reaction mixture was stirred at 25°C for 3h before being diluted with water (10ml) and extracted with EA (3 x 10 ml). The combined organic layers were washed with brine (10 ml), dried over anhydrous Na2SO4, filtered^and concentrated under reduced pressure to afford the crude product that was purified by SFC (Column: Chiralpak IG-350 mm x 4.6mm I.D., 3 ^m; Mobile phase: Phase A for CO2, and Phase B for MeOH+CAN (0.05% DEA); Gradient elution: 40% MeOH+CAN (0.05% DEA) in CO2). The title compound (230 mg) was obtained as a colorless solid as the second eluting diastereomer. LC / MS: m / z =^552.0^[M+H]+; rt: 2.17^min (LC / MS-method A). Intermediate 13: (S)-2-amino-2-(3-chlorophenyl)-N-(4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)- 2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (185 mg) afforded 135 mg of the title compound that was used directly in the next step. LC / MS: m / z =^454.2^[M+H]+; rt: 1.22^min (LC / MS-method A). Intermediate 14: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)-2-(3-fluorophenyl)acetamide Step 1: benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)carbamate To a solution of (S)-1-(1-(2-aminopyridin-4-yl)-2-methoxyethyl)-5,5- difluorotetrahydropyrimidin-2(1H)-one (Intermediate 2; 260 mg) and benzyl (2-amino-1-(3- fluorophenyl)-2-oxoethyl)carbamate (413 mg) ^in^DCM (3 ml)^was added pyridine (0.169 ml)^and EDCI (201 mg) and the reaction mixture was stirred at 25°C for 1h before being concentrated under reduced pressure. The residue was purified by FC (SiO2,PE / EA=1 / 0 to 0 / 1) to afford (250 mg) of the crude product as a colorless solid that was purified by SFC (column: (S,S)Whelk-O150 mm x 4.6mm I.D., 3.5 ^m; mobile phase: Phase A for CO2, and Phase B for EtOH (0.05%DEA);^40% EtOH (0.05% DEA) in CO2) to afford the title compound (150 mg) as the first eluting diastereomer. LC / MS: m / z =^572.2^[M+H]+; rt: 2.11^min (LC / MS-method A). Intermediate 14: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)-2-(3-fluorophenyl)acetamide Prepared following the procedure described for Intermediate 4 employing benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin- 2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)carbamate (120 mg) afforded 90 mg of the title compound that was used directly in the next step. LC / MS: m / z =^438.2^[M+H]+; rt: 1.11^min (LC / MS-method A). Intermediate 15: (S)-2-amino-2-(4-chlorophenyl)-N-(4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydro- pyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 14 (Step 1) employing tert-butyl (S)-(2-amino-1-(4-chlorophenyl)-2-oxoethyl)carbamate (599 mg) and (S)-1-(1-(2-aminopyridin-4-yl)-2-methoxyethyl)-5,5-difluorotetrahydropyrimidin-2(1H)-one (Int.2; 400 mg) using pyridine as solvent afforded 168 mg of the title compound as the first eluting diastereomer with SFC (Column: Chiralpak AS-350 mm x 4.6mm I.D.3 ^m Mobile phase: Phase A for CO2, and Phase B for IPA (0.05%DEA); Gradient elution: IPA (0.05% DEA) in CO2from 5% to 40%). LC / MS: m / z =^554.1^[M+H]+; rt: 2.18^min (LC / MS-method A).^ Intermediate 15: (S)-2-amino-2-(4-chlorophenyl)-N-(4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)- 2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (160 mg) afforded 130 mg of the title compound that was used directly in the next step. LC / MS: m / z =^454.0^[M+H]+; rt: 1.22^min (LC / MS-method A). Intermediate 16: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)-2-(m-tolyl)acetamide Step 1: benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)carbamate To a solution of (S)-1-(1-(2-aminopyridin-4-yl)-2-methoxyethyl)-5,5- difluorotetrahydropyrimidin-2(1H)-one (Intermediate 2; 300 mg) and benzyl (S)-(2-amino- 2-oxo-1-(m-tolyl)ethyl)carbamate (470 mg) ^in^DCM (5 ml)^was added^DMAP (768 mg)^and EDCI (402 mg) and the reaction mixture was stirred at 25°C for 3h before being diluted with water (20 ml) and extracted with EA (3 x 20 ml). The combined organic layers were washed with brine (3 x 10 ml), dried over anhydrous Na2SO4, filtered^and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Phenomenex luna C18150 mm x 25 mm, 10 ^m; mobile phase: [water(FA)-ACN]; gradient: 38%-68% B over 10 min to afford the crude product as a colorless solid that was purified by SFC (column: REGIS(S,S)WHELK-O1 (250 mm x 25 mm,10 ^m); mobile phase: [CO2-ACN / i- PrOH (0.1% NH3H2O)];B%:50%, isocratic elution mode) to afford the title compound (170 mg) as the first eluting diastereomer. LC / MS: m / z =^568.2^[M+H]+; rt: 2.17^min (LC / MS- method A).^ Intermediate 16: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)-2-(m-tolyl)acetamide Prepared following the procedure described for Intermediate 4 employing benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin- 2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)carbamate (100 mg) afforded 74 mg of the title compound that was used directly in the next step. LC / MS: m / z =^434.0^[M+H]+; rt: 1.17^min (LC / MS-method A). Intermediate 17: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)-2-(p-tolyl)acetamide Step 1: benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(p-tolyl)ethyl)carbamate Prepared following the procedure described for Intermediate 16 (Step 1) employing benzyl (S)-(2-amino-2-oxo-1-(p-tolyl)ethyl)carbamate (470 mg) afforded 104 mg of the title compound as the first eluting diastereomer with SFC (Column: REGIS(S,S)WHELK-O1 (250 mm x 25 mm, 10 um); mobile phase: [CO2-ACN / i-PrOH (0.1% NH3.H2O)]; B%: 50%, isocratic elution mode). LC / MS: m / z =^568.2^[M+H]+; rt: 2.17^min (LC / MS-method A). Intermediate 17: (S)-2-amino-N- -1-(5,5-difluoro-2- yl)-2-methoxyethyl)pyridin-2-yl)-2-(p-tolyl)acetamide Prepared following the procedure described for Intermediate 4 employing benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin- 2-yl)amino)-2-oxo-1-(p-tolyl)ethyl)carbamate (50 mg) afforded 38 mg of the title compound that was used directly in the next step. LC / MS: m / z =^434.0^[M+H]+; rt: 1.17^min (LC / MS- method A). Intermediate 18: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)-2-phenylacetamide Step 1: benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)carbamate Prepared following the procedure described for Intermediate 4 (Step 1) employing benzyl (S)-(2-amino-2-oxo-1-phenylethyl)carbamate (398 mg) and (S)-1-(1-(2- aminopyridin-4-yl)-2-methoxyethyl)-5,5-difluorotetrahydropyrimidin-2(1H)-one (Intermediate 2; 698 mg) afforded 160 mg of the title compound as the second eluting diastereomer with SFC (column: DAICEL CHIRALPAK AD (250 mm x 30 mm, 10 ^m); mobile phase: [CO2-ACN / EtOH (0.1% NH3.H2O)]; B%: 55%, isocratic elution mode). LC / MS: m / z =^554.2^[M+H]+; rt: 2.05^min (LC / MS-method A). Intermediate 18: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)-2-phenylacetamide Prepared following the procedure described for Intermediate 4 employing benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin- 2-yl)amino)-2-oxo-1-phenylethyl)carbamate (84 mg) afforded 63 mg of the title compound that was used directly in the next step. LC / MS: m / z =^420.1^[M+H]+; rt: 1.06^min (LC / MS- method A). Intermediate 19: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)-2-(3-(trifluoromethyl)phenyl)acetamide 1: tert- -2-((4-((S)-1-(5,5-difluoro-2- -yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)carbamate To a solution of (S)-1-(1-(2-aminopyridin-4-yl)-2-methoxyethyl)-5,5- difluorotetrahydropyrimidin-2(1H)-one (Intermediate 2; 600 mg) and tert-butyl (2-amino-2- oxo-1-(3-(trifluoromethyl)phenyl)ethyl)carbamate (600 mg) in pyridine (10 ml) was added EDCI (1.21 g) and the mixture was stirred at 25°C for 3h before the reaction mixture was diluted with water (10 ml) and the aqueous layer extracted with EA (3 x 10 ml). The combined organic layers were washed with brine (10 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue that was purified by SFC (column: Chiralpak AD-350 mm x 4.6 mm I.D., 3 ^m; Mobile phase: Phase A for CO2, and Phase B for IPA (0.05%DEA); Gradient elution: IPA (0.05% DEA) in CO2 from 5% to 40%) to afford 516 mg of the title compound as the first eluting diastereomer as a colorless solid. LC / MS: m / z =^588.1^[M+H]+; rt: 2.25^min (LC / MS-method A). Intermediate 19: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)-2-(3-(trifluoromethyl)phenyl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)- pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)carbamate (235 mg) afforded 180 mg of the title compound that was used directly in the next step. LC / MS: m / z =^488.1^[M+H]+; rt: 1.28^min (LC / MS-method A).^ Intermediate 20: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2- -yl)-2-methoxyethyl)pyridin-2-yl)-2-(4- -2-((4-((S)-1-(5,5-difluoro-2- -yl)-2- 2- Prepared following the procedure described for Intermediate 4 (Step 1) employing benzyl (S)-(2-amino-1-(4-fluorophenyl)-2-oxoethyl)carbamate afforded 100 mg of the title compound as the second eluting diastereomer with SFC (column: DAICEL CHIRALPAK AD(250 mm x 30 mm, 10 ^m); mobile phase: [CO2-ACN / EtOH (0.1% NH3H2O)]; B%:55%, isocratic elution mode). LC / MS: m / z =^572.3^[M+H]+; rt: 2.10^min (LC / MS-method A). Intermediate 20: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)-2-(4-fluorophenyl)acetamide Prepared following the procedure described for Intermediate 4 employing benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin- 2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)carbamate (86 mg) afforded 63 mg of the title compound that was used directly in the next step. LC / MS: m / z =^438.1^[M+H]+; rt: 1.13^min (LC / MS-method A). Intermediate 21: (S)-2-amino-2-(4-chloro-3-methylphenyl)-N-(4-((S)-1-(5,5-difluoro- 2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetra- hydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 19 (Step 1) employing tert-butyl (2-amino-1-(4-chloro-3-methylphenyl)-2-oxoethyl)carbamate (2.36 g) afforded 1.34 g of the title compound as the first eluting diastereomer after SFC (Column: Chiralpak AD-350 mm x 4.6 mm I.D., 3 ^m Mobile phase: Phase A for CO2, and Phase B for IPA (0.05%DEA); Gradient elution: IPA (0.05% DEA) in CO2from 10% to 60%) as colorless solid. LC / MS: m / z =^566.0^[M+H]+; rt: 2.29^min (LC / MS-method A). Intermediate 21: (S)-2-amino-2-(4-chloro-3-methylphenyl)-N-(4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (285 mg) afforded 235 mg of the title compound that was used directly in the next step. LC / MS: m / z =^468.1^[M+H]+; rt: 1.32^min (LC / MS-method A). Intermediate 22: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1 -yl)-2-methoxyethyl)pyridin-2-yl)-2-(3,5-dimethylphenyl)acetamide Step 1: benzyl ((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 16 (Step 1) employing benzyl (2-amino-1-(3,5-dimethylphenyl)-2-oxoethyl)carbamate (2.19 g) afforded 2.8 g of the crude product after purification by prep-HPLC (column: Welch Ultimate XB C1820-40 μm; 120 A; mobile phase: [water (0.1% FA)-ACN]; gradient: 30- 50% 45min). The diastereomers were separated by SFC (column: DAICEL CHIRALPAK AD (250 mm x 30 mm,10 ^m); mobile phase: [CO2-ACN / EtOH (0.1% NH3H2O)]; gradient: 45% B over 4.8 min) to afford 1.4 g of the title compound as the second eluting diastereomer. LC / MS: m / z =^568.2^[M+H]+; rt: 2.17^min (LC / MS-method A). Intermediate 22: (S)-2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)-2-(3,5-dimethylphenyl)acetamide Prepared following the procedure described for Intermediate 4 benzyl ((S)-2-((4- ((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2- yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)carbamate (291 mg) afforded 220 mg of the title compound that was used directly in the next step. LC / MS: m / z =^448.1^[M+H]+; rt: 1.27^min (LC / MS-method A). Intermediate 23: (S)-2-amino-2-(3-chloro-4-fluorophenyl)-N-(4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetra- hydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 4 (Step 1) employing tert-butyl (2-amino-1-(3-chloro-4-fluorophenyl)-2-oxoethyl)carbamate (955 mg) and (S)-1- (1-(2-aminopyridin-4-yl)-2-methoxyethyl)-5,5-difluorotetrahydropyrimidin-2(1H)-one (Intermediate 2; 900 mg) afforded 595 mg of the title compound as the first eluting diastereomer with SFC (Column: Chiralpak AD-350 mm x 4.6 mm I.D., 3 ^m; Mobile phase: Phase A for CO2, and Phase B for IPA (0.05%DEA); Gradient elution: IPA (0.05% DEA) in CO2 from 10% to 60%). LC / MS: m / z =^571.1^[M+H]+; rt: 2.20^min (LC / MS-method A). Intermediate 23: (S)-2-amino-2-(3-chloro-4-fluorophenyl)-N-(4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 tert-butyl ((S)-1- (3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (290 mg) afforded 240 mg of the title compound that was used directly in the next step. LC / MS: m / z =^472.1^[M+H]+; rt: 1.24^min (LC / MS-method A). Intermediate 24: (S)-2-amino-2-(3,4-difluorophenyl)-N-(4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate To a solution of tert-butyl (2-amino-1-(3,4-difluorophenyl)-2-oxoethyl)carbamate (2.50 g) and 3-(1-(2-aminopyridin-4-yl)-2-methoxyethyl)-5-fluoropyridin-2(1H)-one (Intermediate 3; 2.73 g) in DCM (125 ml) was added DMAP (8.12 g) and EDCI (2.73 g) and the mixture was stirred at 40°C for 2h. HCl (1 M, aq.) was added until pH = 4~5 and the mixture was extracted DCM (3 x 120 ml) and the combined organic layers were washed with brine (130 ml), dried over anhydrous Na2SO4, filtered^and concentrated under reduced pressure. The residue was purified by FC (SiO2, Petroleum ether / Ethyl acetate=1 / 0 to 3 / 1) to afford the crude product as a diastereomeric mixture (4.28 g). Separation by SFC (Column: Cellulose-2-350 mm x 4.6 mm I.D., 3 ^m; Mobile phase: Phase A for CO2, and Phase B for MeOH (0.05% DEA); Gradient elution: MeOH (0.05% DEA) in CO2from 10% to 60%) afforded two peaks where the first peak was collected and the diastereomers were^separated again by SFC (Column: Chiralpak IC-350 mm x 4.6 mm I.D., 3 ^m; Mobile phase: Phase A for CO2, and Phase B for IPA (0.05% DEA);^Gradient elution: ^IPA (0.05% DEA) in CO2from 10% to 60%)^to afford the title compound (334 mg, colorless solid) as the first eluting diastereomer. LC / MS: m / z =^531.0^[M+H]+; rt: 2.05^min (LC / MS-method A). Intermediate 24: (S)-2-amino-2-(3,4-difluorophenyl)-N-(4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (66 mg) afforded 54 mg of the title compound that was used directly in the next step. LC / MS: m / z =^433.0^[M+H]+; rt: 1.13^min (LC / MS-method A). Intermediate 25: (S)-2-amino-N-(4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)-2-(4-fluoro-3-methylphenyl)acetamide Step 1: tert-butyl ((S)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 24 (Step 1) employing tert-butyl (2-amino-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)carbamate (2.69 g) afforded the product (4.30 g) as a diastereomeric mixture. Separation by SFC (Column: Kromasil (S,S) Whelk-O150 × 4.6 mm I.D., 3.5 ^m; Mobile phase: Phase A for CO2, and Phase B: MeOH (0.05% DEA) in CO2from 5% to 40%) afforded two peaks and the first peak was collected and the diastereomers were^separated again by SFC (Column: Chiralpak IF-350 mm x 4.6 mm I.D., 3 ^m; Mobile phase: Phase A for CO2, and Phase B for IPA (0.05% DEA); Gradient elution: 40% IPA (0.05% DEA) in CO2). The title compound (313 mg, colorless solid) was collected as the second eluting diastereomer. LC / MS: m / z =^529.1^[M+H]+; rt: 2.10^min (LC / MS-method A). Intermediate 25: (S)-2-amino-N-(4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)-2-(4-fluoro-3-methylphenyl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2- yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)carbamate (57 mg) afforded 42 mg of the title compound that was used directly in the next step. LC / MS: m / z =^429.1^[M+H]+; rt: 1.18^min (LC / MS-method A). Intermediate 26: (S)-2-amino-2-(3-chloro-4-fluorophenyl)-N-(4-((R)-1-(5-fluoro-2- oxo-1,2-dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 24 (Step 1) employing tert-butyl (2-amino-1-(3-chloro-4-fluorophenyl)-2-oxoethyl)carbamate (2.50 g) afforded the product (3.50 g) as a diastereomeric mixture. Separation by SFC (Column: Cellulose-250 mm × 4.6 mm I.D., 3um; Mobile phase: Phase A for CO2, and Phase B for EtOH (0.05%DEA); Gradient elution: EtOH (0.05% DEA) in CO2from 5% to 40%) afforded two peaks and the first peak was collected and the diastereomers were^separated again by SFC (Column: Chiralpak AD-350 mm × 4.6 mm I.D., 3 ^m; Mobile phase: Phase A for CO2, and Phase B for IPA (0.05% DEA); Gradient elution: 40% IPA (0.05% DEA) in CO2). The title compound (379 mg, colorless solid) was collected as the first eluting diastereomer. LC / MS: m / z =^549.0^[M+H]+; rt: 2.20^min (LC / MS-method A). Intermediate 26: (S)-2-amino-2-(3-chloro-4-fluorophenyl)-N-(4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)- 2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (54 mg) afforded 44 mg of the title compound that was used directly in the next step. LC / MS: m / z =^449.0^[M+H]+; rt: 1.27^min (LC / MS-method A). 3-yl)-2- 2- Prepared following the procedure described for Intermediate 24 (Step 1) employing tert-butyl (2-amino-1-(3-chlorophenyl)-2-oxoethyl)carbamate (2.50 g) afforded the product (3.90 g) as a diastereomeric mixture. Separation by SFC (Column: (S.S) Whelk-O150 mm ×4.6 mm I.D., 3.5um; Mobile phase: Phase A for CO2, and Phase B for IPA (0.05% DEA); Gradient elution: IPA (0.05% DEA) in CO2 from 5% to 40%) afforded two peaks and the first peak was collected and the diastereomers were^separated again by SFC (Column: Chiralpak AD-350 mm × 4.6 mm I.D., 3 ^m; Mobile phase: Phase A for CO2, and Phase B for EtOH (0.05% DEA); Gradient elution: 40%B in A). The title compound (362 mg, colorless solid) was collected as the second eluting diastereomer. LC / MS: m / z =^531.2^[M+H]+; rt: 2.12^min (LC / MS-method A). Intermediate 27: (S)-2-amino-2-(3-chlorophenyl)-N-(4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(3-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (27 mg) afforded 19 mg of the title compound that was used directly in the next step. LC / MS: m / z =^431.1^[M+H]+; rt: 0.87^min (LC / MS-method B). Intermediate 28: (S)-2-amino-2-(4-chloro-3-fluorophenyl)-N-(4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2- oxoethyl)carbamate Prepared following the procedure described for Intermediate 5 (Step 1) employing tert-butyl (S)-(2-amino-1-(4-chloro-3-fluorophenyl)-2-oxoethyl)carbamate (3.1 g) and (S)- 1-(1-(2-Aminopyridin-4-yl)-2-methoxyethyl)-5,5-difluorotetrahydropyrimidin-2(1H)-one (Intermediate 2; 2.00g) afforded the crude product (3.2g). Separation of the diastereomers by SFC (Column: Chiralpak IE-350 mm × 4.6 mm I.D., 3 ^m Mobile phase: Phase A for CO2, and Phase B for EtOH (0.05% DEA); Gradient elution: 40% EtOH (0.05% DEA) in CO2afforded the title compound (1.3 g, colorless solid) as the second eluting diastereomer. LC / MS: m / z =^572.1^[M+H]+; rt: 2.22^min (LC / MS-method A).^ Intermediate 28: (S)-2-amino-2-(4-chloro-3-fluorophenyl)-N-(4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (290 mg) afforded 195 mg of the title compound that was used directly in the next step. LC / MS: m / z =^472.1^[M+H]+; rt: 1.27^min (LC / MS-method A). Intermediate 29: 2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)-2-(4-fluoro-3-methylphenyl)acetamide Step 1: tert-butyl (2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 19 (Step 1) employing tert-butyl (2-amino-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)carbamate (989 mg) afforded 713 mg of the title compound as the first eluting diastereomer after SFC (Column: Chiralpak AD-350 mm x 4.6 mm I.D., 3 ^m Mobile phase: Phase A for CO2, and Phase B for IPA (0.05% DEA); Gradient elution: IPA (0.05% DEA) in CO2 from 10% to 60%) as colorless solid. LC / MS: m / z =^552.1^[M+H]+; rt: 2.15^min (LC / MS-method A). -yl)-2- Prepared following the procedure described for Intermediate 5 employing tert- butyl (2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)- pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)carbamate (280 mg) afforded 230 mg of the title compound that was used directly in the next step. LC / MS: m / z =^452.1^[M+H]+; rt: 1.22^min (LC / MS-method A). Intermediate 30: 2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)-2-(3-fluoro-4-methylphenyl)acetamide Step 1: benzyl (2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)carbamate Prepared following the procedure described for Intermediate 16 (Step 1) employing benzyl (2-amino-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)carbamate (4.99 g) afforded 1.7 g of the title compound as the first eluting diastereomer with SFC ((column: DAICEL CHIRALPAK AD (250 mm x 30 mm, 10 ^m); mobile phase: [CO2-ACN / i- PrOH(0.1% NH3•H2O)]; gradient:60 % B over 6.5 min). LC / MS: m / z =^586.1^[M+H]+; rt: 2.20^min (LC / MS-method A).^ Intermediate 30: 2-amino-N-(4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)-2-(3-fluoro-4-methylphenyl)acetamide Prepared following the procedure described for Intermediate 4 employing benzyl (2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2- yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)carbamate (295 mg) afforded 215 mg of the title compound that was used directly in the next step. LC / MS: m / z =^452.1^[M+H]+; rt: 1.23^min (LC / MS-method A).^ Intermediate 31: (S)-2-amino-2-(4-chlorophenyl)-N-(4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Step 1: tert-butyl ((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin- 3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate To a solution of tert-butyl (2-amino-1-(4-chlorophenyl)-2-oxoethyl)carbamate (3.91 g) and 3-(1-(2-aminopyridin-4-yl)-2-methoxyethyl)-5-fluoropyridin-2(1H)-one (Intermediate 3; 2.0 g) in pyridine (20 ml) was added EDCI (4.37 g) and the mixture was stirred at 25°C for 1h before the reaction mixture was filtered and diluted with water (50 ml) and extracted with EA (3 x 50 ml). The combined organic layers were washed with brine (2 x 20 ml), dried over anhydrous Na2SO4, filtered^and concentrated under reduced pressure. The residue was purified by prep-HPLC (TFA condition; column: Phenomenex luna C18250 mm x 80 mm x 10 ^m; mobile phase: [water(TFA)-ACN]; gradient: 24%-54% B over 20 min) to afford 2.5 g of the crude product as a colorless solid. Separation by SFC (Column: Chiralpak IK-350 mm x 4.6 mm I.D., 3 ^m Mobile phase: Phase A for CO2, and Phase B for IPA (0.05% DEA); Gradient elution: IPA (0.05% DEA) in CO2from 5% to 40% Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35°C; Back Pressure: 100 Bar) afforded the title compound (430 mg, colorless solid) as the first eluting diastereomer. LC / MS: m / z =^531.1^[M+H]+; rt: 2.11^min (LC / MS-method A). Intermediate 31: (S)-2-amino-2-(4-chlorophenyl)-N-(4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)acetamide Prepared following the procedure described for Intermediate 5 employing tert- butyl ((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (220 mg) afforded 175 mg of the title compound that was used directly in the next step. LC / MS: m / z =^431.1^[M+H]+; rt: 1.18^min (LC / MS-method A). Example Compounds The final coupling step was performed either as described for Example 1 (method A) or Example 2 (method B) as described below. Example 1: N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl- 1H-pyrazole-5-carboxamide Method A: ((S)-2-amino-2-(4-fluorophenyl)-N-(4-((S)-2-methoxy-1-((S)-2-oxo- 4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide (Intermediate 4, 34mg) was dissolved in dry DMF (1.0 ml) and added dropwise to a mixture of 11 mg 2- methylpyrazole-3-carboxylic acid in dry DMF (1.0 ml) containing HATU (43 mg) and DIPEA (39 µl), and the reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was evaporated before being purified by preparative RP-HPLC (Waters Sunfire Prep C18 OBD 5 µm 50 mm x 100 mm; 120 ml / min, H2O (+ 0.1% TFA) / 10 % ACN to 10 % H2O (+0.1% TFA) / 90 %) to afford 40 mg of the title compound after freeze drying of the fractions containing pure product. LC / MS: m / z = 564.2 [M+H]+; rt: 1.75 min (LC / MS-method A);1H NMR (400 MHz, DMSO) δ 10.98 (s, 1H), 8.97 (d, J = 7.0 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 7.98 (s, 1H), 7.65 – 7.58 (m, 3H), 7.46 (d, J = 2.1 Hz, 1H), 7.26 – 7.19 (m, 2H), 7.09 (d, J = 2.1 Hz, 1H), 7.01 (d, J = 5.3 Hz, 1H), 5.89 (d, J = 7.0 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.38 (m, 1H), 4.03 (s, 3H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.79 – 3.69 (m, 2H), 3.32 – 3.24 (m, 4H). Example 2: N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl- 1,2,5-oxadiazole-3-carboxamide Method B: 4-Methyl-1,2,5-oxadiazole-3-carboxylic acid (10 mg) was dissolved in DCM (2.0 ml) with stirring and DIPEA (35 µl) and T3P (118 µl, 50% in EA) were added followed by dropwise addition of ((S)-2-amino-2-(4-fluorophenyl)-N-(4-((S)-2-methoxy-1- ((S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)acetamide (Intermediate 4, 30 mg) dissolved in DCM (1.0 ml). After 16 h stirring was stopped and the reaction mixture was evaporated before being purified by preparative RP-HPLC (Waters Sunfire Prep C18 OBD 5 µm 50 mm x 100 mm; 120 ml / min, H2O (+ 0.1% TFA) / 10 % ACN to 10 % H2O (+0.1% TFA) / 90 %) to afford 26 mg of the title compound after freeze drying of the fractions containing pure product. LC / MS: m / z = 566.2 [M+H]+; rt: min 2.00 (LC / MS- method A);1H NMR (400 MHz, DMSO) δ 11.01 (s, 1H), 9.62 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.66 – 7.59 (m, 3H), 7.27 – 7.19 (m, 2H), 7.01 (d, J = 5.2 Hz, 1H), 5.94 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.70 (m, 2H), 3.32 – 3.25 (m, 4H), 2.47 (s, 3H).^ Example 3: 1-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 using Method A to yield 41 mg of the title compound in 95% yield. LC / MS: m / z = 578.2 [M+H]+; rt: 1.86 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 8.96 (d, J = 6.9 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 7.97 (s, 1H), 7.66 – 7.57 (m, 3H), 7.48 (d, J = 2.1 Hz, 1H), 7.27 – 7.18 (m, 2H), 7.06 (d, J = 2.1 Hz, 1H), 7.01 (d, J = 5.3 Hz, 1H), 5.88 (d, J = 6.9 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.51 – 4.38 (m, 3H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.70 (m, 2H), 3.32 – 3.25 (m, 4H), 1.28 (t, J = 7.1 Hz, 3H). Example 4: 4-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1,2,5- oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 using Method B to yield 29 mg of the title compound in 76% yield. LC / MS: m / z = 580.2 [M+H]+; rt: 2.15 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.66 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.66 – 7.59 (m, 3H), 7.27 – 7.19 (m, 2H), 7.01 (d, J = 5.2 Hz, 1H), 5.94 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.1, 5.0 Hz, 1H), 4.49 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.70 (m, 2H), 3.32 – 3.26 (m, 4H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 5: 4-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-3- carboxamide Prepared analogously to Examples 1-2 using Method B to yield 31 mg of the title compound in 81% yield. LC / MS: m / z = 577.2 [M+H]+; rt: 2.08 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 9.47 (s, 1H), 8.93 (d, J = 6.9 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.98 (s, 1H), 7.65 – 7.57 (m, 3H), 7.27 – 7.19 (m, 2H), 7.00 (d, J = 5.2 Hz, 1H), 5.87 (d, J = 6.9 Hz, 1H), 4.99 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.26 (dd, J = 10.1, 3.9 Hz, 1H), 2.37 (s, 3H). Example 6: N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3- methylisoxazole-4-carboxamide Prepared analogously to Examples 1-2 using Method B to yield 22 mg of the title compound in 59% yield. LC / MS: m / z = 565.2 [M+H]+; rt: 1.79 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 9.47 (s, 1H), 8.93 (d, J = 6.9 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.98 (s, 1H), 7.65 – 7.57 (m, 3H), 7.27 – 7.19 (m, 2H), 7.00 (d, J = 5.2 Hz, 1H), 5.87 (d, J = 6.9 Hz, 1H), 4.99 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.26 (dd, J = 10.1, 3.9 Hz, 1H), 2.37 (s, 3H). Example 7: 3-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-4- carboxamide Prepared analogously to Examples 1-2 using Method B to yield 21 mg of the title compound in 55% yield. LC / MS: m / z = 579.2 [M+H]+; rt: 1.92 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 9.45 (s, 1H), 8.94 (d, J = 6.9 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.65 – 7.57 (m, 3H), 7.27 – 7.19 (m, 2H), 7.00 (d, J = 5.2 Hz, 1H), 5.86 (d, J = 6.9 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.27 (dd, J = 10.1, 3.9 Hz, 1H), 2.83 (q, J = 7.5 Hz, 2H), 1.17 (t, J = 7.5 Hz, 3H). Example 8: 4-ethyl-N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2- oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2- oxoethyl)isoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 5 using Method B to yield 13 mg of the title compound in 68% yield. LC / MS: m / z = 593.2 [M+H]+; rt: 2.20 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.92 (s, 1H), 8.98 (d, J = 7.3 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.63 (d, J = 2.3 Hz, 1H), 7.51 – 7.46 (m, 1H), 7.45 – 7.39 (m, 1H), 7.14 (dd, J = 9.8, 8.5 Hz, 1H), 7.00 (d, J = 5.2 Hz, 1H), 5.86 (d, J = 7.3 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.50 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.32 – 3.25 (m, 4H), 2.58 – 2.50 (m, 2H), 2.22 (d, J = 1.9 Hz, 3H), 1.12 (t, J = 7.5 Hz, 3H). Example 9: N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl- Prepared analogously to Examples 1-2 with Intermediate 5 using Method B to yield 16 mg of the title compound in 86% yield. LC / MS: m / z = 580.2 [M+H]+; rt: 2.13 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.55 (d, J = 7.1 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.63 (d, J = 2.4 Hz, 1H), 7.52 – 7.47 (m, 1H), 7.46 – 7.40 (m, 1H), 7.16 (dd, J = 9.7, 8.4 Hz, 1H), 7.01 (d, J = 5.2 Hz, 1H), 5.89 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.27 (dd, J = 10.1, 3.8 Hz, 1H), 2.47 (s, 3H), 2.23 (d, J = 1.9 Hz, 3H). Example 10: 4-ethyl-N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)- 2-oxo-4-(trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)- 1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 5 using Method B to yield 13 mg of the title compound in 68% yield. LC / MS: m / z = 594.2 [M+H]+; rt: 2.27 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.59 (d, J = 7.1 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.63 (d, J = 2.3 Hz, 1H), 7.52 – 7.40 (m, 2H), 7.16 (dd, J = 9.7, 8.5 Hz, 1H), 7.01 (d, J = 5.2 Hz, 1H), 5.89 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.70 (m, 2H), 3.32 – 3.25 (m, 4H), 2.89 (q, J = 7.5 Hz, 2H), 2.23 (d, J = 1.9 Hz, 3H), 1.23 (t, J = 7.5 Hz, 3H). Example 11: N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- Prepared analogously to Examples 1-2 with Intermediate 5 using Method B to yield 12 mg of the title compound in 65% yield. LC / MS: m / z = 579.2 [M+H]+; rt: 2.08 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 8.95 (d, J = 7.3 Hz, 1H), 8.84 (q, J = 1.1 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.63 (d, J = 2.3 Hz, 1H), 7.51 – 7.46 (m, 1H), 7.46 – 7.40 (m, 1H), 7.14 (dd, J = 9.8, 8.5 Hz, 1H), 7.00 (d, J = 5.2 Hz, 1H), 5.86 (d, J = 7.3 Hz, 1H), 5.00 (dd, J = 8.1, 5.0 Hz, 1H), 4.49 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H, overlapping water), 3.30 (s, 3H), 3.28 (dd, J = 10.1, 3.9 Hz, 1H), 2.23 (d, J = 1.9 Hz, 3H), 2.09 (d, J = 1.1 Hz, 3H). Example 12: N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl- 1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 6 using Method B to yield 17 mg of the title compound in 92% yield. LC / MS: m / z = 584.1 [M+H]+; rt: 2.07 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 9.69 (d, J = 7.2 Hz, 1H), 8.30 (d, J = 5.2 Hz, 1H), 7.95 (br s, 1H), 7.69 – 7.60 (m, 2H), 7.52 – 7.42 (m, 2H), 7.02 (d, J = 5.2 Hz, 1H), 5.95 (d, J = 7.2 Hz, 1H), 5.00 (dd, J = 8.1, 4.9 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.87 – 3.68 (m, 3H, overlapping water), 3.30 (d, J = 1.4 Hz, 3H), 3.26 (dd, J = 10.2, 3.9 Hz, 1H), 2.47 (s, 3H). Example 13: N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl- 1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 6 using Method B to yield 14 mg of the title compound in 74% yield. LC / MS: m / z = 598.1 [M+H]+; rt: 2.22 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 9.72 (d, J = 7.2 Hz, 1H), 8.30 (d, J = 5.2 Hz, 1H), 7.95 (br s, 1H), 7.69 – 7.60 (m, 2H), 7.53 – 7.42 (m, 2H), 7.02 (d, J = 5.2 Hz, 1H), 5.95 (d, J = 7.2 Hz, 1H), 5.00 (dd, J = 8.0, 4.9 Hz, 1H), 4.50 – 4.37 (m, 1H), 3.86 – 3.69 (m, 3H, overlapping water), 3.30 (s, 3H), 3.26 (dd, J = 10.0, 3.9 Hz, 1H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 14 N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 6 using Method B to yield 13 mg of the title compound in 68% yield. LC / MS: m / z = 597.2 [M+H]+; rt: 2.15 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.17 (d, J = 7.3 Hz, 1H), 8.87 (t, J = 1.1 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.95 (br s, 1H), 7.68 – 7.59 (m, 2H), 7.51 – 7.41 (m, 2H), 7.01 (d, J = 5.2 Hz, 1H), 5.92 (d, J = 7.3 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.27 (dd, J = 10.1, 3.8 Hz, 1H), 2.58 – 2.50 (m, 2H), 1.12 (t, J = 7.5 Hz, 3H). Example 15: 1-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 7 using Method A to yield 20 mg of the title compound in 79% yield. LC / MS: m / z = 578.3 [M+H]+; rt: 1.87 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.96 (s, 1H), 8.99 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 7.97 (s, 1H), 7.62 (d, J = 2.3 Hz, 1H), 7.51 – 7.37 (m, 4H), 7.22 – 7.14 (m, 1H), 7.07 (d, J = 2.1 Hz, 1H), 7.00 (d, J = 5.3 Hz, 1H), 5.92 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.51 – 4.37 (m, 3H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.68 (m, 2H), 3.30 (s, 3H), 3.25 (dd, J = 10.1, 3.9 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H). Example 16: N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl- 1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 7 using Method B to yield 17 mg of the title compound in 68% yield. LC / MS: m / z = 566.2 [M+H]+; rt: 2.01 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H), 9.67 (d, J = 7.3 Hz, 1H), 8.30 (d, J = 5.2 Hz, 1H), 7.96 (s, 1H), 7.63 (d, J = 2.3 Hz, 1H), 7.49 – 7.39 (m, 3H), 7.23 – 7.15 (m, 1H), 7.02 (d, J = 5.2 Hz, 1H), 5.98 (d, J = 7.3 Hz, 1H), 5.01 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.27 (dd, J = 10.1, 3.8 Hz, 1H), 2.47 (s, 3H). 1-((S)-2-oxo-4- -1,2,5- oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 7 using Method B to yield 17 mg of the title compound in 68% yield. LC / MS: m / z = 578.1 [M-H]-; rt: 2.17 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.05 (s, 1H), 9.71 (d, J = 7.2 Hz, 1H), 8.30 (d, J = 5.2 Hz, 1H), 7.96 (s, 1H), 7.63 (d, J = 2.3 Hz, 1H), 7.50 – 7.38 (m, 3H), 7.24 – 7.15 (m, 1H), 7.02 (d, J = 5.2 Hz, 1H), 5.98 (d, J = 7.2 Hz, 1H), 5.01 (dd, J = 8.1, 5.0 Hz, 1H), 4.50 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.27 (dd, J = 10.1, 3.8 Hz, 1H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 18: 4-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-3- carboxamide Prepared analogously to Examples 1-2 with Intermediate 7 using Method B to yield 15 mg of the title compound in 59% yield. LC / MS: m / z = 579.2 [M+H]+; rt: 2.10 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.13 (d, J = 7.4 Hz, 1H), 8.88 (s, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.96 (s, 1H), 7.63 (d, J = 2.3 Hz, 1H), 7.48 – 7.38 (m, 3H), 7.21 – 7.14 (m, 1H), 7.02 (d, J = 5.2 Hz, 1H), 5.95 (d, J = 7.4 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.50 – 4.36 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.32 – 3.24 (m, 4H), 2.59 – 2.50 (m, 2H), 1.12 (t, J = 7.5 Hz, 3H). Example 19: N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- Prepared analogously to Examples 1-2 with Intermediate 7 using Method B to yield 20 mg of the title compound in 81% yield. LC / MS: m / z = 563.1 [M-H]-; rt: 1.81 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.49 (s, 1H), 8.98 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 7.96 (s, 1H), 7.62 (d, J = 2.3 Hz, 1H), 7.49 – 7.37 (m, 3H), 7.22 – 7.15 (m, 1H), 7.01 (d, J = 5.3 Hz, 1H), 5.91 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.0, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.0 Hz, 1H), 3.79 – 3.68 (m, 2H), 3.30 (s, 3H), 3.24 (dd, J = 10.1, 3.9 Hz, 1H), 2.37 (s, 3H). Example 20: 3-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-4- carboxamide Prepared analogously to Examples 1-2 with Intermediate 7 using Method B to yield 18 mg of the title compound in 71% yield. LC / MS: m / z = 579.2 [M+H]+; rt: 1.93 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.47 (s, 1H), 8.99 (d, J = 7.0 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 7.96 (s, 1H), 7.62 (d, J = 2.3 Hz, 1H), 7.49 – 7.37 (m, 3H), 7.22 – 7.15 (m, 1H), 7.01 (d, J = 5.3 Hz, 1H), 5.91 (d, J = 7.0 Hz, 1H), 5.00 (dd, J = 8.0, 5.1 Hz, 1H), 4.49 – 4.36 (m, 1H), 3.82 (dd, J = 10.5, 8.0 Hz, 1H), 3.78 – 3.68 (m, 2H), 3.30 (s, 3H), 3.25 (dd, J = 10.1, 3.9 Hz, 1H), 2.83 (q, J = 7.5 Hz, 2H), 1.17 (t, J = 7.5 Hz, 3H). Example 21: N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 8 using Method A to yield 9 mg of the title compound in 63% yield. LC / MS: m / z = 594.2 [M+H]+; rt: 1.99 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 9.02 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.67 – 7.61 (m, 2H), 7.58 – 7.52 (m, 1H), 7.49 (d, J = 2.0 Hz, 1H), 7.46 – 7.39 (m, 2H), 7.07 (d, J = 2.0 Hz, 1H), 7.01 (d, J = 5.2 Hz, 1H), 5.90 (d, J = 7.1 Hz, 1H), 5.01 (dd, J = 8.0, 5.1 Hz, 1H), 4.51 – 4.37 (m, 3H), 3.82 (dd, J = 10.5, 8.0 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.26 (dd, J = 10.1, 3.9 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H). Example 22: N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 8 using Method B to yield 6 mg of the title compound in 31% yield. LC / MS: m / z = 595.2 [M+H]+; rt: 2.22 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.16 (d, J = 7.3 Hz, 1H), 8.87 (s, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.96 (s, 1H), 7.67 – 7.61 (m, 2H), 7.57 – 7.51 (m, 1H), 7.46 – 7.38 (m, 2H), 7.01 (d, J = 5.2 Hz, 1H), 5.92 (d, J = 7.3 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.83 (dd, J = 10.6, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.32 – 3.25 (m, 4H), 2.59 – 2.50 (m, 2H), 1.12 (t, J = 7.5 Hz, 3H). Example 23: N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl- Prepared analogously to Examples 1-2 with Intermediate 8 using Method B to yield 5 mg of the title compound in 26% yield. LC / MS: m / z = 582.2 [M+H]+; rt: 2.14 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 9.69 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.69 – 7.60 (m, 2H), 7.59 – 7.53 (m, 1H), 7.47 – 7.40 (m, 2H), 7.02 (d, J = 5.2 Hz, 1H), 5.95 (d, J = 7.2 Hz, 1H), 5.01 (dd, J = 8.1, 5.1 Hz, 1H), 4.48 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.27 (dd, J = 10.1, 3.9 Hz, 1H), 2.47 (s, 3H). Example 24: N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl- Prepared analogously to Examples 1-2 with Intermediate 8 using Method B to yield 5 mg of the title compound in 26% yield. LC / MS: m / z = 596.2 [M+H]+; rt: 2.28 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H), 9.73 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.68 – 7.61 (m, 2H), 7.59 – 7.52 (m, 1H), 7.47 – 7.40 (m, 2H), 7.02 (d, J = 5.2 Hz, 1H), 5.95 (d, J = 7.2 Hz, 1H), 5.01 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.32 – 3.24 (m, 4H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 25: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 9 using Method B to yield 15 mg of the title compound in 59% yield. LC / MS: m / z = 595.2 [M+H]+; rt: 2.23 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 9.07 (d, J = 7.2 Hz, 1H), 8.87 (s, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.65 – 7.55 (m, 3H), 7.48 – 7.43 (m, 2H), 7.01 (d, J = 5.2 Hz, 1H), 5.91 (d, J = 7.2 Hz, 1H), 5.00 (dd, J = 8.2, 5.1 Hz, 1H), 4.50 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.2 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.32 – 3.25 (m, 4H), 2.59 – 2.50 (m, 2H), 1.12 (t, J = 7.5 Hz, 3H). Example 26: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3- ethylisoxazole-4-carboxamide Prepared analogously to Examples 1-2 with Intermediate 9 using Method B to yield 15 mg of the title compound in 59% yield. LC / MS: m / z = 595.2 [M+H]+; rt: 2.06 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.45 (s, 1H), 8.96 (d, J = 7.0 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.98 (s, 1H), 7.64 – 7.55 (m, 3H), 7.49 – 7.43 (m, 2H), 6.99 (d, J = 5.2 Hz, 1H), 5.88 (d, J = 7.0 Hz, 1H), 4.99 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.82 (dd, J = 10.6, 8.1 Hz, 1H), 3.77 – 3.69 (m, 2H), 3.30 (s, 3H), 3.26 (dd, J = 10.1, 3.9 Hz, 1H), 2.83 (q, J = 7.5 Hz, 2H), 1.17 (t, J = 7.5 Hz, 3H). Example 27: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl- 1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 9 using Method B to yield 12 mg of the title compound in 48% yield. LC / MS: m / z = 582.2 [M+H]+; rt: 2.15 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.63 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.97 (s, 1H), 7.65 – 7.57 (m, 3H), 7.50 – 7.44 (m, 2H), 7.01 (d, J = 5.2 Hz, 1H), 5.94 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.1, 5.1 Hz, 1H), 4.50 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.70 (m, 2H), 3.32 – 3.25 (m, 4H), 2.47 (s, 3H). Example 28: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3- Prepared analogously to Examples 1-2 with Intermediate 9 using Method B to yield 17 mg of the title compound in 68% yield. LC / MS: m / z = 581.2 [M+H]+; rt: 1.94 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.97 (s, 1H), 9.47 (s, 1H), 8.95 (d, J = 7.0 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 7.98 (s, 1H), 7.64 – 7.55 (m, 3H), 7.49 – 7.44 (m, 2H), 6.99 (d, J = 5.2 Hz, 1H), 5.88 (d, J = 7.0 Hz, 1H), 4.99 (dd, J = 8.1, 5.1 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.78 – 3.69 (m, 2H), 3.30 (s, 3H), 3.26 (dd, J = 10.1, 3.9 Hz, 1H), 2.37 (s, 3H). Example 29: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl- 1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 9 using Method B to yield 16 mg of the title compound in 63% yield. LC / MS: m / z = 596.2 [M+H]+; rt: 2.29 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.67 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.1 Hz, 1H), 7.97 (br s, 1H), 7.65 – 7.57 (m, 3H), 7.50 – 7.44 (m, 2H), 7.01 (d, J = 5.1 Hz, 1H), 5.94 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.2, 5.1 Hz, 1H), 4.49 – 4.38 (m, 1H), 3.82 (dd, J = 10.5, 8.2 Hz, 1H), 3.78 – 3.70 (m, 2H), 3.32 – 3.25 (m, 4H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 30: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 9 using Method A to yield 11 mg of the title compound in 43% yield. LC / MS: m / z = 594.2 [M+H]+; rt: 2.00 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.92 (s, 1H), 8.97 (d, J = 7.0 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 7.98 (s, 1H), 7.64 – 7.55 (m, 3H), 7.49 – 7.43 (m, 3H), 7.06 (d, J = 2.1 Hz, 1H), 6.99 (d, J = 5.3 Hz, 1H), 5.89 (d, J = 7.0 Hz, 1H), 5.00 (dd, J = 8.1, 5.2 Hz, 1H), 4.46 (q, J = 7.1 Hz, 3H), 3.82 (dd, J = 10.5, 8.1 Hz, 1H), 3.77 – 3.69 (m, 2H), 3.30 (s, 4H), 1.28 (t, J = 7.1 Hz, 3H). 1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 10 using Method B to yield 16 mg of the title compound in 87% yield. LC / MS: m / z = 598.0 [M-H]-; rt: 2.18 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 9.72 (d, J = 7.1 Hz, 1H), 8.30 (d, J = 5.2 Hz, 1H), 7.96 (br s, 1H), 7.81 (dd, J = 7.1, 2.3 Hz, 1H), 7.64 – 7.58 (m, 2H), 7.49 – 7.42 (m, 1H), 7.02 (d, J = 5.2 Hz, 1H), 5.94 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.0, 5.0 Hz, 1H), 4.49 – 4.37 (m, 1H), 3.86 – 3.69 (m, 3H), 3.30 (d, J = 1.4 Hz, 3H), 3.27 (dd, J = 10.1, 3.9 Hz, 1H), 2.47 (s, 3H). Example 32: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl- Prepared analogously to Examples 1-2 with Intermediate 10 using Method B to yield 15 mg of the title compound in 80% yield. LC / MS: m / z = 614.1 [M+H]+; rt: 2.32 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 9.75 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.96 (br s, 1H), 7.80 (dd, J = 7.1, 2.3 Hz, 1H), 7.65 – 7.57 (m, 2H), 7.49 – 7.43 (m, 1H), 7.02 (d, J = 5.2 Hz, 1H), 5.94 (d, J = 7.1 Hz, 1H), 5.00 (dd, J = 8.1, 4.9 Hz, 1H), 4.50 – 4.37 (m, 1H), 3.86 – 3.68 (m, 3H, 3.30 (s, 3H), 3.27 (dd, J = 10.0, 3.8 Hz, 1H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 33: N-((S)-1-(2-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl- 1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 11 using Method B to yield 15 mg of the title compound in 56% yield. LC / MS: m / z = 596.2 [M+H]+; rt: 2.22 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 9.90 (d, J = 7.4 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.05 (br s, 1H), 7.65 (d, J = 2.3 Hz, 1H), 7.56 – 7.52 (m, 1H), 7.44 – 7.32 (m, 3H), 7.02 (d, J = 5.2 Hz, 1H), 6.18 (d, J = 7.4 Hz, 1H), 5.03 (dd, J = 8.2, 5.1 Hz, 1H), 4.51 – 4.40 (m, 1H), 3.85 (dd, J = 10.5, 8.2 Hz, 1H), 3.80 – 3.72 (m, 2H), 3.34 – 3.28 (m, 4H), 2.92 (q, J = 7.5 Hz, 2H), 1.25 (t, J = 7.5 Hz, 3H). Example 34: 1-ethyl-N-((S)-1-(2-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 12 using Method A to yield 30 mg of the title compound in 94% yield. LC / MS: m / z = 578.3 [M+H]+; rt: 1.83 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.09 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 8.02 (br s, 1H), 7.65 (d, J = 2.3 Hz, 1H), 7.49 – 7.38 (m, 3H), 7.30 – 7.17 (m, 2H), 7.04 – 6.99 (m, 2H), 6.09 (d, J = 7.2 Hz, 1H), 5.03 (dd, J = 8.1, 5.1 Hz, 1H), 4.53 – 4.39 (m, 3H), 3.84 (dd, J = 10.5, 8.1 Hz, 1H), 3.79 – 3.71 (m, 2H), 3.33 – 3.26 (m, 4H), 1.29 (t, J = 7.1 Hz, 3H). Prepared analogously to Examples 1-2 with Intermediate 13 using Method B to yield 24 mg of the title compound in 70% yield. LC / MS: m / z = 578.2 [M+H]+; rt: 2.24 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H), 9.75 (d, J = 7.3 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 8.02 (br s, 1H), 7.70 – 7.66 (m, 1H), 7.59 – 7.54 (m, 1H), 7.48 – 7.40 (m, 2H), 7.06 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 36: N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 13 using Method A to yield 30 mg of the title compound in 89% yield. LC / MS: m / z = 562.2 [M+H]+; rt: 1.83 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 9.06 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 8.01 (s, 1H), 7.69 – 7.65 (m, 1H), 7.59 – 7.54 (m, 1H), 7.48 – 7.42 (m, 3H), 7.12 (d, J = 2.1 Hz, 1H), 7.09 (d, J = 5.3 Hz, 1H), 6.91 (br s, 1H), 5.94 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.6 Hz, 1H), 4.03 (s, 3H), 3.81 (d, J = 6.6 Hz, 2H), 3.71 – 3.29 (m, 7H). Prepared analogously to Examples 1-2 with Intermediate 13 using Method A to yield 30 mg of the title compound in 87% yield. LC / MS: m / z = 576.2 [M+H]+; rt: 1.94 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 9.06 (d, J = 7.1 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 8.00 (s, 1H), 7.69 – 7.65 (m, 1H), 7.59 – 7.54 (m, 1H), 7.49 (d, J = 2.0 Hz, 1H), 7.47 – 7.40 (m, 2H), 7.12 – 7.06 (m, 2H), 6.91 (br s, 1H), 5.92 (d, J = 7.1 Hz, 1H), 5.49 (t, J = 6.6 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 3.86 – 3.29 (m, 9H), 1.28 (t, J = 7.1 Hz, 3H). Example 38: N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 13 using Method B to yield 30 mg of the title compound in 89% yield. LC / MS: m / z = 564.1 [M+H]+; rt: 2.09 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H), 9.71 (d, J = 7.3 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 8.02 (s, 1H), 7.70 – 7.67 (m, 1H), 7.57 (dt, J = 6.7, 2.1 Hz, 1H), 7.47 – 7.40 (m, 2H), 7.06 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.97 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.47 (s, 3H). Example 39: N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 13 using Method B to yield 25 mg of the title compound in 73% yield. LC / MS: m / z = 577.2 [M+H]+; rt: 2.17 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 9.17 (d, J = 7.4 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 8.01 (s, 1H), 7.69 – 7.66 (m, 1H), 7.57 – 7.53 (m, 1H), 7.46 – 7.38 (m, 2H), 7.06 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.93 (d, J = 7.4 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.58 – 2.50 (m, 2H), 1.12 (t, J = 7.5 Hz, 3H). Example 40: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 14 using Method A to yield 28 mg of the title compound in 99% yield. LC / MS: m / z = 560.2 [M+H]+; rt: 1.81 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.00 (d, J = 7.3 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.03 (s, 1H), 7.51 – 7.39 (m, 4H), 7.23 – 7.14 (m, 1H), 7.10 (d, J = 2.1 Hz, 1H), 7.05 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.95 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.6 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 1.28 (t, J = 7.1 Hz, 3H). Example 41: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 14 using Method B to yield 21 mg of the title compound in 76% yield. LC / MS: m / z = 548.1 [M+H]+; rt: 1.96 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 9.68 (d, J = 7.4 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.50 – 7.41 (m, 3H), 7.24 – 7.15 (m, 1H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.99 (d, J = 7.4 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.47 (s, 3H). Example 42: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 14 using Method B to yield 21 mg of the title compound in 74% yield. LC / MS: m / z = 562.1 [M+H]+; rt: 2.11 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.03 (s, 1H), 9.72 (d, J = 7.4 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.50 – 7.40 (m, 3H), 7.24 – 7.15 (m, 1H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.99 (d, J = 7.4 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 43: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-ethylisoxazole- 3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 14 using Method B to yield 21 mg of the title compound in 75% yield. LC / MS: m / z = 561.2 [M+H]+; rt: 2.05 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 9.13 (d, J = 7.5 Hz, 1H), 8.88 (t, J = 1.1 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.01 (s, 1H), 7.48 – 7.39 (m, 3H), 7.22 – 7.14 (m, 1H), 7.06 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.5 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.58 – 2.50 (m, 2H), 1.12 (t, J = 7.5 Hz, 3H). Example 44: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 15 using Method A to yield 24 mg of the title compound in 92% yield. LC / MS: m / z = 562.0 [M+H]+; rt: 1.84 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.04 (br s, 1H), 9.01 (d, J = 7.1 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.01 (s, 1H), 7.63 – 7.57 (m, 2H), 7.51 – 7.44 (m, 3H), 7.11 (d, J = 2.1 Hz, 1H), 7.07 (d, J = 5.2 Hz, 1H), 6.90 (br s, 1H), 5.92 (d, J = 7.1 Hz, 1H), 5.49 (t, J = 6.6 Hz, 1H), 4.03 (s, 3H), 3.84 – 3.29 (m, 9H). Example 45: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 15 using Method A to yield 23 mg of the title compound in 86% yield. LC / MS: m / z = 576.0 [M+H]+; rt: 1.95 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.05 (br s, 1H), 9.00 (d, J = 7.1 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.01 (s, 1H), 7.63 – 7.57 (m, 2H), 7.50 – 7.44 (m, 3H), 7.10 – 7.05 (m, 2H), 6.90 (br s, 1H), 5.91 (d, J = 7.1 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 1.28 (t, J = 7.1 Hz, 3H). Example 46: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 15 using Method B to yield 26 mg of the title compound in 99% yield. LC / MS: m / z = 564.0 [M+H]+; rt: 2.09 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 9.65 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.64 – 7.58 (m, 2H), 7.51 – 7.45 (m, 2H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.47 (s, 3H). Example 47: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- 4-ethyl-1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 15 using Method B to yield 26 mg of the title compound in 97% yield. LC / MS: m / z = 578.0 [M+H]+; rt: 2.23 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 9.69 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (br s, 1H), 7.64 – 7.57 (m, 2H), 7.51 – 7.45 (m, 2H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 48: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 15 using Method B to yield 22 mg of the title compound in 84% yield. LC / MS: m / z = 563.0 [M+H]+; rt: 2.04 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.05 (d, J = 7.4 Hz, 1H), 8.85 (q, J = 1.1 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.01 (s, 1H), 7.63 – 7.57 (m, 2H), 7.49 – 7.43 (m, 2H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.92 (d, J = 7.4 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.09 (d, J = 1.1 Hz, 3H). Example 49: N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- 4-ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 15 using Method B to yield 23 mg of the title compound in 86% yield. LC / MS: m / z = 577.0 [M+H]+; rt: 2.17 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 9.08 (d, J = 7.4 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.01 (s, 1H), 7.63 – 7.57 (m, 2H), 7.49 – 7.43 (m, 2H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.92 (d, J = 7.4 Hz, 1H), 5.48 (t, J = 6.7 Hz, 1H), 3.80 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.58 – 2.50 (m, 2H), 1.12 (t, J = 7.5 Hz, 3H). Example 50: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-methyl-1,2,5-oxadiazole- 3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 16 using Method B to yield 17 mg of the title compound in 75% yield. LC / MS: m / z = 544.1 [M+H]+; rt: 2.03 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.52 (d, J = 7.3 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.03 (s, 1H), 7.43 – 7.36 (m, 2H), 7.31 – 7.25 (m, 1H), 7.16 (br d, J = 7.6 Hz, 1H), 7.05 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.91 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.47 (s, 3H), 2.31 (s, 3H). Example 51: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide Prepared analogously to Examples 1-2 with Intermediate 16 using Method B to yield 21 mg of the title compound in 91% yield. LC / MS: m / z = 558.1 [M+H]+; rt: 2.18 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.94 (s, 1H), 9.56 (d, J = 7.3 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.03 (s, 1H), 7.42 – 7.36 (m, 2H), 7.31 – 7.25 (m, 1H), 7.16 (br d, J = 7.6 Hz, 1H), 7.05 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.91 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 2.31 (s, 3H), 1.23 (t, J = 7.5 Hz, 3H). Example 52: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-methylisoxazole-3- carboxamide Prepared analogously to Examples 1-2 with Intermediate 16 using Method B to yield 14 mg of the title compound in 62% yield. LC / MS: m / z = 543.1 [M+H]+; rt: 1.98 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 8.89 (d, J = 7.5 Hz, 1H), 8.85 (q, J = 1.1 Hz, 1H), 8.27 (d, J = 5.3 Hz, 1H), 8.02 (s, 1H), 7.42 – 7.35 (m, 2H), 7.30 – 7.24 (m, 1H), 7.15 (br d, J = 7.6 Hz, 1H), 7.05 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.88 (d, J = 7.5 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.31 (s, 3H), 2.10 (d, J = 1.1 Hz, 3H). Example 53: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-ethylisoxazole-3- carboxamide Prepared analogously to Examples 1-2 with Intermediate 16 using Method B to yield 17 mg of the title compound in 73% yield. LC / MS: m / z = 555.0 [M-H]-; rt: 2.11 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.92 (s, 1H), 8.92 (d, J = 7.5 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.41 – 7.35 (m, 2H), 7.30 – 7.24 (m, 1H), 7.14 (br d, J = 7.5 Hz, 1H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.88 (d, J = 7.5 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.55 (qd, J = 7.5, 1.0 Hz, 2H), 2.30 (s, 3H), 1.12 (t, J = 7.5 Hz, 3H). Example 54: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(p-tolyl)ethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide Prepared analogously to Examples 1-2 with Intermediate 17 using Method B to yield 11 mg of the title compound in 47% yield. LC / MS: m / z = 558.1 [M+H]+; rt: 2.18 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.92 (s, 1H), 9.55 (d, J = 7.3 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.02 (br s, 1H), 7.49 – 7.44 (m, 2H), 7.23 – 7.17 (m, 2H), 7.04 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.90 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.80 (d, J = 6.7 Hz, 2H, overlapping water), 3.72 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 2.28 (s, 3H), 1.23 (t, J = 7.5 Hz, 3H). Example 55: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(p-tolyl)ethyl)-4-ethylisoxazole-3- carboxamide Prepared analogously to Examples 1-2 with Intermediate 17 using Method B to yield 11 mg of the title compound in 47% yield. LC / MS: m / z = 557.1 [M+H]+; rt: 2.12 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 8.91 (d, J = 7.4 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.01 (s, 1H), 7.49 – 7.43 (m, 2H), 7.22 – 7.16 (m, 2H), 7.04 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.88 (d, J = 7.4 Hz, 1H), 5.48 (t, J = 6.7 Hz, 1H), 3.80 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.60 – 2.51 (m, 2H), 2.28 (s, 3H), 1.12 (t, J = 7.5 Hz, 3H). Prepared analogously to Examples 1-2 with Intermediate 18 using Method B to yield 23 mg of the title compound in 91% yield. LC / MS: m / z = 530.1 [M+H]+; rt: 1.91 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.58 (d, J = 7.3 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.03 (br s, 1H), 7.62 – 7.56 (m, 2H), 7.44 – 7.31 (m, 3H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.28 (m, 7H), 2.47 (s, 3H). Example 57: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide Prepared analogously to Examples 1-2 with Intermediate 18 using Method B to yield 23 mg of the title compound in 88% yield. LC / MS: m / z = 544.2 [M+H]+; rt: 2.06 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.63 (d, J = 7.3 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.03 (br s, 1H), 7.62 – 7.56 (m, 2H), 7.44 – 7.31 (m, 3H), 7.05 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 58: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)-4-ethylisoxazole-3- carboxamide Prepared analogously to Examples 1-2 with Intermediate 18 using Method B to yield 19 mg of the title compound in 73% yield. LC / MS: m / z = 543.2 [M+H]+; rt: 1.99 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.97 (s, 1H), 8.99 (d, J = 7.5 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.02 (s, 1H), 7.61 – 7.55 (m, 2H), 7.42 – 7.30 (m, 3H), 7.05 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.93 (d, J = 7.5 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.28 (m, 7H), 2.55 (qd, J = 7.5, 1.1 Hz, 2H), 1.12 (t, J = 7.5 Hz, 3H). -2- Prepared analogously to Examples 1-2 with Intermediate 19 using Method A to yield 32 mg of the title compound in 93% yield. LC / MS: m / z = 596.1 [M+H]+; rt: 1.93 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 9.12 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.03 (br s, 1H), 7.97 (br s, 1H), 7.90 (br d, J = 7.7 Hz, 1H), 7.72 (br d, J = 7.8 Hz, 1H), 7.68 – 7.62 (m, 1H), 7.47 (d, J = 2.1 Hz, 1H), 7.11 (d, J = 2.1 Hz, 1H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 6.03 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 4.03 (s, 3H), 3.80 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H). Example 60: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-1-ethyl- 1H-pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 19 using Method A to yield 31 mg of the title compound in 88% yield. LC / MS: m / z = 610.1 [M+H]+; rt: 2.03 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.02 (s, 1H), 9.12 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.97 (br s, 1H), 7.90 (br d, J = 7.7 Hz, 1H), 7.72 (br d, J = 7.8 Hz, 1H), 7.68 – 7.62 (m, 1H), 7.49 (d, J = 2.0 Hz, 1H), 7.08 (d, J = 2.1 Hz, 1H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 6.02 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 3.80 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 1.28 (t, J = 7.1 Hz, 3H). Example 61: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4- methyl-1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 19 using Method B to yield 35 mg of the title compound in 98% yield. LC / MS: m / z = 598.2 [M+H]+; rt: 2.17 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 9.81 (d, J = 7.3 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.04 – 7.97 (m, 2H), 7.91 (br d, J = 7.7 Hz, 1H), 7.73 (br d, J = 7.8 Hz, 1H), 7.69 – 7.62 (m, 1H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 6.06 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.47 (s, 3H). Example 62: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4-ethyl- Prepared analogously to Examples 1-2 with Intermediate 19 using Method B to yield 35 mg of the title compound in 96% yield. LC / MS: m / z = 612.2 [M+H]+; rt: 2.30 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.09 (s, 1H), 9.85 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.04 – 7.97 (m, 2H), 7.90 (br d, J = 7.8 Hz, 1H), 7.73 (br d, J = 7.8 Hz, 1H), 7.69 – 7.63 (m, 1H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (s, 1H), 6.06 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.6 Hz, 1H), 3.81 (d, J = 6.6 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 1.22 (t, J = 7.5 Hz, 3H). Example 63: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4- methylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 19 using Method B to yield 33 mg of the title compound in 93% yield. LC / MS: m / z = 597.2 [M+H]+; rt: 2.11 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.06 (s, 1H), 9.26 (d, J = 7.3 Hz, 1H), 8.85 (q, J = 1.1 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.03 – 7.97 (m, 2H), 7.89 (br d, J = 7.7 Hz, 1H), 7.72 (br d, J = 7.8 Hz, 1H), 7.68 – 7.60 (m, 1H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 6.02 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.09 (d, J = 1.1 Hz, 3H). Example 64: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4- ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 19 using Method B to yield 36 mg of the title compound in 99% yield. LC / MS: m / z = 611.2 [M+H]+; rt: 2.24 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.06 (s, 1H), 9.30 (d, J = 7.2 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.03 – 7.97 (m, 2H), 7.89 (br d, J = 7.8 Hz, 1H), 7.72 (br d, J = 7.8 Hz, 1H), 7.67 – 7.61 (m, 1H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 6.02 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.70 – 3.29 (m, 7H), 2.58 – 2.48 (m, 2H), 1.11 (t, J = 7.5 Hz, 3H). Example 65: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 20 using Method A to yield 20 mg of the title compound in 78% yield. LC / MS: m / z = 560.2 [M+H]+; rt: 1.80 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.91 (s, 1H), 8.96 (d, J = 7.1 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.03 (s, 1H), 7.66 – 7.59 (m, 2H), 7.48 (d, J = 2.0 Hz, 1H), 7.27 – 7.19 (m, 2H), 7.08 (d, J = 2.0 Hz, 1H), 7.04 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.90 (d, J = 7.1 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 3.80 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 1.28 (t, J = 7.1 Hz, 3H). Prepared analogously to Examples 1-2 with Intermediate 20 using Method B to yield 18 mg of the title compound in 72% yield. LC / MS: m / z = 548.2 [M+H]+; rt: 1.95 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.63 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.67 – 7.60 (m, 2H), 7.28 – 7.20 (m, 2H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.47 (s, 3H). Example 67: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)-4-(2,2,2- - Prepared analogously to Examples 1-2 with Intermediate 20 using Method B to yield 18 mg of the title compound in 62% yield. LC / MS: m / z = 632.2 [M+H]+; rt: 2.12 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.05 (s, 1H), 9.67 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (br s, 1H), 7.66 – 7.58 (m, 2H), 7.27 – 7.19 (m, 2H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.2 Hz, 1H), 5.48 (t, J = 6.7 Hz, 1H), 5.21 – 5.11 (m, 2H), 3.80 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H). Example 68: N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 21 using Method A to yield 35 mg of the title compound in 98% yield. LC / MS: m / z = 576.0 [M+H]+; rt: 1.97 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.92 (s, 1H), 8.94 (d, J = 7.1 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.55 (br s, 1H), 7.48 – 7.39 (m, 3H), 7.10 (d, J = 2.1 Hz, 1H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.87 (d, J = 7.1 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 4.03 (s, 3H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.34 (s, 3H). Example 69: N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 21 using Method A to yield 36 mg of the title compound in 98% yield. LC / MS: m / z = 590.1 [M+H]+; rt: 2.07 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.91 (s, 1H), 8.93 (d, J = 7.1 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.55 (br s, 1H), 7.48 (d, J = 2.0 Hz, 1H), 7.46 – 7.39 (m, 2H), 7.07 (d, J = 2.1 Hz, 1H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.86 (d, J = 7.1 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 3.80 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.34 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H). Example 70: N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2- oxoethyl)benzamide Prepared analogously to Examples 1-2 with Intermediate 21 using Method A to yield 35 mg of the title compound in 98% yield. LC / MS: m / z = 572.0 [M+H]+; rt: 2.17 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 8.93 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.96 – 7.90 (m, 2H), 7.60 (br s, 1H), 7.58 – 7.52 (m, 1H), 7.51 – 7.40 (m, 4H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.91 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.28 (m, 7H), 2.34 (s, 3H). Example 71: N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 21 using Method B to yield 35 mg of the title compound in 98% yield. LC / MS: m / z = 577.0 [M+H]+; rt: 2.17 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 9.00 (d, J = 7.4 Hz, 1H), 8.85 (q, J = 1.1 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.01 (s, 1H), 7.56 (s, 1H), 7.46 – 7.40 (m, 2H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.88 (d, J = 7.4 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.33 (s, 3H), 2.09 (d, J = 1.1 Hz, 3H). Example 72: N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- 4-ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 21 using Method B to yield 36 mg of the title compound in 98% yield. LC / MS: m / z = 591.1 [M+H]+; rt: 2.30 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.97 (s, 1H), 9.03 (d, J = 7.4 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.00 (s, 1H), 7.56 (s, 1H), 7.46 – 7.40 (m, 2H), 7.05 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.88 (d, J = 7.4 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.59 – 2.51 (m, 2H), 2.33 (s, 3H), 1.12 (t, J = 7.5 Hz, 3H). Example 73: N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 21 using Method B to yield 34 mg of the title compound in 95% yield. LC / MS: m / z = 578.0 [M+H]+; rt: 2.22 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.60 (d, J = 7.3 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.01 (br s, 1H), 7.57 (s, 1H), 7.47 – 7.41 (m, 2H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.91 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.47 (s, 3H), 2.33 (s, 3H). Example 74: N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 21 using Method B to yield 35 mg of the title compound in 95% yield. LC / MS: m / z = 592.0 [M+H]+; rt: 2.36 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.64 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.01 (br s, 1H), 7.56 (br s, 1H), 7.47 – 7.41 (m, 2H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.91 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 2.33 (s, 3H), 1.23 (t, J = 7.5 Hz, 3H). Example 75: N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 21 using Method B to yield 34 mg of the title compound in 91% yield. LC / MS: m / z = 604.0 [M+H]+; rt: 2.39 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.69 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.01 (br s, 1H), 7.57 (s, 1H), 7.49 – 7.41 (m, 2H), 7.06 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.92 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.34 (s, 3H), 2.26 (tt, J = 8.3, 5.0 Hz, 1H), 1.18 – 1.06 (m, 2H), 1.04 – 0.92 (m, 2H). Example 76: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 22 using Method A to yield 40 mg of the title compound in 97% yield. LC / MS: m / z = 556.2 [M+H]+; rt: 1.91 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.83 (s, 1H), 8.85 (d, J = 7.2 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H), 8.03 (s, 1H), 7.46 (d, J = 2.1 Hz, 1H), 7.19 (br s, 2H), 7.12 (d, J = 2.1 Hz, 1H), 7.04 (d, J = 5.2 Hz, 1H), 6.97 (br s, 1H), 6.89 (br s, 1H), 5.82 (d, J = 7.2 Hz, 1H), 5.50 (t, J = 6.7 Hz, 1H), 4.03 (s, 3H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.27 (s, 6H). Example 77: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 22 using Method A to yield 36 mg of the title compound in 94% yield. LC / MS: m / z = 570.2 [M+H]+; rt: 2.01 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.82 (br s, 1H), 8.84 (d, J = 7.2 Hz, 1H), 8.27 (d, J = 5.3 Hz, 1H), 8.03 (br s, 1H), 7.47 (d, J = 2.1 Hz, 1H), 7.19 (br s, 2H), 7.09 (d, J = 2.1 Hz, 1H), 7.04 (d, J = 5.3 Hz, 1H), 6.97 (br s, 1H), 6.89 (br s, 1H), 5.81 (d, J = 7.1 Hz, 1H), 5.50 (t, J = 6.7 Hz, 1H), 4.47 (q, J = 7.1 Hz, 2H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.27 (s, 6H), 1.28 (t, J = 7.1 Hz, 3H). Example 78: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4-methyl- Prepared analogously to Examples 1-2 with Intermediate 22 using Method B to yield 35 mg of the title compound in 93% yield. LC / MS: m / z = 558.1 [M+H]+; rt: 2.17 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.92 (s, 1H), 9.46 (d, J = 7.3 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.02 (s, 1H), 7.20 (br s, 2H), 7.05 (d, J = 5.3 Hz, 1H), 6.98 (br s, 1H), 6.89 (br s, 1H), 5.86 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.47 (s, 3H), 2.27 (s, 6H). Example 79: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 22 using Method B to yield 30 mg of the title compound in 78% yield. LC / MS: m / z = 572.2 [M+H]+; rt: 2.31 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.92 (s, 1H), 9.51 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 8.02 (s, 1H), 7.20 (br s, 2H), 7.05 (d, J = 7.3 Hz, 1H), 6.98 (br s, 1H), 6.89 (br s, 1H), 5.86 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 2.27 (s, 6H), 1.23 (t, J = 7.5 Hz, 3H). Example 80: 4-cyclopropyl-N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydro- pyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2- - Prepared analogously to Examples 1-2 with Intermediate 22 using Method B to yield 34 mg of the title compound in 87% yield. LC / MS: m / z = 584.2 [M+H]+; rt: 2.34 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 9.57 (d, J = 7.3 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.21 (br s, 2H), 7.05 (d, J = 5.2 Hz, 1H), 6.98 (br s, 1H), 6.89 (br s, 1H), 5.87 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.30 – 2.21 (m, 7H), 1.18 – 1.07 (m, 2H), 1.02 – 0.93 (m, 2H). Example 81: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4- Prepared analogously to Examples 1-2 with Intermediate 22 using Method B to yield 32 mg of the title compound in 86% yield. LC / MS: m / z = 557.1 [M+H]+; rt: 2.11 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 8.87 – 8.80 (m, 2H), 8.28 (d, J = 5.2 Hz, 1H), 8.01 (s, 1H), 7.19 (s, 2H), 7.05 (d, J = 5.2 Hz, 1H), 6.96 (s, 1H), 6.89 (s, 1H), 5.83 (d, J = 7.5 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.26 (s, 6H), 2.10 (d, J = 1.1 Hz, 3H). Example 82: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 22 using Method B to yield 35 mg of the title compound in 91% yield. LC / MS: m / z = 571.2 [M+H]+; rt: 2.24 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 8.89 – 8.83 (m, 2H), 8.28 (d, J = 5.3 Hz, 1H), 8.01 (s, 1H), 7.19 (br s, 2H), 7.05 (d, J = 5.3 Hz, 1H), 6.96 (br s, 1H), 6.89 (br s, 1H), 5.83 (d, J = 7.5 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.72 – 3.29 (m, 7H), 2.55 (qd, J = 7.5, 1.0 Hz, 2H), 2.26 (s, 6H), 1.13 (t, J = 7.5 Hz, 3H). Example 83: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 23 using Method A to yield 42 mg of the title compound in 97% yield. LC / MS: m / z = 580.1 [M+H]+; rt: 1.88 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 9.03 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.81 (dd, J = 7.1, 2.2 Hz, 1H), 7.61 (ddd, J = 8.7, 4.7, 2.2 Hz, 1H), 7.50 – 7.43 (m, 2H), 7.11 (d, J = 2.1 Hz, 1H), 7.07 – 7.03 (m, 1H), 6.89 (br s, 1H), 5.93 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 4.03 (s, 3H), 3.81 (d, J = 6.7 Hz, 2H), 3.70 – 3.29 (m, 7H). Prepared analogously to Examples 1-2 with Intermediate 23 using Method A to yield 38 mg of the title compound in 97% yield. LC / MS: m / z = 594.1 [M+H]+; rt: 1.98 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.97 (s, 1H), 9.02 (d, J = 7.1 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 7.81 (dd, J = 7.2, 2.3 Hz, 1H), 7.61 (ddd, J = 8.6, 4.7, 2.3 Hz, 1H), 7.51 – 7.42 (m, 2H), 7.09 – 7.03 (m, 2H), 6.89 (br s, 1H), 5.91 (d, J = 7.1 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 3.80 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 1.28 (t, J = 7.1 Hz, 3H). Example 85: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2- oxoethyl)benzamide Prepared analogously to Examples 1-2 with Intermediate 23 using Method A to yield 36 mg of the title compound in 98% yield. LC / MS: m / z = 576.1 [M+H]+; rt: 2.09 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.02 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.04 – 8.00 (m, 1H), 7.95 – 7.90 (m, 2H), 7.85 (dd, J = 7.2, 2.2 Hz, 1H), 7.64 (ddd, J = 8.7, 4.7, 2.2 Hz, 1H), 7.59 – 7.53 (m, 1H), 7.52 – 7.42 (m, 3H), 7.05 (d, J = 5.2 Hz, 1H), 6.88 (br s, 1H), 5.95 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.28 (m, 7H). Example 86: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- 4-methyl-1,2,5-oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 23 using Method B to yield 35 mg of the title compound in 94% yield. LC / MS: m / z = 582.1 [M+H]+; rt: 2.12 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H), 9.73 (d, J = 7.3 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.01 (br s, 1H), 7.83 (dd, J = 7.1, 2.2 Hz, 1H), 7.62 (ddd, J = 8.7, 4.6, 2.2 Hz, 1H), 7.51 – 7.42 (m, 1H), 7.07 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.47 (s, 3H). Example 87: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 23 using Method B to yield 35 mg of the title compound in 92% yield. LC / MS: m / z = 596.1 [M+H]+; rt: 2.26 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.04 (s, 1H), 9.77 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 8.01 (br s, 1H), 7.82 (dd, J = 7.1, 2.3 Hz, 1H), 7.61 (ddd, J = 8.7, 4.7, 2.3 Hz, 1H), 7.50 – 7.43 (m, 1H), 7.07 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.96 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.89 (q, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz, 3H). Example 88: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 23 using Method B to yield 36 mg of the title compound in 93% yield. LC / MS: m / z = 608.1 [M+H]+; rt: 2.30 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.05 (s, 1H), 9.81 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.01 (s, 1H), 7.83 (dd, J = 7.1, 2.3 Hz, 1H), 7.62 (ddd, J = 8.7, 4.7, 2.3 Hz, 1H), 7.51 – 7.44 (m, 1H), 7.09 – 7.05 (m, 1H), 6.89 (br s, 1H), 5.97 (d, J = 7.2 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.31 – 2.23 (m, 1H), 1.18 – 1.08 (m, 2H), 1.01 – 0.93 (m, 2H). Example 89: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 23 using Method B to yield 33 mg of the title compound in 89% yield. LC / MS: m / z = 581.1 [M+H]+; rt: 2.07 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 9.19 (d, J = 7.3 Hz, 1H), 8.85 (q, J = 1.1 Hz, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.01 (s, 1H), 7.82 (dd, J = 7.2, 2.2 Hz, 1H), 7.61 (ddd, J = 8.6, 4.6, 2.2 Hz, 1H), 7.49 – 7.41 (m, 1H), 7.06 (d, J = 5.2 Hz, 1H), 6.89 (br s, 1H), 5.92 (d, J = 7.3 Hz, 1H), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.09 (d, J = 1.1 Hz, 3H). Example 90: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 23 using Method B to yield 35 mg of the title compound in 92% yield. LC / MS: m / z = 595.1 [M+H]+; rt: 2.20 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 9.22 (d, J = 7.3 Hz, 1H), 8.87 (t, J = 1.0 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 8.01 (s, 1H), 7.82 (dd, J = 7.2, 2.3 Hz, 1H), 7.60 (ddd, J = 8.6, 4.7, 2.3 Hz, 1H), 7.48 – 7.42 (m, 1H), 7.06 (d, J = 5.3 Hz, 1H), 6.89 (br s, 1H), 5.92 (d, J = 7.3 Hz, 1H, overlapping water), 5.49 (t, J = 6.7 Hz, 1H), 3.81 (d, J = 6.7 Hz, 2H), 3.71 – 3.29 (m, 7H), 2.58 – 2.50 (m, 2H), 1.12 (t, J = 7.5 Hz, 3H). Example 91: N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 24 using Method A to yield 14 mg of the title compound in 65% yield. LC / MS: m / z = 541.1 [M+H]+; rt: 1.73 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.00 (d, J = 7.2 Hz, 1H), 8.21 (d, J = 5.2 Hz, 1H), 7.93 (s, 1H), 7.69 – 7.61 (m, 1H), 7.54 (dd, J = 8.5, 3.3 Hz, 1H), 7.52 – 7.43 (m, 4H), 7.10 (d, J = 2.1 Hz, 1H), 7.08 (dd, J = 5.2, 1.6 Hz, 1H), 5.92 (d, J = 7.2 Hz, 1H), 4.32 (t, J = 7.1 Hz, 1H), 4.02 (s, 3H), 3.85 – 3.74 (m, 2H), 3.23 (s, 3H). Example 92: N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 24 using Method B to yield 13 mg of the title compound in 59% yield. LC / MS: m / z = 555.1 [M+H]+; rt: 1.83 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.94 (s, 1H), 8.99 (d, J = 7.1 Hz, 1H), 8.21 (d, J = 5.2 Hz, 1H), 7.93 (s, 1H), 7.69 – 7.61 (m, 1H), 7.54 (dd, J = 8.5, 3.2 Hz, 1H), 7.51 – 7.42 (m, 4H), 7.10 – 7.05 (m, 2H), 5.90 (d, J = 7.1 Hz, 1H), 4.44 (q, J = 7.1 Hz, 2H), 4.32 (t, J = 7.2 Hz, 1H), 3.85 – 3.74 (m, 2H), 3.23 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H). Example 93: N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 24 using Method B to yield 14 mg of the title compound in 64% yield. LC / MS: m / z = 556.1 [M+H]+; rt: 2.06 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.97 (s, 1H), 9.18 (d, J = 7.3 Hz, 1H), 8.89 – 8.86 (m, 1H), 8.22 (d, J = 5.2 Hz, 1H), 7.92 (s, 1H), 7.69 – 7.61 (m, 1H), 7.55 (dd, J = 8.5, 3.3 Hz, 1H), 7.52 – 7.42 (m, 3H), 7.08 (dd, J = 5.2, 1.6 Hz, 1H), 5.92 (d, J = 7.3 Hz, 1H), 4.32 (t, J = 7.0 Hz, 1H), 3.85 – 3.74 (m, 2H), 3.24 (s, 3H), 2.57 – 2.50 (m, 2H, partially overlapping solvent), 1.11 (t, J = 7.5 Hz, 3H). Example 94: N-((S)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1- Prepared analogously to Examples 1-2 with Intermediate 25 using Method A to yield 16 mg of the title compound in 64% yield. LC / MS: m / z = 537.2 [M+H]+; rt: 1.78 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.88 (s, 1H), 8.91 (d, J = 7.0 Hz, 1H), 8.20 (d, J = 5.3 Hz, 1H), 7.93 (s, 1H), 7.54 (dd, J = 8.5, 3.2 Hz, 1H), 7.52 – 7.39 (m, 4H), 7.15 (dd, J = 9.7, 8.4 Hz, 1H), 7.10 (d, J = 2.1 Hz, 1H), 7.07 (dd, J = 5.3, 1.6 Hz, 1H), 5.84 (d, J = 7.0 Hz, 1H), 4.32 (t, J = 7.0 Hz, 1H), 4.02 (s, 3H), 3.85 – 3.74 (m, 2H), 3.24 (s, 3H), 2.24 (d, J = 1.8 Hz, 3H). 2- Prepared analogously to Examples 1-2 with Intermediate 25 using Method A to yield 15 mg of the title compound in 58% yield. LC / MS: m / z = 551.2 [M+H]+; rt: 1.88 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.86 (s, 1H), 8.89 (d, J = 7.1 Hz, 1H), 8.20 (d, J = 5.3 Hz, 1H), 7.93 (s, 1H), 7.54 (dd, J = 8.5, 3.3 Hz, 1H), 7.52 – 7.39 (m, 4H), 7.15 (dd, J = 9.8, 8.5 Hz, 1H), 7.09 – 7.05 (m, 2H), 5.83 (d, J = 7.0 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.32 (t, J = 7.0 Hz, 1H), 3.85 – 3.74 (m, 2H), 3.23 (s, 3H), 2.24 (d, J = 1.8 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H). Example 96: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 26 using Method A to yield 21 mg of the title compound in 80% yield. LC / MS: m / z = 557.1 [M+H]+; rt: 1.83 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.94 (s, 1H), 9.02 (d, J = 7.2 Hz, 1H), 8.21 (d, J = 5.2 Hz, 1H), 7.93 (s, 1H), 7.81 (dd, J = 7.2, 2.2 Hz, 1H), 7.61 (ddd, J = 8.6, 4.8, 2.2 Hz, 1H), 7.57 – 7.42 (m, 4H), 7.10 (d, J = 2.1 Hz, 1H), 7.08 (dd, J = 5.2, 1.6 Hz, 1H), 5.91 (d, J = 7.2 Hz, 1H), 4.32 (t, J = 7.0 Hz, 1H), 4.02 (s, 3H), 3.85 – 3.74 (m, 2H), 3.23 (s, 3H). Example 97: N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 26 using Method A to yield 21 mg of the title compound in 79% yield. LC / MS: m / z = 571.1 [M+H]+; rt: 1.93 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 9.01 (d, J = 7.1 Hz, 1H), 8.21 (d, J = 5.3 Hz, 1H), 7.93 (s, 1H), 7.81 (dd, J = 7.2, 2.2 Hz, 1H), 7.61 (ddd, J = 8.6, 4.7, 2.2 Hz, 1H), 7.57 – 7.42 (m, 4H), 7.10 – 7.05 (m, 2H), 5.90 (d, J = 7.1 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.32 (t, J = 7.0 Hz, 1H), 3.85 – 3.74 (m, 2H), 3.23 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H). Example 98: N-((S)-1-(3-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 27 using Method A to yield 15 mg of the title compound in 61% yield. LC / MS: m / z = 553.1 [M+H]+; rt: 1.89 min (LC / MS-method A).1H NMR (400 MHz, DMSO-d6) δ 10.94 (s, 1H), 9.01 (d, J = 7.2 Hz, 1H), 8.21 (d, J = 5.2 Hz, 1H), 7.93 (s, 1H), 7.68 – 7.65 (m, 1H), 7.58 – 7.38 (m, 6H), 7.10 – 7.06 (m, 2H), 5.91 (d, J = 7.2 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H), 4.32 (t, J = 7.0 Hz, 1H), 3.85 – 3.74 (m, 2H), 3.23 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H). Example 99: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 28 using Method A to yield 37 mg of the title compound in 94% yield. LC / MS: m / z = 580.0 [M+H]+; rt: 1.90 min (LC / MS-method A). Example 100: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 28 using Method A to yield 37 mg of the title compound in 96% yield. LC / MS: m / z = 594.1 [M+H]+; rt: 2.01 min (LC / MS-method A). Example 101: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 32 mg of the title compound in 81% yield. LC / MS: m / z = 581.0 [M+H]+; rt: 2.10 min (LC / MS-method A). Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 33 mg of the title compound in 82% yield. LC / MS: m / z = 595.0 [M+H]+; rt: 2.23 min (LC / MS-method A). Example 103: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 34 mg of the title compound in 86% yield. LC / MS: m / z = 582.0 [M+H]+; rt: 2.15 min (LC / MS-method A). Example 104: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 33 mg of the title compound in 82% yield. LC / MS: m / z = 594.0 [M+H]+; rt: 2.28 min (LC / MS-method A). Example 105: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 9 mg of the title compound in 39% yield. LC / MS: m / z = 612.1 [M+H]+; rt: 2.19 min (LC / MS-method A). Example 106: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- 2-fluorobenzamide Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 16 mg of the title compound in 67% yield. LC / MS: m / z = 594.1 [M+H]+; rt: 2.17 min (LC / MS-method A). Example 107: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- 2-fluoro-6-methylbenzamide Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 7 mg of the title compound in 30% yield. LC / MS: m / z = 608.1 [M+H]+; rt: 2.16 min (LC / MS-method A). Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 15 mg of the title compound in 66% yield. LC / MS: m / z = 591.1 [M+H]+; rt: 2.19 min (LC / MS-method A). Example 109: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 3 mg of the title compound in 5% yield. LC / MS: m / z = 662.1 [M+H]+; rt: 2.20 min (LC / MS-method A). Example 110: N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)- 3-(difluoromethyl)picolinamide Prepared analogously to Examples 1-2 with Intermediate 28 using Method B to yield 15 mg of the title compound in 59% yield. LC / MS: m / z = 627.1 [M+H]+; rt: 2.28 min (LC / MS-method A). Example 111: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1- Prepared analogously to Examples 1-2 with Intermediate 29 using Method A to yield 47 mg of the title compound in 99% yield. LC / MS: m / z = 560.1 [M+H]+; rt: 1.83 min (LC / MS-method A). Example 112: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4- Prepared analogously to Examples 1-2 with Intermediate 29 using Method B to yield 36 mg of the title compound in 90% yield. LC / MS: m / z = 561.1 [M+H]+; rt: 2.02 min (LC / MS-method A). Example 113: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 29 using Method B to yield 36 mg of the title compound in 88% yield. LC / MS: m / z = 575.1 [M+H]+; rt: 2.15 min (LC / MS-method A). Prepared analogously to Examples 1-2 with Intermediate 29 using Method A to yield 48 mg of the title compound in 90% yield. LC / MS: m / z = 574.1 [M+H]+; rt: 1.93 min (LC / MS-method A). Example 115: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4- Prepared analogously to Examples 1-2 with Intermediate 29 using Method B to yield 34 mg of the title compound in 85% yield. LC / MS: m / z = 562.1 [M+H]+; rt: 2.08 min (LC / MS-method A). Example 116: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4-ethyl- Prepared analogously to Examples 1-2 with Intermediate 29 using Method B to yield 35 mg of the title compound in 86% yield. LC / MS: m / z = 576.1 [M+H]+; rt: 2.22 min (LC / MS-method A). Example 117: 4-cyclopropyl-N-((S)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3- - - Prepared analogously to Examples 1-2 with Intermediate 29 using Method B to yield 34 mg of the title compound in 81% yield. LC / MS: m / z = 588.1 [M+H]+; rt: 2.26 min (LC / MS-method A). Example 118: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)-1- Prepared analogously to Examples 1-2 with Intermediate 30 using Method A to yield 32 mg of the title compound in 95% yield. LC / MS: m / z = 560.2 [M+H]+; rt: 1.83 min (LC / MS-method A). Example 119: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2- oxoethyl)picolinamide Prepared analogously to Examples 1-2 with Intermediate 30 using Method A to yield 34 mg of the title compound in 98% yield. LC / MS: m / z = 557.1 [M+H]+; rt: 2.02 min (LC / MS-method A). Example 120: N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)-1-ethyl- 1H-pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 30 using Method A to yield 35 mg of the title compound in 98% yield. LC / MS: m / z = 574.2 [M+H]+; rt: 1.93 min (LC / MS-method A). Example 121: N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 31 using Method A to yield 26 mg of the title compound in 72% yield. LC / MS: m / z = 539.2 [M+H]+; rt: 1.80 min (LC / MS-method A). Example 122: N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide Prepared analogously to Examples 1-2 with Intermediate 31 using Method A to yield 22 mg of the title compound in 59% yield. LC / MS: m / z = 553.2 [M+H]+; rt: 1.90 min (LC / MS-method A). Example 123: N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide Prepared analogously to Examples 1-2 with Intermediate 31 using Method B to yield 18 mg of the title compound in 49% yield. LC / MS: m / z = 541.1 [M+H]+; rt: 2.05 min (LC / MS-method A). Prepared analogously to Examples 1-2 with Intermediate 31 using Method B to yield 21 mg of the title compound in 56% yield. LC / MS: m / z = 555.2 [M+H]+; rt: 2.19 min (LC / MS-method A). Example 125: N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2- dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)picolinamide Prepared analogously to Examples 1-2 with Intermediate 31 using Method A to yield 22 mg of the title compound in 61% yield. LC / MS: m / z = 536.1 [M+H]+; rt: 2.00 min (LC / MS-method A). Biological Assays The biological activity of the compounds of the present disclosure was determined utilising the assays described herein. Inhibition is reported as a pIC50 value, where pIC50 = -log10(IC50) and where IC50 is the concentration of example compound needed to inhibit 50% of the binding of IL-17A to its receptor, IL-17RA. These values may fluctuate depending on the daily assay performance, and fluctuations of this kind are known to those skilled in the art. These results show that the compounds of the present disclosure are capable of inhibiting the biological action of IL-17A. In general, the compounds of the present invention possess pIC50 values of 30 ^M or less (pIC50 > 4.52) against IL-17A in the assays described herein. Suitably, the compounds of the present invention possess IC50 values of 10 ^M or less (pIC50 ≥ 5.00) (such as 1^^M or less, 500 nM or less, or 250 nM or less) against IL-17A in the assays described herein. More suitably, the compounds of the present invention possess IC50values of 100 nM or less (pIC50≥ 7.00) against IL-17A in the assays described herein IL-17A AlphaLISA assay The ability of the compounds to block binding of IL-17A to its receptor, IL-17RA, was analysed in a competition assay using AlphaLISA technology (Perkin Elmer). The assay is a bead based AlphaLISA where the IL-17RA is captured on the acceptor bead via an Fc tag, and IL-17A is captured on the streptavidin donor bead via a biotinylated anti- IL17A antibody. Assay buffer was prepared by adding 0.05% Tween-20 (v / v) and 0.1% BSA to Phosphate Buffered Saline (PBS). The assay was carried out in 384-well white low volume plates (Perkin Elmer #6008359).10 ^L of a 7.5 nM stock of human recombinant IL-17A (R&D Systems 7955-IL / CF) diluted in assay buffer was dispensed into the assay plate, and compounds or DMSO vehicle control were added in a volume of 75 nL using an acoustic dispenser (Beckman). The compounds were pre-incubated with the IL-17A for 30 min at room temperature prior to addition of 5 ^L of a 5nM stock of human recombinant IL- 17RA / Fc chimera (R&D Systems 177-IR-100) diluted in assay buffer. The IL-17A was incubated with the receptor for a further 90 minutes at room temperature before addition of 5 ^L of a mixture of anti-human Fc IgG acceptor beads (75 ^g / mL, Perkin Elmer AL103C) and anti-IL-17A biotin conjugated antibody (5 nM, Abcam, #ab155575) in assay buffer. After a further 30 min incubation at room temperature, 5 ^L of streptavidin donor beads (75 ^g / mL, Perkin Elmer 6760002S) were added, and the plate was incubated for 3 h in the dark. The AlphaLisa signal was measured using the PheraSTAR plate reader (BMG). Data were analysed using GeneData Screener and fitted to a 4-parameter logistic equation. The IC50 values were calculated using the DMSO vehicle as the negative control and a high concentration (4^M) of a reference IL-17A inhibitor as the positive control. All compounds were analysed at least in duplicate (n ≥ 2). Activity of the Example compounds is reported in Table A as the mean pIC50values. Table A Ex. pIC50Ex. pIC50Ex. pIC50Ex. pIC50Ex. pIC5016.99267.36517.24767.361017.2726.65277.22527.36777.291027.603 7.25 28 7.15 53 7.03 78 7.62 103 7.18 47.08297.03546.85797.731047.7357.09307.23556.17807.701056.5667.13317.12566.10817.321066.7477.42327.40576.56827.371076.2887.65335.69586.54837.481085.2796.89345.96597.21847.441096.04107.24357.58607.49857.481105.17117.42367.19617.43867.461117.2612 7.02 37 7.20 62 7.66 87 7.87 112 7.29 137.32377.43637.42887.571137.63147.50397.47647.43897.421147.3415 7.21 40 7.25 65 7.05 90 7.57 115 7.32 166.56416.71666.58917.201167.84176.96427.11677.06927.171177.81186.93437.37687.82937.301187.30197.08447.19697.56947.281195.70207.25457.29707.69957.231207.3821 7.29 46 6.75 71 7.53 96 7.36 121 7.59 227.40477.11727.69977.281227.24237.06486.68737.53987.621236.96247.52496.99747.78997.501247.26257.50506.72757.561007.521255.27While particular embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practising the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby. The disclosures of all patent and scientific literature cited herein are expressly incorporated herein in their entirety by reference. To the extent that any incorporated material is inconsistent with the express content of this disclosure, the express content controls.

Claims

CLAIMS 1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:wherein: R1is 5- or 6-membered heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1- 3alkyl, C1-3alkoxy, C1-3haloalkyl, and oxo; R2is C1-3alkyl; R3is 5- or 6-membered monocyclic heteroaryl or phenyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from halo, C1-4alkyl, C1-3haloalkyl, C1-3haloalkoxy, and C3-6cycloalkyl; R4is independently selected at each instance from fluoro, chloro, bromo, C1-3alkyl, C1- 3alkoxy, C1-3haloalkyl and C1-3haloalkoxy; R5is independently selected at each instance from fluoro, chloro, and C1-3alkyl; n is 0, 1, 2 or 3; p is 0, 1 or 2.

2. The compound according to claim 1, having a structure according to Formula IA or Formula IB, or a pharmaceutically acceptable salt thereof:,wherein R1, R2, R3, R4, R5, n, and p are as defined in claim 1.

3. The compound according to claim 1 or claim 2, wherein R1is 5- or 6-membered nitrogen-containing heterocyclyl, which is either saturated or partially unsaturated, and is substituted with one to three substituents independently selected from halo, C1-3haloalkyl, and oxo.

4. The compound according to claim 3, wherein R1is selected from:, wherein is the point of attachment to the rest of the compound of Formula I, and wherein R1is further substituted with one or two substituents independently selected from fluoro, methyl, and C1-3fluoroalkyl.

5. The compound according to claim 4, wherein R1is selected from:, wherein is the point of attachment to the rest of the compound of Formula I.

6. The compound according to any one of claims 1 to 5, wherein R2is methyl.

7. The compound according to any one of claims 1 to 6, wherein R3is 5- or 6-membered monocyclic heteroaryl or phenyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from fluoro, C1-3alkyl, C1- 2fluoroalkyl, C1-2fluoroalkoxy, and C3-4cycloalkyl.

8. The compound according to claim 7, wherein R3is selected from phenyl, pyrazolyl, oxadiazolyl, isoxazolyl, and pyridyl, wherein each group is unsubstituted or substituted with one or two substituents independently selected from fluoro, methyl, ethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethoxy, and cyclopropyl.

9. The compound according to any one of claims 1 to 8, wherein R4is independently selected at each instance from fluoro, chloro, C1-3alkyl, and C1-3haloalkyl; such as being independently selected at each instance from fluoro, chloro, methyl, and trifluoromethyl.

10. The compound according to any one of claims 1 to 9, wherein n is 1 or 2.

11. The compound according to any one of claims 1 to 10, wherein p is 0.

12. The compound according to claim 1, having a structure according to any one of Formulae IC to IH, or a pharmaceutically acceptable salt thereof:wherein R1, R2, R3, R4, and n are as defined in any one of claims 1 to 10.

13. The compound according to claim 1, wherein the compound is selected from one of the following compounds, or a pharmaceutically acceptable salt thereof: N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide;N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; 1-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H-pyrazole-5- carboxamide; 4-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)I;midazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1,2,5- oxadiazole-3-carboxamide 4-ethyl-N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-3- carboxamide; N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- methylisoxazole-3-carboxamide; N-((S)-1-(4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3- methylisoxazole-4-carboxamide; 4-ethyl-N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-3- carboxamide; N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; 4-ethyl-N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(4-fluoro-3-methylphenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- methylisoxazole-3-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide;N-((S)-1-(3,4-difluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide; 1-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H-pyrazole-5- carboxamide; N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; 4-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1,2,5- oxadiazole-3-carboxamide; 4-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-3- carboxamide; N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- methylisoxazole-3-carboxamide; 3-ethyl-N-((S)-1-(3-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)isoxazole-4- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide;N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3- ethylisoxazole-4-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-3- methylisoxazole-4-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(2-chlorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; 1-ethyl-N-((S)-1-(2-fluorophenyl)-2-((4-((S)-2-methoxy-1-((S)-2-oxo-4- (trifluoromethyl)imidazolidin-1-yl)ethyl)pyridin-2-yl)amino)-2-oxoethyl)-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide;N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-1-ethyl-1H-pyrazole- 5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluorophenyl)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole-3-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide;N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-methylisoxazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(m-tolyl)ethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(p-tolyl)ethyl)-4-methylisoxazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(p-tolyl)ethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-phenylethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-1-methyl- 1H-pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4-methyl- 1,2,5-oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4-ethyl- 1,2,5-oxadiazole-3-carboxamide;N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4- methylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxo-1-(3-(trifluoromethyl)phenyl)ethyl)-4- ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)-1-ethyl-1H-pyrazole- 5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluorophenyl)-2-oxoethyl)-4-(2,2,2- trifluoroethoxy)-1,2,5-oxadiazole-3-carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1- methyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1- ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2- oxoethyl)benzamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- methylisoxazole-3-carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- methyl-1,2,5-oxadiazole-3-carboxamide; N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- ethyl-1,2,5-oxadiazole-3-carboxamide;N-((S)-1-(4-chloro-3-methylphenyl)-2-((4-((S)-1-(5,5-difluoro-2- oxotetrahydropyrimidin-1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4- cyclopropyl-1,2,5-oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4-methyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4-ethyl-1,2,5- oxadiazole-3-carboxamide; 4-cyclopropyl-N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4- methylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3,5-dimethylphenyl)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)benzamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole- 3-carboxamide;N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-cyclopropyl-1,2,5- oxadiazole-3-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole-3- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(3,4-difluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3-carboxamide; N-((S)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2-methoxyethyl)pyridin-2- yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide; 1-ethyl-N-((S)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1H- pyrazole-5-carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chloro-4-fluorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3- yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-1-(3-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5- carboxamide;N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methylisoxazole-3- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethylisoxazole-3- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole- 3-carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-4-fluoro-1H- pyrazole-5-carboxamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-2-fluorobenzamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-2-fluoro-6- methylbenzamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-3-methylpicolinamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-2-fluoro-6- (trifluoromethyl)benzamide; N-((S)-1-(4-chloro-3-fluorophenyl)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin- 1(2H)-yl)-2-methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-3- (difluoromethyl)picolinamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1-methyl- 1H-pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4- methylisoxazole-3-carboxamide;N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4- ethylisoxazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4-methyl- 1,2,5-oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-4-ethyl- 1,2,5-oxadiazole-3-carboxamide; 4-cyclopropyl-N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(4-fluoro-3-methylphenyl)-2-oxoethyl)-1,2,5- oxadiazole-3-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)-1-methyl- 1H-pyrazole-5-carboxamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2- oxoethyl)picolinamide; N-((S)-2-((4-((S)-1-(5,5-difluoro-2-oxotetrahydropyrimidin-1(2H)-yl)-2- methoxyethyl)pyridin-2-yl)amino)-1-(3-fluoro-4-methylphenyl)-2-oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-methyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-1-ethyl-1H-pyrazole-5-carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-methyl-1,2,5-oxadiazole-3- carboxamide; N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)-4-ethyl-1,2,5-oxadiazole-3- carboxamide; and N-((S)-1-(4-chlorophenyl)-2-((4-((R)-1-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)-2- methoxyethyl)pyridin-2-yl)amino)-2-oxoethyl)picolinamide.

14. A pharmaceutical composition comprising a compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

15. A compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 14, for use in the treatment of acute lung injury, Alzheimer’s Disease, ankylosing spondylitis, axial spondyloarthritis and other spondyloarthropathies, arthritis, asthma (including severe asthma), atopic dermatitis, autoimmune diabetes, other autoimmune disorders, autoimmune thyroiditis, bone resorption, cancer (both solid tumours (such as melanomas, sarcomas, squamous cell carcinomas, transitional call cancers, and ovarian cancers) and hematologic malignancies; in particular acute myelogenous leukaemia, chronic lymphocytic leukemia, gastric cancer, and colon cancer), Castleman’s disease, contact dermatitis, Crohn’s Disease, chronic myelogenous leukemia, chronic obstructive pulmonary disease (COPD), coeliac disease, cystic fibrosis, dermatomyositis, discoid lupus erythematosus, eczema, enthesitis-related arthritis, endotoxic shock associated with infection, exophthalmos, fibrosing disorders including pulmonary fibrosis, gall bladder disease, giant cell arteritis, graft-versus-host disease, hepatoblastomas, hypochlorhydria, immune mediated inflammatory disorders of the central and peripheral nervous system such as multiple sclerosis and Guillain- Barr syndrome, Hidradenitis Suppurativa, inflammatory bowel disease, insulin dependent diabetes type I, intravascular coagulation, irritable bowel syndrome, Lichen Planus, liver fibrosis, lupus nephritis, lyme arthritis, meningoencephalitis, myocarditis, meningoencephalitis, Necrobiosis Lipoidica Diabeticorum, osteoporosis, pancreatitis, Papulopustular Rosacea, Parkinson’s disease, pelvic inflammatory disease, periodontitis, peritonitis, Peyronie’s Disease, Pilonidal disease, psoriasis, psoriatic arthritis (PsA), Pyoderma Gangrenosum, renal fibrosis, rheumatoid arthritis, scleroderma or systemic sclerosis, stroke, surgical adhesions, systemic lupus erythematosus (SLE), systemic onset juvenile idiopathic arthritis (JIA), trauma (surgery), transplant rejection, Type I diabetes, ulcerative colitis, uveitis, or vasculitis.

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