Heterocyclic derivative and use thereof

Abstract

The present invention relates to a novel heterocyclic derivative useful for the preparation of a drug for treating cancer and, more specifically, to a novel heterocyclic derivative which is a low-molecular-weight substance having inhibitory activity against the interaction between a stimulator of interferon genes (STING) protein and a tripartite motif-containing protein 29 (TRIM29) protein, and is effectively used for the preparation of a drug for anticancer treatment. In particular, the drug stimulates the immune system by activating suppressed immune functions, and thus is useful for the treatment of immune-related cancers.

Description

Heterocyclic derivatives and their uses

[0001] The present invention relates to a novel heterocycle derivative useful for manufacturing a drug for treating cancer, and more specifically, to a novel heterocycle derivative useful for manufacturing a drug for anticancer treatment using a small molecule having an inhibitory effect on the interaction between STING (stimulator of interferon genes) protein and TRIM29 (tripartitemotif-containing protein 29) protein.

[0002] The above-mentioned medicine is useful for the treatment of immune-related cancers by stimulating the immune system, particularly by activating suppressed immune functions.

[0003] Cancer is generally defined as a disease in which abnormalities in the cell cycle of human tissues cause cells to fail to differentiate normally and continue to divide; it develops through three stages: initiation, promotion, and progression. The cause of cancer is known to be mutations in the genes of normal cells or tumor suppressor genes triggered by carcinogens found in the environment or food. These cells then proliferate abnormally under continuous stimulation from carcinogens, eventually forming cancerous tissue.

[0004] Cancer treatment generally involves the use of surgical procedures, radiation therapy, and immunotherapy in conjunction with chemotherapy. Research methods for anticancer drugs include identifying substances that directly cytotoxic to cancer cells, substances that regulate the body's immune capacity, substances that inhibit cancer metastasis, and substances that inhibit angiogenesis. However, most anticancer drugs currently used in clinical practice are chemically synthesized substances that cause problems such as toxicity to normal cells; consequently, therapies utilizing immune responses have recently been gaining attention as a solution to these issues.

[0005]

[0006] Meanwhile, STING (stimulator of interferon genes) plays a pivotal role in DNA-sensing antiviral immunity. Specifically, upon detecting abnormal cytoplasmic DNA, cGAMP (cyclic GMP-AMP), which acts as an innate immune agent, is produced by cGAMP synthase (cGAS), and cGAMP activates the immune receptor STING.

[0007] Furthermore, activated STING induces the production of type I interferon and pro-inflammatory cytokines to recruit adaptive immune cells for the elimination of damaged host cells. Thus, STING acts as a central interface between innate and adaptive immunity. Indeed, recent studies have revealed that intratumoral administration of STING agonists activates local immunity within the tumor microenvironment (TME) to recruit effector cells for the elimination of cancer.

[0008] Furthermore, TRIM29 (tripartite motif-containing protein 29) E3 ligase is a direct regulator of STING, and TRIM29-mediated STING ubiquitination degrades STING in both host immune cells and cancer cells in a K48 linkage-specific manner. Under normal conditions, TRIM29 promotes the non-immunogenic degradation of STING, whereas, in contrast, overexpression of TRIM29 interferes with the immune response and reduces cytokine production during STING agonist therapy. However, many studies have reported that direct inhibition of TRIM29 induces cancer metastasis. TRIM29 is a highly downregulated gene in metastatic melanoma, and loss of TRIM29 increases the metastatic profile of squamous cell carcinoma by disrupting keratin distribution. However, it is not yet known that specific perturbations of protein-protein interactions (PPIs) between STING and TRIM29 can increase cellular STING levels without potential metastasis risk, thereby overcoming the reduced efficacy of STING agonists.

[0009]

[0010] Accordingly, the inventors of the present invention have strived to develop an immunotherapeutic agent that prevents the degradation of STING by TRIM29 by inhibiting the STING-TRIM29 interaction. As a result, they established a high-efficiency bioactive screening method capable of screening compounds that inhibit the interaction between STING and TRIM29, and through the established system, they discovered a heterocyclic derivative having a core scaffold of the oxopiperazine structure. Furthermore, they confirmed that the heterocyclic derivative can increase the immunotherapeutic efficacy of cGAMP and the immune checkpoint inhibitor anti-PD-1 therapy by further activating the STING agonist cGAMP-mediated immune response through an increase in the intracellular amount of STING. Therefore, the present invention was completed by demonstrating that the STING-TRIM29 interaction inhibitor of the present invention can be usefully utilized as an active ingredient in immunotherapeutic agents and immunotherapeutic adjuvants.

[0011] [Prior Art Literature]

[0012] [Non-patent literature]

[0013] Q. Chen, L. Sun, ZJ Chen, Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat. Immunol. 17, 1142-1149 (2016)

[0014] L. Sun, J. Wu, F. Du, X. Chen, Z. J. Chen, Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway. Science. 339, 786-791 (2013)

[0015] The objective of the present invention is to provide a novel heterocycle derivative, or a pharmaceutically acceptable salt or isomer thereof, capable of enhancing intratumoral immune activity by inhibiting the interaction between STING (Stimulator of interferon genes) and TRIM29 (Tripartite motif-containing protein 29).

[0016] In addition, the present invention has another technical objective of providing a pharmaceutical composition comprising the above heterocycle derivative, or a pharmaceutically acceptable salt or isomer thereof, as an active ingredient together with a pharmaceutically acceptable carrier.

[0017] According to one aspect of the present invention, a compound of the following formula 1, or a pharmaceutically acceptable salt or isomer thereof is provided:

[0018] [Chemical Formula 1]

[0019]

[0020]

[0021] In the above chemical formula 1,

[0022] R1 is an alkyl, hydroxyalkyl, cycloalkyl, aryl, heteroaryl, aryl-alkyl, heteroaryl-alkyl, heterocycloalkyl-alkyl, or partially unsaturated heterocyclyl-alkyl; Herein, the alkyl, cycloalkyl, aryl, and heteroaryl are hydroxy, halo, amino, carboxy(-COOH), alkyl, alkenyl, alkynyl, alkoxy, alkylthio, hydroxyalkyl, hydroxycycloalkyl, haloalkyl, cyanoalkyl, haloalkoxy, alkoxy-alkyl, alkoxy-alkoxy, alkyl-phosphine oxide, dialkylamino, dialkylaminoalkoxy, dialkylaminoalkoxyalkyl, dialkylaminoalkoxy-alkoxyalkyl, alkylsulfonyl, alkylsulfonylamino, heterocycloalkyl-alkoxy, heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl, alkyl-substituted heterocycloalkyl-alkoxy, alkyl-substituted heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl carbonyl, It may be optionally substituted with one or more substituents selected from the group consisting of alkoxy-alkoxy-alkoxy-alkoxy, alkoxy-alkoxy-alkoxy-alkoxyalkyl, dialkylaminoalkylcarbonyloxyalkyl, phosphonoalkylcarbonylalkoxyalkyl, dihydrogen phosphate-alkyl, dihydrogen phosphate-alkylcarbonyloxyalkyl, dihydrogen phosphate-alkoxyalkyl, diaminooxyphosphoryloxy-alkoxycarbonyloxyalkyl, disodium oxyphosphoryloxy-alkoxycarbonyloxyalkyl, and heteroaryl;The above heterocycloalkyl and partially unsaturated heterocyclyl are hydroxy, halo, amino, carboxy, oxo, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, hydroxyalkyl, hydroxycycloalkyl haloalkyl, cyanoalkyl, haloalkoxy, alkoxy-alkoxy, dialkylamino, dialkylaminoalkoxy, dialkylaminoalkoxyalkyl, dialkylaminoalkoxy-alkoxyalkyl, alkylsulfonyl, alkylsulfonylamino, heterocycloalkyl-alkoxy, heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl, alkyl-substituted heterocycloalkyl-alkoxy, alkyl-substituted heterocycloalkyl-alkoxy, alkoxy-alkoxy-alkoxy-alkoxy, alkoxy-alkoxy-alkoxy-alkoxy, alkoxy-alkoxy-alkoxy-alkoxy, It may optionally be substituted with one or more substituents selected from the group consisting of alkoxy-alkoxy-alkoxy-alkoxy-alkoxyalkyl, dialkylaminoalkylcarbonyloxyalkyl, dihydrogen phosphate-alkyl, dihydrogen phosphate-alkylcarbonyloxyalkyl, and heteroaryl;

[0023] R2 is -H, alkyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl-alkyl, or aryl-alkyl; Herein, the cycloalkyl, aryl, heteroaryl, and heterocycloalkyl are hydroxy, halo, amino, carboxy, alkyl, alkoxy, deuterium alkoxy, hydroxyalkyl, haloalkyl, haloalkoxy, dialkylamino, dialkylaminoalkyl, dialkylaminoalkoxyalkyl, azide, amide, alkyl-substituted heterocycloalkyl, heterocycloalkyl-alkyl, heterocycloalkyl-alkoxy, heterocycloalkyl-amino, heterocycloalkyl-aminoalkyl, alkyl-substituted heterocycloalkyl-oxy-alkyl, oxo-substituted heterocycloalkyl-aminoalkyl, alkyl-substituted heterocycloalkyl-aminoalkyl, heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl-alkoxyalkyl, carboxy-substituted heterocycloalkyl-alkyl, alkyl-substituted heterocycloalkyl-alkyl, It may optionally be substituted with one or more substituents selected from the group consisting of alkylsulfonyl-substituted heterocycloalkyl-alkyl, heteroaryl, and alkyl-substituted heteroaryl-alkylaminoalkyl;

[0024] R3 is hydroxy, cyano(-CN), nitro(-NO2), alkyl, alkoxy, haloalkyl, amino, alkylamino, dialkylamino, carboxy, or alkoxycarbonyl;

[0025] L is a direct bond, alkylene, haloalkylene, -C(=O)-, -C(=O)O-, -CH2NRa-, -C(=O)NRa-, or -NRaC(=O)-; where Ra is -H, alkyl, or dialkylaminoalkyl;

[0026] R4 is hydroxy, halo, cyano, amino, carboxy, alkyl, hydroxyalkyl, haloalkyl, carboxyalkyl, alkoxy, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, alkyl-substituted phosphonate, dihydrogen phosphite, aryl, heteroaryl, partially unsaturated heterocycloyl, aryl-alkyl, heterocycloalkyl-alkyl, heteroaryl-alkyl, alkylamino, dialkylamino, dialkylaminoalkyl, arylamino, alkylcarbonylamino, arylcarbonylamino, alkylsulfonylamino, arylsulfonylamino, or -BR6R7; wherein R6 and R7 are each independently hydroxyl, or R6 and R7 may form an alkyl-substituted heterocycloalkyl with a boron (B) atom to which they are connected and bonded; The above alkyl, cycloalkyl, heterocycloalkyl and partially unsaturated heterocyclyl are cycloalkyl, heterocycloalkyl, alkoxy, hydroxyalkyl, haloalkyl, carboxyalkyl, aminoalkyl, haloalkoxy, dialkylamino, aminocarbonyl, aryl, aryl-alkylcarbonyl, alkyl-carbonyloxy, alkylaminocarbonyloxy, aminoalkylcarbonyloxy, aminoalkylcarbonyloxy-alkyl, dialkylaminoalkylcarbonyloxy-alkyl, alkylaminoalkylcarbonyloxy-alkyl, guanidino, alkylcarbonyloxy-alkyl, aminocarbonyl, and alkylcarbonyloxy-alkyl substituted with amino, alkylcarbonyloxy-alkyl substituted with amino, alkylcarbonyloxy-alkyl substituted with amino, guanidino, and amino substituted with amino, aminocarbonyl and amino substituted with alkylcarbonyloxy-alkyl, Carboxyalkylcarbonyloxy-alkyl, carboxyalkoxycarbonyloxy-alkyl, carboxyalkoxyalkoxyalkoxyalkylcarbonyloxy-alkyl, heteroaryl-carbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl, dihydrogenphosphate-alkyl, alkoxycarbonylalkylaminocarbonyloxy-alkyl, (alkylaminoalkyl)(alkyl)aminocarbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-carbonyloxy-alkyl, aminosulfonyloxy-alkyl, alkoxy-alkoxycarbonyloxy-alkyl, dialkylaminoalkoxycarbonyloxy-alkyl,Dialkylaminothiocarbonyloxy-alkyl, alkylaminothiocarbonyloxy-alkyl, dialkylaminocarbonyloxy-alkyl, sodium oxycarbonylalkoxycarbonyloxy-alkyl, phosphonoalkylcarbonyloxy-alkyl, dihydrogenphosphatealkylcarbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl, alkoxycarbonyl-substituted heterocycloalkyl-carbonyloxy-alkyl, heterocycloalkyl-alkoxy-alkyl, alkyl-substituted heterocycloalkyl-alkoxy-alkyl, heterocycloalkyl-alkoxy-carbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-alkoxy-carbonyloxy-alkyl, heterocycloalkyl-alkylaminocarbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-alkylaminocarbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-alkylaminocarbonyloxy-alkyl, (alkyl-substituted It may optionally be substituted with one or more substituents selected from the group consisting of heterocycloalkyl-alkyl)(alkyl)aminocarbonyloxy-alkyl, and heterocycloalkyl-oxy-alkyl substituted with carboxyl and hydroxyl; The above aryl and heteroaryl are hydroxy, halo, amino, oxide, carboxy, alkyl, alkoxy, hydroxyalkyl, haloalkyl, carboxyalkyl, aminoalkyl, haloalkoxy, dialkylamino, aminocarbonyl, aryl, aryl-alkylcarbonyl, amino-substituted alkyl-carbonyloxy, alkylaminocarbonyloxy, aminoalkylcarbonyloxy, dialkylaminoalkylcarbonyloxy-alkyl, amino-substituted alkylcarbonyloxy-alkyl, heteroaryl-carbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl, dihydrogenphosphate-alkyl, alkoxycarbonylalkylaminocarbonyloxy-alkyl, (alkylaminoalkyl)(alkyl)aminocarbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-carbonyloxy-alkyl, aminosulfonyloxy-alkyl, alkoxy-alkoxycarbonyloxy-alkyl, Dialkylaminothiocarbonyloxy-alkyl, alkylaminothiocarbonyloxy-alkyl, dialkylaminocarbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl substituted with alkoxycarbonyl, heterocycloalkyl-alkoxy-alkyl, heterocycloalkyl-alkoxy-carbonyloxy-alkyl,It may optionally be substituted with one or more substituents selected from the group consisting of heterocycloalkyl-alkylaminocarbonyloxyalkyl, and heterocycloalkyl-oxyalkyl substituted with carboxyl and hydroxyl;

[0027] n is 1 or 2, and;

[0028] R5 is -H, alkyl, hydroxyalkyl, cycloalkyl, cycloalkyl-alkyl, or aryl-alkyl; when m is 2, two R5s may be connected to each other to form a cycloalkyl group with a bonded carbon atom; wherein the aryl group may optionally be substituted with one or more substituents selected from the group consisting of halo, alkyl, and alkoxy;

[0029] m is 1 or 2, and;

[0030] The above heterocycloalkyl, partially unsaturated heterocyclyl, and heteroaryl have one or more heteroatoms selected from N, O, and S;

[0031] However, if R1 is a benzyl substituted with one hydroxyl and R3 is a nitro, R4 is not an alkyl or heterocycloalkyl-alkyl.

[0032]

[0033]

[0034] The present invention will be described in more detail below.

[0035]

[0036] The following terms in the present invention have the meanings described below unless otherwise indicated. Any undefined term has the meaning understood in the art.

[0037]

[0038] In the present invention, the terms “halo” or “halogen” refer to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I), whether used alone or in combination with other additional terms (e.g., haloalkyl).

[0039] In this invention, the term “hydroxy” group means -OH.

[0040] In this invention, the term “nitro” group means -NO2.

[0041] In the present invention, the term “amino” group may refer to a primary, secondary, or tertiary amino group bonded through a nitrogen atom, either alone or in combination.

[0042] In this invention, the term “azide” group means -N3.

[0043] In the present invention, the term “amide” may refer to an organic compound in which a nitrogen atom is connected to a carbonyl group.

[0044] In this invention, the term “guanidino” refers to -NH-C(=NH)-NH2.

[0045] In this invention, the term “cyano” group means -CN.

[0046] In this invention, the term “carboxy” group means -COOH.

[0047] In this invention, the term “carbonyl” group means -C(=O)-.

[0048] In this invention, the term “thiocarbonyl” group means -C(=S)-.

[0049] In this invention, the term “sulfonyl” group means -S(=O)2-.

[0050] In the present invention, the term “oxo” group refers to =O (i.e., oxygen having a double bond).

[0051] In this invention, the term “oxide” group means -O.

[0052] In the present invention, the term “alkyl” refers to a radical of a saturated aliphatic hydrocarbon group having, for example, 1 to 7 carbon atoms, which is straight-chain or branch-chain, when used alone or in combination with other additional terms (e.g., haloalkyl). Examples of typical alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, and 1,2-dimethylpropyl.

[0053] In the present invention, the term “alkoxy” means an alkyloxy (-O-alkyl group), for example, an alkyloxy having 1 to 7 carbon atoms.

[0054] In the present invention, the term “deuterium alkoxy” means an alkyloxy having deuterium instead of hydrogen.

[0055] In the present invention, the term “alkylthio” means a -S-alkyl group, for example, a -S-alkyl group having 1 to 7 carbon atoms.

[0056] In the present invention, the term “alkyl-phosphine oxide” means -P(=O) substituted with an alkyl group, for example, -P(=O) substituted with an alkyl group having 1 to 7 carbon atoms.

[0057] In the present invention, the term “alkyl-substituted phosphonate” means -P(=O)O2 substituted with two alkyl groups, for example -P(=O)O2 substituted with two alkyl groups having 1 to 7 carbon atoms.

[0058] In this invention, the term “phosphono” means -P(=O)OH2.

[0059] In the present invention, the term “dihydrogen phosphate” means -OP(=O)OH2.

[0060] In the present invention, the term “diaminooxyphosphoryloxy” means -OP(=O)-(ONH2)2.

[0061] In the present invention, the term “disodiumoxyphosphoryloxy” means -OP(=O)-(ONa)2.

[0062] In the present invention, the term “dihydrogen phosphite” means -H2PO3.

[0063] In the present invention, the term “alkylene” means a radical of the group of saturated aliphatic hydrocarbons having, for example, 1 to 7 carbon atoms, of a divalent straight-chain or side-chain type.

[0064] In the present invention, the term “alkynyl” means a radical of the aliphatic hydrocarbon group containing at least one carbon-carbon triple bond and having, for example, 2 to 7 carbon atoms.

[0065] In the present invention, the term “cycloalkyl” refers to a radical of a saturated aliphatic hydrocarbon group having cyclic, for example, 3 to 12 carbon atoms or 3 to 10 carbon atoms. The cycloalkyl may include a bridged structure, a fused structure, or a spiro structure. Examples of typical cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.

[0066] In the present invention, the term “aryl” means an aromatic hydrocarbon having, for example, 6 to 10 carbon atoms, and specific examples include, but are not limited to, phenyl and naphthyl.

[0067] In the present invention, the term “heterocycloalkyl” means a cyclic, for example, saturated aliphatic hydrocarbon comprising one or more heteroatoms selected from N, O, and S as a reducer, such as 3 to 10 members or 4 to 8 members.

[0068] In the present invention, the term “heteroaryl” refers to an aromatic hydrocarbon comprising, for example, one or more heteroatoms selected from N, O, and S as a reducer, and having 5 to 10 or 5 to 8 atoms. For example, the above heteroaryls are pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isooxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, Includes, but is not limited to, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, triazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, or furopyridinyl.

[0069] In the present invention, the term “partially unsaturated heterocyclile” means a cyclic, for example, partially unsaturated hydrocarbon comprising one or more heteroatoms selected from N, O, and S as a reducer, such as 3 to 10 members or 4 to 8 members.

[0070]

[0071] According to one embodiment of the present invention, in the above formula 1

[0072] R1 is a C1-C7 alkyl, hydroxy-C1-C7 alkyl, C3-C 12 Cycloalkyl, C6-C 10 Aryl, 5 to 10-membered heteroaryl, C6-C 10 aryl-C1-C7 alkyl, 5 to 10-membered heteroaryl-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkyl, or partially unsaturated 3 to 10-membered heterocycloalkyl-C1-C7 alkyl; wherein the alkyl, cycloalkyl, aryl, and heteroaryl are hydroxy, halo, amino, carboxyl, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 alkoxy, C1-C7 alkylthio, hydroxy-C1-C7 alkyl, hydroxy-C3-C 12Cycloalkyl, halo-C1-C7alkyl, cyano-C1-C7alkyl, halo-C1-C7alkoxy, C1-C7alkoxy-C1-C7alkyl, C1-C7alkoxy-C1-C7alkoxy, C1-C7alkyl-phosphine oxide, di(C1-C7alkyl)amino, di(C1-C7alkyl)amino-C1-C7alkoxy, di(C1-C7alkyl)amino-C1-C7alkoxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkoxy-C1-C7alkyl, C1-C7alkylsulfonyl, C1-C7alkylsulfonylamino, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy, 3 to 10-membered Heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkylcarbonyl substituted with C1-C7 alkyl, C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy, C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy, C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkyl, di(C1-C7 alkyl)amino-C1-C7 alkylcarbonyloxy-C1-C7 alkyl, phosphono-C1-C7 alkylcarbonyl-C1-C7 alkoxy-C1-C7 alkyl, dihydrogen phosphate-C1-C7 alkylcarbonyloxy-C1-C7 alkyl, dihydrogen phosphate-C1-C7 alkoxy-C1-C7 alkyl, diaminooxyphosphoryloxy-C1-C7 alkoxycarbonyloxy-C1-C7 alkyl, disodium oxyphosphoryloxy-C1-C7 alkoxycarbonyloxy-C1-C7 alkyl and 5 to 10 It can be optionally substituted with 1 to 4 substituents selected from the heteroaryl group;The above heterocycloalkyl and partially unsaturated heterocyclyl are hydroxy, halo, amino, carboxy, oxo, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 alkoxy, C1-C7 alkylthio, hydroxy-C1-C7 alkyl, hydroxy-C3-C; 12 Cycloalkyl, halo-C1-C7alkyl, cyano-C1-C7alkyl, halo-C1-C7alkoxy, C1-C7alkoxy-C1-C7alkyl, C1-C7alkoxy-C1-C7alkoxy, C1-C7alkyl-phosphine oxide, di(C1-C7alkyl)amino, di(C1-C7alkyl)amino-C1-C7alkoxy, di(C1-C7alkyl)amino-C1-C7alkoxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkoxy-C1-C7alkyl, C1-C7alkylsulfonyl, C1-C7alkylsulfonylamino, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy, 3 to 10-membered Heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl substituted with C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy substituted with C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with C1-C7alkyl, C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy, C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkylcarbonyloxy-C1-C7alkyl, It may optionally be substituted with one to four substituents selected from the group consisting of dihydrogen phosphate-C1-C7alkyl, dihydrogen phosphate-C1-C7alkylcarbonyloxy-C1-C7alkyl, and 5 to 10-membered heteroaryls;

[0073] R2 is hydrogen, C1-C7 alkyl, C2-C7 alkynyl, C3-C 12 Cycloalkyl, C6-C 10 Aryl, 5 to 10-membered heteroaryl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl or C6-C 10It is an aryl-C1-C7 alkyl; Herein, the cycloalkyl, aryl, heteroaryl, and heterocycloalkyl are 3 to 10-membered heterocycloalkyls substituted with hydroxy, halo, amino, carboxyl, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 deuterium alkoxy, hydroxy-C1-C7 alkyl, halo-C1-C7 alkyl, halo-C1-C7 alkoxy, di(C1-C7 alkyl)amino, di(C1-C7 alkyl)amino-C1-C7 alkyl, azide, amide, C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkoxy, 3 to 10-membered heterocycloalkyl-amino, 3 to 10-membered heterocycloalkyl-amino-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-oxy-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-amino-C1-C7alkyl substituted with oxo, 3 to 10-membered heterocycloalkyl-amino-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with carboxyl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl substituted with C1-C7 alkylsulfonyl It may optionally be substituted with 1 to 4 substituents selected from the group consisting of heterocycloalkyl-C1-C7alkyl, 5 to 10-membered heteroaryl, and 5 to 10-membered heteroaryl-C1-C7alkylamino-C1-C7alkyl substituted with C1-C7alkyl;

[0074] R3 is hydroxy, cyano, nitro, C1-C7 alkyl, C1-C7 alkoxy, halo-C1-C7 alkyl, amino, C1-C7 alkylamino, di(C1-C7 alkyl)amino, carboxy, or C1-C7 alkoxycarbonyl;

[0075] L is a direct bond, C1-C7 alkylene, halo-C1-C7 alkylene, -C(=O)-, -C(=O)O-, -CH2NRa-, -C(=O)NRa-, or -NRaC(=O)-; where Ra is hydrogen, C1-C7 alkyl, or di(C1-C7 alkyl)amino-C1-C7 alkyl;

[0076] R4 is hydroxy, halo, cyano, amino, carboxy, C1-C7 alkyl, hydroxy-C1-C7 alkyl, halo-C1-C7 alkyl, carboxy-C1-C7 alkyl, C1-C7 alkoxy, C3-C 12 Cycloalkyl, C3-C 12 Cycloalkyl-C1-C7alkyl, 3 to 10-membered heterocycloalkyl, C1-C7alkyl-substituted phosphonate, dihydrogen phosphite, C6-C 10 Aryl, 5 to 10-membered heteroaryl, partially unsaturated 3 to 10-membered heterocyclil, C6-C 10 Aryl-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkyl, 5 to 10-membered heteroaryl-C1-C7 alkyl, C1-C7 alkylamino, di(C1-C7 alkyl)amino, di(C1-C7 alkyl)amino-C1-C7 alkyl, C6-C 10 Arylamino, C1-C7 alkylcarbonylamino, C6-C 10 Arylcarbonylamino, C1-C7 alkylsulfonylamino, C6-C 10 It is arylsulfonylamino or -BR6R7; wherein R6 and R7 are each independently hydroxyl, or R6 and R7 may form a 3 to 10-membered heterocycloalkyl group substituted with a C1-C7 alkyl together with a boron (B) atom to which they are linked; and the alkyl, cycloalkyl, heterocycloalkyl and unsaturated heterocycloyl are hydroxyl, halo, amino, oxo, oxide, carboxyl, C1-C7 alkyl, C3-C 12 C3-C substituted with cycloalkyl, hydroxy-C1-C7alkyl 12Cycloalkyl, 3 to 10-membered heterocycloalkyl, C1-C7 alkoxy, hydroxy-C1-C7 alkyl, halo-C1-C7 alkyl, carboxy-C1-C7 alkyl, amino-C1-C7 alkyl, halo-C1-C7 alkoxy, di(C1-C7 alkyl)amino, aminocarbonyl, C6-C 10 Aryl, C6-C 10Aryl-C1-C7 alkylcarbonyl, amino-substituted C1-C7 alkyl-carbonyloxy, C1-C7 alkylaminocarbonyloxy, amino-C1-C7 alkylcarbonyloxy, amino-C1-C7 alkylcarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkylcarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkoxycarbonyloxy-C1-C7alkyl, amino-substituted C1-C7 alkylcarbonyloxy-C1-C7alkyl, guanidino and amino-substituted C1-C7 alkylcarbonyloxy-C1-C7alkyl, aminocarbonyl and amino-substituted C1-C7 alkylcarbonyloxy-C1-C7alkyl, carboxy-C1-C7 alkylcarbonyloxy-C1-C7alkyl, Carboxy-C1-C7 alkoxycarbonyloxy-C1-C7 alkyl, carboxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkylcarbonyloxy-C1-C7 alkyl, 5 to 10-membered heteroaryl-carbonyloxy-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7 alkyl, dihydrogen phosphate-C1-C7 alkyl, C1-C7 alkoxycarbonyl-C1-C7 alkylaminocarbonyloxy-C1-C7 alkyl, (C1-C7 alkylamino-C1-C7 alkyl)(C1-C7 alkyl)aminocarbonyloxy-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7 alkyl substituted with C1-C7 alkyl, Aminosulfonyloxy-C1-C7alkyl, C1-C7alkoxy-C1-C7alkoxycarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkoxycarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)aminothiocarbonyloxy-C1-C7alkyl, C1-C7alkylaminothiocarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)aminocarbonyloxy-C1-C7alkyl, sodium oxycarbonyl-C1-C7alkoxycarbonyloxy-C1-C7alkyl, phosphono-C1-C7alkylcarbonyloxy-C1-C7alkyl, dihydrogenphosphate-C1-C7alkylcarbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7alkyl, 3 to 10 heterocycloalkyl-carbonyloxy-C1-C7alkyl substituted with C1-C7 alkoxycarbonyl,3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-carbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-carbonyloxy-C1-C7alkyl substituted with C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkylaminocarbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkylaminocarbonyloxy-C1-C7alkyl substituted with C1-C7alkyl, (3 to 10 members substituted with C1-C7alkyl The aryl and heteroaryl may optionally be substituted with one to four substituents selected from the group consisting of heterocycloalkyl-C1-C7alkyl)(C1-C7alkyl)aminocarbonyloxy-C1-C7alkyl, and 3 to 10 heterocycloalkyl-oxy-C1-C7alkyl substituted with carboxy and hydroxyl; said aryl and heteroaryl may be optionally substituted with hydroxy, halo, amino, oxide, carboxy, C1-C7alkyl, C1-C7 alkoxy, hydroxy-C1-C7alkyl, halo-C1-C7alkyl, carboxy-C1-C7alkyl, amino-C1-C7alkyl, halo-C1-C7 alkoxy, di(C1-C7alkyl)amino, aminocarbonyl, C6-C, 10 Aryl, C6-C 10Aryl-C1-C7 alkylcarbonyl, amino-substituted C1-C7 alkyl-carbonyloxy, C1-C7 alkylaminocarbonyloxy, amino-C1-C7 alkylcarbonyloxy, di(C1-C7 alkyl)amino-C1-C7 alkylcarbonyloxy-C1-C7 alkyl, amino-substituted C1-C7 alkylcarbonyloxy-C1-C7 alkyl, 5 to 10-membered heteroaryl-carbonyloxy-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7 alkyl, dihydrogenphosphate-C1-C7 alkyl, C1-C7 alkoxycarbonyl-C1-C7 alkylaminocarbonyloxy-C1-C7 alkyl, (C1-C7 alkylamino-C1-C7 alkyl)(C1-C7 alkyl)aminocarbonyloxy-C1-C7 alkyl, 3 to 10 heterocycloalkyl-carbonyloxy-C1-C7alkyl substituted with C1-C7 alkyl, aminosulfonyloxy-C1-C7alkyl, C1-C7 alkoxy-C1-C7 alkoxycarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)aminothionyloxy-C1-C7alkyl, C1-C7 alkylaminothionyloxy-C1-C7alkyl, di(C1-C7alkyl)aminocarbonyloxy-C1-C7alkyl, 3 to 10 heterocycloalkyl-carbonyloxy-C1-C7alkyl, 3 to 10 heterocycloalkyl-carbonyloxy-C1-C7alkyl substituted with C1-C7 alkoxycarbonyl, 3 to 10 heterocycloalkyl-C1-C7 alkoxy-C1-C7alkyl, 3 to 10 It may optionally be substituted with one to four substituents selected from the group consisting of heterocycloalkyl-C1-C7alkoxy-carbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkylaminocarbonyloxy-C1-C7alkyl, and 3 to 10-membered heterocycloalkyl-oxy-C1-C7alkyl substituted with carboxy and hydroxy.

[0077] n is 1 or 2, and;

[0078] R5 is -H, C1-C7alkyl, hydroxy-C1-C7alkyl, C3-C 12 Cycloalkyl, C3-C 12 Cycloalkyl-C1-C7alkyl or C6-C 10It is an aryl-C1-C7 alkyl; and when m is 2, two R5s are connected to each other with a carbon atom bonded to C3-C 10 A cycloalkyl group can be formed, wherein the aryl group may optionally be substituted with one to four substituents selected from the group consisting of halos, C1-C7 alkyls, and C1-C7 alkoxys;

[0079] m is 1 or 2, and;

[0080] The above heterocycloalkyl, partially unsaturated heterocyclil, and heteroaryl have 1 to 4 heteroatoms selected from N, O, and S;

[0081] However, if R1 is a benzyl substituted with one hydroxyl and R3 is a nitro, R4 is not a C1-C7 alkyl and a 3 to 10-membered heterocycloalkyl-C1-C7 alkyl.

[0082]

[0083] Representative examples of compounds of Formula 1 according to the present invention may include, but are not limited to, the following compounds:

[0084] 1) 4-((R)-5-benzyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0085] 2) (R)-N-(2,3-dihydrobenzofuran-5-yl)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0086] 3) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-hydroxypyridine-2-yl)methyl)-3-nitrobenzamide;

[0087] 4) 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((1r,4R)-4-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0088] 5) (R)-N-(3-carbamoylcyclobutyl)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0089] 6) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxycyclobutyl)-3-nitrobenzamide;

[0090] 7) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((3-hydroxycyclobutyl) methyl)-3-nitrobenzamide;

[0091] 8) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0092] 9) (R)-3-cyano-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0093] 9-1) 3-cyano-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0094] 10) (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-nitrobenzamide;

[0095] 11) (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl) methyl)-3-nitrobenzamide;

[0096] 12) 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0097] 13) (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide;

[0098] 14) (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0099] 15) 4-((R)-5-cyclopentyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0100] 16) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-morpholino-3-(trifluoromethyl)benzamide;

[0101] 17) 3-cyano-4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0102] 18) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0103] 19) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0104] 19-1) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0105] 20) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0106] 21) 4-((S)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0107] 22) (4-((S)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0108] 23) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-methylfuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0109] 24) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1r,4R)-4-hydroxycyclohexyl)-3-(trifluoromethyl)benzamide;

[0110] 25) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0111] 26) (S)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0112] 27) (R)-2-(4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)pyridine 1-oxide;

[0113] 28) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-morpholinoethyl)-3-(trifluoromethyl)benzamide;

[0114] 29) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methylpiperidine-4-yl)methyl)-3-(trifluoromethyl)benzamide;

[0115] 30) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-ethylpiperidine-4-yl)methyl)-3-(trifluoromethyl)benzamide;

[0116] 31) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1,1-deoxydothiomophorino)-3-(trifluoromethyl)benzamide;

[0117] 32) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-(1,1-deoxydothiomophorino)ethyl)-3-(trifluoromethyl)benzamide;

[0118] 33) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(trifluoromethyl)benzamide;

[0119] 34) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-fluoropyridine-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0120] 35) (R)-2-((4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)-5-fluoropyridine 1-oxide;

[0121] 36) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)benzamide;

[0122] 37) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-methyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0123] 38) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-ethyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0124] 39) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methoxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0125] 40) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methylcyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0126] 41) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0127] 42) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)-3-(trifluoromethyl)benzamide;

[0128] 43) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3-(trifluoromethyl)benzamide;

[0129] 44) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-3-yl)methyl)-3-(trifluoromethyl)benzamide;

[0130] 45) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxetane-3-ylmethyl)-3-(trifluoromethyl)benzamide;

[0131] 46) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-tetrahydrofuran-3-yl)-3-(trifluoromethyl)benzamide;

[0132] 47) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-tetrahydrofuran-3-yl)-3-(trifluoromethyl)benzamide;

[0133] 48) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide;

[0134] 49) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0135] 50) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-3-ylmethyl)-3-(trifluoromethyl)benzamide;

[0136] 51) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide;

[0137] 52) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1-methylazetidine-3-yl)-3-(trifluoromethyl)benzamide;

[0138] 53) (R)-N-((1H-imidazole-4-yl)methyl)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0139] 54) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methyl-1H-imidazole-4-yl)methyl)-3-(trifluoromethyl)benzamide;

[0140] 55) 4-[(2R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-5-[(4-methoxyphenyl)methyl]-2-(1-methylethyl)-3-oxo-2H-pyrazine-1-yl]-N-[[1-(hydroxymethyl)cyclohexyl]methyl]-3-(trifluoromethyl)benzamide;

[0141] 56) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0142] 57) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0143] 58) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0144] 59) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0145] 60) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0146] 61) (R)-4-(5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0147] 62) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-methyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0148] 63) N-((3S,5S,7S)-adamantan-1-yl)-4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0149] 64) N-(((3R,5R,7R)-adamantan-1-yl)methyl)-4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0150] 65) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0151] 66) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0152] 67) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide;

[0153] 68) 4-((R)-5-cyclopropyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0154] 69) (R)-4-(5-cyclopropyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0155] 70) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0156] 71) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0157] 72) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0158] 73) 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0159] 74) (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0160] 75) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0161] 76) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0162] 77) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0163] 78) 3-cyano-4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0164] 79) 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0165] 80) 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0166] 81) (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0167] 82) (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0168] 83) (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0169] 84) 4-((R)-5-(4-fluorobenzyl)-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0170] 85) 4-((R)-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0171] 86) 4-((R)-5-benzyl-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0172] 87) 4-((R)-4-(4-(dimethylamino)benzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0173] 88) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-((1-methylpiperidine-4-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0174] 89) 4-((R)-4-((1-ethylpiperidine-4-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0175] 90) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0176] 91) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-(4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0177] 92) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-(4-(3-morpholinopropoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0178] 93) (R)-4-(4-(3-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0179] 94) (R)-4-(4-(3-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0180] 95) 4-((R)-4-(3-hydroxy-4-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0181] 96) 4-((R)-5-benzyl-2-isopropyl-3-oxo-4-(pyridine-2-ylmethyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0182] 97) 4-((R)-5-benzyl-2-isopropyl-3-oxo-4-(pyridine-2-ylmethyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0183] 98) (R)-4-(4-benzyl-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0184] 98-1) 4-((R)-4-benzyl-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0185] 99) 4-((R)-4-benzyl-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0186] 100) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0187] 100-1) 4-((R)-5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0188] 101) (R)-4-(4-(4-fluorobenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0189] 102) 3-cyano-4-((R)-4-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0190] 103) (R)-3-cyano-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0191] 103-1) 3-cyano-4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0192] 104) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0193] 105) 4-((R)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-4-((5-(trifluoromethyl)pyridine-2-yl)methyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0194] 106) 4-((R)-5-benzyl-2-isopropyl-3-oxo-4-((5-(trifluoromethyl)pyridine-2-yl)methyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0195] 107) (R)-N-isobutyl-4-(2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0196] 108) (R)-N,N-diethyl-4-(2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0197] 109) Hydroxycyclohexyl)-4-((R)-2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0198] 110) (R)-4-(2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0199] 110-1) 4-((R)-2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0200] 111) 3-cyano-4-((R)-5-(4-fluorobenzyl)-2-isopropyl-4-((5-methylfuran-2-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0201] 112) 4-((R)-5-(4-fluorobenzyl)-2-isopropyl-4-((5-methylfuran-2-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0202] 113) 4-((R)-4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0203] 114) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzoic acid;

[0204] 114-1) 4-((R)-4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0205] 115) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0206] 115-1) 4-((R)-4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0207] 116) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0208] 116-1) 4-((R)-4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0209] 117) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0210] 117-1) 4-((R)-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide;

[0211] 118) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0212] 119) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-nitrobenzamide;

[0213] 120) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4-(3-(trifluoromethoxy)benzyl)-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0214] 121) (R)-4-(2-isopropyl-3-oxo-4,5-bis(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0215] 121-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4,5-bis(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0216] 122) (R)-N-((1-(dimethylamino)cyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4,5-bis(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0217] 123) (R)-1-((4-(2-isopropyl-3-oxo-4,5-bis(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexane-1-carboxylic acid;

[0218] 124) (R)-4-(2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0219] 124-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0220] 125) (R)-4-(2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methoxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0221] 126) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-(4-(methylsulfonamido)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0222] 127) (R)-4-(4-(4-(dimethylamino)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0223] 128) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0224] 129) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0225] 130) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0226] 131) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0227] 132) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methyl-1H-imidazole-4-yl)methyl)-3-(trifluoromethyl)benzamide;

[0228] 133) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxazole-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0229] 134) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0230] 135) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide;

[0231] 136) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0232] 137) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0233] 138) (R)-4-(5-cyclopropyl-2-isopropyl-4-(4-(3-morpholinopropoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0234] 139) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-(4-(3-morpholinopropoxy)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0235] 140) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxazole-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0236] 141) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(thiazole-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0237] 142) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0238] 143) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide;

[0239] 144) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxazole-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0240] 145) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(thiazole-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0241] 146) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide;

[0242] 147) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide;

[0243] 148) 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-((3S,4S,5R,6S)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)benzamide;

[0244] 149) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0245] 150) N-((1r,3S,5R,7S)-3-hydroxyadamantan-1-yl)-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0246] 151) (S)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(2-(4-(2-phenylacetyl)piperazine-1-yl)ethyl)benzamide;

[0247] 152) (R)-4-(5-cyclopentyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0248] 153) 4-((R)-5-(4-(dimethylamino)benzyl)-4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0249] 154) 4-((R)-5-(4-bromobenzyl)-4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0250] 155) 4-((R)-4-(3,4-dihydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0251] 156) 4-((R)-4-(4-hydroxy-3-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0252] 157) 4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0253] 158) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0254] 159) 4-((R)-4-(2-hydroxyethyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0255] 160) 4-((R)-2-isopropyl-4-methyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0256] 161) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-methyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0257] 162) 4-((R)-4-(2-hydroxyethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0258] 163) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0259] 164) Methyl (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzoate;

[0260] 165) 4-((R)-5-cyclopentyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0261] 166) (R)-4-(5-cyclopentyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide;

[0262] 167) 3-amino-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0263] 168) 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(methylamino)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0264] 169) 3-(dimethylamino)-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0265] 170) 3-amino-4-((2R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxopiperazine-1-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0266] 171) Ethyl 2-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-((((S)-tetrahydrofuran-2-yl)methyl)carbamoyl)benzoate;

[0267] 172) Methyl 2-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-((((S)-tetrahydrofuran-2-yl)methyl)carbamoyl)benzoate;

[0268] 173) 2-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-((((S)-tetrahydrofuran-2-yl)methyl)carbamoyl)benzoic acid;

[0269] 174) 4-(((R)-6-(4-(dimethylamino)benzyl)-3-isopropyl-4-(2-nitro-4-((((S)-tetrahydrofuran-2-yl)methyl)carbamoyl)phenyl)-2-oxo-3,4-dihydropyrazine-1(2H)-yl)methyl)benzoic acid;

[0270] 175) 4-((R)-5-(4-azidobenzyl)-4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0271] 176) 4-((R)-5-(4-azidobenzyl)-4-(4-ethynylbenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0272] 177) 4-((R)-4-(4-(hydroxymethyl)benzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0273] 178) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0274] 179) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0275] 180) (R)-4-(4-(3-fluoro-4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0276] 181) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0277] 182) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0278] 183) 4-[2-(1-methylethyl)-3-oxydanylidene-4,5-bis[[4-[tris(fluoranyl)methoxy]phenyl]methyl]-2H-pyrazine-1-yl]-N-[[1-(oxydanylmethyl)cyclohexyl]methyl]-3-[tris(fluoranyl)methyl]benzamide;

[0279] 184) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(5-(4-(hydroxymethyl)phenyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0280] 185) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(5-(4-(hydroxymethyl)phenyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0281] 186) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-5-(4-(piperidine-1-ylmethyl)phenyl)-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0282] 187) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-5-(4-(morpholinomethyl)phenyl)-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0283] 188) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-5-(4-((4-methylpiperazine-1-yl)methyl)phenyl)-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0284] 189) (4-((R)-4-(4-(((1-hydroxycyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-5-isopropyl-6-oxo-1-(4-(trifluoromethoxy)benzyl)-1,4,5,6-tetrahydropyrazine-2-yl)benzyl)-L-proline;

[0285] 190) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0286] 191) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide;

[0287] 192) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0288] 193) (R)-N-((1H-1,2,4-triazole-3-yl)methyl)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0289] 194) (R)-N-((1H-tetrazole-5-yl)methyl)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0290] 195) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1H-tetrazole-5-yl)-3-(trifluoromethyl)benzamide;

[0291] 196) (R)-N-(2-(1H-imidazole-4-yl)ethyl)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0292] 197) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-(pyridine-4-yl)ethyl)-3-(trifluoromethyl)benzamide;

[0293] 198) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0294] 199) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(pyridine-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0295] 200) (R)-3-cyano-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(pyridine-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)benzamide;

[0296] 201) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0297] 201-1) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0298] 202) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0299] 203) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0300] 204) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclopropyl)methyl)-3-(trifluoromethyl)benzamide;

[0301] 205) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((4-hydroxy-1,1-deoxydotetrahydro-2H-thiopyran-4-yl)methyl)-3-(trifluoromethyl)benzamide;

[0302] 206) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((4-(hydroxymethyl)-1,1-deoxydotetrahydro-2H-thiopyran-4-yl)methyl)-3-(trifluoromethyl)benzamide;

[0303] 207) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0304] 208) (R)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0305] 209) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-5-(4-(hydroxymethyl)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0306] 210) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(piperidine-1-ylmethyl)phenyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0307] 211) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-5-(4-(morpholinomethyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0308] 212) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-5-(4-((4-methylpiperazine-1-yl)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0309] 213) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide;

[0310] 214) (R)-3-cyano-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzamide;

[0311] 215) 3-cyano-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide;

[0312] 216) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0313] 216-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0314] 217) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0315] 218) (R)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0316] 219) (R)-1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexane-1-carboxylic acid;

[0317] 220) (R)-2-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)acetic acid;

[0318] 221) N-((1-(aminomethyl)cyclohexyl)methyl)-4-((2R)-4-((4-(hydroxymethyl)-3-methoxycyclohexa-1,5-diene-1-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0319] 222) 4-[[(2R,4R)-1-[4-[[1-(hydroxymethyl)cyclohexyl]methylcarbamoyl]-2-(trifluoromethyl)phenyl]-2-(1-methylethyl)-3-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2H-pyrazine-4-yl]methyl]-2-methoxy-benzoic acid;

[0320] 223) (R)-4-(4-(4-((2-(dimethylamino)ethoxy)methyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0321] 224) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-((3-morpholinopropoxy)methyl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0322] 225) (R)-4-(4-(4-((3-(dimethylamino)propoxy)methyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0323] 226) (R)-4-(4-(4-((3-(dimethylamino)propoxy)methyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0324] 227) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-((3-(4-methylpiperazine-1-yl)propoxy)methyl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0325] 228) (R)-4-(4-(3-fluoro-4-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(pyridine-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0326] 229) (R)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0327] 229-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0328] 230) (R)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0329] 231) (R)-4-(4-(4-bromobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0330] 232) (R)-4-(4-(4-bromobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0331] 233) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-(4-(4-methylpiperazine-1-yl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0332] 234) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(4-(4-methylpiperazine-1-yl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0333] 235) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-(4-(methylsulfonamido)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0334] 236) (R)-4-(2-isopropyl-4-(4-(methylsulfonamido)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0335] 236-1) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(4-(methylsulfonamido)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0336] 237) (R)-4-(4-((1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0337] 238) (R)-4-(4-((1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0338] 239) 4-((2R)-4-((4-hydroxycroman-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0339] 240) 4-((2R)-4-((4-hydroxycroman-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0340] 241) 4-((2R)-4-((4-hydroxycroman-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0341] 242) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0342] 243) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0343] 244) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0344] 245) (R)-4-(4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0345] 245-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0346] 246) (R)-4-(4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0347] 247) (R)-4-(4-((4H-benzo[d][1,3]dioxin-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0348] 247-1) (R)-4-(4-((4H-benzo[d][1,3]dioxin-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0349] 248) (R)-4-(4-((4H-benzo[d][1,3]dioxin-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0350] 249) (R)-4-(4-((4H-benzo[d][1,3]dioxin-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0351] 250) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(2-hydroxypropane-2-yl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0352] 251) (R)-4-(4-(4-(2-hydroxypropane-2-yl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methylcyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0353] 252) (R)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-4-(4-(4-(2-hydroxypropane-2-yl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0354] 253) (R)-4-(4-(3-fluoro-4-(2-hydroxypropane-2-yl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0355] 254) (R)-4-(4-(3,5-difluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0356] 255) (R)-4-(4-(3,5-difluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0357] 256) (R)-4-(4-(3,5-difluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0358] 257) (R)-4-(4-(4-(1-hydroxycyclobutyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0359] 258) (R)-4-(4-(4-(1-hydroxycyclobutyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0360] 259) (R)-4-(4-(4-(1-hydroxycyclobutyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0361] 260) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(methylthio)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0362] 261) (R)-4-(4-(4-(hydroxymethyl)-3-(methylthio)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0363] 262) (R)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(methylthio)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0364] 263) (R)-4-(4-(3-fluoro-4-(methylsulfonyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0365] 264) (R)-4-(4-(3-fluoro-4-isopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0366] 265) (R)-4-(4-(3-fluoro-4-isopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0367] 266) (R)-4-(4-(3-fluoro-4-isopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0368] 267) (R)-4-(4-(3,4-diisopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0369] 268) (R)-4-(4-(3,4-diisopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0370] 269) (R)-4-(4-(3,4-diisopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0371] 270) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0372] 271) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0373] 272) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0374] 273) (R)-4-(4-(3-fluoro-4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0375] 274) (R)-4-(4-(3-fluoro-4-(3-morpholinopropoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0376] 275) (R)-4-(4-(4-(3-(dimethylamino)propoxy)-3-fluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0377] 276) (R)-4-(4-(3-fluoro-4-(3-(4-methylpiperazine-1-yl)propoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0378] 277) (R)-4-(4-(3,4-diisopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0379] 278) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-5-(4-(hydroxymethyl)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0380] 279) (R)-4-(5-(4-(chloromethyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0381] 280) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((4-methylpiperazine-1-yl)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0382] 281) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(piperidine-1-ylmethyl)phenyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0383] 282) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(morpholinomethyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0384] 283) (R)-4-(5-(4-((dimethylamino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0385] 284) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((((1-methyl-1H-imidazole-5-yl)methyl)amino)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0386] 285) (R)-4-(5-cyclopropyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0387] 286) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(4-methylpiperazine-1-yl)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0388] 287) (4-((R)-1-(3-fluoro-4-methoxybenzyl)-4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-5-isopropyl-6-oxo-1,4,5,6-tetrahydropyrazine-2-yl)benzyl)-L-proline;

[0389] 288) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((morpholinoamino)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0390] 289) (R)-4-(5-(4-(((1,1-deoxydothiomorpholino)amino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0391] 290) (R)-4-(5-(4-((3-(dimethylamino)propoxy)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0392] 291) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((3-morpholinopropoxy)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0393] 292) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((3-(4-methylpiperazine-1-yl)propoxy)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0394] 293) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((4-(methylsulfonyl)piperazine-1-yl)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0395] 294) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(((1-methylazetidin-3-yl)amino)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0396] 295) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(((1-methylpiperidin-4-yl)oxy)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0397] 296) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(pyridine-2-yl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0398] 297) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(pyridine-4-yl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0399] 298) (R)-4-(5-((1,3-dioxolane-2-yl)methyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0400] 299) (R)-4-(5-((1,3-dioxolane-2-yl)methyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0401] 300) (R)-4-(4-((1H-indazole-5-yl)methyl)-2-isopropyl-3-ox7so-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0402] 301) (R)-4-(4-((1H-indazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0403] 302) (R)-4-(4-((1H-benzo[d][1,2,3]triazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0404] 303) (R)-4-(4-((1H-benzo[d][1,2,3]triazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0405] 304) (R)-4-(4-((5-fluoro-6-methoxypyridine-3-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0406] 305) (R)-4-(4-((5-fluoro-6-methoxypyridine-3-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0407] 306) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(3-morpholinopropoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0408] 307) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(morpholinoamino)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0409] 308) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4-(quinoxalin-6-ylmethyl)-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0410] 309) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4-(quinoxalin-6-ylmethyl)-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0411] 310) (R)-4-(4-(3-fluoro-4-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0412] 311) (R)-4-(4-(3-fluoro-4-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0413] 312) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(((3aR,6aS)-tetrahydro-1H-puro[3,4-c]pyrrole-5(3H)-yl)methyl)phenyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0414] 313) (R)-4-(5-(4-((2-oxa-6-azaspiro[3.3]heptane-6-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0415] 314) 4-((2R)-5-(4-((3-oxa-7-azabicyclo[3.3.1]nonan-7-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0416] 315) 4-((R)-5-(4-(((2S,6R)-2,6-dimethylmorpholino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0417] 316) (R)-4-(5-(4-((2,2-dimethylmorpholino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0418] 317) (R)-4-(5-(4-((3,3-dimethylmorpholino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0419] 318) (R)-4-(5-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0420] 319) 4-((R)-5-(4-(((3S,5R)-3,5-dimethylmorpholino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0421] 320) (R)-4-(4-(3-fluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0422] 321) (R)-4-(5-(4-((4-oxa-7-azaspiro[2.5]octane-7-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0423] 322) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((4-isopropylpiperazine-1-yl)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0424] 323) (R)-4-(5-(4-((4-(tert-butyl)piperazine-1-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0425] 324) (R)-4-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0426] 325) (R)-4-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0427] 326) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-(methoxymethyl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0428] 327) (R)-4-(4-(4-(dimethylphosphoryl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0429] 328) (R)-4-(4-(4-(dimethylphosphoryl)-3-fluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0430] 329) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((1-methyl-1H-indazole-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0431] 330) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((1-methyl-1H-benzo[d][1,2,3]triazole-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0432] 331) (R)-4-(4-((1-(cyanomethyl)-1H-indazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0433] 332) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-(pyridine-2-yl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0434] 333) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0435] 334) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0436] 335) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((2-methoxypyrimidine-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0437] 336) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-((2-methoxypyrimidine-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0438] 337) (R)-4-(5-benzyl-2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0439] 338) (R)-4-(5-benzyl-2-isopropyl-4-((2-methoxypyrimidine-5-yl))methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0440] 339) (R)-4-(4-((1H-indazole-5-yl)methyl)-5-benzyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0441] 340) 4-((R)-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide;

[0442] 341) (R)-4-(5-benzyl-4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0443] 342) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0444] 343) (R)-3-cyano-4-(5-(4-fluorophenyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0445] 344) (R)-3-cyano-4-(2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0446] 345) (R)-3-cyano-4-(2-isopropyl-5-methyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0447] 346) (R)-3-cyano-4-(2-isopropyl-3-oxo-5-(prop-2-fin-1-yl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0448] 347) (R)-4-(5-(2-bromobenzyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0449] 348) (R)-3-cyano-4-(5-(2,6-difluorobenzyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0450] 349) (R)-3-cyano-4-(2-isopropyl-3-oxo-5-phenethyl-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0451] 350) (R)-3-cyano-4-(2-isopropyl-5-(2-methylbenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0452] 351) (R)-3-cyano-4-(5-(2,5-difluorobenzyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0453] 352) (R)-3-cyano-4-(2-isopropyl-5-(3-methylbenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0454] 353) (R)-3-cyano-4-(5-(3,5-difluorobenzyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0455] 354) (R)-3-cyano-4-(2-isopropyl-5-(3-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0456] 355) (R)-3-cyano-4-(2,5-dibenzyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0457] 356) 4-(5-benzyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0458] 357) tert-butyl (R)-4-(5-benzyl-2-methyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate;

[0459] 358) (R)-4-(5-benzyl-2-methyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0460] 359) 4-(5-benzyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide;

[0461] 360) (R)-4-(5-benzyl-2-methyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide;

[0462] 361) (R)-3-cyano-4-(2,5-dibenzyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N,N-dimethylbenzamide;

[0463] 362) 4-(6-benzyl-8-oxo-7-(4-(trifluoromethyl)benzyl)-4,7-diazaspiro[2.5]oc-5-ten-4-yl)-3-cyanobenzoic acid;

[0464] 363) 4-(5-benzyl-2,2-dimethyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0465] 364) 4-((R)-5-benzyl-2-((S)-1-hydroxyethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0466] 365) 4-((S)-5-benzyl-2-((R)-1-hydroxyethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0467] 366) (R)-4-(5-benzyl-2-(hydroxymethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid

[0468] 367) (S)-4-(5-benzyl-2-(hydroxymethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0469] 368) (R)-4-(5-benzyl-2-isobutyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0470] 369) (S)-4-(5-benzyl-2-isobutyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0471] 370) (R)-4-(5-benzyl-2-(cyclohexylmethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0472] 371) (S)-4-(5-benzyl-2-(cyclohexylmethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0473] 372) (S)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0474] 373) (S)-3-cyano-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0475] 374) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0476] 375) (R)-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0477] 376) (R)-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0478] 377) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N,N-dimethyl-3-nitrobenzamide;

[0479] 378) tert-butyl (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate;

[0480] 379) Methyl (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate;

[0481] 380) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N,N-dimethyl-3-nitrobenzamide;

[0482] 381) (R)-2-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(morpholine-4-carbonyl)benzonitrile;

[0483] 382) (R)-2-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(4-methylpiperazine-1-carbonyl)benzonitrile;

[0484] 383) (R)-3-cyano-N,N-diethyl-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzamide;

[0485] 384) (R)-5-(3-ethyl-1,2,4-oxadiazole-5-yl)-2-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzonitrile;

[0486] 385) (3-cyano-4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoyl)proline;

[0487] 386) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-bromobenzonitrile;

[0488] 387) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-chlorobenzonitrile;

[0489] 388) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N,3-dicyanobenzamide;

[0490] 389) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(2,2,2-trifluoroethyl)benzamide;

[0491] 390) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(2,2,2-trifluoroethyl)benzamide;

[0492] 391) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N'-phenylbenzohydrazide;

[0493] 392) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N'-methylbenzohydrazide;

[0494] 393) (R)-N'-benzoyl-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzohydrazide;

[0495] 394) (R)-N'-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoyl)benzenesulfonohydrazide;

[0496] 395) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(5-methyl-1,3,4-oxadiazole-2-yl)benzonitrile;

[0497] 396) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(5-phenyl-1,3,4-oxadiazole-2-yl)benzonitrile;

[0498] 397) Diethyl (R)-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)phosphonate;

[0499] 398) (R)-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)phosphorous acid;

[0500] 399) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(dimethylamino)benzonitrile;

[0501] 400) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(isooxazole-4-yl)benzonitrile;

[0502] 401) (R)-N'-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoyl)methanesulfonohydrazide;

[0503] 402) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzohydrazide;

[0504] 403) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-hydroxybenzamide;

[0505] 404) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile;

[0506] 405) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(hydroxymethyl)benzonitrile;

[0507] 406) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(1H-pyrazol-4-yl)benzonitrile;

[0508] 407) (R)-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)boronic acid;

[0509] 408) (R)-5-(azetidine-1-yl)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzonitrile;

[0510] 409) (R)-2-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)-2-methylpropionic acid;

[0511] 410) (R)-2-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)acetic acid;

[0512] 411) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(3-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0513] 412) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(2-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0514] 413) (R)-4-(5-benzyl-4-(3-fluoro-4-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0515] 414) (R)-4-(5-benzyl-4-(2-fluoro-4-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0516] 415) (S)-4-(5-benzyl-4-(3-fluoro-4-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0517] 416) (R)-3-cyano-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0518] 417) (S)-4-(5-benzyl-4-(4-(difluoromethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0519] 418) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide;

[0520] 419) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-benzyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0521] 420) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0522] 421) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0523] 422) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(3-chloro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0524] 423) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(3,5-difluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0525] 424) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0526] 425) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-(difluoromethoxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0527] 426) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0528] 427) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-ethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0529] 428) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-isopropoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0530] 429) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-(methoxy-d3)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0531] 430) (R)-4-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0532] 431) (R)-4-(4-(benzo[d]oxazole-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0533] 432) (R)-4-(4-(benzofuran-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0534] 433) (R)-4-(4-((2,3-dihydrobenzofuran-5-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0535] 434) (R)-4-(4-((1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0536] 435) (R)-4-(4-(4-(tert-butyl)benzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0537] 436) (R)-4-(4-(4-(tert-butyl)benzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0538] 437) (R)-4-(4-(4-(tert-butyl)benzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0539] 438) (R)-4-(4-(4-(tert-butyl)benzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide;

[0540] 439) (S)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0541] 440) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0542] 441) Methyl (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate;

[0543] 442) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide;

[0544] 443) (R)-2-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-(morpholine-4-carbonyl)benzonitrile;

[0545] 444) (R)-2-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-(4-methylpiperazine-1-carbonyl)benzonitrile formate;

[0546] 445) (R)-2-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-(3-ethyl-1,2,4-oxadiazole-5-yl)benzonitrile;

[0547] 446) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(2-(dimethylamino)ethyl)-N-methylbenzamide;

[0548] 447) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-diethylbenzamide;

[0549] 448) (4-((R)-5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoyl)-L-proline;

[0550] 449) (R)-3-cyano-4-(5-cyclopentyl-4-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0551] 450) (R)-3-cyano-4-(2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0552] 451) (R)-3-cyano-4-(4-(4-fluorobenzyl)-2-isopropyl-5-methyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0553] 452) (R)-3-cyano-4-(5-cyclobutyl-4-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0554] 453) (R)-3-cyano-4-(4-(4-fluorobenzyl)-5-isobutyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0555] 454) (R)-3-cyano-4-(4-(4-fluorobenzyl)-5-(furan-2-yl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0556] 455) (R)-3-cyano-4-(4-(4-fluorobenzyl)-5-(furan-3-yl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0557] 456) (R)-4-(5-benzyl-2-isopropyl-4-(4-methylbenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0558] 457) (R)-4-(5-benzyl-4-(3-fluoro-4-methylbenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0559] 458) (R)-4-(5-benzyl-4-(2-fluoro-4-methylbenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0560] 459) (R)-4-(5-benzyl-4-(4-bromobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0561] 460) (R)-4-(4-(3-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0562] 461) (R)-4-(4-(3,4-dihydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid;

[0563] 462) (R)-3-cyano-4-(2-isopropyl-4-(4-methoxybenzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid;

[0564] 463) (R)-4-(5-benzyl-2-isopropyl-4-((5-methylfuran-2-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0565] 464) (R)-4-(5-benzyl-2-isopropyl-4-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid;

[0566] 465) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-(2,5,8,11,14-pentaoxapentadecyl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0567] 466) (R)-4-(4-(4-((2,5,8,11-tetraoxatridecan-13-yl)oxy)-3-fluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0568] 467) [1-[[[4-[(1S,2R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-5-[(4-methoxyphenyl)methyl]-2-(1-methylethyl)-3-oxo-2H-pyrazine-1-yl]-3-(trifluoromethyl)benzoyl]amino]methyl]cyclohexyl] 2-amino-3-methyl-butanoate;

[0569] 468) (R)-1-((4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl glycinate;

[0570] 469) 1-((4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl D-alaninate;

[0571] 470) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate;

[0572] 471) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl L-leucinate;

[0573] 472) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate;

[0574] 473) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl picolinate;

[0575] 474) (1-((4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl prolinate;

[0576] 475) [1-[[[4-[(1S,2R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-5-[(4-methoxyphenyl)methyl]-2-(1-methylethyl)-3-oxo-2H-pyrazine-1-yl]-3-(trifluoromethyl)benzoyl]amino]methyl]cyclohexyl] 2-amino-3-methyl-butanoate;

[0577] 476) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate;

[0578] 477) (1-((4-((R)-4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl L-leucinate formate;

[0579] 478) 1-((4-((R)-4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl L-leucinate formate;

[0580] 479) (R)-(1-((4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate;

[0581] 480) (R)-2-(1-((4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)ethyl dimethylglycinate;

[0582] 481) (R)-1-((4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl 3-aminopropanoate;

[0583] 482) (R)-4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl dimethylglycinate;

[0584] 483) (R)-4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl dihydrogen phosphate;

[0585] 484) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dihydrogen phosphate;

[0586] 485) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dihydrogen phosphate;

[0587] 486) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl phosphate;

[0588] 487) (R)-(1-((4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dihydrogen phosphate;

[0589] 488) (R)-4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl 2-(phosphonooxy)acetate;

[0590] 489) Methyl (2S)-2-[[1-[[[4-[(2R)-4-[(3-fluoro-4-methoxy-phenyl)methyl]-2-isopropyl-3-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2H-pyrazine-1-yl]-3-(trifluoromethyl)benzoyl]amino]methyl]cyclohexyl]methoxycarbonylamino]-3-methyl-butanoate;

[0591] 490) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl methyl(2-(methylamino)ethyl)carbamate;

[0592] 491) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl methyl(2-(methylamino)ethyl)carbamate;

[0593] 492) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methylsulfamate;

[0594] 493) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-methoxyethyl) carbonate;

[0595] 494) (R)-O-((1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) dimethylcarbamothioate;

[0596] 495) (R)-O-((1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) ethylcarbamothioate;

[0597] 496) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl diethylcarbamate;

[0598] 497) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl methyl(2-(methylamino)ethyl)carbamate;

[0599] 498) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methylmorpholine-4-carboxylate;

[0600] 499) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate;

[0601] 500) 1-((1-((4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) 2-methyl (S)-pyrrolidine-1,2-dicarboxylate;

[0602] 501) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-((2-morpholinoethoxy)methyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide formate;

[0603] 502) (R)-4-(5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0604] 503) (R)-(1-((4-(5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate formate;

[0605] 504) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl methyl(2-(methylamino)ethyl)carbamate formate;

[0606] 505) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate;

[0607] 506) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-5-benzyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0608] 507) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-5-benzyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate formate;

[0609] 508) (R)-(1-((4-(5-benzyl-4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate;

[0610] 509) (R)-(1-((4-(2-isopropyl-4-((2-methoxypyrimidine-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate;

[0611] 510) (R)-(1-((4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate formate;

[0612] 511) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate;

[0613] 512) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl)carbamate;

[0614] 513) (2S,3S,4S,5R)-6-((1-((4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid;

[0615] 514) (R)-N-(1,3-dihydroxy-2-(hydroxymethyl)propane-2-yl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0616] 515) N-((2R,3R)-1,3-dihydroxybutane-2-yl)-4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0617] 516) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide;

[0618] 517) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-1-hydroxy-3-methylbutane-2-yl)-3-(trifluoromethyl)benzamide;

[0619] 518) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide;

[0620] 519) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide;

[0621] 520) N-((R)-2,3-dihydroxypropyl)-4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0622] 521) N-(3-(dimethylamino)-2-hydroxypropyl)-4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0623] 522) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(2-((2-hydroxyethyl)(methyl)amino)ethyl)-3-(trifluoromethyl)benzamide;

[0624] 523) (R)-N-(3-(bis(2-hydroxyethyl)amino)propyl)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0625] 524) N-((R)-1-hydroxybutane-2-yl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0626] 525) N-((R)-1-hydroxy-3-methylbutane-2-yl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0627] 526) N-((R)-1-hydroxy-4-methylpentane-2-yl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0628] 527) N-((2R,3R)-1,3-dihydroxybutane-2-yl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0629] 528) N-((R)-2,3-dihydroxypropyl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0630] 529) (R)-N-(3-hydroxy-2,2-dimethylpropyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0631] 530) (R)-N-(1,3-dihydroxy-2-(hydroxymethyl)propane-2-yl)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0632] 531) N-(3-amino-2-hydroxypropyl)-4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0633] 532) (R)-N-(2-(bis(2-hydroxyethyl)amino)ethyl)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0634] 533) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)-N-((3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)benzamide;

[0635] 534) (R)-4-(4-(4,4-bis(hydroxymethyl)peperidin-1-carbonyl)-2-(trifluoromethyl)phenyl)-1-(3-fluoro-4-methoxybenzyl)-3-isopropyl-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-2(1H)-one;

[0636] 535) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide;

[0637] 536) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-1-hydroxy-3-methylbutane-2-yl)-3-(trifluoromethyl)benzamide;

[0638] 537) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide;

[0639] 538) (R)-4-(5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide;

[0640] 539) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((2R,3R)-1,3-dihydroxybutane-2-yl)-3-(trifluoromethyl)benzamide;

[0641] 540) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-2,3-dihydroxypropyl)-3-(trifluoromethyl)benzamide;

[0642] 541) N-(3-(dimethylamino)-2-hydroxypropyl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0643] 542) (R)-N-(2-((2-hydroxyethyl)(methyl)amino)ethyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0644] 543) (R)-N-(3-(bis(2-hydroxyethyl)amino)propyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0645] 544) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide;

[0646] 545) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-3-methylbutane-2-yl)-3-(trifluoromethyl)benzamide;

[0647] 546) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide;

[0648] 547) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((2R,3R)-1,3-dihydroxybutane-2-yl)-3-(trifluoromethyl)benzamide;

[0649] 548) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-2,3-dihydroxypropyl)-3-(trifluoromethyl)benzamide;

[0650] 549) (R)-4-(5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide;

[0651] 550) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide;

[0652] 551) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide;

[0653] 552) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide;

[0654] 553) 4-((R)-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide;

[0655] 554) 4-((R)-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-3-methylbutane-2-yl)-3-(trifluoromethyl)benzamide;

[0656] 555) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide;

[0657] 556) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((1-(4-methylpiperazine-1-carbonyl)-1H-indazole-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0658] 557) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-N-(2-morpholinoethyl)-3-(trifluoromethyl)benzamide;

[0659] 558) (R)-N-(4-(hydroxymethyl)-3-methoxybenzyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide

[0660] 559) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((6-methoxypyridine-3-yl)methyl)-3-(trifluoromethyl)benzamide;

[0661] 560) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((6-methoxypyridine-3-yl)methyl)-3-(trifluoromethyl)benzamide;

[0662] 561) (R)-N-(4-(hydroxymethyl)-3-methoxybenzyl)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0663] 562) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate;

[0664] 563) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate;

[0665] 564) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl)carbamate;

[0666] 565) (R)-(1-((4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl)carbamate;

[0667] 566) (R)-(1-((4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate;

[0668] 567) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,3-dimethylmorpholino)ethyl)carbamate;

[0669] 568) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(4-methylpiperazine-1-yl)ethyl) carbonate;

[0670] 569) (R)-2-(dimethylamino)ethyl ((1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) carbonate;

[0671] 570) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate;

[0672] 571) (R)-(1-((4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate;

[0673] 572) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,3-dimethylmorpholino)ethyl)carbamate;

[0674] 573) (1-((4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,5-dimethylmorpholino)ethyl)carbamate;

[0675] 574) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(7-oxa-4-azaspiro[2.5]octane-4-yl)ethyl)carbamate;

[0676] 575) (R)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-((2-morpholinoethoxy)methyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0677] 576) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-((2-morpholinoethoxy)methyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide;

[0678] 577) (R)-N-((1-((2-(3,3-dimethylmorpholino)ethoxy)methyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0679] 578) (R)-N-((1-((2-(3,3-dimethylmorpholino)ethoxy)methyl)cyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide;

[0680] 579) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,3-dimethylmorpholino)ethyl)(methyl)carbamate;

[0681] 580) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-((2R,6S)-2,6-dimethylmorpholino)ethyl)(methyl)carbamate;

[0682] 581) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,3-dimethylmorpholino)ethyl)(ethyl)carbamate;

[0683] 582) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-((2R,6S)-2,6-dimethylmorpholino)ethyl)(ethyl)carbamate;

[0684] 583) (R)-2-(dimethylamino)ethyl ((1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) carbonate;

[0685] 584) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(4-methylpiperazine-1-yl)ethyl) carbonate;

[0686] 585) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate;

[0687] 586) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl glycinate;

[0688] 587) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl L-arginine;

[0689] 588) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl L-glutaminate;

[0690] 589) (R)-3-((((1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)carbonyl)oxy)propionic acid;

[0691] 590) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate;

[0692] 591) Sodium (R)-3-((((1-((4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)carbonyl)oxy)propanoate;

[0693] 592) (R)-(3-((1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)-3-oxopropyl)phosphorous acid;

[0694] 593) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 3-(phosphonooxy)propanoate;

[0695] 594) (R)-1-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)-3-oxo-2,6,9,12-tetraoxapentadeca-15-noic acid;

[0696] 595) (R)-4-((1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)-4-oxobutanoic acid;

[0697] 596) (R)-(3-((4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl)oxy)-3-oxopropyl)phosphorous acid;

[0698] 597) (R)-4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl 2-(phosphonooxy)acetate;

[0699] 598) (R)-((4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl)oxy)methyl dihydrogen phosphate;

[0700] 599) (R)-2-((bis((λ5-azaneyl)oxy)phosphoryl)oxy)ethyl (4-((4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl) carbonate; and

[0701] 600) Sodium (R)-2-((((4-((4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl)oxy)carbonyl)oxy)ethyl phosphate.

[0702]

[0703] The names of the compounds described above were written in accordance with the naming convention provided by CambridgeSoft's CS ChemDraw Ultra (version: 19.0.1.28) software.

[0704]

[0705] The compound of Formula 1 according to the present invention may have an asymmetric carbon center and an asymmetric axis or an asymmetric plane, and thus may exist as stereoisomers such as E or Z isomers, R or S isomers, or racemics, and all such isomers and mixtures are included within the scope of the present invention. The compound of Formula 1 according to the present invention may be a racemic mixture, and this racemic mixture may be separated into its respective isomers by a conventional separation method, for example, by using a normal-phase or reverse-phase chiral column chromatography apparatus and using a corresponding developing solvent, preferably a solvent mixed with hexane, ethyl acetate, dichloromethane, and methanol in the normal phase, and a mixture of water and acetonitrile in the reverse phase.

[0706]

[0707] The compound of Formula 1 according to the present invention may also form a pharmaceutically acceptable salt. Representative acids that can be used to prepare such pharmaceutically acceptable salts include, but are not limited to, the following: acid addition salts formed by acids that form non-toxic acid addition salts containing anions, such as inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromide, hydroiodide, etc.; organic carboxylic acids such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid or trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, etc.; and sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid or naphthalsulfonic acid, etc., and also include salts formed with alkali metals such as sodium and potassium. In addition, it may include salts with other acids or bases known and used in the technical field to which aromatic amidine derivatives or lactam derivatives belong. These are manufactured by commonly known processes.

[0708]

[0709] The compounds of the present invention having the structure of Chemical Formula 1 above can be prepared according to the method described in the following examples, but are not limited thereto.

[0710]

[0711] According to another aspect of the present invention, a pharmaceutical composition for immuno-anticancer treatment is provided, comprising a therapeutically effective amount of the compound of Formula 1, or a pharmaceutically acceptable salt or isomer thereof, as an active ingredient, together with a pharmaceutically acceptable carrier.

[0712] The pharmaceutical composition according to the present invention can inhibit the interaction between STING (stimulator of interferon genes) protein and TRIM29 (tripartitemotif-containing protein 29).

[0713] Examples of cancers to which the pharmaceutical composition for immuno-anticancer therapy according to the present invention may be applied include pseudomyxoma, intrahepatic cholangiocarcinoma, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, mycosis fungoides, acute myeloid leukemia, acute lymphoblastic leukemia, basal cell carcinoma, ovarian epithelial carcinoma, ovarian germ cell carcinoma, male breast cancer, brain cancer, pituitary adenoma, multiple myeloma, gallbladder cancer, cholangiocarcinoma, colorectal cancer, chronic myeloid leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal melanoma, ampulla of Vater (AOV) cancer, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, paranasal sinus cancer, non-small cell lung cancer, tongue cancer, astrocytoma, small cell lung cancer, pediatric brain cancer, pediatric lymphoma, pediatric leukemia, small intestine cancer, meningioma. Esophageal cancer, glioma, renal pelvis cancer, kidney cancer, heart cancer, duodenal cancer, malignant soft tissue cancer, malignant bone cancer, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye cancer, vulvar cancer, ureteral cancer, urethral cancer, cancer of unknown primary site, gastric lymphoma, gastric cancer, gastric carcinoid tumor, gastrointestinal stromal cancer, Wilms tumor, breast cancer, triple-negative breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational trophoblastic disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, rectal cancer, rectal carcinoid tumor, vaginal cancer, spinal cord cancer, acoustic neuroma (vestibular schwannoma), pancreatic cancer, salivary gland cancer, Kaposi sarcoma, Paget's disease, tonsil cancer, squamous cell carcinoma, lung adenocarcinoma, lung cancer, pulmonary squamous cell carcinoma, skin cancer, anal cancer, It may include, but is not limited to, rhabdomyosarcoma, laryngeal cancer, pleural cancer, blood cancer and thymic cancer.

[0714]

[0715] A pharmaceutical composition according to the present invention may be prepared by mixing a pharmaceutically acceptable carrier, receptor, binder, stabilizer and / or diluent with a therapeutically effective amount of the compound of Formula 1, or a pharmaceutically acceptable salt or isomer thereof, as an active ingredient. Additionally, when preparing a pharmaceutical composition according to the present invention in the form of an injectable solution, a pharmaceutically acceptable buffer, solubilizing agent and / or isotonic agent may be mixed with the compound of Formula 1 of the present invention, or a pharmaceutically acceptable salt or isomer thereof.

[0716] A pharmaceutical composition according to the present invention may be prepared in a delivery form comprising one or more dosage units of a pharmaceutical composition by using compounding techniques available to or known to those skilled in the art and suitable pharmaceutical excipients. In the method of the present invention, the composition may be administered by a suitable delivery route, e.g., oral or parenteral administration, extraintestinal, rectal, topical, or inhalation. The pharmaceutical preparation may be in the form of a tablet, capsule, sachet, coated tablet, powder, granule, lozenge, powder for reconstitution, liquid preparation, or suppository. For example, the composition is formulated for intravenous infusion, nebulization, topical administration, or oral administration.

[0717] When manufacturing oral formulations, conventional pharmaceutical carriers may be used. For example, for oral liquid formulations such as suspensions, syrups, elixirs, and solutions, water, glycol, oil, alcohol, etc., may be used as a carrier, and for solid formulations such as powders, pills, capsules, and tablets, starch, sugar, kaolin, lubricants, binders, disintegrants, etc., may be used. Tablets and capsules are the most convenient forms of administration due to ease of administration, and it is preferable to manufacture tablets and pills with an enteric coating.

[0718] For parenteral formulations, sterile water is typically used as the carrier, and other components such as solubilizing agents may also be included. Injectable formulations, for example, sterile injectable aqueous or oily suspensions, can be prepared using suitable dispersants, wetting agents, or suspending agents according to known techniques. Solvents that may be used for this purpose include water, Ringer's solution, and isotonic NaCl solution, and sterile fixation oils are also typically used as solvents or suspension media. Any non-irritating fixation oil containing mono- or di-glycerides may be used for this purpose, and fatty acids such as oleic acid may also be used in injectable formulations.

[0719] In the case of transdermal formulations, penetration promoters and / or suitable humectants may be used as carriers, optionally in combination with suitable additives that are not irritating to the skin. As additives, those that facilitate administration through the skin and / or help in preparing the desired composition are selected. Transdermal formulations are administered in various ways, such as transdermal patches, drops, or ointments.

[0720] The compound of Formula 1 according to the present invention, or a pharmaceutically acceptable salt or isomer thereof, inhibits the degradation of STING protein by TRIM29 protein and further activates the STING-activated cGAMP-mediated immune response by inducing an increase in the amount of intracellular STING protein, and since an anticancer effect has been confirmed in a syngenic mouse model transplanted with CT26 cancer cells, it can effectively treat various cancer diseases.

[0721] Figure 1 is a graph showing the results of differential scanning fluorescence (DSF).

[0722] Figure 2 is a graph showing the results of measuring the tumor growth inhibitory effect.

[0723] The present invention will be explained in more detail below through the following examples and experimental examples. However, these examples and experimental examples are merely illustrative and do not limit the scope of the present invention in any way.

[0724]

[0725] The definitions of the abbreviations used in the following examples are as follows.

[0726]

[0727]

[0728] Synthesis of intermediate 1:N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-phenylpropane-2-amine

[0729] (a)Synthesis of N-(4-((tert-butyldiphenylsilyl)oxy)phenyl)methaneamine

[0730] 4-hydroxybenzylamine (25 g, 198.94 mmol) was dissolved in dichloromethane (500 mL), then chloranyl-[1,1-di(methyl)ethyl]-di(phenyl)silane (84.6 g, 298.41 mmol, 79.03 mL) and imidazole (27.64 g, 397.88 mmol) were added, and the mixture was stirred at room temperature for 12 hours. When the reaction was complete, the reaction mixture was washed with an aqueous solution of saturated sodium bicarbonate and an aqueous solution of saturated sodium chloride. The separated organic layer was dried with anhydrous sodium sulfate, concentrated by filtration and vacuum distillation, and purified by MPLC (dichloromethane : methanol = 7 : 3 v / v) to obtain (4-((tert-butyldiphenylsilyl)oxy)phenyl)methaneamine (44.8 g, 123.94 mmol, 62%).

[0731]

[0732] (b) Synthesis of (E)-N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2,2-dimethoxyethane-1-imine

[0733] (4-((tert-butyldiphenylsilyl)oxy)phenyl)methaneamine (46.3 g, 128.06 mmol) synthesized in intermediate 1(a) above was dissolved in dichloromethane (450 mL), then glyoxal dimethylacetal (60% aqueous solution) (44.44 g, 256.12 mmol) was added and stirred at room temperature for 12 hours. When the reaction was complete, the reaction mixture was washed with water and an aqueous sodium chloride solution. The separated organic layer was dried with sodium sulfate, then concentrated by filtration and vacuum distillation to obtain (E)-N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2,2-dimethoxyethane-1-imine (55.42 g, 123.80 mmol, 96.68%).

[0734]

[0735] (c)Synthesis of N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-phenylpropane-2-amine

[0736] (E)-N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2,2-dimethoxyethane-1-imine (1 g, 2.23 mmol) synthesized in intermediate 1(b) above was dissolved in anhydrous tetrahydrofuran (10 mL) and cooled to 0°C. Then, benzyl magnesium chloride (1.2 mL, 2.45 mmol, 2 M diethyl ether solution) was added dropwise and stirred at room temperature for 2 hours. When the reaction was complete, the reaction mixture was added to a saturated aqueous ammonium chloride solution, quenched, and extracted with ethyl acetate. The separated organic layer was washed with a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate, concentrated by filtration and vacuum distillation, and separated by MPLC (ethyl acetate:hexane = 3:7, v / v) to obtain N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-phenylpropane-2-amine (1.21 g, 1.65 mmol, 73%).

[0737]

[0738] Synthesis of Intermediate 2:N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine

[0739] Magnesium turnings (840.4 mg, 34.57 mmol) and iodine (26.53 mg, 0.207 mmol) were added to anhydrous tetrahydrofuran (40 mL), and then 1-(chloromethyl)-4-methoxybenzene (3.31 g, 20.74 mmol) was added dropwise, and the reaction mixture was stirred at room temperature for 1 hour to prepare the Grignard reagent. (E)-N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2,2-dimethoxyethane-1-imine (6.19 g, 13.83 mmol), synthesized in the same manner as intermediate 1(b) above, was dissolved in anhydrous tetrahydrofuran (30 mL), cooled to 0°C, and then the prepared Grignard reagent was added and stirred at room temperature for 2 hours. When the reaction was complete, the reaction mixture was added to a saturated aqueous ammonium chloride solution, quenched, and extracted with ethyl acetate. The separated organic layer was washed with a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate, concentrated by filtration and vacuum distillation, and separated by MPLC (ethyl acetate : hexane = 3 : 7, v / v) to obtain N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine (5.95 g, 10.44 mmol, 75%).

[0740]

[0741] Synthesis of the intermediate 3:N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-3-(4-fluorophenyl-1,1-dimethoxypropane-2-amine

[0742] The title compound (29%) was obtained by performing the same method as intermediate 2, except that 1-(bromomethyl)-4-fluorobenzene was used as the starting material.

[0743]

[0744] Synthesis of the intermediate 4:N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[0745] The title compound (36%) was obtained by performing the same method as intermediate 1, except that (4-(trifluoromethoxy)benzyl)magnesium bromide (1M diethyl ether solution) was used as the starting material.

[0746]

[0747] Synthesis of the intermediate 5:N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1-cyclopentyl-2,2-dimethoxyethane-1-amine

[0748] The title compound (44%) was obtained in the same way as intermediate 1, except that cyclopentyl magnesium bromide (2M diethyl ether solution) was used as the starting material.

[0749]

[0750] Synthesis of intermediate 6:N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-3-cyclohexyl-1,1-dimethoxypropane-2-amine

[0751] The title compound was quantitatively obtained using the same method as intermediate 1, except that (cyclohexylmethyl)magnesium bromide (0.25 M tetrahydrofuran solution) was used as the starting material.

[0752]

[0753] Synthesis of the intermediate 7:N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1-cyclopropyl-2,2-dimethoxyethane-1-amine

[0754] The title compound was quantitatively obtained using the same method as intermediate 1, except that cyclopropyl magnesium bromide (0.7 M tetrahydrofuran solution) was used as the starting material.

[0755]

[0756] Synthesis of Intermediate 8:N-(3-((tert-butyldiphenylsilyl)oxy)benzyl-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0757] The title compound (52%) was obtained by performing the same method as intermediate 1, except that 3-hydroxybenzylamine and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0758]

[0759] Synthesis of intermediate 9:N-(4-(((tert-butyldiphenylsilyl)oxy)methyl)benzyl)-1,1-dimethoxy-3-phenylpropane-2-amine

[0760] The title compound was quantitatively obtained using the same method as intermediate 1, except that (4-(aminomethyl)phenyl)methanol was used as the starting material.

[0761]

[0762] Intermediate 10: Synthesis of 4-2-((4-(((tert-butyldiphenylsilyl)oxy)methyl)benzyl)amino)-3,3-dimethoxypropyl)-N,N-dimethylaniline

[0763] The title compound was quantitatively obtained using the same method as intermediate 2, except that (4-(aminomethyl)phenyl)methanol and 4-(chloromethyl)-N,N-dimethylaniline were used as starting materials.

[0764]

[0765] Synthesis of intermediate 11:N-benzyl-1,1-dimethoxy-3-phenylpropane-2-amine

[0766] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that phenylmethaneamine was used as the starting material.

[0767]

[0768] Synthesis of intermediate 12:N-benzyl-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0769] The title compound was quantitatively obtained by performing the same method as intermediate 2, except that phenylmethaneamine was used as the starting material.

[0770]

[0771] Synthesis of intermediate 13:N-(4-fluorobenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine

[0772] The title compound was quantitatively obtained in the same manner as steps (b) and (c) of intermediate 1, except that (4-fluorophenyl)methaneamine was used as the starting material.

[0773]

[0774] Synthesis of intermediate 14:N-(4-fluorobenzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0775] The title compound (64%) was obtained by performing the same method as intermediate 2, except that (4-fluorophenyl)methaneamine was used as the starting material.

[0776]

[0777] Synthesis of intermediate 15:N-(4-fluorobenzyl)-3-(4-fluorophenyl)-1,1-dimethoxypropane-2-amine

[0778] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (4-fluorophenyl)methaneamine and (4-fluorobenzyl)magnesium bromide (0.25 M tetrahydrofuran solution) were used.

[0779]

[0780] Synthesis of intermediate 16:N-(4-fluorobenzyl)-2,2-dimethoxyethane-1-amine

[0781] (a) Synthesis of (E)-N-(4-fluorobenzyl)-2,2-dimethoxyethane-1-imine

[0782] The title compound was quantitatively obtained by performing the same method as step (b) of intermediate 1, except that (4-fluorophenyl)methaneamine was used as the starting material.

[0783]

[0784] (b) Synthesis of N-(4-fluorobenzyl)-2,2-dimethoxyethane-1-amine

[0785] (E)-N-(4-fluorobenzyl)-2,2-dimethoxyethane-1-imine (1 g, 4.69 mmol) was dissolved in methanol (40 mL) and cooled to 0–5°C, after which sodium borohydride (375 mg, 9.38 mmol) was added and stirred at room temperature for 23 hours. Once the reaction was complete, the solvent was removed by vacuum distillation of the reaction mixture, and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate, and then concentrated by filtration and vacuum distillation to quantitatively obtain the title compound.

[0786]

[0787] Intermediate 17: Synthesis of 1,1-Dimethoxy-3-Phenyl-N-(4-(Trifluoromethyl)Benzyl)Propan-2-Amine

[0788] The title compound (68%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (4-(trifluoromethyl)phenyl)methaneamine was used as the starting material.

[0789]

[0790] Intermediate 18: Synthesis of 1,1-Dimethoxy-3-(4-Methoxyphenyl)-N-(4-(Trifluoromethyl)Benzyl)Propan-2-Amine

[0791] The title compound was quantitatively obtained by performing the same method as intermediate 2, except that (4-(trifluoromethyl)phenyl)methaneamine was used as the starting material.

[0792]

[0793] Intermediate 19: Synthesis of 3-(4-fluorophenyl)-1,1-dimethoxy-N-(4-(trifluoromethyl)benzyl)propane-2-amine

[0794] The title compound (46%) was obtained by performing the same method as intermediate 2, except that (4-(trifluoromethyl)phenyl)methaneamine and 1-(bromomethyl)-4-fluorobenzene were used as starting materials.

[0795]

[0796] Intermediate 20: Synthesis of 1,1-Dimethoxy-3-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)benzyl)propane-2-amine

[0797] The title compound (26%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (4-(trifluoromethyl)phenyl)methaneamine and ((4-trifluoromethoxy)benzyl)magnesium bromide (1M tetrahydrofuran solution) were used as starting materials.

[0798]

[0799] Intermediate 21: Synthesis of 1,1-Dimethoxy-N-(4-Methoxybenzyl)-3-Phenylpropane-2-Amine

[0800] The title compound (57%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (4-methoxyphenyl)methaneamine was used as the starting material.

[0801]

[0802] Intermediate 22: Synthesis of 1,1-Dimethoxy-N-(4-Methoxybenzyl)-3-(4-Methoxyphenyl)Propan-2-Amine

[0803] The title compound (62%) was obtained by performing the same method as intermediate 2, except that (4-methoxyphenyl)methaneamine was used as the starting material.

[0804]

[0805] Intermediate 23: Synthesis of 3-(4-fluorophenyl)-1,1-dimethoxy-N-(4-methoxybenzyl)propane-2-amine

[0806] The title compound (50%) was obtained by performing the same method as intermediate 2, except that (4-methoxyphenyl)methaneamine and 1-(bromomethyl)-4-fluorobenzene were used as starting materials.

[0807]

[0808] Synthesis of the intermediate 24:N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine

[0809] The title compound (67%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine was used as the starting material.

[0810]

[0811] Synthesis of intermediate 25:N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0812] The title compound (41%) was obtained by performing the same method as intermediate 2, except that (3,4-dimethoxyphenyl)methaneamine was used as the starting material.

[0813]

[0814] Synthesis of intermediate 26:N-(3,4-dimethoxybenzyl)-3-(4-fluorophenyl)-1,1-dimethoxypropane-2-amine

[0815] The title compound (55%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and 4-fluorobenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0816]

[0817] Synthesis of intermediate 27:N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine (SM1-8D)

[0818] The title compound (27%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and (4-(trifluoromethoxy))benzyl magnesium bromide (0.25 M tetrahydrofuran solution) were used as starting materials.

[0819]

[0820] Intermediate 28: Synthesis of 1-Cyclopentyl-N-(3,4-Dimethoxybenzyl)-2,2-Dimethoxyethane-1-Amine

[0821] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and cyclopentyl magnesium bromide (2M diethyl ether solution) were used as starting materials.

[0822]

[0823] Intermediate 29: Synthesis of 1-Cyclopropyl-N-(3,4-Dimethoxybenzyl)-2,2-Dimethoxyethane-1-Amine

[0824] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and cyclopropylmagnesium bromide (0.7 M tetrahydrofuran solution) were used as starting materials.

[0825]

[0826] Intermediate 30: Synthesis of 4-(1-((3,4-Dimethoxybenzyl)amino)-2,2-Dimethoxyethyl)-N,N-Dimethylaniline

[0827] The title compound (38%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and (4-(dimethylamino)phenyl)magnesium bromide (0.5 M tetrahydrofuran solution) were used as starting materials.

[0828]

[0829] Synthesis of intermediate 31:N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(4-methoxyphenyl)ethane-1-amine

[0830] The title compound (31%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and (4-methoxyphenyl)magnesium bromide (0.5 M tetrahydrofuran solution) were used as starting materials.

[0831]

[0832] Synthesis of intermediate 32:N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(3-methoxyphenyl)ethane-1-amine

[0833] The title compound (11%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and (3-methoxyphenyl)magnesium bromide (1M tetrahydrofuran solution) were used as starting materials.

[0834]

[0835] Synthesis of intermediate 33:N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(thiophene-2-yl)ethane-1-amine

[0836] The title compound (16%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and (thiophene-2-yl)magnesium bromide (1M tetrahydrofuran solution) were used as starting materials.

[0837]

[0838] Synthesis of intermediate 34:N-(3,4-dimethoxybenzyl)-1-(4-fluorophenyl)-2,2-dimethoxyethane-1-amine

[0839] The title compound (20%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-dimethoxyphenyl)methaneamine and (4-fluorophenyl)magnesium bromide (1M tetrahydrofuran solution) were used as starting materials.

[0840]

[0841] Intermediate 35: Synthesis of 1,1-Dimethoxy-3-Phenyl-N-(Pyridine-2-ylmethyl)propane-2-amine

[0842] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that pyridine-2-ylmethanamine was used as the starting material.

[0843]

[0844] Synthesis of intermediate 36:N-((5-fluoropyridine-2-yl)methyl)-1,1-dimethoxy-3-phenylpropane-2-amine

[0845] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (5-fluoropyridine-2-yl)methaneamine was used as the starting material.

[0846]

[0847] Synthesis of intermediate 37:N-((5-fluoropyridine-2-yl)methyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0848] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (5-fluoropyridine-2-yl)methaneamine and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0849]

[0850] Intermediate 38: Synthesis of 3-(4-fluorophenyl)-N-((5-fluoropyridine-2-yl)methyl)-1,1-dimethoxypropane-2-amine

[0851] The title compound (16%) was obtained by performing the same method as intermediate 2, except that (5-fluoropyridine-2-yl)methaneamine and 1-(bromomethyl)-4-fluorobenzene were used as starting materials.

[0852]

[0853] Intermediate 39: Synthesis of 1,1-Dimethoxy-3-phenyl-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)propane-2-amine

[0854] The title compound (32%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (5-(trifluoromethyl)pyridine-2-yl)methaneamine was used as the starting material.

[0855]

[0856] Intermediate 40: Synthesis of 1,1-Dimethoxy-3-(4-Methoxyphenyl)-N-((5-(Trifluoromethyl)Pyridine-2-yl)Methyl)Propan-2-Amine

[0857] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (5-(trifluoromethyl)pyridine-2-yl)methaneamine and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0858]

[0859] Intermediate 41: Synthesis of 3-(4-fluorophenyl)-1,1-dimethoxy-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)propane-2-amine

[0860] The title compound (12%) was obtained by performing the same method as intermediate 2, except that (5-(trifluoromethyl)pyridine-2-yl)methaneamine and 1-(bromomethyl)-4-fluorobenzene were used as starting materials.

[0861]

[0862] Intermediate 42: Synthesis of 1,1-Dimethoxy-3-(4-Methoxyphenyl)-N-((5-Methylfuran-2-yl)Methyl)Propan-2-Amine

[0863] The title compound (83%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (5-methylfuran-2-yl)methaneamine and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0864]

[0865] Intermediate 43: Synthesis of 3-(4-fluorophenyl)-1,1-dimethoxy-N-((5-methylfuran-2-yl)methyl)propane-2-amine

[0866] The title compound (47%) was obtained by performing the same method as intermediate 2, except that (5-methylfuran-2-yl)methaneamine and 1-(bromomethyl)-4-fluorobenzene were used as starting materials.

[0867]

[0868] Synthesis of the intermediate 44:N-(benzo[d][1,3]dioxol-5-ylmethyl)-1,1-dimethoxy-3-phenylpropane-2-amine

[0869] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that benzo[d][1,3]dioxol-5-ylmethanamine was used as the starting material.

[0870]

[0871] Synthesis of the intermediate 45:N-(benzo[d][1,3]dioxol-5-ylmethyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0872] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that benzo[d][1,3]dioxol-5-ylmethanamine and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0873]

[0874] Synthesis of the intermediate 46:N-(benzo[d][1,3]dioxol-5-ylmethyl)-3-(4-fluorophenyl)-1,1-dimethoxypropane-2-amine

[0875] The title compound (11%) was obtained by performing the same method as intermediate 2, except that benzo[d][1,3]dioxol-5-ylmethanamine and 1-(bromomethyl)-4-fluorobenzene were used as starting materials.

[0876]

[0877] Intermediate 47: Synthesis of 4-(((1,1-Dimethoxy-3-(4-methoxyphenyl)propane-2-yl)amino)methyl)-N,N-Dimethylaniline

[0878] The title compound was quantitatively obtained by performing the same method as intermediate 2, except that 4-(aminomethyl)-N,N-dimethylaniline was used as the starting material.

[0879]

[0880] Synthesis of intermediate 48:N-(4-(tert-butyl)benzyl)-1,1-dimethoxy-3-phenylpropane-2-amine

[0881] The title compound (55%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (4-(tert-butyl)phenyl)methaneamine was used as the starting material.

[0882]

[0883] Intermediate 49: Synthesis of 1,1-Dimethoxy-3-(4-methoxyphenyl)-N-((1-methylpiperidine-4-yl)methyl)propane-2-amine

[0884] The title compound was quantitatively obtained by performing the same method as intermediate 2, except that (1-methylpiperidine-4-yl)methaneamine was used as the starting material.

[0885]

[0886] Intermediate 50: Synthesis of 1-Cyclopropyl-2,2-Dimethoxy-N-((1-methylpiperidine-4-yl)methyl)ethane-1-amine

[0887] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (1-methylpiperidine-4-yl)methaneamine and cyclopropylmagnesium bromide (0.7 M tetrahydrofuran solution) were used as starting materials.

[0888]

[0889] Synthesis of intermediate 51:N-((1-ethylpiperidine-4-yl)methyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0890] The title compound was quantitatively obtained by performing the same method as intermediate 2, except that (1-ethylpiperidine-4-yl)methaneamine was used as the starting material.

[0891]

[0892] Intermediate 52: Synthesis of 1,1-Dimethoxy-3-(4-methoxyphenyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)propane-2-amine

[0893] The title compound (24%) was obtained by performing the same method as intermediate 2, except that (tetrahydro-2H-pyran-4-yl)methaneamine was used as the starting material.

[0894]

[0895] Synthesis of intermediate 53:N-(4-((tert-butyldiphenylsilyl)oxy)-3-methoxybenzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0896] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that 4-(aminomethyl)-2-methoxyphenol and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0897]

[0898] Synthesis of intermediate 54:N-(3,4-bis((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0899] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that 4-(aminomethyl)benzene-1,2-diol and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0900]

[0901] Synthesis of intermediate 55:N-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0902] The title compound was quantitatively obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (2,2-difluorobenzo[d][1,3]dioxol-5-yl)methaneamine and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0903]

[0904] Synthesis of intermediate 56:N-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[0905] The title compound (58%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (2,2-difluorobenzo[d][1,3]dioxol-5-yl)methaneamine and ((4-trifluoromethoxy)benzyl)magnesium chloride (1M tetrahydrofuran solution) were used as starting materials.

[0906]

[0907] Intermediate 57: Synthesis of 1,1-Dimethoxy-N-(3-(trifluoromethoxy)benzyl)-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[0908] The title compound (17%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3-(trifluoromethoxy)phenyl)methaneamine and ((4-trifluoromethoxy)benzyl)magnesium bromide (1M diethyl ether solution) were used as starting materials.

[0909]

[0910] Intermediate 58: Synthesis of 1,1-Dimethoxy-N-(4-(trifluoromethoxy)benzyl)-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[0911] The title compound (33%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (4-(trifluoromethoxy)phenyl)methaneamine and ((4-trifluoromethoxy)benzyl)magnesium bromide (1M diethyl ether solution) were used as starting materials.

[0912]

[0913] Synthesis of intermediate 59:N-(4-(((1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-yl)amino)methyl)phenyl)methanesulfonamide

[0914] The title compound (33%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that N-(4-(aminomethyl)phenyl)methanesulfonamide and ((4-trifluoromethoxy)benzyl)magnesium bromide (1M diethyl ether solution) were used as starting materials.

[0915]

[0916] Intermediate 60: Synthesis of 4-(((1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-yl)amino)methyl)-N,N-dimethylaniline

[0917] The title compound (38%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that 4-(aminomethyl)-N,N-dimethylaniline and ((4-trifluoromethoxy)benzyl)magnesium bromide (1M diethyl ether solution) were used as starting materials.

[0918]

[0919] Synthesis of intermediate 61:N-(3,4-difluorobenzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[0920] The title compound (64%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-difluorobenzyl)methaneamine and ((4-trifluoromethoxy)benzyl)magnesium bromide (1M diethyl ether solution) were used as starting materials.

[0921]

[0922] Intermediate 62: Synthesis of 1-Cyclopropyl-N-(3,4-Difluorobenzyl)-2,2-Dimethoxyethane-1-Amine

[0923] The title compound (64%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-difluorobenzyl)methaneamine and cyclopropylmagnesium bromide (0.7 M tetrahydrofuran solution) were used as starting materials.

[0924]

[0925] Intermediate 63: Synthesis of 1-Cyclopentyl-N-(3,4-Difluorobenzyl)-2,2-Dimethoxyethane-1-Amine

[0926] The title compound (26%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-difluorobenzyl)methaneamine and cyclopentyl magnesium bromide (2M tetrahydrofuran solution) were used as starting materials.

[0927]

[0928] Intermediate 64: Synthesis of 4-(1-((3,4-difluorobenzyl)amino)-2,2-dimethoxyethyl)-N,N-dimethylaniline

[0929] The title compound (59%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that (3,4-difluorobenzyl)methaneamine and (4-(dimethylamino)phenyl)magnesium bromide (0.5 M tetrahydrofuran solution) were used as starting materials.

[0930]

[0931] Intermediate 65: Synthesis of N-(3-((tert-butyldiphenylsilyl)oxy)benzyl)-4-methoxybenzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0932] The title compound (87%) was obtained by performing the same method as steps (b) and (c) of intermediate 1, except that 5-(aminomethyl)-2-methoxyphenol and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0933]

[0934] Intermediate 66: Synthesis of (4-(Tert-butoxycarbonyl)-2-nitrophenyl)-D-valine

[0935] (a) Synthesis of Tert-Butyl 4-Fluoro-3-Nitrobenzoate

[0936] 4-fluoro-3-nitrobenzoic acid (50 g, 264.71 mmol) was dissolved in t-butanol, followed by the addition of dimethylaminopyridan (6.53 g, 52.94 mmol) and di-tert-butyl dicarbonate (116.71 g, 529.42 mmol) at room temperature, and the mixture was stirred at 50°C for 72 hours. Upon completion of the reaction, the reaction mixture was concentrated by vacuum distillation, and the resulting residue was dissolved in ethyl acetate and washed with an aqueous solution of saturated sodium bicarbonate and a saturated aqueous solution of sodium chloride. The separated organic layer was dried with sodium sulfate, filtered, and concentrated by vacuum distillation to quantitatively obtain the title compound (63.9 g).

[0937]

[0938] (b) Synthesis of (4-(Tert-butoxycarbonyl)-2-nitrophenyl)-D-valine

[0939] The tert-butyl-4-fluoro-3-nitrobenzoate (63.9 g, 264.70 mmol) synthesized in the above step was dissolved in N,N-dimethylformamide (600 mL), after which D-valine (46.51 g, 397.05 mmol) and N,N-diisopropylethylamine (68.42 g, 529.40 mmol) were added at room temperature and stirred at 50 °C for 24 hours. Once the reaction was complete, the reaction mixture was concentrated by vacuum distillation. After removing byproducts from the obtained residue by acid-base extraction, the remaining excess D-valine was removed by MPLC (hexane:ethyl acetate = 1:1 v / v) to obtain the title compound (55 g, 162.55 mmol, 61.4%).

[0940]

[0941] Intermediate 67: Synthesis of (4-(Tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-D-valine

[0942] The title compound (47%) was obtained by performing the same method as intermediate 66, except that 4-fluoro-3-(trifluoromethyl)benzoic acid was used as the starting material.

[0943]

[0944] Intermediate 68: Synthesis of (4-(Tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-L-valine

[0945] The title compound (31%) was obtained by performing the same method as intermediate 66, except that 4-fluoro-3-(trifluoromethyl)benzoic acid and L-valine were used as starting materials.

[0946]

[0947] Intermediate 69: Synthesis of (4-(Tert-butoxycarbonyl)-2-cyanophenyl)-D-valine

[0948] (a) Synthesis of Tert-Butyl 3-Cyano-4-Fluorobenzoate

[0949] Except for using 3-cyano-4-fluorobenzoic acid as the starting material, the title compound was quantitatively obtained by performing step (a) of intermediate 66 and one method.

[0950]

[0951] (b) Synthesis of (4-(Tret-butoxycarbonyl)-2-cyanophenyl)-D-valine

[0952] The title compound (91%) was obtained in the same manner as step (b) of intermediate 66, except that tert-butyl 3-cyano-4-fluorobenzoate was used as the starting material and ethanol and water (1:1, v / v) were used as solvents.

[0953]

[0954] Intermediate 70: Synthesis of (R)-2-((4-(tert-butoxycarbonyl)-2-nitrophenyl)amino)-3-(4-methoxyphenyl)propanoic acid

[0955] The title compound was quantitatively obtained by performing the same method as intermediate 66, except that (R)-2-(4-methoxybenzyl)-3-methylbutanoic acid was used as the starting material.

[0956]

[0957] Intermediate 71: Synthesis of (S)-2-((4-(tert-butoxycarbonyl)-2-nitrophenyl)amino)-3-(4-methoxyphenyl)propanoic acid

[0958] The title compound was quantitatively obtained by performing the same method as intermediate 66, except that (S)-2-(4-methoxybenzyl)-3-methylbutanoic acid was used as the starting material.

[0959]

[0960] Intermediate 72: Synthesis of (S)-2-((4-(tert-butoxycarbonyl)-2-nitrophenyl)amino)-3-(4-fluorophenyl)propanoic acid

[0961] The title compound was quantitatively obtained by performing the same method as intermediate 66, except that (S)-2-(4-fluorobenzyl)-3-methylbutanoic acid was used as the starting material.

[0962]

[0963] Intermediate 73: Synthesis of (S)-2-((4-(tert-butoxycarbonyl)-2-nitrophenyl)amino)-3-(p-tolyl)propanoic acid

[0964] The title compound was quantitatively obtained by performing the same method as intermediate 66, except that (S)-3-methyl-2-(4-methylbenzyl)butanoic acid was used as the starting material.

[0965]

[0966] Intermediate 74: Synthesis of (2,4-bis(ethoxycarbonyl)phenyl)-D-valine

[0967] The title compound was quantitatively obtained by performing the same method as intermediate 66, except that 4-fluoroisophthalic acid, diethyl carbonate, and potassium carbonate were used as starting materials.

[0968]

[0969] Intermediate 75: Synthesis of (2,4-bis(methoxycarbonyl)phenyl)-D-valine

[0970] The title compound was quantitatively obtained by performing the same method as intermediate 66, except that 4-fluoroisophthalic acid, dimethyl carbonate, and potassium carbonate were used as starting materials.

[0971]

[0972] Intermediate 76: Synthesis of N-(4-(((tert-butyldiphenylsilyl)oxy)methyl)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0973] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that (4-(aminomethyl)phenyl)methanol and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0974]

[0975] Intermediate 77: Synthesis of 3-(4-bromophenyl)-N-(4-(((tert-butyldiphenylsilyl)oxy)methyl)benzyl)-1,1-dimethoxypropane-2-amine

[0976] The title compound was quantitatively obtained by performing the same method as intermediate 2, except that (4-(aminomethyl)phenyl)methanol and 1-bromo-4-(bromomethyl)benzene were used as starting materials.

[0977]

[0978] Intermediate 78: Synthesis of N-(4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-methoxybenzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0979] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that (4-(aminomethyl)-2-methoxyphenyl)methanol and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0980]

[0981] Intermediate 79: Synthesis of N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2,2-dimethoxyethane-1-amine

[0982] The title compound was quantitatively obtained by performing the same method as intermediate 16, except that N-(4-((tert-butyldiphenylsilyl)oxy)phenyl)methaneamine synthesized in step (a) of intermediate 1 was used as the starting material.

[0983]

[0984] Intermediate 80: Synthesis of 3-(4-bromophenyl)-N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxypropane-2-amine

[0985] The title compound was quantitatively obtained by performing the same method as intermediate 2, except that 1-bromo-4-(bromomethyl)benzene was used as the starting material.

[0986]

[0987] Intermediate 81: Synthesis of N-(2-((tert-butyldiphenylsilyl)oxy)ethyl)-2,2-dimethoxyethane-1-amine

[0988] Except for using 2-aminoethanol-1-ol as the starting material, the title compound was quantitatively obtained by performing the same method as steps (a) and (b) of intermediate 1 and step (b) of intermediate 16.

[0989]

[0990] Intermediate 82: Synthesis of N-(2-((tert-butyldiphenylsilyl)oxy)ethyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine

[0991] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that 2-aminoethanol-1-ol and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0992]

[0993] Intermediate 83: Synthesis of 2,2-Dimethoxy-N-Methylethane-1-Amine

[0994] Except for using methaneamine as the starting material, the title compound was quantitatively obtained by performing the same method as steps (a) and (b) of intermediate 1 and step (b) of intermediate 16.

[0995]

[0996] Intermediate 84: Synthesis of 1,1-Dimethoxy-3-(4-Methoxyphenyl)-N-Methylpropane-2-Amine

[0997] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that methanolamine and 4-methoxybenzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[0998]

[0999] Intermediate 85: Synthesis of N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxybutane-2-amine

[1000] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that ethyl magnesium bromide (3.0 M diethyl ether solution) was used as the starting material.

[1001]

[1002] Intermediate 86: Synthesis of N-(4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-methoxybenzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[1003] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that (4-(aminomethyl)-2-methoxyphenyl)methanol and 4-(trifluoromethoxy)benzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[1004]

[1005] Intermediate 87: Synthesis of N-(4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(trifluoromethoxy)benzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[1006] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that (4-(aminomethyl)-2-(trifluoromethoxy)phenyl)methanol and 4-(trifluoromethoxy)benzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[1007]

[1008] Intermediate 88: Synthesis of N-(4-((tert-butyldiphenylsilyl)oxy)-3-fluorobenzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[1009] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that 4-(aminomethyl)-2-fluorophenol and 4-(trifluoromethoxy)benzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[1010]

[1011] Intermediate 89: Synthesis of N-(4-((tert-butyldiphenylsilyl)oxy)-3-fluorobenzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine

[1012] The title compound was quantitatively obtained by performing the same method as intermediate 1, except that 4-(aminomethyl)-2-fluorophenol and 4-(trifluoromethoxy)benzyl magnesium chloride (0.25 M tetrahydrofuran solution) were used as starting materials.

[1013]

[1014] Example 1: Synthesis of 4-((R)-5-benzyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1015]

[1016]

[1017] (a) Synthesis of tert-butyl 4-(((2R)-1-((4-((tert-butyldiphenylsilyl)oxy)benzyl)(1,1-dimethoxy-3-phenylpropane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)amino)-3-cyanobenzoate

[1018] (4-(tert-butoxycarbonyl)-2-cyanophenyl)-D-valine (1.89 g, 3.57 mmol) was dissolved in dichloromethane (30 mL), then N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-phenylpropane-2-amine (2.1 g, 3.89 mmol) and EDC (2.09 g, 10.71 mmol) were added sequentially, and the mixture was stirred at room temperature for 18 hours. When the reaction was complete, the reaction mixture was diluted with dichloromethane (30 mL) and washed with a saturated sodium chloride aqueous solution. The separated organic layer was dried with anhydrous sodium sulfate, concentrated by filtration and vacuum distillation, and purified by MPLC (hexane:ethyl acetate = 8:2 v / v) to obtain tert-butyl 4-(((2R)-1-((4-((tert-butyldiphenylsilyl)oxy)benzyl)(1,1-dimethoxy-3-phenylpropane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)amino)-3-cyanobenzoate (0.8 g, 0.96 mmol, 27%).

[1019]

[1020] (b) Synthesis of tert-butyl (S)-4-(5-benzyl-4-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate

[1021] The tert-butyl 4-(((2S)-1-((4-((tert-butyldiphenylsilyl)oxy)benzyl)(1,1-dimethoxy-3-phenylpropane-2-yl)amino)-3-methyl-1-oxobutane-2-yl)amino)-3-cyanobenzoate (0.8 g, 0.96 mmol) synthesized in step (a) above was dissolved in dichloromethane (6 mL), then formic acid (3 mL) was added and stirred at room temperature for 2 hours. After the reaction was completed, the next step was immediately carried out.

[1022]

[1023] (c) Synthesis of (R)-4-(5-benzyl-4-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid

[1024] Trifluoroacetic acid (3 mL) was added to the reaction mixture of step (b) above, and the mixture was stirred at room temperature for 2 hours. When the reaction was complete, the mixture was concentrated by vacuum distillation and purified by MPLC (dichloromethane : methanol = 9 : 1 v / v) to obtain (R)-4-(5-benzyl-4-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid (0.25 g, 0.34 mmol, 36%).

[1025]

[1026] (d) Synthesis of 4-((R)-5-benzyl-4-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1027] (R)-4-(5-benzyl-4-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid (50 mg, 0.0695 mmol) synthesized in step (c) above was dissolved in dichloromethane (15 mL), then (S)-(tetrahydrofuran-2-yl)methaneamine (36 mg, 0.347 mmol), HCTU (57 mg, 0.139 mmol), and DIPEA (45 mg, 0.06 mL, 0.347 mmol) were added, and the mixture was stirred at room temperature for 1 hour. When the reaction was complete, the solution was concentrated by vacuum distillation and purified by MPLC (hexane : ethyl acetate = 4 : 6 v / v) to obtain 4-((R)-5-benzyl-4-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide (47 mg, 0.059 mmol, 84%).

[1028]

[1029] (e) Synthesis of 4-((R)-5-benzyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1030] 4-((R)-5-benzyl-4-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide (47 mg, 0.059 mmol) synthesized in step (d) above was dissolved in tetrahydrofuran (5 mL), then TBAF (0.117 mL, 0.117 mmol, 1 M tetrahydrofuran solution) was added, and the mixture was stirred at room temperature for 1 hour. When the reaction was finished, the reaction mixture was washed with a saturated aqueous sodium chloride solution, the separated organic layer was dried with anhydrous sodium sulfate, concentrated by filtration and vacuum distillation, and purified by MPLC (hexane:ethyl acetate = 3:7 v / v) to obtain 4-((R)-5-benzyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide (24 mg, 0.043 mmol, 73%).

[1031] 1H NMR (400 MHz, MeOD) δ8.09 (d, J = 2.1 Hz, 1H), 7.97 (dd, J = 9.0, 2.2 Hz, 1H), 7.34 - 7.19 (m, 6H), 7.00 (d, J = 8.2 Hz, 2H), 6.72 (d, J = 8.1 Hz, 2H), 6.20 (s, 1H), 5.15 (d, J = 15.9 Hz, 1H), 4.49 - 4.39 (m, 2H), 4.14 - 4.03 (m, 2H), 3.89 (q, J = 7.1 Hz, 1H), 3.76 (q, J = 7.2 Hz, 1H), 3.67 - 3.55 (m, 2H), 3.48 (dd, J = 13.7, 4.7 Hz, 1H), 3.39 (dd, J = 13.6, 7.1 Hz, 1H), 2.15 - 1.98 (m, 3H), 1.91 (hept, J = 7.3 Hz, 2H), 1.69 - 1.59 (m, 1H), 1.05 (t, J = 6.3 Hz, 6H).

[1032] LC-MS (ESI) m / z 565.2 [M+1]

[1033]

[1034] Example 2: Synthesis of (R)-N-(2,3-dihydrobenzofuran-5-yl)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide

[1035] The title compound (48 mg, 72%) was obtained by performing the same method as in Example 1, except that (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine,N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and 2,3-dihydrobenzofuran-5-amine were used as starting materials.

[1036] 1H NMR (500 MHz, DMSO-d6) δ10.13 (s, 1H), 9.32 (s, 1H), 8.39 (d, J = 2.2 Hz, 1H), 8.10 (dd, J = 8.9, 2.2 Hz, 1H), 7.70 - 7.66 (m, 1H), 7.64 (d, J = 2.2 Hz, 1H), 7.58 (d, J = 9.1 Hz, 1H), 7.39 (d, J = 1.9 Hz, 1H), 7.37 (dd, J = 3.2, 1.9 Hz, 1H), 7.16 - 7.10 (m, 2H), 7.09 - 7.04 (m, 2H), 6.90 - 6.84 (m, 2H), 6.74 (d, J = 8.5 Hz, 1H), 6.72 - 6.69 (m, 2H), 5.43 (d, J = 1.8 Hz, 1H), 5.02 (d, J = 15.9 Hz, 1H), 4.52 (t, J = 8.7 Hz, 2H), 4.40 - 4.37 (m, 1H), 4.35 (d, J = 1.6 Hz, 1H), 3.72 (s, 3H), 3.50 - 3.39 (m, 2H), 3.33 (s, 3H), 3.19 (t, J = 8.6 Hz, 2H), 2.04 (dt, J) = 10.8, 6.7 Hz, 1H), 1.01 - 0.94 (m, 7H).

[1037] LC-MS (ESI) m / z 649.2 [M+1]

[1038]

[1039] Example 3: Synthesis of (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-hydroxypyridine-2-yl)methyl)-3-nitrobenzamide

[1040] The title compound (5.8 mg, 63%) was obtained by performing the same method as in Example 1, except that (4-(Tert-butoxycarbonyl)-2-nitrophenyl)-D-valine,N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and 6-(aminomethyl)pyridine-3-ol were used as starting materials.

[1041] 1 H NMR (500 MHz, DMSO-d6) δ9.74 (s, 1H), 9.27 (s, 1H), 9.07 (t, J = 5.9 Hz, 1H), 8.32 (d, J = 2.1 Hz, 1H), 8.04 (dd, J = 8.8, 2.3 Hz, 2H), 7.53 (d, J = 9.1 Hz, 1H), 7.17 - 7.09 (m, 4H), 7.05 (d, J = 8.2 Hz, 2H), 6.86 (d, J = 8.3 Hz, 2H), 6.70 (d, J = 8.3 Hz, 2H), 5.42 (s, 1H), 5.01 (d, J = 16.0 Hz, 2H), 4.45 (d, J = 5.8 Hz, 2H), 4.37 (d, J = 15.9 Hz, 2H), 4.31 (d, J = 9.6 Hz, 1H), 3.73 (s, 3H), 2.07 - 1.99 (m, 2H), 1.00 - 0.93 (m, 6H).

[1042] LC-MS (ESI) m / z 638.2 [M+1]

[1043]

[1044] Example 4: Synthesis of 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((1r,4R)-4-hydroxycyclohexyl)methyl)-3-nitrobenzamide

[1045] The title compound (8 mg, 19%) was obtained by performing the same method as in Example 1, except that (4-(Tert-butoxycarbonyl)-2-nitrophenyl)-D-valine,N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and 4-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1046] 1 H NMR (500 MHz, CDCl3) δ8.11 (d, J = 2.2 Hz, 1H), 7.91 (dd, J = 8.9, 2.2 Hz, 1H), 7.14 (d, J = 8.6 Hz, 3H), 7.06 (d, J = 8.4 Hz, 2H), 6.88 - 6.84 (m, 2H), 6.83 - 6.79 (m, 2H), 6.43 (t, J = 6.0 Hz, 1H), 5.76 (s, 1H), 5.26 (d, J = 15.9 Hz, 1H), 5.02 (s, 1H), 4.45 (dd, J = 15.9, 5.6 Hz, 1H), 4.29 (dd, J = 9.4, 1.9 Hz, 1H), 4.04 (s, 1H), 3.81 (d, J = 3.5 Hz, 3H), 3.46 (q, J = 16.4 Hz, 2H), 3.34 (h, J = 6.7 Hz, 2H), 2.23 - 2.14 (m, 1H), 2.09 - 1.97 (m, 1H), 1.78 (d, J = 12.9 Hz, 2H), 1.73 - 1.65 (m, 1H), 1.58 - 1.53 (m, 3H), 1.48 (d, J = 15.5 Hz, 3H), 1.31 - 1.23 (m, 1H), 1.13 (d, J = 6.7 Hz, 3H), 1.06 (d, J = 6.9 Hz, 3H).

[1047] LC-MS (ESI) m / z 643.1 [M+1]

[1048]

[1049] Example 5: Synthesis of (R)-N-(3-carbamoylcyclobutyl)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide

[1050] The title compound (31 mg, 64%) was obtained by performing the same method as in Example 1, except that (4-(Tert-butoxycarbonyl)-2-nitrophenyl)-D-valine,N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and 3-aminocyclobutane-1-carboxamide were used as starting materials.

[1051] 1 H NMR (400 MHz, DMSO-d6) δ9.34 (s, 1H), 8.77 (d, J = 7.6 Hz, 1H), 8.31 (d, J = 2.1 Hz, 1H), 8.05 - 7.98 (m, 1H), 7.51 (d, J = 9.0 Hz, 1H), 7.12 (d, J = 8.2 Hz, 2H), 7.05 (d, J = 8.2 Hz, 2H), 6.86 (d, J = 8.3 Hz, 2H), 6.72 - 6.67 (m, 2H), 5.42 (s, 1H), 5.01 (d, J = 15.9 Hz, 1H), 4.40 - 4.32 (m, 2H), 4.32 - 4.27 (m, 1H), 3.72 (s, 3H), 3.43 (s, 2H), 3.19 - 3.13 (m, 4H), 2.18 (q, J = 9.9 Hz, 2H), 2.06 - 1.98 (m, 1H), 1.56 (d, J = 8.9 Hz, 4H), 1.34 - 1.27 (m, 4H), 0.99 - 0.94 (m, 6H).

[1052] LC-MS (ESI) m / z 628.2 [M+1]

[1053]

[1054] Example 6: Synthesis of (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxycyclobutyl)-3-nitrobenzamide

[1055] The title compound (44 mg, 60%) was obtained by performing the same method as in Example 1, except that (4-(Tert-butoxycarbonyl)-2-nitrophenyl)-D-valine,N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and 3-aminocyclobutan-1-ol were used as starting materials.

[1056] 1 H NMR (400 MHz, MeOD) δ8.25 - 8.19 (m, 1H), 7.98 (dd, J = 8.7, 2.2 Hz, 1H), 7.39 (d, J = 8.9 Hz, 1H), 7.12 - 7.05 (m, 4H), 6.83 (d, J = 8.1 Hz, 2H), 6.78 - 6.71 (m, 2H), 5.32 (d, J = 1.8 Hz, 1H), 5.12 (d, J = 15.9 Hz, 1H), 4.51 (d, J = 15.9 Hz, 1H), 4.25 (dd, J = 10.0, 1.9 Hz, 1H), 4.07 - 3.92 (m, 2H), 3.76 (s, 3H), 3.47 (s, 2H), 3.10 - 3.02 (m, 1H), 2.78 - 2.67 (m, 2H), 2.21 - 2.11 (m, 1H), 2.03 - 1.92 (m, 2H), 1.72 - 1.59 (m, 1H), 1.41 (h, J = 7.3 Hz, 1H), 1.07 - 1.01 (m, 6H).

[1057] LC-MS (ESI) m / z 601.2 [M+1]

[1058]

[1059] Example 7: Synthesis of (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((3-hydroxycyclobutyl)methyl)-3-nitrobenzamide

[1060] The title compound (32 mg, 41%) was obtained by performing the same method as in Example 1, except that (4-(Tert-butoxycarbonyl)-2-nitrophenyl)-D-valine,N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and 3-(aminomethyl)cyclobutan-1-ol were used as starting materials.

[1061] 1 H NMR (500 MHz, DMSO-d6) δ9.34 (s, 1H), 8.56 (t, J = 5.8 Hz, 1H), 8.27 (d, J = 2.1 Hz, 1H), 8.00 (dd, J = 8.9, 2.2 Hz, 1H), 7.53 (d, J = 9.0) Hz, 1H), 7.13 (d, J = 8.3 Hz, 2H), 7.06 (d, J = 8.2 Hz, 2H), 6.89 - 6.84 (m, 2H), 6.73 - 6.67 (m, 2H), 5.42 (s, 1H), 5.01 (d, J = 15.9 Hz, 1H), 4.94 (d, J = 6.7 Hz, 1H), 4.40 - 4.30 (m, 2H), 3.88 (h, J = 7.4 Hz, 1H), 3.73 (s, 3H), 3.44 (d, J = 3.5 Hz, 2H), 3.26 (q, J = 6.9 Hz, 2H), 2.27 - 2.19 (m, 2H), 2.03 (qd, J = 6.8, 3.3 Hz, 1H), 1.94 - 1.85 (m, 1H), 1.52 (q, J = 8.7 Hz, 2H), 0.98 (d, J = 6.7 Hz, 3H), 0.95 (d, J = 6.8 Hz, 3H).

[1062] LC-MS (ESI) m / z 615.2 [M+1]

[1063]

[1064] Example 8: Synthesis of (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1065] The title compound (21 mg, 61%) was obtained by performing the same method as in Example 1, except that (4-(Tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-D-valine,N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1066] 1 H NMR (500 MHz, MeOD) δ8.20 (s, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.14 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.87 (d, J =8.0 Hz, 2H), 6.73 (d, J = 7.9 Hz, 2H), 6.03 (s, 1H), 5.17 (d, J = 15.7 Hz, 1H), 4.40 (d, J = 15.6 Hz, 1H), 4.03 (d, J = 8.9 Hz, 1H), 3.78 (d, J = 1.4 Hz, 3H),3.50 (d, J = 8.0 Hz, 1H), 3.42 (s, 2H), 2.20 - 2.13 (m, 1H), 1.69 - 1.62 (m, 2H),1.61 - 1.46 (m, 7H), 1.32 (d, J = 24.2 Hz, 2H), 0.99 (dd, J = 15.2, 6.7 Hz, 6H).

[1067] LC-MS (ESI) m / z 666.3 [M+1]

[1068]

[1069] Example 9: Synthesis of (R)-3-cyano-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid

[1070] The title compound (60.0 mg, 70%) was obtained by performing the same method as steps (a) through (c) of Example 1, except that N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine was used as the starting material.

[1071] LC-MS (ESI) m / z 512.1 [M+1]

[1072]

[1073] Example 9-1: Synthesis of 3-cyano-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1074] The title compound (3.2 mg, 9%) was obtained by performing the same method as in Example 1, except that N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine was used as the starting material.

[1075] 1H NMR (500 MHz, CDCl3) δ7.86 (d, J = 2.4 Hz, 1H), 7.70 - 7.67 (m, 1H), 7.05 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 7.9 Hz, 2H), 6.84 (d, J = 9.1 Hz, 1H), 6.80 - 6.76 (m, 2H), 6.72 - 6.67 (m, 2H), 6.38 (s, 1H), 5.86 (s, 1H), 5.17 (s, 1H), 5.09 (d, J = 15.8 Hz, 1H), 4.35 (d, J = 15.7 Hz, 1H), 4.24 (d, J = 9.9 Hz, 1H), 3.99 (d, J = 7.6 Hz, 1H), 3.85 - 3.80 (m, 1H), 3.72 (s, 3H), 3.71 - 3.68 (m, 1H), 3.51 (d, J = 16.3 Hz, 1H), 3.43 (d, J) = 16.3 Hz, 1H), 3.25 - 3.19 (m, 1H), 2.08 - 2.03 (m, 1H), 1.96 (p, J = 6.6 Hz, 2H), 1.88 - 1.83 (m, 2H), 1.03 (d, J = 6.7 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H).

[1076] LC-MS (ESI) m / z 595.2 [M+1]

[1077]

[1078] Example 10: Synthesis of (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-nitrobenzamide

[1079] The title compound (30 mg, 58%) was obtained by performing the same method as in Example 1, except that N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-trifluorophenyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and 1-(aminomethyl)cyclopentan-1-ol were used as starting materials.

[1080] 1 H NMR (500 MHz, DMSO-d6) δ9.33 (s, 1H), 8.43 (t, J = 6.1 Hz, 1H), 8.31 (d, J = 2.2 Hz, 1H), 8.02 (dd, J = 9.0, 2.2 Hz, 1H), 7.54 (d, J = 9.1 Hz, 1H), 7.33 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 7.07 - 6.99 (m, 2H), 6.72 - 6.64 (m, 2H), 5.50 (s, 1H), 5.03 (d, J = 15.9) Hz, 1H), 4.50 (s, 1H), 4.40 (d, J = 15.9 Hz, 1H), 4.34 (d, J = 9.7 Hz, 1H), 3.57 (s, 2H), 3.38 (s, 2H), 1.98 - 1.90 (m, 1H), 1.74 - 1.64 (m, 2H), 1.64 - 1.55 (m, 2H), 1.55 - 1.46 (m, 4H), 0.95 (dd, J = 8.9, 6.7 Hz, 6H).

[1081] LC-MS (ESI) m / z 683.3 [M+1]

[1082]

[1083] Example 11: Synthesis of (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide

[1084] The title compound (35 mg, 77%) was obtained by performing the same method as in Example 1, except that N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-trifluorophenyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and 1-(aminomethyl)cyclophenhexane-1-ol were used as starting materials.

[1085] 1 H NMR (500 MHz, DMSO-d6) δ9.33 (s, 1H), 8.34 (t, J = 6.1 Hz, 1H), 8.31 (d, J = 2.1 Hz, 1H), 8.03 (dd, J = 8.9, 2.2 Hz, 1H), 7.54 (d, J = 9.1 Hz, 1H), 7.33 (d, J = 8.7 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.69 (d, J = 8.5 Hz, 2H), 5.50 (s, 1H), 5.03 (d, J) = 15.9 Hz, 1H), 4.40 (d, J = 15.9 Hz, 1H), 4.36 - 4.31 (m, 2H), 3.57 (s, 2H), 3.34 (s, 3H), 3.26 (t, J = 5.5 Hz, 2H), 1.99 - 1.89 (m, 1H), 1.55 (m, 2H), 1.42 (s, 5H), 1.37 - 1.28 (m, 2H), 1.24 - 1.15 (m, 2H), 0.95 (dd, J = 9.4, 6.8 Hz, 6H).

[1086] LC-MS (ESI) m / z 697.4 [M+1]

[1087]

[1088] Example 12: Synthesis of 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1089] The title compound (15 mg, 20%) was obtained by performing the same method as in Example 1, except that N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-trifluorophenyl)propane-2-amine and (4-(tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-D-valine were used as starting materials.

[1090] 1 H NMR (400 MHz, CDCl3) δ8.06 (d, J = 2.2 Hz, 1H), 7.82 - 7.77 (m, 1H), 7.15 (d, J = 8.5 Hz, 5H), 7.03 (d, J = 8.1 Hz, 2H), 6.75 (d, J = 8.3 Hz, 2H), 6.55 (s, 1H), 5.77 (s, 1H), 5.63 (s, 1H), 5.22 (d, J = 15.7 Hz, 1H), 4.31 (d, J = 15.7 Hz, 1H), 4.12 - 4.02 (m, 2H), 3.90 (q, J) = 7.2 Hz, 1H), 3.81 (p, J = 7.8 Hz, 2H), 3.52 (q, J = 16.3 Hz, 2H), 3.30 (ddd, J = 13.3, 7.9, 4.7 Hz, 1H), 2.07 (tq, J = 12.5, 6.9 Hz, 2H), 1.94 (p, J = 6.9 Hz, 2H), 1.63 (t, J = 7.8 Hz, 1H), 1.04 (d, J = 6.8 Hz, 6H).

[1091] LC-MS (ESI) m / z 692.3 [M+1]

[1092]

[1093] Example 13: Synthesis of (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide

[1094] The title compound (17 mg, 23%) was obtained by performing the same method as in Example 1, except that N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-trifluorophenyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-D-valine and 1-(aminomethyl)cyclopentan-1-ol were used as starting materials.

[1095] 1 H NMR (400 MHz, CDCl3) δ8.03 (s, 1H), 7.80 (d, J = 8.6 Hz, 1H), 7.16 (s, 5H), 7.01 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 6.64 (d, J = 6.2 Hz, 1H), 5.75 (s, 1H), 5.54 (s, 1H), 5.20 (d, J = 15.7 Hz, 1H), 4.30 (d, J = 15.7 Hz, 1H), 4.04 (d, J = 8.7 Hz, 1H), 3.56 (d, J = 5.8 Hz, 2H), 3.53 - 3.43 (m, 2H), 2.23 (s, 1H), 2.06 (dt, J = 14.6, 7.4 Hz, 1H), 1.81 (s, 2H), 1.73 - 1.63 (m, 6H), 1.06 - 0.98 (m, 6H).

[1096] LC-MS (ESI) m / z 706.3 [M+1]

[1097]

[1098] Example 14: Synthesis of (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1099] The title compound (15 mg, 20%) was obtained by performing the same method as in Example 1, except that N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-trifluorophenyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-D-valine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1100] 1 H NMR (400 MHz, CDCl3) δ8.04 (d, J = 2.1 Hz, 1H), 7.80 (d, J = 8.5 Hz, 1H), 7.15 (d, J = 6.8 Hz, 5H), 7.00 (d, J = 8.1 Hz, 2H), 6.72 (d, J = 8.1 Hz, 2H), 6.60 (t, J = 5.8 Hz, 1H), 5.75 (s, 1H), 5.70 (s, 1H), 5.20 (d, J = 15.7 Hz, 1H), 4.29 (d, J = 15.7 Hz, 1H), 4.04 (d, J = 8.6 Hz, 1H), 3.56 - 3.43 (m, 4H), 2.21 (s, 1H), 2.06 (dt, J = 14.1, 7.1 Hz, 1H), 1.54 (s, 8H), 1.34 (s, 1H), 1.03 (dd, J = 6.6, 2.3 Hz, 6H).

[1101] LC-MS (ESI) m / z 720.3 [M+1]

[1102]

[1103] Example 15: Synthesis of 4-((R)-5-cyclopentyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1104] The title compound (8 mg, 38%) was obtained by performing the same method as in Example 1, except that N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1-cyclopentyl-2,2-dimethoxyethane-1-amine and (4-(tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-D-valine were used as starting materials.

[1105] 1 H NMR (500 MHz, CDCl3) δ8.06 (t, J = 2.0 Hz, 1H), 7.75 - 7.69 (m, 1H), 7.03 (dd, J = 8.9, 7.1 Hz, 3H), 6.74 - 6.69 (m, 2H), 6.66 (ddd, J = 11.1, 6.8, 4.7 Hz, 1H), 6.37 - 6.31 (m, 1H), 5.90 (s, 1H), 5.26 (d, J = 15.4 Hz, 1H), 4.42 (d, J = 15.4 Hz, 1H), 4.11 - 4.05 (m, 1H), 4.00 (ddd, J = 13.8, 9.2, 1.8 Hz, 1H), 3.90 (dtd, J = 8.5, 6.7, 1.8 Hz, 1H), 3.81 (dqd, J = 7.3, 5.5, 1.9 Hz, 2H), 3.30 (dddd, J = 13.9, 7.8, 4.7, 1.4 Hz, 1H), 2.74 (p, J = 7.4 Hz, 1H), 1.98 - 1.84 (m, 3H), 1.73 (qd, J = 9.7, 8.8, 5.1 Hz, 2H), 1.65 - 1.51 (m, 5H), 1.34 - 1.28 (m, 1H), 1.11 - 1.07 (m, 3H), 1.02 (d, J = 6.8 Hz, 3H).

[1106] LC-MS (ESI) m / z 586.2 [M+1]

[1107]

[1108] Example 16: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-morpholino-3-(trifluoromethyl)benzamide

[1109]

[1110]

[1111] (a) Synthesis of Tert-butyl 4-(((2R)-1-((1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-yl)(3,4-dimethoxybenzyl)amino)-3-methyl-1-oxobutane-2-yl)amino)-3-(trifluoromethyl)benzoate

[1112] (4-(Tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-D-valine (2 g, 5.91 mmol) was dissolved in dichloromethane (40 mL), after which N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine (2.2 g, 5.91 mmol) and EDC (3.4 g, 17.73 mmol) were added sequentially, and the mixture was stirred at room temperature for 18 hours. Once the reaction was complete, the reaction mixture was diluted with dichloromethane (30 mL) and washed with an aqueous solution of saturated sodium chloride. The separated organic layer was dried with anhydrous sodium sulfate, and then concentrated by filtration and vacuum distillation to obtain the title compound (4.1 g, quant.).

[1113]

[1114] (b) Synthesis of Tert-butyl (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoate

[1115] (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid (4.1 g, 5.91 mmol) synthesized in step (a) above was dissolved in dichloromethane (25 mL), then formic acid (4 mL) was added and stirred at room temperature for 2 hours. When the reaction was complete, the solution was concentrated by vacuum distillation and purified by MPLC (hexane : ethyl acetate = 5 : 5 v / v) to obtain the title compound (750 mg, 1.19 mmol, 20%).

[1116]

[1117] (c) Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid

[1118] The tert-butyl (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoate synthesized in step (b) above was dissolved in dichloromethane (10 mL), then trifluoroacetic acid (5 mL) was added and stirred at room temperature for 2 hours. When the reaction was complete, the solution was concentrated by vacuum distillation and purified by MPLC (hexane : ethyl acetate = 3 : 7 v / v) to obtain the title compound (456 mg, 0.700 mmol, 58%).

[1119]

[1120] (d) Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-morpholino-3-(trifluoromethyl)benzamide

[1121] (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid (75 mg, 0.115 mmol) synthesized in step (c) above was dissolved in dichloromethane (10 mL), and then morpholine-4-amine (19 mg, 0.172 mmol), HCTU (95 mg, 0.229 mmol), and DIPEA (42 mg, 0.056 mL, 0.321 mmol) were added, followed by stirring at room temperature for 1 hour. Once the reaction was complete, the solution was concentrated by vacuum distillation and purified by MPLC (dichloromethane:methanol = 9:1 v / v) to obtain the title compound (77 mg, 94%).

[1122] 1 H NMR (500 MHz, CDCl3) δ7.98 (s, 1H), 7.81 (s, 1H), 7.20 (d, J = 8.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 6.81 (d, J = 8.1 Hz, 2H), 6.71 (s, 1H), 5.16 (d, J = 15.7 Hz, 1H), 4.42 (d, J = 15.9 Hz, 1H), 4.15 - 4.09 (m, 1H), 4.06 (d, J = 8.8 Hz, 1H), 3.87 (s, 3H), 3.80 (s, 3H), 3.77 (s, 3H), 3.72 (d, J = 4.3 Hz, 4H), 3.46 (d, J = 6.1 Hz, 2H), 3.18 (d, J = 3.1 Hz, 4H), 2.18 - 2.12 (m, 1H), 2.03 (d, J = 12.3 Hz, 1H), 1.05 (dd, J = 11.8, 6.8 Hz, 6H).

[1123] LC-MS (ESI) m / z 683.3 [M+1]

[1124]

[1125] Example 17: Synthesis of 3-cyano-4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1126] The title compound (25 mg, 51%) was obtained by performing the same method as in Example 16, except that (4-(Tert-butoxycarbonyl)-2-cyanophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1127] 1 H NMR (400 MHz, DMSO-d6) δ8.59 (t, J = 5.8 Hz, 1H), 8.17 (d, J = 2.3 Hz, 1H), 7.99 (dd, J = 9.0, 2.3 Hz, 1H), 7.34 (d, J = 9.1 Hz, 1H), 7.20 (d, J = 8.2 Hz, 2H), 6.86 (dd, J = 11.8, 8.3 Hz, 3H), 6.69 - 6.64 (m, 2H), 6.40 (d, J = 1.8 Hz, 1H), 5.00 (d, J = 16.1 Hz, 1H), 4.50 - 4.40 (m, 2H), 3.96 (p, J = 6.3 Hz, 1H), 3.77 (q, J = 7.0 Hz, 2H), 3.72 (d, J = 7.9 Hz, 6H), 3.63 (s, 4H), 3.54 (d, J = 5.7 Hz, 1H), 3.29 (t, J = 5.4 Hz, 2H), 2.01 (dt, J = 9.9, 6.7 Hz, 1H), 1.90 (ddt, J = 15.2, 10.3, 5.3 Hz, 2H), 1.80 (td, J = 12.7, 12.0, 6.0 Hz, 2H), 1.57 (td, J = 11.0, 10.0, 6.9 Hz, 1H), 0.98 (dd, J = 6.8, 3.4 Hz, 6H).

[1128] LC-MS (ESI) m / z 639.2 [M+1]

[1129]

[1130] Example 18: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1131] The title compound (42 mg, 69%) was obtained by performing the same method as in Example 16, except that (4-(Tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1132] 1 H NMR (500 MHz, MeOD) δ8.25 (d, J = 2.1 Hz, 1H), 8.00 (dd, J = 8.8, 2.2Hz, 1H), 7.44 (d, J = 8.9 Hz, 1H), 7.11 - 7.07 (m, 2H), 6.92 - 6.90 (m, 1H),6.86 - 6.81 (m, 3H), 6.79 - 6.76 (m, 1H), 5.42 - 5.40 (m, 1H), 5.15 (d, J =16.0 Hz, 1H), 4.58 (d, J = 16.0 Hz, 1H), 4.26 (dd, J = 9.7, 1.9 Hz, 1H), 4.12 -4.07 (m, 1H), 3.92 - 3.87 (m, 1H), 3.83 (s, 3H), 3.80 - 3.72 (m, 7H), 3.52 -3.47 (m, 3H), 3.43 - 3.38 (m, 1H), 2.22 - 2.16 (m, 1H), 2.06 - 2.01 (m, 1H),1.97 - 1.90 (m, 2H), 1.69 - 1.62 (m, 1H), 1.06 (dd, J = 10.8, 6.8 Hz, 6H).

[1133] LC-MS (ESI) m / z 659.2 [M+1]

[1134]

[1135] Example 19: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid

[1136] The title compound was obtained in step (c) of Example 16.

[1137] LC-MS (ESI) m / z 599.1 [M+1]

[1138]

[1139] Example 19-1: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1140] The title compound (36 mg, 63%) was obtained by performing the same method as in Example 16, except that (S)-(tetrahydrofuran-2-yl)methaneamine was used as the starting material.

[1141] 1H NMR (400 MHz, DMSO-d6) δ8.73 (t, J = 5.9 Hz, 1H), 8.17 (d, J = 2.2 Hz, 1H), 8.07 (dd, J = 8.7, 2.1 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.16 (d, J = 8.3 Hz, 2H), 6.91 - 6.84 (m, 3H), 6.77 - 6.70 (m, 2H), 6.14 (s, 1H), 5.07 (d, J = 15.9 Hz, 1H), 4.34 (d, J = 15.8 Hz, 1H), 4.04 - 3.91 (m, 2H), 3.82 - 3.75 (m, 1H), 3.73 (s, 6H), 3.66 - 3.60 (m, 4H), 3.51 - 3.41 (m, 2H), 3.32 - 3.28 (m, 2H), 2.11 - 1.99 (m, 1H), 1.97 - 1.88 (m, 1H), 1.88 - 1.74 (m, J = 6.0, 5.2 Hz, 2H), 1.63 - 1.50 (m, 1H), 0.94 - 0.87 (m, 6H).

[1142] LC-MS (ESI) m / z 682.5 [M+1]

[1143]

[1144] Example 20: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1145] The title compound (35 mg, 21%) was obtained by performing the same method as in Example 16, except that (R)-(tetrahydrofuran-2-yl)methaneamine was used as the starting material.

[1146] 1H NMR (500 MHz, CDCl3) δ8.05 (d, J = 2.2 Hz, 1H), 7.83 (dd, J = 8.7, 2.3 Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 7.07 (d, J = 8.3 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 6.80 (d, J =8.2 Hz, 1H), 6.76 - 6.70 (m, 2H), 6.43 (d, J = 6.0 Hz, 1H), 5.79 (s, 1H), 5.17 (d, J =15.6 Hz, 1H), 4.41 (d, J = 15.7 Hz, 1H), 4.10 - 4.03 (m, 2H), 3.92 - 3.86 (m, 4H), 3.81 -3.77 (m, 7H), 3.50 - 3.41 (m, 2H), 3.35 - 3.29 (m, 1H), 2.19 - 2.11 (m, 1H), 2.06 - 2.01(m, 1H), 1.93 (p, J = 6.9 Hz, 2H), 1.63 - 1.58 (m, 1H), 1.05 (dd, J = 10.2, 6.8 Hz, 6H).

[1147] LC-MS (ESI) m / z 682.3 [M+1]

[1148]

[1149] Example 21: Synthesis of 4-((S)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1150] The title compound (54 mg, 24%) was obtained by performing the same method as in Example 16, except that (4-(Tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-L-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1151] 1H NMR (500 MHz, DMSO-d6) δ8.73 (t, J = 5.9 Hz, 1H), 8.18 (d, J = 2.1 Hz, 1H), 8.07 (dd, J = 8.7, 2.2 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.17 (d, J = 8.6 Hz, 2H), 6.93 - 6.83 (m, 3H), 6.78 - 6.67 (m, 2H), 6.14 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.35 (d, J = 15.8 Hz, 1H), 4.01 (dd, J = 8.9, 1.9 Hz, 1H), 3.99 - 3.94 (m, 1H), 3.81 - 3.75 (m, 1H), 3.73 (s, 6H), 3.65 (s, 3H), 3.46 - 3.43 (m, 2H), 3.31 (d, J = 5.9 Hz, 2H), 2.11 - 2.02 (m, 1H), 1.95 - 1.87 (m, 1H), 1.86 - 1.76 (m, 2H), 1.63 - 1.52 (m, 1H), 0.95 - 0.87 (m, 6H).

[1152] LC-MS (ESI) m / z 682.3 [M+1]

[1153]

[1154] Example 22: Synthesis of 4-((S)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1155] The title compound (49 mg, 23%) was obtained by performing the same method as in Example 16, except that (4-(Tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-L-valine and (R)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1156] 1H NMR (500 MHz, DMSO-d6) δ8.73 (t, J = 5.8 Hz, 1H), 8.18 (d, J = 2.2 Hz, 1H), 8.08 (dd, J = 8.7, 2.2 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.17 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.3 Hz, 3H), 6.77 - 6.68 (m, 2H), 6.15 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.35 (d, J = 15.8 Hz, 1H), 4.01 (dd, J = 8.9, 1.9 Hz, 1H), 3.97 (q, J = 6.3 Hz, 1H), 3.78 (dt, J = 8.0, 6.8 Hz, 1H), 3.73 (s, 6H), 3.65 (s, 3H), 3.63 - 3.59 (m, 1H), 3.51 - 3.39 (m, 2H), 3.33 - 3.29 (m, 2H), 2.12 - 2.02 (m, 1H), 1.96 - 1.86 (m, 1H), 1.86 - 1.75 (m, 2H), 1.63 - 1.52 (m, 1H), 0.97 - 0.84 (m, 6H).

[1157] LC-MS (ESI) m / z 682.4 [M+1]

[1158]

[1159] Example 23: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-methylfuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1160] The title compound (1 mg, 2.9%) was obtained by performing the same method as in Example 16, except that (5-methylfuran-2-yl)methaneamine was used as the starting material.

[1161] LC-MS (ESI) m / z 692.1 [M+1]

[1162]

[1163] Example 24: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1r,4R)-4-hydroxycyclohexyl)-3-(trifluoromethyl)benzamide

[1164] The title compound (36 mg, 62%) was obtained by performing the same method as in Example 16, except that (1r,4r)-4-aminocyclohexane-1-ol was used as the starting material.

[1165] 1 H NMR (500 MHz, DMSO-d6) δ8.34 (d, J = 7.8 Hz, 1H), 8.14 (d, J = 2.2 Hz, 1H), 8.05 (dd, J = 8.7, 2.2 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.18 - 7.14 (m, 2H), 6.89 - 6.86 (m, 3H), 6.74 - 6.71 (m, 2H), 6.14 (s, 1H), 5.06 (d, J = 15.8 Hz, 1H), 4.57 (d, J = 4.4 Hz, 1H), 4.33 (d, J) = 15.9 Hz, 1H), 4.00 (dd, J = 8.9, 1.9 Hz, 1H), 3.73 (s, 6H), 3.64 (s, 3H), 3.45 - 3.43 (m, 1H), 3.41 - 3.36 (m, 1H), 2.10 - 2.03 (m, 1H), 1.88 - 1.79 (m, 4H), 1.40 - 1.32 (m, 2H), 1.27 - 1.20 (m, 2H), 0.90 (dd, J = 6.8, 4.0 Hz, 6H).

[1166] LC-MS (ESI) m / z 696.2 [M+1]

[1167]

[1168] Example 25: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1169] The title compound (36 mg, 59%) was obtained by performing the same method as in Example 16, except that 1-(aminomethyl)cyclohexane-1-ol was used as the starting material.

[1170] 1 H NMR (500 MHz, DMSO-d6) δ8.40 (t, J = 6.1 Hz, 1H), 8.18 (d, J = 2.1 Hz, 1H), 8.08 (dd, J = 8.8, 2.2 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.18 - 7.14 (m, 2H), 6.88 (d, J = 8.5 Hz, 3H), 6.75 - 6.72 (m, 2H), 6.13 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.36 - 4.32 (m, 2H), 4.00 (dd, J) = 8.8, 1.8 Hz, 1H), 3.73 (s, 6H), 3.64 (s, 3H), 3.47 - 3.41 (m, 2H), 3.26 (d, J = 6.1 Hz, 2H), 2.09 - 2.03 (m, 1H), 1.57 - 1.51 (m, 2H), 1.47 - 1.38 (m, 5H), 1.36 - 1.30 (m, 2H), 1.23 - 1.16 (m, 1H), 0.94 - 0.88 (m, 6H).

[1171] LC-MS (ESI) m / z 710.2 [M+1]

[1172]

[1173] Example 26: Synthesis of (S)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1174] The title compound (36 mg, 59%) was obtained by performing the same method as in Example 16, except that (4-(Tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-L-valine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1175] 1 H NMR (500 MHz, DMSO-d6) δ 8.40 (t, J = 6.1 Hz, 1H), 8.19 (d, J = 2.1 Hz, 1H), 8.09 (dd, J = 8.6, 2.2 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.17 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.3 Hz, 3H), 6.78 - 6.69 (m, 2H), 6.13 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.41 - 4.30 (m, 2H), 4.01 (dd, J = 8.8, 1.8 Hz, 1H), 3.73 (s, 6H), 3.65 (s, 3H), 3.49 - 3.40 (m, 2H), 3.27 (d, J = 6.1 Hz, 2H), 2.13 - 2.01 (m, 1H), 1.62 - 1.50 (m, 2H), 1.50 - 1.38 (m, 5H), 1.38 - 1.28 (m, 2H), 1.25 - 1.15 (m, 1H), 0.97 - 0.85 (m, 6H).

[1176] LC-MS (ESI) m / z 710.4 [M+1]

[1177]

[1178] Example 27: Synthesis of (R)-2-(4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)pyridine 1-oxide

[1179] The title compound (5 mg, 8.7%) was obtained by performing the same method as in Example 16, except that 2-aminopyridine 1-oxide was used as the starting material.

[1180] 1 H NMR (500 MHz, DMSO-d6) δ10.91 (s, 1H), 8.47 (d, J = 6.5 Hz, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.21 (s, 1H), 8.13 (d, J = 8.9 Hz, 1H), 7.64 (d, J = 8.7 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.23 (t, J = 7.1 Hz, 1H), 7.16 (d, J = 8.1 Hz, 2H), 6.88 (d, J = 8.2 Hz, 3H), 6.74 (d, J = 7.7 Hz, 2H), 6.11 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.40 (d, J = 15.7 Hz, 1H), 4.13 (d, J = 9.2 Hz, 1H), 3.72 (d, J = 12.0 Hz, 7H), 3.65 (d, J = 6.3 Hz, 3H), 3.49 (d, J = 3.4 Hz, 1H), 2.69 (s, 5H), 2.09 (q, J = 6.8 Hz, 1H), 1.59 - 1.54 (m, 1H), 0.95 (q, J = 7.1 Hz, 5H).

[1181] LC-MS (ESI) m / z 691.3 [M+1]

[1182]

[1183] Example 28: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-morpholinoethyl)-3-(trifluoromethyl)benzamide

[1184] The title compound (14 mg, 24%) was obtained by performing the same method as in Example 16, except that 2-morphoethane-1-amine was used as the starting material.

[1185] 1 H NMR (500 MHz, DMSO-d6) δ8.69 (s, 1H), 8.16 (d, J = 2.2 Hz, 1H), 8.08 - 8.05 (m, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.17 (d, J = 8.2 Hz, 2H), 6.88 (d, J = 8.1 Hz, 4H), 6.74 (d, J = 8.4 Hz, 2H), 6.14 (s, 1H), 5.07 (d, J = 15.7 Hz, 1H), 4.35 (d, J = 16.3 Hz, 1H), 4.02 (d, J = 8.9 Hz, 1H), 3.73 (s, 7H), 3.65 (s, 8H), 3.45 (d, J = 4.4 Hz, 3H), 2.64 (s, 6H), 2.07 (h, J = 6.8 Hz, 1H), 1.25 (s, 1H), 0.91 (t, J = 6.0 Hz, 6H).

[1186] LC-MS (ESI) m / z 711.3 [M+1]

[1187]

[1188] Example 29: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methylpiperidine-4-yl)methyl)-3-(trifluoromethyl)benzamide

[1189] The title compound (9 mg, 6%) was obtained by performing the same method as in Example 16, except that (1-methylpiperidine-4-yl)methaneamine was used as the starting material.

[1190] 1H NMR (400 MHz, DMSO-d6) δ8.69 - 8.57 (m, 1H), 8.15 (d, J = 2.2 Hz, 1H), 8.06 (d, J = 8.7 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.16 (d, J = 8.2 Hz, 2H), 6.90 - 6.85 (m, 3H), 6.76 - 6.70 (m, 2H), 6.12 (s, 1H), 5.06 (d, J = 15.8 Hz, 1H), 4.34 (d, J = 15.6 Hz, 1H), 4.00 (d, J = 8.7 Hz, 1H), 3.74 - 3.70 (m, 7H), 3.64 (s, 3H), 3.15 (t, J = 6.4 Hz, 4H), 2.82 (d, J = 11.2 Hz, 2H), 2.20 (s, 3H), 2.11 - 2.01 (m, 2H), 1.94 (t, J = 11.2 Hz, 2H), 1.64 (d, J = 12.4 Hz, 2H), 0.94 - 0.86 (m, 6H).

[1191] LC-MS (ESI) m / z 709.3 [M+1]

[1192]

[1193] Example 30: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1,1-deoxydothiomophorino)-3-(trifluoromethyl)benzamide

[1194] The title compound (10 mg, 6%) was obtained by performing the same method as in Example 16, except that (1-ethylpiperidine-4-yl)methaneamine was used as the starting material.

[1195] 1H NMR (400 MHz, DMSO-d6) δ8.67 - 8.56 (m, 1H), 8.16 (d, J = 2.1 Hz, 1H), 8.06 (dd, J = 8.9, 2.1 Hz, 1H), 7.56 (d, J = 8.6 Hz, 1H), 7.16 (d, J = 8.1 Hz, 2H), 6.87 (d, J = 8.4 Hz, 3H), 6.73 (d, J = 7.5 Hz, 2H), 6.12 (s, 1H), 5.06 (d, J = 15.7 Hz, 1H), 4.34 (d, J = 15.6 Hz, 1H), 4.00 (d, J = 8.8 Hz, 1H), 3.73 (s, 6H), 3.64 (s, 3H), 3.49 - 3.39 (m, 4H), 3.15 (t, J = 6.5 Hz, 3H), 2.90 (d, J = 11.1 Hz, 2H), 2.11 - 2.03 (m, 1H), 1.90 (t, J = 11.3 Hz, 3H), 1.66 (d, J = 12.5 Hz, 3H), 0.99 (d, J = 7.1 Hz, 3H), 0.94 - 0.88 (m, 6H).

[1196] LC-MS (ESI) m / z 723.3 [M+1]

[1197]

[1198] Example 31: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1,1-deoxydothiomophorino)-3-(trifluoromethyl)benzamide

[1199] The title compound (34 mg, 28%) was obtained by performing the same method as in Example 16, except that 4-aminothiomorpholine 1,1-dioxide was used as the starting material.

[1200] 1H NMR (500 MHz, MeOD) δ8.16 (s, 1H), 8.03 - 7.97 (m, 1H), 7.50 (d, J = 8.7 Hz, 1H), 7.13 (d, J = 8.2 Hz, 2H), 6.91 (d, J = 8.2 Hz, 1H), 6.87 (d, J = 8.3 Hz, 2H), 6.81 (d, J = 8.4 Hz, 1H), 6.75 (s, 1H), 6.09 (s, 1H), 5.18 (d, J = 15.7 Hz, 1H), 4.62 (s, 1H), 4.52 (d, J = 15.8 Hz, 1H), 4.07 (d, J = 9.1 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H), 3.75 (d, J = 6.6 Hz, 2H), 3.72 (s, 3H), 3.54 (d, J = 8.3 Hz, 1H), 3.48 - 3.41 (m, 4H), 3.37 - 3.34 (m, 4H), 3.25 (q, J = 7.4 Hz, 3H), 2.27 - 2.15 (m, 1H), 1.05 - 0.99 (m, 6H).

[1201] LC-MS (ESI) m / z 731.2 [M+1]

[1202]

[1203] Example 32: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-(1,1-deoxydothiomophorino)ethyl)-3-(trifluoromethyl)benzamide

[1204] The title compound (6 mg, 8%) was obtained by performing the same method as in Example 16, except that 4-(2-aminoethyl)thiomorpholine 1,1-dioxide was used as the starting material.

[1205] 1H NMR (500 MHz, MeOD) δ8.55 (s, 1H), 8.17 (d, J = 2.2 Hz, 1H), 7.99 (dd, J = 8.5, 2.0 Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.12 (d, J = 8.3Hz, 2H), 6.89 (d, J = 8.1 Hz, 1H), 6.85 (d, J = 8.2 Hz, 2H), 6.80 (d, J =8.0 Hz, 1H), 6.73 (s, 1H), 6.07 (s, 1H), 5.16 (d, J = 15.9 Hz, 1H), 4.50 (d,J = 15.7 Hz, 1H), 4.04 (d, J = 8.9 Hz, 1H), 3.82 (s, 3H), 3.77 (s, 3H), 3.70 (s, 3H), 3.52 (d, J = 7.2 Hz, 3H), 3.09 (d, J = 3.5 Hz, 10H), 2.76 (t, J =6.3 Hz, 2H), 2.21 - 2.15 (m, 1H), 1.01 (dd, J = 12.4, 6.8 Hz, 6H).

[1206] LC-MS (ESI) m / z 759.3 [M+1]

[1207]

[1208] Example 33: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(trifluoromethyl)benzamide

[1209] The title compound (5 mg, 7%) was obtained by performing the same method as in Example 16, except that (tetrahydro-2H-pyran-4-yl)methaneamine was used as the starting material.

[1210] 1H NMR (500 MHz, MeOD) δ8.17 (d, J = 2.1 Hz, 1H), 8.00 (dd, J = 8.7, 2.2 Hz, 1H), 7.47 (d, J = 8.6 Hz, 1H), 7.11 (d, J = 8.3 Hz, 2H), 6.89 (d, J = 8.5 Hz, 1H), 6.86 - 6.83(m, 2H), 6.79 (d, J = 8.1 Hz, 1H), 6.73 (d, J = 1.8 Hz, 1H), 6.07 (s, 1H), 5.16 (d, J =15.8 Hz, 1H), 4.49 (d, J = 15.7 Hz, 1H), 4.04 (dd, J = 9.0, 1.7 Hz, 1H), 3.99 - 3.93 (m,3H), 3.82 (s, 3H), 3.79 - 3.76 (m, 4H), 3.72 - 3.69 (m, 4H), 3.51 (d, J = 9.0 Hz, 1H),3.44 - 3.38 (m, 3H), 3.28 (d, J = 6.9 Hz, 2H), 2.22 - 2.14 (m, 1H), 1.93 - 1.88 (m, 1H),1.71 - 1.66 (m, 3H), 1.09 (dd, J = 13.2, 6.8 Hz, 2H), 1.00 (dd, J = 11.8, 6.8 Hz, 6H).

[1211] LC-MS (ESI) m / z 696.2 [M+1]

[1212]

[1213] Example 34: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-fluoropyridine-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1214] The title compound (2.5 mg, 2%) was obtained by performing the same method as in Example 16, except that (5-fluoropyridine-2-yl)methaneamine was used as the starting material.

[1215] 1H NMR (400 MHz, MeOD) δ8.41 (d, J = 2.9 Hz, 1H), 8.24 (d, J = 2.1Hz, 1H), 8.06 (d, J = 9.2 Hz, 1H), 7.60 (td, J = 8.7, 3.0 Hz, 1H), 7.51 -7.45 (m, 2H), 7.11 (d, J = 8.2 Hz, 2H), 6.89 (d, J = 8.2 Hz, 1H), 6.85 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.3 Hz, 1H), 6.73 (d, J = 1.8 Hz, 1H), 6.08 (s,1H), 5.16 (d, J = 15.9 Hz, 1H), 4.67 (s, 2H), 4.50 (d, J = 15.9 Hz, 1H),4.05 (d, J = 9.1 Hz, 1H), 3.82 (s, 3H), 3.77 (s, 3H), 3.70 (s, 3H), 3.52 (d, J = 5.9 Hz, 2H), 2.22 - 2.15 (m, 1H), 1.01 (dd, J = 9.8, 6.8 Hz, 6H).

[1216] LC-MS (ESI) m / z 707.2 [M+1]

[1217]

[1218] Example 35: Synthesis of (R)-2-((4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)-5-fluoropyridine 1-oxide

[1219] The title compound (10 mg, 17%) was obtained by performing the same method as in Example 16, except that 2-(aminomethyl)-5-fluoropyridine 1-oxide was used as the starting material.

[1220] 1H NMR (400 MHz, CDCl3) δ8.17 (s, 1H), 8.04 (s, 1H), 7.79 (d, J = 8.7 Hz, 1H), 7.59 (t, J = 6.0 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.18 (d, J = 8.7 Hz,1H), 7.11 - 7.02 (m, 3H), 6.84 - 6.77 (m, 3H), 6.74 - 6.68 (m, 2H), 5.75 (s,1H), 5.14 (d, J = 15.6 Hz, 1H), 4.74 (d, J = 6.1 Hz, 2H), 4.40 (d, J = 15.6 Hz,1H), 4.05 (d, J = 8.6 Hz, 1H), 3.85 (d, J = 1.4 Hz, 3H), 3.79 - 3.74 (m, 6H),3.48 - 3.38 (m, 2H), 2.17 - 2.09 (m, 1H), 1.02 (dd, J = 12.8, 6.7 Hz, 6H).

[1221] LC-MS (ESI) m / z 723.4 [M+1]

[1222]

[1223] Example 36: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)benzamide

[1224] The title compound (15 mg, 17%) was obtained by performing the same method as in Example 16, except that (5-(trifluoromethyl)pyridine-2-yl)methaneamine was used as the starting material.

[1225] 1H NMR (500 MHz, MeOD) δ8.85 (s, 1H), 8.28 (d, J = 2.2 Hz, 1H), 8.18 - 8.05 (m, 2H), 7.62 (d, J = 8.3 Hz, 1H), 7.52 (d, J = 8.6 Hz, 1H), 7.14 (d, J = 8.1 Hz, 2H), 6.92 (d, J = 8.2 Hz, 1H), 6.87 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.3 Hz, 1H), 6.75 (s, 1H), 6.11 (s, 1H), 5.18 (d, J = 15.8 Hz, 1H), 4.79 (s, 2H), 4.62 (s, 1H), 4.52 (d, J = 15.7 Hz, 1H), 4.08 (d, J = 9.0 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H), 3.72 (s, 3H), 3.58 - 3.50 (m, 2H), 2.83 (d, J = 1.3 Hz, 2H), 2.27 - 2.16 (m, 1H), 1.09 - 0.94 (m, 6H).

[1226] LC-MS (ESI) m / z 757.3 [M+1]

[1227]

[1228] Example 37: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-methyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1229] 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide (100 mg, 0.147 mmol) synthesized in Example 19 was dissolved in dimethylformamide (1 mL) and cooled to 0–5°C, then sodium hydride (11.7 mg, 0.293 mmol) was added and stirred for 10 minutes. Iodomethane (53 mg, 0.366 mmol) was added to the reaction mixture and stirred at 0–5°C for 3 hours. When the reaction was complete, water was added for quenching and extracted with dichloromethane, then the separated organic layer was dried with anhydrous sodium sulfate, concentrated by filtration and vacuum distillation, and purified by MPLC (ethyl acetate : hexane = 0 : 100 ~ 60 : 40, v / v) to obtain the title compound (70 mg, 68%).

[1230] 1 H NMR (500 MHz, DMSO-d6) δ7.69 (s, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.52 (d, J = 8.5 Hz, 1H), 7.16 (d, J = 8.2 Hz, 2H), 6.91 - 6.85 (m, 3H), 6.75 (d, J = 7.5 Hz, 2H), 6.12 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.35 (d, J = 15.9 Hz, 1H), 4.09 (s, 1H), 3.94 (d, J = 8.4 Hz, 1H), 3.73 (s, 6H), 3.65 (s, 3H), 3.44 (d, J = 5.4 Hz, 2H), 2.99 (s, 3H), 2.10 - 2.01 (m, 1H), 1.99 - 1.71 (m, 3H), 1.59 (s, 1H), 1.33 - 1.23 (m, 1H), 0.91 (dd, J = 17.9, 6.6 Hz, 6H).

[1231] LC-MS (ESI) m / z 696.4 [M+1]

[1232]

[1233] Example 38: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-ethyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1234] The title compound (43 mg, 41%) was obtained by performing the same method as in Example 37, except that iodoethane was used as the starting material.

[1235] 1 H NMR (500 MHz, CDCl3) δ7.68 (s, 1H), 7.50 (s, 1H), 7.22 (d, J = 8.4 Hz, 1H), 7.09 - 7.05 (m, 2H), 6.86 - 6.83 (m, 2H), 6.80 (d, J = 8.0 Hz, 1H), 6.77 - 6.72 (m, 2H), 5.77 (s, 1H), 5.16 (d, J = 15.7 Hz, 1H), 4.41 (d, J = 15.7 Hz, 1H), 4.22 (s, 1H), 4.00 (dd, J = 8.7, 1.8 Hz, 1H), 3.87 (s, 5H), 3.79 (d, J = 6.0 Hz, 8H), 3.44 (q, J = 16.3 Hz, 3H), 3.27 (s, 1H), 2.18 - 1.99 (m, 2H), 1.89 (s, 2H), 1.25 (s, 2H), 1.12 (s, 3H), 1.05 (dd, J = 6.8, 1.6 Hz, 6H).

[1236] LC-MS (ESI) m / z 710.4 [M+1]

[1237]

[1238] Example 39: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methoxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1239] The title compound (59 mg, 70%) was obtained by performing the same method as in Example 16, except that (1-methoxycyclohexyl)methaneamine was used as the starting material.

[1240] 1 H NMR (500 MHz, CDCl3) δ8.07 (d, J = 2.2 Hz, 1H), 7.84 (dd, J = 8.6, 2.3 Hz, 1H), 7.25 (d, J = 8.6 Hz, 1H), 7.13 - 7.06 (m, 2H), 6.89 - 6.84 (m, 2H), 6.83 (d, J = 8.1 Hz, 1H), 6.79 - 6.75 (m, 1H), 6.74 (d, J = 2.0 Hz, 1H), 6.28 (t, J = 5.1 Hz, 1H), 5.80 (s, 1H), 5.20 (d, J = 15.8 Hz, 1H), 4.44 (d, J = 15.8 Hz, 1H), 4.09 (dd, J = 8.8, 1.8 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.52 (d, J = 5.0 Hz, 2H), 3.48 (d, J = 7.5 Hz, 2H), 3.25 (s, 3H), 2.21 - 2.12 (m, 1H), 1.82 - 1.70 (m, 3H), 1.67 - 1.59 (m, 5H), 1.59 - 1.49 (m, 6H), 1.47 - 1.33 (m, 4H), 1.08 (dd, J = 10.0, 6.8 Hz, 6H).

[1241] LC-MS (ESI) m / z 724.3 [M+1]

[1242]

[1243] Example 40: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methylcyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1244] The title compound (10 mg, 17%) was obtained by performing the same method as in Example 16, except that (1-methylcyclohexyl)methaneamine was used as the starting material.

[1245] 1 H NMR (500 MHz, CDCl3) δ8.02 (d, J = 2.2 Hz, 1H), 7.81 (dd, J = 8.7, 2.2Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 7.07 (d, J = 8.2 Hz, 2H), 6.84 (d, J = 8.3Hz, 2H), 6.82 - 6.79 (m, 1H), 6.76 - 6.71 (m, 2H), 6.04 (t, J = 6.4 Hz, 1H),5.78 (s, 1H), 5.18 (d, J = 15.8 Hz, 1H), 4.41 (d, J = 15.8 Hz, 1H), 4.06 (dd, J= 8.9, 1.8 Hz, 1H), 3.87 (s, 3H), 3.80 (s, 3H), 3.77 (s, 3H), 3.50 - 3.41 (m,2H), 3.33 (d, J = 6.3 Hz, 2H), 2.19 - 2.11 (m, 1H), 1.51 - 1.42 (m, 4H), 1.33(t, J = 5.8 Hz, 6H), 1.05 (t, J = 7.5 Hz, 6H).

[1246] LC-MS (ESI) m / z 708.5 [M+1]

[1247]

[1248] Example 41: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1249] The title compound (13 mg, 21%) was obtained by performing the same method as in Example 16, except that 1-(aminomethyl)-N,N-dimethylcyclohexane-1-amine was used as the starting material.

[1250] 1 H NMR (400 MHz, CDCl3) δ8.14 (s, 1H), 7.93 (d, J = 8.7 Hz, 1H), 7.50 (s, 1H), 7.05 (d, J = 8.2 Hz, 2H), 6.81 (dd, J = 11.8, 8.2 Hz, 3H), 6.75 - 6.69 (m, 2H),5.76 (s, 1H), 5.15 (d, J = 16.0 Hz, 1H), 4.41 (d, J = 15.6 Hz, 1H), 4.08 (d, J = 8.8Hz, 1H), 3.85 (s, 3H), 3.81 - 3.75 (m, 8H), 3.45 - 3.44 (m, 1H), 2.67 (s, 6H),2.18 - 2.10 (m, 1H), 1.82 - 1.59 (m, 11H), 1.04 (dd, J = 9.9, 6.9 Hz, 6H).

[1251] LC-MS (ESI) m / z 737.4 [M+1]

[1252]

[1253] Example 42: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)-3-(trifluoromethyl)benzamide

[1254] The title compound (21 mg, 35%) was obtained by performing the same method as in Example 16, except that 4-(aminomethyl)tetrahydro-2H-pyran-4-ol was used as the starting material.

[1255] 1H NMR (500 MHz, CDCl3) δ8.04 (d, J = 2.2 Hz, 1H), 7.83 (dd, J = 8.7, 2.2 Hz, 1H), 7.20 (d, J = 8.7 Hz, 1H), 7.09 - 7.04 (m, 2H), 6.86 - 6.83 (m, 2H), 6.80 (d, J = 8.2 Hz, 1H), 6.75 (dd, J = 8.2, 2.0 Hz, 1H), 6.71 (d, J = 2.0 Hz, 1H), 6.51 (t, J = 6.1 Hz, 1H), 5.77 (s, 1H), 5.17(d, J = 15.7 Hz, 1H); 4.42 (d, J = 15.7 Hz, 1H), 4.06 (dd, J = 9.0, 1.8 Hz, 1H), 3.87 (s, 3H),3.81 - 3.75 (m, 10H), 3.53 (d, J = 6.0 Hz, 2H), 3.51 - 3.43 (m, 2H), 2.72 (s, 1H), 2.19 - 2.11(m, 1H), 1.75 - 1.69 (m, 2H), 1.59 (d, J = 13.1 Hz, 2H), 1.05 (dd, J = 10.8, 6.8 Hz, 6H).

[1256] LC-MS (ESI) m / z 712.3 [M+1]

[1257]

[1258] Example 43: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3-(trifluoromethyl)benzamide

[1259] The title compound (10 mg, 17%) was obtained by performing the same method as in Example 16, except that 2-(tetrahydro-2H-pyran-4-yl)ethane-1-amine was used as the starting material.

[1260] 1H NMR (500 MHz, CDCl3) δ8.00 (d, J = 2.2 Hz, 1H), 7.81 (d, J = 9.0 Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 7.07 (d, J = 8.3 Hz, 2H), 6.87 - 6.79 (m, 3H), 6.77 - 6.71 (m, 2H), 6.00 (t, J = 5.8 Hz, 1H), 5.78 (s, 1H), 5.17 (d, J = 15.7 Hz, 1H), 4.42 (d, J = 15.7 Hz, 1H), 4.05 (d, J = 8.8 Hz, 1H), 3.97 (dd, J = 11.5, 4.3 Hz, 2H), 3.87 (s, 3H), 3.80 (s, 3H), 3.77 (s, 3H), 3.56 - 3.43 (m, 4H), 3.39 (t, J = 11.4 Hz, 2H), 2.18 - 2.12 (m, 1H), 1.67(d, J = 13.6 Hz, 2H), 1.59 (t, J = 6.7 Hz, 3H), 1.39 - 1.33 (m, 2H), 1.05 (t, J = 7.5 Hz, 6H).

[1261] LC-MS (ESI) m / z 710.4 [M+1]

[1262]

[1263] Example 44: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-3-yl)methyl)-3-(trifluoromethyl)benzamide

[1264] The title compound (13 mg, 23%) was obtained by performing the same method as in Example 16, except that (S)-(tetrahydrofuran-3-yl)methaneamine was used as the starting material.

[1265] 1H NMR (500 MHz, CDCl3) δ8.02 (d, J = 2.2 Hz, 1H), 7.80 (dd, J = 8.7, 2.2 Hz, 1H), 7.21 (d, J= 8.6 Hz, 1H), 7.09 - 7.05 (m, 2H), 6.86 - 6.83 (m, 2H), 6.81 - 6.78 (m, 1H), 6.76 - 6.71 (m,2H), 6.32 (t, J = 5.8 Hz, 1H), 5.77 (s, 1H), 5.17 (d, J = 15.7 Hz, 1H), 4.42 (d, J = 15.7) Hz, 1H),4.06 (dd, J = 9.0, 1.8 Hz, 1H), 3.95 - 3.91 (m, 1H), 3.87 (s, 3H), 3.83 (d, J = 2.1 Hz, 1H), 3.80(s, 3H), 3.77 (s, 3H), 3.64 (dd, J = 8.9, 4.7 Hz, 1H), 3.51 - 3.45 (m, 4H), 2.64 - 2.58 (m, 1H),2.18 - 2.07 (m, 2H), 1.75 - 1.64 (m, 2H), 1.05 (dd, J = 9.3, 6.8 Hz, 6H).

[1266] LC-MS (ESI) m / z 662.4 [M+1]

[1267]

[1268] Example 45: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxetane-3-ylmethyl)-3-(trifluoromethyl)benzamide

[1269] The title compound (15 mg, 27%) was obtained by performing the same method as in Example 16, except that oxetane-3-ylmethanamine was used as the starting material.

[1270] 1H NMR (500 MHz, CDCl3) δ8.01 (d, J = 2.2 Hz, 1H), 7.81 (dd, J = 8.6, 2.2 Hz, 1H), 7.20 (d, J = 8.6Hz, 1H), 7.07 (d, J = 8.5 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 8.2 Hz, 1H), 6.78 - 6.70 (m, 2H),6.32 - 6.25 (m, 1H), 5.77 (s, 1H), 5.17 (d, J = 15.6 Hz, 1H), 4.85 (dd, J = 7.7, 6.3 Hz, 2H), 4.48 (t, J =6.0 Hz, 2H), 4.42 (d, J = 15.7 Hz, 1H), 4.06 (dd, J = 8.9, 1.8 Hz, 1H), 3.87 (s, 3H), 3.82 - 3.73 (m, 8H),3.52 - 3.41 (m, 2H), 3.30 (p, J = 6.7 Hz, 1H), 2.19 - 2.11 (m, 1H), 1.05 (dd, J = 10.9, 6.8 Hz, 6H).

[1271] LC-MS (ESI) m / z 668.3 [M+1]

[1272]

[1273] Example 46: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-tetrahydrofuran-3-yl)-3-(trifluoromethyl)benzamide

[1274] The title compound (22 mg, 39%) was obtained by performing the same method as in Example 16, except that (S)-tetrahydrofuran-3-amine was used as the starting material.

[1275] 1H NMR (500 MHz, CDCl3) δ8.00 (d, J = 2.2 Hz, 1H), 7.80 (dd, J = 8.6,2.2 Hz, 1H), 7.20 (d, J = 8.7 Hz, 1H), 7.09 - 7.04 (m, 2H), 6.87 - 6.82 (m,2H), 6.80 (d, J = 8.2 Hz, 1H), 6.76 - 6.70 (m, 2H), 6.22 (d, J = 7.5 Hz, 1H),5.77 (s, 1H), 5.17 (d, J = 15.8 Hz, 1H), 4.75 - 4.69 (m, 1H), 4.42 (d, J =15.6 Hz, 1H), 4.06 (dd, J = 8.8, 1.8 Hz, 1H), 4.01 (q, J = 7.9 Hz, 1H), 3.91 -3.87 (m, 4H), 3.85 - 3.76 (m, 8H), 3.51 - 3.42 (m, 2H), 2.41 - 2.34 (m, 1H),2.19 - 2.11 (m, 1H), 1.96 - 1.90 (m, 1H), 1.05 (dd, J = 11.2, 6.8 Hz, 6H).

[1276] LC-MS (ESI) m / z 668.4 [M+1]

[1277]

[1278] Example 47: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-tetrahydrofuran-3-yl)-3-(trifluoromethyl)benzamide

[1279] The title compound (20 mg, 36%) was obtained by performing the same method as in Example 16, except that (R)-tetrahydrofuran-3-amine was used as the starting material.

[1280] 1H NMR (400 MHz, CDCl3) δ8.00 (s, 1H), 7.83 - 7.78 (m, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.07 (d, J = 8.2 Hz, 2H), 6.84 (d, J = 8.1 Hz, 2H), 6.80 (d, J = 8.2 Hz, 1H), 6.76- 6.71 (m, 2H), 6.20 (d, J = 7.5 Hz, 1H), 5.77 (s, 1H), 5.17 (d, J = 15.7 Hz, 1H), 4.72(s, 1H), 4.42 (d, J = 15.8 Hz, 1H), 4.04 (dd, J = 18.3, 8.6 Hz, 2H), 3.89 - 3.84 (m,5H), 3.82 - 3.78 (m, 5H), 3.77 (d, J = 1.1 Hz, 3H), 3.46 (d, J = 5.4 Hz, 1H), 2.42 -2.33 (m, 1H), 2.19 - 2.10 (m, 1H), 1.97 - 1.89 (m, 1H), 1.05 (t, J = 7.8 Hz, 6H).

[1281] LC-MS (ESI) m / z 668.3 [M+1]

[1282]

[1283] Example 48: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide

[1284] The title compound (21 mg, 36%) was obtained by performing the same method as in Example 16, except that 1-(aminomethyl)cyclopentan-1-ol was used as the starting material.

[1285] 1H NMR (500 MHz, CDCl3) δ8.05 (d, J = 2.3 Hz, 1H), 7.83 (dd, J = 8.6, 2.2 Hz, 1H), 7.22 (d, J = 8.7 Hz, 1H), 7.10 - 7.04 (m, 2H), 6.88 - 6.81 (m, 2H), 6.80 (d, J= 8.2 Hz, 1H), 6.75 (dd, J = 8.2, 2.0 Hz, 1H), 6.72 (d, J = 2.0 Hz, 1H), 6.54 (t, J= 5.6 Hz, 1H), 5.78 (s, 1H), 5.17 (d, J = 15.8 Hz, 1H), 4.42 (d, J = 15.7 Hz, 1H),4.06 (dd, J = 8.8, 1.8 Hz, 1H), 3.87 (s, 3H), 3.80 (s, 3H), 3.77 (s, 3H), 3.58 (d, J = 5.7 Hz, 2H), 3.52 - 3.40 (m, 2H), 2.20 - 2.09 (m, 1H), 2.03 (d, J = 8.2 Hz, 1H),1.87 - 1.80 (m, 2H), 1.69 (d, J = 6.4 Hz, 6H), 1.05 (dd, J = 8.4, 6.8 Hz, 6H).

[1286] LC-MS (ESI) m / z 696.3 [M+1]

[1287]

[1288] Example 49: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide

[1289] The title compound (11 mg, 10%) was obtained by performing the same method as in Example 16, except that pyridine-2-ylmethanamine was used as the starting material.

[1290] 1H NMR (500 MHz, DMSO-d6) δ9.30 (t, J = 6.0 Hz, 1H), 8.55 - 8.48 (m, 1H), 8.25 (d, J = 2.2 Hz, 1H), 8.14 (dd, J = 8.7, 2.2 Hz, 1H), 7.81 - 7.72 (m, 1H), 7.60 (d, J = 8.7 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.31 - 7.24 (m, 1H), 7.17 (d, J = 8.5 Hz, 2H), 6.93 - 6.85 (m, 3H), 6.78 - 6.70 (m, 2H), 6.15 (s, 1H), 5.07 (d, J = 15.9 Hz, 1H), 4.58 (d, J = 5.9 Hz, 2H), 4.35 (d, J = 15.8 Hz, 1H), 4.03 (dd, J = 9.0, 1.8 Hz, 1H), 3.73 (s, 6H), 3.65 (s, 3H), 3.45 (d, J = 4.8 Hz, 2H), 2.13 - 2.03 (m, 1H), 0.99 - 0.84 (m, 6H).

[1291] LC-MS (ESI) m / z 689.3 [M+1]

[1292]

[1293] Example 50: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-3-ylmethyl)-3-(trifluoromethyl)benzamide

[1294] The title compound (17 mg, 15%) was obtained by performing the same method as in Example 16, except that pyridine-3-ylmethanamine was used as the starting material.

[1295] 1H NMR (500 MHz, DMSO-d6) δ9.24 (t, J = 5.9 Hz, 1H), 8.56 (d, J = 2.3 Hz, 1H), 8.47 (dd, J = 4.7, 1.7 Hz, 1H), 8.21 (d, J = 2.2 Hz, 1H), 8.10 (dd, J = 8.8, 2.2 Hz, 1H), 7.78 - 7.69 (m, 1H), 7.59 (d, J = 8.7 Hz, 1H), 7.37 (dd, J = 7.8, 4.7 Hz, 1H), 7.17 (d, J = 8.5 Hz, 2H), 6.92 - 6.83 (m, 3H), 6.77 - 6.69 (m, 2H), 6.14 (s, 1H), 5.07 (d, J = 15.9 Hz, 1H), 4.51 (d, J = 5.8 Hz, 2H), 4.35 (d, J = 15.8 Hz, 1H), 4.03 (dd, J = 8.9, 1.8 Hz, 1H), 3.73 (s, 6H), 3.64 (s, 3H), 3.45 (d, J = 4.6 Hz, 2H), 2.15 - 1.99 (m, 1H), 0.91 (dd, J = 6.7, 5.3 Hz, 6H).

[1296] LC-MS (ESI) m / z 689.4 [M+1]

[1297]

[1298] Example 51: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide

[1299] The title compound (10 mg, 9%) was obtained by performing the same method as in Example 16, except that pyridine-4-ylmethanamine was used as the starting material.

[1300] 1H NMR (500 MHz, DMSO-d6) δ9.29 (t, J = 6.0 Hz, 1H), 8.56 - 8.45 (m, 2H), 8.23 ​​(d, J = 2.2 Hz, 1H), 8.12 (dd, J = 8.8, 2.2 Hz, 1H), 7.60 (d, J = 8.7 Hz, 1H), 7.37 - 7.25 (m, 2H), 7.17 (d, J = 8.5 Hz, 2H), 6.93 - 6.85 (m, 3H), 6.78 - 6.67 (m, 2H), 6.14 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.51 (d, J = 5.9 Hz, 2H), 4.36 (d, J = 15.9 Hz, 1H), 4.04 (dd, J = 8.9, 1.8 Hz, 1H), 3.73 (s, 6H), 3.65 (s, 3H), 3.45 (d, J = 4.6 Hz, 2H), 2.15 - 1.99 (m, 1H), 0.99 - 0.81 (m, 6H).

[1301] LC-MS (ESI) m / z 689.3 [M+1]

[1302]

[1303] Example 52: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1-methylazetidin-3-yl)-3-(trifluoromethyl)benzamide

[1304] The title compound (15 mg, 20%) was obtained by performing the same method as in Example 16, except that 1-methylazetidine-3-amine was used as the starting material.

[1305] 1H NMR (500 MHz, CDCl3) δ8.58 (s, 1H), 8.18 (s,1H), 7.98 (d, J = 8.6 Hz, 1H), 7.24 (s, 1H), 7.09 -7.04 (m, 2H), 6.87 - 6.82 (m, 2H), 6.80 (d, J = 8.2 Hz,1H), 6.76 - 6.73 (m, 1H), 6.71 (d, J = 1.9 Hz, 1H),5.80 (s, 1H), 5.17 (d, J = 15.7 Hz, 1H), 4.89 (s, 1H),4.42 (d, J = 15.7 Hz, 1H), 4.09 (dd, J = 8.9, 1.8 Hz,1H), 3.90 - 3.74 (m, 12H), 3.66 (s, 1H), 3.49 - 3.41(m, 2H), 2.55 (s, 3H), 2.18 - 2.12 (m, 1H), 1.06 (dd,J = 9.6, 6.8 Hz, 6H).

[1306] LC-MS (ESI) m / z 667.3 [M+1]

[1307]

[1308] Example 53: Synthesis of (R)-N-((1H-imidazole-4-yl)methyl)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide

[1309] The title compound (32 mg, 28%) was obtained by performing the same method as in Example 16, except that (1H-imidazole-4-yl)methaneamine was used as the starting material.

[1310] 1H NMR (500 MHz, DMSO-d6) δ9.11 - 8.97 (m, 1H), 8.32 (s, 1H), 8.21 (d, J = 2.2 Hz, 1H), 8.13 - 8.07 (m, 1H), 8.01 (d, J = 1.4 Hz, 1H), 7.61 - 7.53 (m, 1H), 7.34 (d, J = 1.3 Hz, 1H), 7.20 - 7.14 (m, 2H), 6.91 - 6.85 (m, 3H), 6.74 (d, J = 7.1 Hz, 2H), 6.15 (s, 1H), 5.07 (d, J) = 15.9 Hz, 1H), 4.45 - 4.29 (m, 3H), 4.05 - 3.97 (m, 1H), 3.73 (s, 6H), 3.65 (s, 3H), 2.48 (s, 2H), 2.12 - 1.99 (m, 1H), 0.97 - 0.83 (m, 6H).

[1311] LC-MS (ESI) m / z 678.3 [M+1]

[1312]

[1313] Example 54: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methyl-1H-imidazole-4-yl)methyl)-3-(trifluoromethyl)benzamide

[1314] The title compound (35 mg, 30%) was obtained by performing the same method as in Example 16, except that (1-methyl-1H-imidazole-4-yl)methaneamine was used as the starting material.

[1315] 1H NMR (500 MHz, DMSO-d6) δ9.01 (t, J = 5.7 Hz, 1H), 8.20 (d, J = 2.4 Hz, 1H), 8.10 (dd, J = 8.7, 2.2 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.49 (s, 1H), 7.17 (d, J = 8.5 Hz, 2H), 6.97 (s, 1H), 6.92 - 6.84 (m, 3H), 6.74 (d, J = 6.8 Hz, 2H), 6.15 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.42 - 4.27 (m, 3H), 4.00 (dd, J = 8.8, 1.8 Hz, 1H), 3.73 (s, 6H), 3.65 (s, 3H), 3.60 (s, 3H), 3.44 (d, J = 5.5 Hz, 2H), 2.12 - 2.01 (m, 1H), 0.97 - 0.82 (m, 6H).

[1316] LC-MS (ESI) m / z 692.4 [M+1]

[1317]

[1318] Example 55: Synthesis of 4-[(2R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-5-[(4-methoxyphenyl)methyl]-2-(1-methylethyl)-3-oxo-2H-pyrazine-1-yl]-N-[[1-(hydroxymethyl)cyclohexyl]methyl]-3-(trifluoromethyl)benzamide

[1319] The title compound (119 mg, 49.21%) was obtained by performing the same method as in Example 16, except that (1-(aminomethyl)cyclohexyl)methanol was used as the starting material.

[1320] 1H NMR (400 MHz, cdcl3) δ8.04 (s, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.09 - 7.06 (m, 2H), 6.85 (d, J = 8.1 Hz, 2H), 6.82 - 6.76 (m, 2H), 6.72 (s, 1H), 6.68 (s, 1H), 5.77 (s, 1H), 5.18 (d, J = 15.7 Hz, 1H), 4.42 (d, J = 15.7 Hz, 1H), 4.04 (s, 1H), 3.87 (s, 3H), 3.80 (s, 3H), 3.76 (s, 3H), 3.47 (d, J = 5.4 Hz, 2H), 3.43 (d, J = 6.7 Hz, 4H), 3.41 - 3.34 (m, 2H), 2.18 - 2.10 (m, 1H), 1.48 (s, 8H), 1.09 - 1.03 (m, 6H).

[1321] LC-MS (ESI) m / z 724.23 [M+1]

[1322]

[1323] Example 56: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1324] The title compound (49 mg, 37.65%) was obtained by performing the same method as in Example 16, except that 2-(1-(aminomethyl)cyclohexyl)ethanol-1-ol was used as the starting material.

[1325] LC-MS (ESI) m / z 738.28 [M+1]

[1326]

[1327] Example 57: Synthesis of 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1328] The title compound (41 mg, 78%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1329] 1 H NMR (400 MHz, DMSO-d6) δ8.59 (t, J = 5.8 Hz, 1H), 8.18 (d, J = 2.3 Hz, 1H), 8.00 (dd, J = 9.0, 2.3 Hz, 1H), 7.33 (dd, J = 14.6, 7.8 Hz, 4H), 7.30 - 7.19 (m, 3H), 6.86 - 6.83 (m, 1H), 6.68 (d, J = 8.4 Hz, 2H), 6.45 (d, J = 1.9 Hz, 1H), 5.01 (d, J = 16.0 Hz, 1H), 4.50 - 4.41 (m, 2H), 3.96 (p, J = 6.2 Hz, 1H), 3.77 (q, J = 7.0 Hz, 2H), 3.71 (s, 3H), 3.62 (d, J = 3.4 Hz, 6H), 3.29 (t, J = 5.4 Hz, 2H), 2.04 - 1.95 (m, 1H), 1.91 (t, J = 4.4 Hz, 1H), 1.82 (q, J = 6.8 Hz, 2H), 0.97 (d, J = 6.7 Hz, 6H).

[1330] LC-MS (ESI) m / z 609.2 [M+1]

[1331]

[1332] Example 58: Synthesis of 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1333] The title compound (52 mg, 45%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1334] 1 H NMR (500 MHz, MeOD) δ8.25 (d, J = 2.2 Hz, 1H), 8.00 (dd, J = 8.9, 2.3 Hz, 1H), 7.44 (d, J = 8.9 Hz, 1H), 7.30 - 7.26 (m, 2H), 7.24 - 7.21 (m, 1H), 7.21 - 7.17(m, 2H), 6.92 (d, J = 8.3 Hz, 1H), 6.86 (dd, J = 8.2, 2.0 Hz, 1H), 6.80 (d, J = 2.0 Hz,1H), 5.44 (d, 1H), 5.16 (d, J = 16.0 Hz, 1H), 4.56 (d, J = 16.0 Hz, 1H), 4.25 (dd, J =9.8, 1.9 Hz, 1H), 4.13 - 4.06 (m, 2H), 3.92 - 3.87 (m, 1H), 3.82 (s, 3H), 3.79 - 3.74(m, 4H), 3.57 (s, 2H), 3.51 - 3.47 (m, 1H), 3.42 - 3.38 (m, 1H), 2.20 - 2.14 (m, 1H),2.06 - 2.00 (m, 2H), 1.97 - 1.89 (m, 2H), 1.68 - 1.62 (m, 1H), 1.08 - 1.03 (m, 6H).

[1335] LC-MS (ESI) m / z 629.3 [M+1]

[1336]

[1337] Example 59: Synthesis of 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1338] The title compound (41 mg, 66%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1339] 1 H NMR (400 MHz, DMSO-d6) δ8.74 (t, J = 5.9 Hz, 1H), 8.18 (d, J = 2.2 Hz, 1H), 8.08 (dd, J = 8.5, 2.2 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.33 (t, J = 7.4 Hz, 2H), 7.28 - 7.21 (m, 3H), 6.88 (d, J = 8.7 Hz, 1H), 6.77 - 6.71 (m, 2H), 6.19 (s, 1H), 5.08 (d, J = 15.9 Hz, 1H), 4.34 (d, J = 15.9 Hz, 1H), 4.01 (dd, J = 8.9, 1.8 Hz, 1H), 3.96 (q, J = 6.2 Hz, 1H), 3.77 (q, J = 7.1 Hz, 1H), 3.73 (s, 3H), 3.64 (s, 4H), 3.56 - 3.46 (m, 2H), 3.32 - 3.28 (m, 2H), 2.05 (q, J = 7.2 Hz, 1H), 1.97 - 1.75 (m, 3H), 1.63 - 1.51 (m, 1H), 0.89 (dd, J = 8.7, 6.7 Hz, 6H).

[1340] LC-MS (ESI) m / z 625.2 [M+1]

[1341]

[1342] Example 60: Synthesis of 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1343] The title compound (50 mg, 87%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine and (R)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1344] 1 H NMR (500 MHz, CDCl3) δ8.05 (d, J = 2.2 Hz, 1H), 7.84 (dd, J = 8.6, 2.2 Hz, 1H), 6.81 (d, J = 8.2 Hz, 1H), 6.75 (dd, J = 8.1, 2.0 Hz, 1H), 6.71 (d, J = 2.0 Hz, 1H), 6.45 (t, J = 5.7 Hz, 1H), 5.81 (s, 1H), 5.18 (d, J = 15.7 Hz, 1H), 4.40 (d, J = 15.8 Hz, 1H), 4.10 - 4.02 (m, 2H), 3.93 - 3.85 (m, 4H), 3.78 (d, J = 10.7 Hz, 6H), 3.57 - 3.45 (m, 2H), 3.31 (ddd, J = 13.7, 7.7, 4.7 Hz, 1H), 2.22 - 2.12 (m, 1H), 2.04 (dq, J = 13.2, 6.7 Hz, 1H), 1.94 (q, J = 7.0 Hz, 2H), 1.05 (dd, J = 8.1, 6.9 Hz, 6H).

[1345] LC-MS (ESI) m / z 652.3 [M+1]

[1346]

[1347] Example 61: Synthesis of (R)-4-(5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1348] The title compound (24 mg, 40%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1349] 1 H NMR (500 MHz, CDCl3) δ8.05 (d, J = 2.2 Hz, 1H), 7.86 - 7.80 (m, 1H), 7.31 (t, J = 7.4 Hz, 2H), 7.25 - 7.20 (m, 2H), 7.16 (d, J = 7.5 Hz, 2H), 6.81 (d, J = 8.1 Hz, 1H), 6.75 (d, J = 8.3 Hz, 1H), 6.71 (s, 1H), 5.81 (s, 1H), 5.18 (d, J = 15.7 Hz, 1H), 4.40 (d, J = 15.9 Hz, 1H), 4.07 (d, J = 8.8 Hz, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 3.51 (dd, J = 12.0, 8.0 Hz, 3H), 2.22 - 2.09 (m, 1H), 1.56 (s, 10H), 1.05 (t, J = 7.4 Hz, 6H).

[1350] LC-MS (ESI) m / z 680.4 [M+1]

[1351]

[1352] Example 62: Synthesis of 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-methyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1353] The title compound (61 mg, 60%) was obtained by performing the same method as in Example 37, except that 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide synthesized in Example 58 was used as the starting material.

[1354] 1 H NMR (500 MHz, CDCl3) δ7.74 (d, J = 27.0 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.31 (dd, J = 8.0, 6.7 Hz, 2H), 7.24 (t, J = 8.4 Hz, 2H), 7.16 (dd, J = 7.0, 1.8 Hz, 2H), 6.80 (d, J = 8.1 Hz, 1H), 6.77 - 6.72 (m, 2H), 5.80 (s, 1H), 5.17 (d, J = 15.7 Hz, 1H), 4.41 (d, J = 15.8 Hz, 1H), 4.15 (d, J = 62.1 Hz, 1H), 4.01 (dd, J = 8.7, 1.8 Hz, 1H), 3.87 (s, 4H), 3.78 (s, 4H), 3.51 (q, J = 16.2 Hz, 2H), 3.33 (d, J = 15.1 Hz, 1H), 3.17 - 3.06 (m, 3H), 2.95 (s, 1H), 2.88 (s, 1H), 2.14 (d, J = 8.6 Hz, 2H), 1.92 (d, J = 6.8 Hz, 2H), 1.05 (dd, J = 6.8, 2.7 Hz, 6H).

[1355] LC-MS (ESI) m / z 666.3 [M+1]

[1356]

[1357] Example 63: Synthesis of N-((3S,5S,7S)-adamantan-1-yl)-4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide

[1358] The title compound (88 mg, 71%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine and (3s,5s,7s)-adamantan-1-amine were used as starting materials.

[1359] 1 H NMR (400 MHz, CDCl3) δ7.96 (d, J = 2.2 Hz, 1H), 7.77 (d, J = 8.5 Hz, 1H), 7.34 - 7.28 (m, 2H), 7.22 (t, J = 8.3 Hz, 2H), 7.18 - 7.13 (m, 2H), 6.80 (s, 1H), 6.78 - 6.70 (m, 2H), 5.81 (s, 1H), 5.70 (s, 1H), 5.18 (d, J = 15.8 Hz, 1H), 4.40 (d, J = 15.7 Hz, 1H), 4.05 (d, J = 8.6 Hz, 1H), 3.87 (d, J = 1.2 Hz, 3H), 3.76 (d, J = 1.2 Hz, 3H), 3.57 - 3.45 (m, 2H), 2.12 (s, 11H), 2.04 (d, J = 1.2 Hz, 1H), 1.73 (s, 7H), 1.04 (t, J = 6.3) Hz, 6H).

[1360] LC-MS (ESI) m / z 702.3 [M+1]

[1361]

[1362] Example 64: Synthesis of N-(((3R,5R,7R)-adamantan-1-yl)methyl)-4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide

[1363] The title compound (91 mg, 73%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-phenylpropane-2-amine and ((3r,5r,7r)-adamantan-1-yl)methaneamine were used as starting materials.

[1364] 1 H NMR (500 MHz, CDCl3) δ8.03 (d, J = 2.3 Hz, 1H), 7.82 (dd, J = 8.6, 2.2 Hz, 1H), 7.31 (t, J = 7.4 Hz, 2H), 7.25 - 7.21 (m, 2H), 7.16 (d, J = 7.5 Hz, 2H), 6.81 (d, J = 8.2 Hz, 1H), 6.77 - 6.74 (m, 1H), 6.72 (d, J = 2.0 Hz, 1H), 6.10 (t, J = 6.4 Hz, 1H), 5.81 (s, 1H), 5.18 (d, J = 15.7 Hz, 1H), 4.41 (d, J = 15.7 Hz, 1H), 4.06 (dd, J = 8.9, 1.8 Hz, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 3.59 - 3.46 (m, 2H), 3.16 (d, J = 6.3 Hz, 2H), 2.19 - 2.09 (m, 1H), 2.00 (d, J = 5.5 Hz, 3H), 1.73 (d, J = 12.4 Hz, 3H), 1.63 (s, 4H), 1.60 (s, 1H), 1.05 (t, J = 6.3 Hz, 6H).

[1365] LC-MS (ESI) m / z 716.3 [M+1]

[1366]

[1367] Example 65: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1368] The title compound (8.3 mg, 7%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propane-2-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1369] 1 H NMR (500 MHz, DMSO-d6) δ8.74 (t, J = 5.8 Hz, 1H), 8.18 (d, J = 2.2 Hz, 1H), 8.08 (dd, J = 8.7, 2.2 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.36 (d, J = 8.7 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 6.87 (d, J = 8.1 Hz, 1H), 6.77 - 6.69 (m, 2H), 6.19 (s, 1H), 5.08 (d, J = 15.9 Hz, 1H), 4.41 (d, J = 15.8 Hz, 1H), 4.03 (dd, J = 8.8, 1.8 Hz, 1H), 4.00 - 3.93 (m, 1H), 3.81 - 3.75 (m, 1H), 3.73 (s, 3H), 3.67 - 3.61 (m, 4H), 3.57 (s, 2H), 3.32 - 3.30 (m, 2H), 2.06 - 1.95 (m, 1H), 1.95 - 1.87 (m, 1H), 1.87 - 1.75 (m, 2H), 1.65 - 1.51 (m, 1H), 0.89 (dd, J = 10.2, 6.8 Hz, 6H).

[1370] LC-MS (ESI) m / z 736.3 [M+1]

[1371]

[1372] Example 66: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1373] The title compound (38 mg, 32%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propan-2-amine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1374] 1 H NMR (500 MHz, DMSO-d6) δ8.41 (t, J = 6.1 Hz, 1H), 8.19 (d, J = 2.2 Hz, 1H), 8.10 (dd, J = 8.6, 2.2 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.36 (d, J = 8.5 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 6.90 - 6.83 (m, 1H), 6.77 - 6.69 (m, 2H), 6.18 (s, 1H), 5.08 (d, J = 15.8 Hz, 1H), 4.41 (d, J = 15.8 Hz, 1H), 4.36 - 4.29 (m, 1H), 4.02 (dd, J = 8.9, 1.8 Hz, 1H), 3.73 (s, 3H), 3.68 (d, J = 6.1 Hz, 1H), 3.64 (s, 3H), 3.57 (s, 1H), 3.27 (d, J = 6.1 Hz, 2H), 2.03 - 1.95 (m, 1H), 1.62 - 1.50 (m, 2H), 1.50 - 1.38 (m, 4H), 1.38 - 1.28 (m, 2H), 1.22 - 1.14 (m, 2H), 0.89 (dd, J = 10.8, 6.8 Hz, 6H).

[1375] LC-MS (ESI) m / z 764.3 [M+1]

[1376]

[1377] Example 67: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide

[1378] The title compound (64 mg, 28%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1,1-dimethoxy-3-(4-(trifluoromethoxy)phenyl)propan-2-amine and 1-(aminomethyl)cyclopentan-1-ol were used as starting materials.

[1379] 1 H NMR (500 MHz, DMSO-d6) δ8.50 (t, J = 6.1 Hz, 1H), 8.19 (d, J = 2.2 Hz, 1H), 8.09 (dd, J = 8.7, 2.2 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.36 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 6.87 (d, J = 8.0 Hz, 1H), 6.73 (d, J = 9.0 Hz, 2H), 6.18 (s, 1H), 5.08 (d, J = 15.9 Hz, 1H), 4.51 (s, 1H), 4.41 (d, J = 15.9 Hz, 1H), 4.03 (dd, J = 8.9, 1.8 Hz, 1H), 3.73 (s, 3H), 3.64 (s, 3H), 3.57 (s, 2H), 3.39 (d, J = 6.0 Hz, 2H), 2.05 - 1.95 (m, 1H), 1.74 - 1.65 (m, 2H), 1.65 - 1.55 (m, 2H), 1.55 - 1.43 (m, 4H), 0.94 - 0.80 (m, 6H).

[1380] LC-MS (ESI) m / z 750.4 [M+1]

[1381]

[1382] Example 68: Synthesis of 4-((R)-5-cyclopropyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1383] The title compound (102 mg, 88%) was obtained by performing the same method as in Example 16, except that 1-cyclopropyl-N-(3,4-dimethoxybenzyl)-2,2-dimethoxyethane-1-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1384] 1 H NMR (500 MHz, DMSO-d6) δ8.72 (t, J = 5.8 Hz, 1H), 8.17 (d, J = 2.2 Hz, 1H), 8.05 (dd, J = 8.7, 2.2 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.82 (d, J = 2.0 Hz, 1H), 6.74 (dd, J = 8.3, 2.0 Hz, 1H), 5.97 (s, 1H), 5.03 (d, J = 15.6 Hz, 1H), 4.90 (d, J = 15.6) Hz, 1H), 4.06 (dd, J = 8.7, 1.8 Hz, 1H), 4.00 - 3.94 (m, 1H), 3.81 - 3.74 (m, 1H), 3.72 (s, 3H), 3.68 (s, 3H), 3.66 - 3.60 (m, 1H), 3.33 - 3.29 (m, 2H), 2.09 - 2.00 (m, 1H), 1.97 - 1.85 (m, 1H), 1.86 - 1.75 (m, 2H), 1.62 - 1.51 (m, 1H), 1.42 - 1.33 (m, 1H), 1.00 (d, J = 6.7 Hz, 3H), 0.93 (d, J = 6.8 Hz, 3H), 0.77 - 0.70 (m, 1H), 0.69 - 0.61 (m, 1H), 0.51 - 0.43 (m, 1H), 0.43 - 0.35 (m, 1H).

[1385] LC-MS (ESI) m / z 602.3 [M+1]

[1386]

[1387] Example 69: Synthesis of (R)-4-(5-cyclopropyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1388] The title compound (105 mg, 86%) was obtained by performing the same method as in Example 16, except that 1-cyclopropyl-N-(3,4-dimethoxybenzyl)-2,2-dimethoxyethane-1-amine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1389] 1 H NMR (500 MHz, DMSO-d6) δ8.39 (t, J = 6.1 Hz, 1H), 8.18 (d, J = 2.2 Hz, 1H), 8.07 (dd, J = 8.7, 2.2 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H), 6.82 (d, J = 2.1 Hz, 1H), 6.74 (dd, J = 8.2, 2.0 Hz, 1H), 5.97 (s, 1H), 5.04 (d, J = 15.6 Hz, 1H), 4.90 (d, J = 15.6 Hz, 1H), 4.35 (s, 1H), 4.06 (dd, J = 8.6, 1.8 Hz, 1H), 3.72 (s, 3H), 3.68 (s, 3H), 3.27 (d, J = 6.1 Hz, 2H), 2.09 - 2.01 (m, 1H), 1.61 - 1.50 (m, 2H), 1.47 - 1.28 (m, 8H), 1.25 - 1.15 (m, 1H), 1.00 (d, J = 6.8 Hz, 3H), 0.94 (d, J = 6.8 Hz, 3H), 0.77 - 0.70 (m, 1H), 0.70 - 0.62 (m, 1H), 0.52 - 0.44 (m, 1H), 0.44 - 0.35 (m, 1H).

[1390] LC-MS (ESI) m / z 630.3 [M+1]

[1391]

[1392] Example 70: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1393] The title compound (11 mg, 9%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(4-methoxyphenyl)ethane-1-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1394] 1 H NMR (400 MHz, CDCl3) δ8.06 (d, J = 2.3 Hz, 1H), 7.81 (dd, J =8.6, 2.3 Hz, 1H), 7.18 - 7.11 (m, 3H), 6.92 - 6.86 (m, 2H), 6.66 (d, J = 8.0 Hz, 1H), 6.52 - 6.44 (m, 3H), 6.04 (s, 1H), 5.15 (d, J = 14.5Hz, 1H), 4.26 (d, J = 14.6 Hz, 1H), 4.14 (dd, J = 8.4, 1.9 Hz, 1H),4.10 - 4.03 (m, 1H), 3.91 - 3.87 (m, 1H), 3.83 (d, J = 4.1 Hz, 6H),3.81 - 3.76 (m, 2H), 3.71 (s, 3H), 3.35 - 3.28 (m, 1H), 2.28 - 2.20(m, 1H), 2.07 - 2.00 (m, 1H), 1.97 - 1.90 (m, 2H), 1.66 - 1.60 (m,2H), 1.20 (d, J = 6.8 Hz, 3H), 1.07 (d, J = 6.9 Hz, 3H).

[1395] LC-MS (ESI) m / z 668.3 [M+1]

[1396]

[1397] Example 71: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1398] The title compound (15 mg, 19%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(4-methoxyphenyl)ethane-1-amine and (R)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1399] 1 H NMR (400 MHz, CDCl3) δ8.06 (d, J = 2.3 Hz, 1H), 7.83 - 7.78 (m, 1H), 7.31 (d, J =8.0 Hz, 1H), 7.15 - 7.12 (m, 2H), 6.89 (d, J = 8.5 Hz, 2H), 6.66 (d, J = 8.1 Hz, 1H), 6.53 -6.48 (m, 2H), 6.04 (s, 1H), 5.15 (d, J = 14.7 Hz, 1H), 4.27 (d, J = 14.6 Hz, 1H), 4.14 (d, J = 8.3 Hz, 1H), 4.06 (dd, J = 7.3, 3.0 Hz, 1H), 3.90 - 3.87 (m, 2H), 3.83 (d, J = 4.1 Hz, 6H),3.78 - 3.75 (m, 2H), 3.71 (s, 3H), 3.36 - 3.29 (m, 1H), 2.30 - 2.23 (m, 1H), 2.09 - 1.99 (m,2H), 1.96 - 1.90 (m, 2H), 1.20 (d, J = 6.7 Hz, 3H), 1.07 (d, J = 6.9 Hz, 3H).

[1400] LC-MS (ESI) m / z 668.4 [M+1]

[1401]

[1402] Example 72: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1403] The title compound (12 mg, 14%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(4-methoxyphenyl)ethane-1-amine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1404] 1 H NMR (400 MHz, CDCl3) δ8.07 (d, J = 2.3 Hz, 1H),7.83 - 7.76 (m, 1H), 7.16 - 7.10 (m, 3H), 6.92 - 6.87 (m,2H), 6.67 (dd, J = 8.2, 2.0 Hz, 1H), 6.53 - 6.49 (m, 2H),6.49 - 6.46 (m, 1H), 6.04 (s, 1H), 5.16 (d, J = 14.6 Hz,1H), 4.26 (d, J = 14.6 Hz, 1H), 4.13 (d, J = 8.4 Hz, 1H),3.86 - 3.81 (m, 6H), 3.70 (s, 3H), 3.50 (dd, J = 6.1, 1.9Hz, 2H), 2.29 - 2.21 (m, 1H), 2.08 - 1.96 (m, 1H), 1.56 -1.49 (m, 8H), 1.38 - 1.33 (m, 1H), 1.20 (dd, J = 6.8, 2.0 Hz, 3H), 1.07 (dd, J = 6.9, 2.0 Hz, 3H).

[1405] LC-MS (ESI) m / z 696.4 [M+1]

[1406]

[1407] Example 73: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1408] The title compound (10 mg, 9%) was obtained by performing the same method as in Example 16, except that 4-(1-((3,4-dimethoxybenzyl)amino)-2,2-dimethoxyethyl)-N,N-dimethylaniline and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1409] 1 H NMR (400 MHz, CDCl3) δ8.05 (s, 1H), 7.78 (d, J = 8.6 Hz, 1H), 7.14 - 7.06 (m, 3H), 6.73 - 6.66 (m, 3H), 6.57 (d, J = 8.3 Hz, 1H), 6.53 (s, 1H), 6.46 - 6.39 (m, 1H), 6.01 (s, 1H), 5.13 (d, J = 14.5 Hz, 1H), 4.32 (d, J= 14.5 Hz, 1H), 4.12 (d, J = 8.5 Hz, 1H), 4.09 - 4.02 (m, 1H), 3.93 - 3.87 (m, 1H), 3.82 (s, 3H), 3.79 (d, J = 7.6 Hz, 2H), 3.71 (s, 3H), 3.37 - 3.28 (m, 1H), 3.01 - 2.96 (m, 6H), 2.30 - 2.20 (m, 1H), 2.07 - 1.99 (m, 1H), 1.93 (p, J = 6.8 Hz, 2H), 1.65 - 1.59 (m, 1H), 1.20 (d, J = 6.7 Hz, 3H), 1.06 (d, J = 6.8 Hz, 3H).

[1410] LC-MS (ESI) m / z 681.3 [M+1]

[1411]

[1412] Example 74: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1413] The title compound (10 mg, 9%) was obtained by performing the same method as in Example 16, except that 4-(1-((3,4-dimethoxybenzyl)amino)-2,2-dimethoxyethyl)-N,N-dimethylaniline and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1414] 1 H NMR (400 MHz, CDCl3) δ8.06 (s, 1H), 7.76 (d, J = 8.7 Hz, 1H), 7.09 (t, J = 9.7 Hz, 3H), 6.74 - 6.66 (m, 3H), 6.59 - 6.52 (m, 2H), 6.51 - 6.45 (m, 1H), 6.01 (s, 1H), 5.14 (d, J = 14.4 Hz, 1H), 4.31 (d, J = 14.4 Hz, 1H), 4.10 (d, J = 8.7 Hz, 1H), 3.82 (s, 3H), 3.70 (s, 3H), 3.49 (d, J = 5.7 Hz, 2H), 2.99 (s, 6H), 2.30 - 2.20 (m, 1H), 2.05 (s, 1H), 1.56 - 1.48 (m, 8H), 1.36 (s, 1H), 1.20 (d, J = 6.6 Hz, 3H), 1.06 (d, J = 6.8 Hz, 3H).

[1415] LC-MS (ESI) m / z 709.4 [M+1]

[1416]

[1417] Example 75: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1418] The title compound (68 mg, 84%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(thiophene-2-yl)ethane-1-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1419] 1 H NMR (400 MHz, CDCl3) δ8.06 (d, J = 2.2 Hz, 1H), 7.85 (dd, J =8.5, 2.2 Hz, 1H), 7.29 (dd, J = 5.2, 1.2 Hz, 1H), 7.22 (d, J = 8.6 Hz, 1H), 6.99 (dd, J = 5.1, 3.5 Hz, 1H), 6.88 (dd, J = 3.6, 1.2 Hz, 1H),6.70 (d, J = 7.9 Hz, 1H), 6.61 - 6.54 (m, 2H), 6.49 (t, 1H), 6.24 (s,1H), 5.17 (d, J = 14.8 Hz, 1H), 4.47 (d, J = 14.8 Hz, 1H), 4.16 (dd,J = 7.9, 1.9 Hz, 1H), 4.10 - 4.03 (m, 1H), 3.92 - 3.87 (m, 1H), 3.83(s, 3H), 3.81 - 3.77 (m, 2H), 3.75 (s, 3H), 3.35 - 3.27 (m, 1H), 2.29 - 2.19 (m, 1H), 2.07 - 2.00 (m, 1H), 1.97 - 1.89 (m, 2H), 1.62 -1.56 (m, 1H), 1.18 (d, J = 6.7 Hz, 3H), 1.08 (d, J = 6.8 Hz, 3H).

[1420] LC-MS (ESI) m / z 644.3 [M+1]

[1421]

[1422] Example 76: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1423] The title compound (67 mg, 83.35%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(thiophene-2-yl)ethane-1-amine and (R)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1424] 1 H NMR (400 MHz, CDCl3) δ8.07 (d, J = 2.2 Hz, 1H), 7.85 (dd, J = 8.4, 2.2 Hz, 1H), 7.29 (d, J = 5.1 Hz, 1H), 7.23 (d, J = 8.6 Hz, 1H), 6.99 (dd, J = 5.2, 3.5 Hz, 1H), 6.88 (d, J = 3.6 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.60 - 6.54 (m, 2H), 6.50 - 6.43 (m, 1H),6.25 (s, 1H), 5.17 (d, J = 14.8 Hz, 1H), 4.47 (d, J = 14.8 Hz, 1H), 4.20 - 4.13 (m, 1H),4.06 (dd, J = 7.2, 3.2 Hz, 1H), 3.92 - 3.86 (m, 1H), 3.86 - 3.81 (m, 4H), 3.80 - 3.77(m, 1H), 3.75 (s, 3H), 3.35 - 3.28 (m, 1H), 2.29 - 2.19 (m, 1H), 2.08 - 2.00 (m, 1H),1.97 - 1.89 (m, 2H), 1.18 (d, J = 6.8 Hz, 3H), 1.08 (d, J = 6.9 Hz, 3H).

[1425] LC-MS (ESI) m / z 644.3 [M+1]

[1426]

[1427] Example 77: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1428] The title compound (67 mg, 80%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-2,2-dimethoxy-1-(thiophene-2-yl)ethanol-1-amine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1429] 1 H NMR (400 MHz, CDCl3) δ8.07 (d, J = 2.2 Hz, 1H), 7.84 (dd, J = 8.5, 2.2 Hz, 1H), 7.29 (dd, J = 5.1, 1.2 Hz, 1H), 7.21 (d, J = 8.6 Hz, 1H), 7.00 (dd, J = 5.1,3.6 Hz, 1H), 6.88 (dd, J = 3.5, 1.2 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.58 (s,1H), 6.56 - 6.52 (m, 1H), 6.25 (s, 1H), 5.17 (d, J = 14.8 Hz, 1H), 4.47 (d, J =14.8 Hz, 1H), 4.15 (dd, J = 8.0, 1.8 Hz, 1H), 3.83 (s, 3H), 3.74 (s, 3H), 3.49 (d,J = 5.8 Hz, 2H), 2.24 (h, J = 6.9 Hz, 1H), 2.08 - 1.96 (m, 1H), 1.57 - 1.44 (m,8H), 1.41 - 1.33 (m, 1H), 1.18 (d, J = 6.7 Hz, 3H), 1.08 (d, J = 6.8 Hz, 3H).

[1430] LC-MS (ESI) m / z 672.4 [M+1]

[1431]

[1432] Example 78: Synthesis of 3-cyano-4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1433] The title compound (48 mg, 64%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-3-(4-fluorophenyl)-1,1-dimethoxypropane-2-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1434] 1 H NMR (500 MHz, DMSO-d6) δ8.58 (t, J = 5.8 Hz, 1H), 8.17 (d, J = 2.2 Hz, 1H), 8.00 (dd, J = 9.0, 2.3 Hz, 1H), 7.36 - 7.28 (m, 3H), 7.14 - 7.10 (m, 2H), 6.85 - 6.82 (m, 1H), 6.68 - 6.65 (m,2H), 6.42 (d, J = 1.8 Hz, 1H), 5.00 (d, J = 16.1 Hz, 1H), 4.51 - 4.44 (m, 2H), 3.96 (p, J = 6.4 Hz, 1H), 3.80 - 3.74 (m, 1H), 3.71 (s, 3H), 3.63 (s, 3H), 3.62 (d, J = 4.2 Hz, 2H), 3.31 - 3.26 (m,2H), 2.00 - 1.93 (m, 1H), 1.92 - 1.87 (m, 1H), 1.85 - 1.77 (m, 2H), 1.62 - 1.51 (m, 2H), 1.00 - 0.94 (m, 6H).

[1435] LC-MS (ESI) m / z 627.4 [M+1]

[1436]

[1437] Example 79: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1438] The title compound (1 mg, 12%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-3-(4-fluorophenyl)-1,1-dimethoxypropane-2-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1439] 1 H NMR (500 MHz, MeOD) δ8.15 (d, J = 2.2 Hz, 1H), 7.91 (dd, J = 8.8, 2.2 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H), 7.11 - 7.05 (m, 2H), 6.92 - 6.85 (m, 2H), 6.81 (d, J = 8.3 Hz, 1H), 6.76 - 6.70 (m, 1H), 6.69 (d, J = 2.0 Hz, 1H), 5.30 (s, 1H), 5.06 (d, J = 16.0 Hz, 1H), 4.48 (d, J = 16.0 Hz, 1H), 4.18 (dd, J = 9.9, 1.9 Hz, 1H), 4.04 - 3.95 (m, 1H), 3.83 - 3.76 (m, 2H), 3.72 (s, 3H), 3.65 (s, 3H), 3.39 (dd, J = 13.7, 4.7 Hz, 1H), 3.30 (dd, J = 13.6, 7.1 Hz, 1H), 2.10 - 2.03 (m, 1H), 1.97 - 1.90 (m, 2H), 1.88 - 1.79 (m, 2H), 0.97 (dd, J = 13.9, 6.8 Hz, 6H).

[1440] LC-MS (ESI) m / z 647.1 [M+1]

[1441]

[1442] Example 80: Synthesis of 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1443] The title compound (12 mg, 34%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-3-(4-fluorophenyl)-1,1-dimethoxypropane-2-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1444] 1 H NMR (500 MHz, DMSO-d6) δ8.73 (t, J = 5.8 Hz, 1H), 8.18 (d, J = 2.3 Hz, 1H), 8.07 (dd, J = 8.7, 2.2 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.31 - 7.24 (m, 2H), 7.17 - 7.10 (m, 2H), 6.90 - 6.84 (m, 1H), 6.76 - 6.71 (m, 2H), 6.16 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.37 (d, J = 15.8 Hz, 1H), 4.01 (dd, J = 8.8, 1.9 Hz, 1H), 3.97 (p, J = 6.3 Hz, 1H), 3.80 - 3.75 (m, 1H), 3.73 (s, 3H), 3.67 - 3.58 (m, 4H), 3.30 (s, 1H), 2.07 - 1.96 (m, 1H), 1.96 - 1.74 (m, 4H), 1.62 - 1.52 (m, 1H), 0.96 - 0.83 (m, 6H).

[1445] LC-MS (ESI) m / z 670.2 [M+1]

[1446]

[1447] Example 81: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1448] The title compound (30 mg, 25%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-3-(4-fluorophenyl)-1,1-dimethoxypropane-2-amine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1449] LC-MS (ESI) m / z 697.3 [M+1]

[1450]

[1451] Example 82: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1452] The title compound (47 mg, 39%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1-(4-fluorophenyl)-2,2-dimethoxyethane-1-amine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1453] 1H NMR (400 MHz, CDCl3) δ8.10 - 8.05 (m, 1H),7.83 (d, J = 8.6 Hz, 1H), 7.20 - 7.12 (m, 3H), 7.08 -7.01 (m, 2H), 6.65 (d, J = 8.2 Hz, 1H), 6.53 - 6.46 (m,2H), 6.41 (d, J = 8.2 Hz, 1H), 6.06 (s, 1H), 5.18 (d, J= 14.7 Hz, 1H), 4.22 (d, J = 14.6 Hz, 1H), 4.17 (d, J =8.3 Hz, 1H), 3.85 - 3.80 (m, 3H), 3.74 - 3.68 (m, 3H),3.50 (d, J = 5.8 Hz, 2H), 2.28 - 2.18 (m, 1H), 1.97 (s,1H), 1.57 - 1.47 (m, 8H), 1.36 (s, 1H), 1.20 (d, J = 6.7Hz, 3H), 1.08 (d, J = 6.9 Hz, 3H).

[1454] LC-MS (ESI) m / z 684.3 [M+1]

[1455]

[1456] Example 83: Synthesis of (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1457] The title compound (23 mg, 19%) was obtained by performing the same method as in Example 16, except that N-(3,4-dimethoxybenzyl)-1-(4-fluorophenyl)-2,2-dimethoxyethane-1-amine and 1-(aminomethyl)-N,N-dimethylcyclohexane-1-amine were used as starting materials.

[1458] 1H NMR (400 MHz, CDCl3) δ8.18 (s, 1H), 7.88 (d, J =8.6 Hz, 1H), 7.21 (d, J = 8.8 Hz, 1H), 7.16 - 7.11 (m, 2H),7.06 - 7.00 (m, 2H), 6.65 (d, J = 8.2 Hz, 1H), 6.48 (s, 1H),6.40 (d, J = 8.0 Hz, 1H), 6.06 (s, 1H), 5.16 (d, J = 14.7Hz, 1H), 4.25 - 4.17 (m, 2H), 4.02 (s, 2H), 3.82 (d, J = 1.0Hz, 3H), 3.71 (d, J = 1.0 Hz, 3H), 3.29 (s, 6H), 2.22 -2.17 (m, 3H), 1.87 - 1.75 (m, 4H), 1.65 - 1.58 (m, 4H),1.19 (d, J = 6.7 Hz, 3H), 1.07 (d, J = 7.0 Hz, 3H).

[1459] LC-MS (ESI) m / z 711.4 [M+1]

[1460]

[1461] Example 84: Synthesis of 4-((R)-5-(4-fluorobenzyl)-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide

[1462] The title compound (39 mg, 70%) was obtained by performing the same method as in Example 16, except that 3-(4-fluorophenyl)-N-((5-fluoropyridine-2-yl)methyl)-1,1-dimethoxypropane-2-amine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1463] 1H NMR (400 MHz, CDCl3) δ8.40 (d, J = 2.7 Hz, 1H), 8.08 (d, J = 2.2 Hz, 1H), 7.88 (d, J = 8.7 Hz, 1H), 7.42 - 7.36 (m, 1H), 7.34 (d, J = 4.5 Hz, 1H), 7.18 - 7.09 (m, 3H), 6.98 (t, J = 8.5 Hz, 2H), 6.40 (s, 1H), 5.36 (d, J = 16.2 Hz, 1H), 5.00 (s, 1H), 4.63 (d, J = 16.3 Hz, 1H), 4.27 (d, J = 9.4 Hz, 1H), 4.04 (d, J = 8.0 Hz, 1H), 3.89 (q, J = 7.2 Hz, 1H), 3.78 (q, J = 7.2 Hz, 2H), 3.56 (s, 2H), 3.34 - 3.24 (m, 1H), 2.15 (d, J = 8.6 Hz, 1H), 2.09 - 1.98 (m, 1H), 1.93 (p, J = 6.9 Hz, 2H), 1.63 (m, 1H), 1.13 - 1.03 (m, 6H).

[1464] LC-MS (ESI) m / z 606.3 [M+1]

[1465]

[1466] Example 85: Synthesis of 4-((R)-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1467] The title compound (7 mg, 4%) was obtained by performing the same method as in Example 16, except that N-((5-fluoropyridine-2-yl)methyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine, and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1468] 1H NMR (500 MHz, DMSO-d6) δ8.69 (t, J = 5.8 Hz, 1H), 8.49 (d, J = 2.9 Hz, 1H), 8.29 (d, J = 2.2 Hz, 1H), 8.01 (dd, J = 8.9, 2.2 Hz, 1H), 7.65 (td, J = 8.8, 3.0 Hz, 1H), 7.54 (d, J = 9.1 Hz, 1H), 7.19 (dd, J = 8.8, 4.4 Hz, 1H), 7.10 (d, J = 8.5 Hz, 2H), 6.81 (d, J = 8.6 Hz, 2H), 5.49 (d, J = 1.7 Hz, 1H), 5.07 (d, J = 16.4 Hz, 1H), 4.60 (d, J = 16.4 Hz, 1H), 4.34 (d, J = 9.8 Hz, 1H), 3.94 (t, J = 6.3 Hz, 1H), 3.78 - 3.73 (m, 1H), 3.70 (s, 3H), 3.61 (q, J = 7.3 Hz, 1H), 3.57 - 3.48 (m, 2H), 3.29 (t, J = 6.1 Hz, 2H), 2.13 - 2.02 (m, 1H), 1.89 (td, J = 13.0, 7.2 Hz, 1H), 1.81 (p, J = 7.6 Hz, 2H), 1.59 - 1.51 (m, 1H), 0.96 (dd, J = 6.8, 5.2 Hz, 6H).

[1469] LC-MS (ESI) m / z 618.2 [M+1]

[1470]

[1471] Example 86: Synthesis of 4-((R)-5-benzyl-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1472] The title compound (30 mg, 42%) was obtained by performing the same method as in Example 16, except that N-((5-fluoropyridine-2-yl)methyl)-1,1-dimethoxy-3-phenylpropane-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1473] 1 H NMR (500 MHz, CDCl3) δ8.40 (d, J = 2.9 Hz, 1H), 8.09 (d, J = 2.1 Hz, 1H), 7.88 (dd, J = 8.9, 2.2 Hz, 1H), 7.39 (td, J = 8.4, 2.9 Hz, 1H), 7.36 - 7.26 (m, 3H), 7.23 (t, J = 7.3 Hz, 5H), 7.15 (t, J = 7.6 Hz, 3H), 6.42 (s, 1H), 5.38 (d, J = 16.3 Hz, 1H), 5.05 (s, 1H), 4.63 (d, J = 16.3 Hz, 1H), 4.27 (d, J = 10.2 Hz, 1H), 4.05 (dd, J = 7.2, 3.0 Hz, 1H), 3.89 (d, J = 7.5 Hz, 1H), 3.79 (t, J = 7.5 Hz, 2H), 3.56 (s, 2H), 3.36 - 3.25 (m, 1H), 2.25 - 2.13 (m, 1H), 2.03 (dd, J = 12.5, 6.5 Hz, 1H), 1.93 (p, J = 7.0 Hz, 2H), 1.14 - 1.01 (m, 6H).

[1474] LC-MS (ESI) m / z 588.1 [M+1]

[1475]

[1476] Example 87: Synthesis of 4-((R)-4-(4-(dimethylamino)benzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1477] The title compound (110 mg, 57%) was obtained by performing the same method as in Example 16, except that 4-(((1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-yl)amino)methyl)-N,N-dimethylaniline, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine, and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1478] 1 H NMR (500 MHz, CDCl3) δ8.09 (d, J = 2.2 Hz, 1H), 7.85 (dd, J = 8.9, 2.2 Hz, 1H), 7.18 - 7.14 (m, 2H), 7.12 (d, J = 8.9 Hz, 1H), 7.08 - 7.04 (m, 2H), 6.87 - 6.81 (m, 2H), 6.75 - 6.69 (m, 2H), 6.39 (d, J = 5.9 Hz, 1H), 5.13 (d, J = 15.8 Hz, 1H), 4.97 (d, J = 2.0 Hz, 1H), 4.54 (d, J = 15.8 Hz, 1H), 4.26 (dd, J = 9.5, 1.9 Hz, 1H), 4.05 (qd, J = 7.2, 3.2 Hz, 1H), 3.89 (dt, J = 8.3, 6.7 Hz, 1H), 3.80 (s, 3H), 3.79 - 3.75 (m, 2H), 3.53 - 3.41 (m, 2H), 3.31 (ddd, J = 13.6, 7.7, 4.7 Hz, 1H), 2.93 (s, 6H), 2.21 - 2.12 (m, 1H), 2.02 (dt, J = 13.1, 6.8 Hz, 1H), 1.92 (q, J = 7.1 Hz, 2H), 1.62 - 1.57 (m, 1H), 1.13 (d, J = 6.8 Hz, 3H), 1.04 (d, J = 6.9 Hz, 3H).

[1479] LC-MS (ESI) m / z 542.3 [M+1]

[1480]

[1481] Example 88: Synthesis of 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-((1-methylpiperidine-4-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1482] The title compound (17 mg, 49%) was obtained by performing the same method as in Example 16, except that 1,1-dimethoxy-3-(4-methoxyphenyl)-N-((1-methylpiperidin-4-yl)methyl)propane-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1483] 1 H NMR (500 MHz, CDCl3) δ8.08 (t, J = 2.0 Hz, 1H), 7.85 (dd, J = 8.8, 2.3 Hz, 1H), 7.10 (dd, J = 8.8, 5.7 Hz, 3H), 6.86 (d, J = 8.6 Hz, 2H), 6.40 (t, J = 5.8 Hz, 1H), 4.99 (s, 1H), 4.19 (dd, J = 9.5, 1.9 Hz, 1H), 4.08 - 3.98 (m, 2H), 3.89 (dt, J = 8.4, 6.7 Hz, 1H), 3.80 (s, 3H), 3.77 (dt, J = 6.7, 2.3 Hz, 1H), 3.57 - 3.45 (m, 2H), 3.30 (dt, J = 12.4, 6.9 Hz, 1H), 3.13 (dd, J = 13.9, 5.6 Hz, 1H), 2.89 (dd, J = 32.4, 11.3 Hz, 2H), 2.29 (s, 3H), 2.06 - 1.98 (m, 4H), 1.93 (p, J = 7.0 Hz, 4H), 1.60 (dt, J = 12.1, 7.8 Hz, 2H), 1.40 (dd, J = 24.2, 11.8 Hz, 2H), 1.06 (d, J = 6.7 Hz, 3H), 1.01 (d, J = 6.8 Hz, 3H).

[1484] LC-MS (ESI) m / z 620.2 [M+1]

[1485]

[1486] Example 89: Synthesis of 4-((R)-4-((1-ethylpiperidine-4-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1487] The title compound (18 mg, 22%) was obtained by performing the same method as in Example 16, except that N-((1-ethylpiperidine-4-yl)methyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1488] 1 H NMR (500 MHz, CDCl3) δ8.08 (t, J = 1.9 Hz, 1H), 7.85 (dd, J = 8.9, 2.1 Hz, 1H), 7.10 (dd, J = 8.8, 5.0 Hz, 3H), 6.88 - 6.83 (m, 2H), 6.39 (d, J = 6.5 Hz, 1H), 4.99 (s, 1H), 4.22 - 4.17 (m, 1H), 4.03 (ddt, J = 17.6, 14.0, 7.7 Hz, 2H), 3.93 - 3.85 (m, 1H), 3.80 (s, 3H), 3.77 (dd, J = 8.0, 6.5 Hz, 2H), 3.58 - 3.45 (m, 3H), 3.30 (ddd, J = 13.7, 7.8, 4.6 Hz, 1H), 3.13 (dd, J = 14.0, 5.8 Hz, 1H), 2.97 (s, 1H), 2.07 - 2.01 (m, 2H), 1.93 (p, J = 7.1 Hz, 4H), 1.83 (s, 8H), 1.60 (dt, J = 12.2, 7.7 Hz, 2H), 1.06 (d, J = 6.7 Hz, 3H), 1.01 (d, J = 6.9 Hz, 3H).

[1489] LC-MS (ESI) m / z 634.3 [M+1]

[1490]

[1491] Example 90: Synthesis of 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1492] The title compound (45 mg, 33%) was obtained by performing the same method as in Example 16, except that 1,1-dimethoxy-3-(4-methoxyphenyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)propane-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1493] 1H NMR (500 MHz, CDCl3) δ8.08 (d, J = 2.2 Hz, 1H), 7.86 (dd, J = 8.9, 2.2 Hz, 1H), 7.11 (t, J = 9.0 Hz, 3H), 6.89 - 6.84 (m, 2H), 6.41 (t, J = 5.7 Hz, 1H), 5.00 (d, J = 1.6 Hz, 1H), 4.19 (dd, J = 9.6, 1.8 Hz, 1H), 4.12 (q, J = 7.1 Hz, 1H), 4.07 - 3.98 (m, 3H), 3.92 (dd, J = 10.0, 7.6 Hz, 1H), 3.90 - 3.86 (m, 1H), 3.80 (s, 3H), 3.79 - 3.75 (m, 2H), 3.58 - 3.46 (m, 2H), 3.40 (ddd, J = 11.9, 10.3, 6.5 Hz, 2H), 3.29 (ddd, J = 13.9, 7.8, 4.6 Hz, 1H), 3.13 (dd, J = 14.1, 5.5 Hz, 1H), 2.10 - 1.99 (m, 4H), 1.92 (p, J = 6.9 Hz, 4H), 1.67 (t, J = 10.4 Hz, 2H), 1.06 (d, J = 6.7) Hz, 3H), 1.01 (d, J = 6.9 Hz, 3H).

[1494] LC-MS (ESI) m / z 607.3 [M+1]

[1495]

[1496] Example 91: Synthesis of 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-(4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1497] Except for using N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine as starting materials, the same method as in Example 1 was performed to obtain 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; then, 16 mg (0.026 mmol) of this was taken and dissolved in tetrahydrofuran (2 mL), and then 1-bromo-2-(2-(2-methoxyethoxy)ethoxy)ethane (8.87 mg, 0.039 mmol) and 60% sodium hydride (1.56 mg, 0.065 mmol) were added and stirred at room temperature for 3 hours. When the reaction was complete, the reaction mixture was washed with an aqueous solution of saturated sodium bicarbonate and an aqueous solution of saturated sodium chloride. The separated organic layer was dried with anhydrous sodium sulfate, concentrated by filtration and vacuum distillation, and purified by MPLC (dichloromethane:methanol = 9:1, v / v) to obtain the title compound (8 mg, 39%).

[1498] 1H NMR (500 MHz, CDCl3) δ8.09 (d, J = 2.2 Hz, 1H), 7.86 (dd, J = 8.9, 2.2 Hz, 1H), 7.18 (d, J = 8.6 Hz, 2H), 7.12 (d, J = 9.0 Hz, 1H), 7.07 - 7.03 (m, 2H), 6.90 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H), 6.40 (t, J = 5.6 Hz, 1H), 5.19 (d, J = 16.0 Hz, 1H), 4.98 (s, 1H), 4.51 (d, J = 15.9 Hz, 1H), 4.27 (dd, J = 9.3, 1.8 Hz, 1H), 4.12 (td, J = 4.7, 2.4 Hz, 2H), 4.04 (tt, J = 7.3, 3.7 Hz, 1H), 3.89 (dt, J = 8.4, 6.7 Hz, 1H), 3.85 (t, J = 4.9 Hz, 2H), 3.79 (s, 3H), 3.77 (dd, J = 4.3, 2.4 Hz, 1H), 3.74 (dd, J = 5.8, 3.5 Hz, 2H), 3.70 - 3.68 (m, 1H), 3.68 - 3.64 (m, 2H), 3.57 - 3.53 (m, 2H), 3.49 - 3.40 (m, 2H), 3.38 (s, 3H), 3.30 (ddd, J = 13.8, 7.7, 4.7 Hz, 1H), 2.17 (dq, J = 14.3, 6.8 Hz, 1H), 2.03 (dq, J = 12.9, 6.8 Hz, 2H), 1.93 (p, J = 6.9 Hz, 2H), 1.66 - 1.58 (m, 2H), 1.12 (d, J = 6.7 Hz, 3H), 1.04 (d, J = 6.9 Hz, 3H).

[1499] LC-MS (ESI) m / z 761.3 [M+1]

[1500]

[1501] Example 92: Synthesis of 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-(4-(3-morphorinopropoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1502] Except for using N-(4-((tert-butyldiphenylsilyl)oxy)benzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine and (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine as starting materials, the same method as in Example 1 was performed to obtain 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; then, 50 mg (0.081 mmol) of this was taken and dissolved in dimethylformamide (3 mL), and then 4-(3-chloropropyl)morpholine (16.30 mg, 0.098 mmol) and Anhydrous potassium carbonate (45.20 mg, 0.325 mmol) was added and stirred at 100°C for 4 hours. When the reaction was complete, the reaction mixture was washed with a saturated aqueous sodium chloride solution. The separated organic layer was dried with anhydrous sodium sulfate, concentrated by filtration and vacuum distillation, and purified by MPLC (dichloromethane:methanol = 9:1, v / v) to obtain the title compound (30 mg, 95%).

[1503] 1H NMR (500 MHz, DMSO-d6) δ8.69 (t, J = 5.9 Hz, 1H), 8.30 (d, J = 2.1 Hz, 1H), 8.02 (dd, J = 9.0, 2.2 Hz, 1H), 7.55 (d, J = 9.0 Hz, 1H), 7.15 (dd, J = 13.9, 8.3 Hz, 4H), 6.87 (dd, J = 8.6, 3.5 Hz, 4H), 5.46 (s, 1H), 5.04 (d, J = 16.0 Hz, 1H), 4.42 (d, J = 15.9 Hz, 1H), 4.34 (d, J = 9.9 Hz, 1H), 4.03 - 3.93 (m, 3H), 3.81 - 3.74 (m, 1H), 3.73 (s, 3H), 3.63 (q, J = 7.3 Hz, 2H), 3.57 (t, J = 4.7 Hz, 4H), 3.44 (d, J = 4.4 Hz, 3H), 2.41 (t, J = 7.1 Hz, 1H), 2.36 (s, 3H), 2.08 - 1.98 (m, 2H), 1.95 - 1.74 (m, 6H), 1.62 - 1.48 (m, 1H), 0.97 (dd, J = 14.9, 6.8 Hz, 6H).

[1504] LC-MS (ESI) m / z 742.5 [M+1]

[1505]

[1506] Example 93: Synthesis of (R)-4-(4-(3-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide

[1507] The title compound (29 mg, 58%) was obtained by performing the same method as in Example 1, except that N-(3-((tert-butyldiphenylsilyl)oxy)benzyl-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1508] 1 H NMR (400 MHz, CDCl3) δ8.04 (d, J = 2.1 Hz, 1H), 7.84 (dd, J = 9.0, 2.2 Hz, 1H), 7.21 (t, J = 7.7 Hz, 1H), 7.09 (d, J = 8.9 Hz, 1H), 7.02 (d, J) = 8.2 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 6.81 - 6.75 (m, 3H), 6.66 (t, J = 5.7 Hz, 1H), 5.93 (s, 1H), 5.40 (d, J = 16.4 Hz, 1H), 5.04 (s, 1H), 4.37 (d, J = 16.5 Hz, 1H), 4.34 - 4.27 (m, 1H), 3.79 (d, J = 0.9 Hz, 3H), 3.48 (q, J = 7.2, 6.4 Hz, 2H), 3.43 - 3.32 (m, 2H), 2.27 (s, 1H), 2.18 (dt, J = 15.7, 7.4 Hz, 1H), 1.50 (d, J = 10.9 Hz, 9H), 1.40 - 1.28 (m, 2H), 1.12 (d, J = 6.7 Hz, 3H), 1.04 (d, J = 6.8 Hz, 3H).

[1509] LC-MS (ESI) m / z 643.3 [M+1]

[1510]

[1511] Example 94: Synthesis of (R)-4-(4-(3-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide

[1512] The title compound (23 mg, 62%) was obtained by performing the same method as in Example 1, except that N-(3-((tert-butyldiphenylsilyl)oxy)benzyl-1,1-dimethoxy-3-(4-methoxyphenyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-(trifluoromethyl)phenyl)-D-valine and 1-(aminomethyl)cyclohexane-1-ol were used as starting materials.

[1513] 1 H NMR (400 MHz, CDCl3) δ8.04 (d, J = 2.1 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.17 (dd, J = 14.0, 7.9 Hz, 2H), 7.07 (d, J = 8.3 Hz, 2H), 6.84 (d, J = 8.2 Hz, 2H), 6.73 (t, J = 8.9 Hz, 2H), 6.64 (s, 2H), 5.79 (s, 2H), 5.26 (d, J = 16.0 Hz, 1H), 4.31 (d, J = 16.0 Hz, 1H), 4.04 (d, J = 8.9 Hz, 1H), 3.84 - 3.76 (m, 3H), 3.48 (d, J = 5.8 Hz, 2H), 3.44 - 3.41 (m, 2H), 2.26 (s, 1H), 2.15 (dt, J = 14.8, 7.1 Hz, 2H), 1.58 - 1.47 (m, 8H), 1.33 (d, J = 18.8 Hz, 2H), 1.05 (d, J = 6.8 Hz, 6H).

[1514] LC-MS (ESI) m / z 666.4 [M+1]

[1515]

[1516] Example 95: Synthesis of 4-((R)-4-(3-hydroxy-4-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1517] The title compound (5 mg, 11%) was obtained by performing the same method as in Example 1, except that N-(3-((tert-butyldiphenylsilyl)oxy)benzyl)-4-methoxybenzyl)-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1518] 1 H NMR (500 MHz, CDCl3) δ8.08 (d, J = 2.1 Hz, 1H), 7.85 (dd, J = 8.8, 2.2 Hz, 1H), 7.11 (d, J = 8.9 Hz, 1H), 7.05 (d, J = 8.3 Hz, 2H), 6.82 (ddd, J = 7.6, 5.4, 2.7 Hz, 4H), 6.76 (dd, J = 8.3, 2.2 Hz, 2H), 6.48 (s, 1H), 5.71 (s, 1H), 5.20 (d, J = 16.1 Hz, 1H), 5.00 (s, 1H), 4.42 (d, J = 16.1 Hz, 1H), 4.27 (dd, J = 9.6, 2.0 Hz, 1H), 4.04 (qd, J = 7.2, 3.2 Hz, 2H), 3.94 - 3.83 (m, 5H), 3.78 (s, 3H), 3.76 (dd, J = 6.5, 3.0 Hz, 2H), 3.42 (q, J = 16.5 Hz, 2H), 3.29 (ddd, J = 18.1, 8.7, 5.0 Hz, 2H), 1.92 (p, J = 7.0 Hz, 3H), 1.12 (s, 2H), 1.04 (s, 2H), 0.89 - 0.86 (m, 6H).

[1519] LC-MS (ESI) m / z 645.6 [M+1]

[1520]

[1521] Example 96: Synthesis of 4-((R)-5-benzyl-2-isopropyl-3-oxo-4-(pyridine-2-ylmethyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1522] The title compound (5 mg, 11%) was obtained by performing the same method as in Example 16, except that 1,1-dimethoxy-3-phenyl-N-(pyridine-2-ylmethyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-nitrophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1523] 1 H NMR (500 MHz, CDCl3) δ8.55 (dd, J = 5.0, 1.4 Hz, 1H), 8.10 (d, J = 2.1 Hz, 1H), 7.69 (td, J = 7.7, 1.8 Hz, 1H), 7.33 - 7.27 (m, 2H), 7.24 - 7.18 (m, 2H), 7.17 - 7.13 (m, 3H), 6.51 (d, J = 6.0 Hz, 1H), 5.43 (d, J = 16.6 Hz, 1H), 5.04 (s, 1H), 4.67 (d, J = 16.6 Hz, 1H), 4.30 (dd, J = 9.4, 1.9 Hz, 1H), 4.05 (qd, J = 7.2, 3.0 Hz, 1H), 3.89 (dt, J = 8.8, 6.7 Hz, 1H), 3.78 (ddt, J = 13.0, 6.7, 3.2 Hz, 3H), 3.53 (d, J = 3.7 Hz, 2H), 3.30 (ddd, J = 13.0, 7.7, 4.5 Hz, 1H), 2.24 - 2.12 (m, 2H), 2.03 (dt, J = 13.0, 6.6 Hz, 2H), 1.93 (p, J = 7.1 Hz, 3H), 1.64 - 1.57 (m, 1H), 1.49 (dd, J = 11.3, 6.6 Hz, 2H), 1.11 (d, J = 6.8 Hz, 3H), 1.05 (d, J = 6.8 Hz, 3H).

[1524] LC-MS (ESI) m / z 570.1 [M-1]

[1525]

[1526] Example 97: Synthesis of 4-((R)-5-benzyl-2-isopropyl-3-oxo-4-(pyridine-2-ylmethyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide

[1527] The title compound (3.2 mg, 14%) was obtained by performing the same method as in Example 16, except that 1,1-dimethoxy-3-phenyl-N-(pyridine-2-ylmethyl)propan-2-amine, (4-(tert-butoxycarbonyl)-2-cyanophenyl)-D-valine and (S)-(tetrahydrofuran-2-yl)methaneamine were used as starting materials.

[1528] LC-MS (ESI) m / z 548.1 [M-1]

[1529]

[1530] Example 98: Synthesis of (R)-4-(4-benzyl-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid

[1531] The title compound (200.6 mg, 34.4%) was obtained by performing the same method as steps (a) through (c) of Example 16, except that N-benzyl-1,1-dimethoxy-3-(4-methoxyphenyl)propane-2-amine and (4-(tert-butoxycarbonyl)-2-cyanophenyl)-D-valine were used as starting materials.

[1532] LC-MS (ESI) m / z 495.17 [M+1]

[1533]

[1534] Example 98-1: Synthesis of 4-((R)-4-benzyl-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl...

Claims

1. A compound of the following chemical formula 1, or a pharmaceutically acceptable salt or isomer thereof: [Chemical Formula 1] In the above chemical formula 1, R1 is an alkyl, hydroxyalkyl, cycloalkyl, aryl, heteroaryl, aryl-alkyl, heteroaryl-alkyl, heterocycloalkyl-alkyl, or partially unsaturated heterocyclyl-alkyl; Herein, the alkyl, cycloalkyl, aryl, and heteroaryl are hydroxy, halo, amino, carboxy(-COOH), alkyl, alkenyl, alkynyl, alkoxy, alkylthio, hydroxyalkyl, hydroxycycloalkyl, haloalkyl, cyanoalkyl, haloalkoxy, alkoxy-alkyl, alkoxy-alkoxy, alkyl-phosphine oxide, dialkylamino, dialkylaminoalkoxy, dialkylaminoalkoxyalkyl, dialkylaminoalkoxy-alkoxyalkyl, alkylsulfonyl, alkylsulfonylamino, heterocycloalkyl-alkoxy, heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl, alkyl-substituted heterocycloalkyl-alkoxy, alkyl-substituted heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl carbonyl, It may be optionally substituted with one or more substituents selected from the group consisting of alkoxy-alkoxy-alkoxy-alkoxy, alkoxy-alkoxy-alkoxy-alkoxy-alkoxy, alkoxy-alkoxy-alkoxy-alkoxyalkyl, dialkylaminoalkylcarbonyloxyalkyl, phosphonoalkylcarbonylalkoxyalkyl, dihydrogen phosphate-alkyl, dihydrogen phosphate-alkylcarbonyloxyalkyl, dihydrogen phosphate-alkoxyalkyl, diaminooxyphosphoryloxy-alkoxycarbonyloxyalkyl, disodium oxyphosphoryloxy-alkoxycarbonyloxyalkyl, and heteroaryl;The above heterocycloalkyl and partially unsaturated heterocyclyl are hydroxy, halo, amino, carboxy, oxo, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, hydroxyalkyl, hydroxycycloalkyl haloalkyl, cyanoalkyl, haloalkoxy, alkoxy-alkoxy, dialkylamino, dialkylaminoalkoxy, dialkylaminoalkoxyalkyl, dialkylaminoalkoxy-alkoxyalkyl, alkylsulfonyl, alkylsulfonylamino, heterocycloalkyl-alkoxy, heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl, alkyl-substituted heterocycloalkyl-alkoxy, alkyl-substituted heterocycloalkyl-alkoxy, alkoxy-alkoxy-alkoxy-alkoxy, alkoxy-alkoxy-alkoxy-alkoxy-alkoxyalkyl, alkoxy-alkoxy-alkoxy-alkoxy-alkoxyalkyl, It may optionally be substituted with one or more substituents selected from the group consisting of dialkylaminoalkylcarbonyloxyalkyl, dihydrogen phosphate-alkyl, dihydrogen phosphate-alkylcarbonyloxyalkyl, and heteroaryl; R2 is -H, alkyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl-alkyl, or aryl-alkyl; Herein, the cycloalkyl, aryl, heteroaryl, and heterocycloalkyl are hydroxy, halo, amino, carboxy, alkyl, alkoxy, deuterium alkoxy, hydroxyalkyl, haloalkyl, haloalkoxy, dialkylamino, dialkylaminoalkyl, dialkylaminoalkoxyalkyl, azide, amide, alkyl-substituted heterocycloalkyl, heterocycloalkyl-alkyl, heterocycloalkyl-alkoxy, heterocycloalkyl-amino, heterocycloalkyl-aminoalkyl, alkyl-substituted heterocycloalkyl-oxy-alkyl, oxo-substituted heterocycloalkyl-aminoalkyl, alkyl-substituted heterocycloalkyl-aminoalkyl, heterocycloalkyl-alkoxyalkyl, alkyl-substituted heterocycloalkyl-alkoxyalkyl, carboxy-substituted heterocycloalkyl-alkyl, alkyl-substituted heterocycloalkyl-alkyl, It may optionally be substituted with one or more substituents selected from the group consisting of alkylsulfonyl-substituted heterocycloalkyl-alkyl, heteroaryl, and alkyl-substituted heteroaryl-alkylaminoalkyl; R3 is hydroxy, cyano(-CN), nitro(-NO2), alkyl, alkoxy, haloalkyl, amino, alkylamino, dialkylamino, carboxy, or alkoxycarbonyl; L is a direct bond, alkylene, haloalkylene, -C(=O)-, -C(=O)O-, -CH2NRa-, -C(=O)NRa-, or -NRaC(=O)-; where Ra is -H, alkyl, or dialkylaminoalkyl; R4 is hydroxy, halo, cyano, amino, carboxy, alkyl, hydroxyalkyl, haloalkyl, carboxyalkyl, alkoxy, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, alkyl-substituted phosphonate, dihydrogen phosphite, aryl, heteroaryl, partially unsaturated heterocycloyl, aryl-alkyl, heterocycloalkyl-alkyl, heteroaryl-alkyl, alkylamino, dialkylamino, dialkylaminoalkyl, arylamino, alkylcarbonylamino, arylcarbonylamino, alkylsulfonylamino, arylsulfonylamino, or -BR6R7; wherein R6 and R7 are each independently hydroxyl, or R6 and R7 may form an alkyl-substituted heterocycloalkyl with a boron (B) atom to which they are connected and bonded; The above alkyl, cycloalkyl, heterocycloalkyl and partially unsaturated heterocyclyl are cycloalkyl, heterocycloalkyl, alkoxy, hydroxyalkyl, haloalkyl, carboxyalkyl, aminoalkyl, haloalkoxy, dialkylamino, aminocarbonyl, aryl, aryl-alkylcarbonyl, alkyl-carbonyloxy, alkylaminocarbonyloxy, aminoalkylcarbonyloxy, aminoalkylcarbonyloxy-alkyl, dialkylaminoalkylcarbonyloxy-alkyl, alkylaminoalkylcarbonyloxy-alkyl, guanidino, alkylcarbonyloxy-alkyl, aminocarbonyl, and alkylcarbonyloxy-alkyl substituted with amino, alkylcarbonyloxy-alkyl substituted with amino, alkylcarbonyloxy-alkyl substituted with amino, guanidino, and amino substituted with amino, aminocarbonyl and amino substituted with alkylcarbonyloxy-alkyl, Carboxyalkylcarbonyloxy-alkyl, carboxyalkoxycarbonyloxy-alkyl, carboxyalkoxyalkoxyalkoxyalkylcarbonyloxy-alkyl, heteroaryl-carbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl, dihydrogenphosphate-alkyl, alkoxycarbonylalkylaminocarbonyloxy-alkyl, (alkylaminoalkyl)(alkyl)aminocarbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-carbonyloxy-alkyl, aminosulfonyloxy-alkyl, alkoxy-alkoxycarbonyloxy-alkyl, dialkylaminoalkoxycarbonyloxy-alkyl,Dialkylaminothiocarbonyloxy-alkyl, alkylaminothiocarbonyloxy-alkyl, dialkylaminocarbonyloxy-alkyl, sodium oxycarbonylalkoxycarbonyloxy-alkyl, phosphonoalkylcarbonyloxy-alkyl, dihydrogenphosphatealkylcarbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl, alkoxycarbonyl-substituted heterocycloalkyl-carbonyloxy-alkyl, heterocycloalkyl-alkoxy-alkyl, alkyl-substituted heterocycloalkyl-alkoxy-alkyl, heterocycloalkyl-alkoxy-carbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-alkoxy-carbonyloxy-alkyl, heterocycloalkyl-alkylaminocarbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-alkylaminocarbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-alkylaminocarbonyloxy-alkyl, (alkyl-substituted It may optionally be substituted with one or more substituents selected from the group consisting of heterocycloalkyl-alkyl)(alkyl)aminocarbonyloxy-alkyl, and heterocycloalkyl-oxy-alkyl substituted with carboxyl and hydroxyl; The above aryl and heteroaryl are hydroxy, halo, amino, oxide, carboxy, alkyl, alkoxy, hydroxyalkyl, haloalkyl, carboxyalkyl, aminoalkyl, haloalkoxy, dialkylamino, aminocarbonyl, aryl, aryl-alkylcarbonyl, amino-substituted alkyl-carbonyloxy, alkylaminocarbonyloxy, aminoalkylcarbonyloxy, dialkylaminoalkylcarbonyloxy-alkyl, amino-substituted alkylcarbonyloxy-alkyl, heteroaryl-carbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl, dihydrogenphosphate-alkyl, alkoxycarbonylalkylaminocarbonyloxy-alkyl, (alkylaminoalkyl)(alkyl)aminocarbonyloxy-alkyl, alkyl-substituted heterocycloalkyl-carbonyloxy-alkyl, aminosulfonyloxy-alkyl, alkoxy-alkoxycarbonyloxy-alkyl, Dialkylaminothiocarbonyloxy-alkyl, alkylaminothiocarbonyloxy-alkyl, dialkylaminocarbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl, heterocycloalkyl-carbonyloxy-alkyl substituted with alkoxycarbonyl, heterocycloalkyl-alkoxy-alkyl, heterocycloalkyl-alkoxy-carbonyloxy-alkyl,It may optionally be substituted with one or more substituents selected from the group consisting of heterocycloalkyl-alkylaminocarbonyloxyalkyl, and heterocycloalkyl-oxyalkyl substituted with carboxyl and hydroxyl; n is 1 or 2, and; R5 is -H, alkyl, hydroxyalkyl, cycloalkyl, cycloalkyl-alkyl, or aryl-alkyl; when m is 2, two R5s may be connected to each other to form a cycloalkyl group with a bonded carbon atom; wherein the aryl group may optionally be substituted with one or more substituents selected from the group consisting of halo, alkyl, and alkoxy; m is 1 or 2, and; The above heterocycloalkyl, partially unsaturated heterocyclyl, and heteroaryl have one or more heteroatoms selected from N, O, and S; However, if R1 is a benzyl substituted with one hydroxyl and R3 is a nitro, R4 is not an alkyl or heterocycloalkyl-alkyl.

2. In Paragraph 1, R1 is a C1-C7 alkyl, hydroxy-C1-C7 alkyl, C3-C 12 Cycloalkyl, C6-C 10 Aryl, 5 to 10-membered heteroaryl, C6-C 10 aryl-C1-C7 alkyl, 5 to 10-membered heteroaryl-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkyl, or partially unsaturated 3 to 10-membered heterocycloalkyl-C1-C7 alkyl; wherein the alkyl, cycloalkyl, aryl, and heteroaryl are hydroxy, halo, amino, carboxyl, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 alkoxy, C1-C7 alkylthio, hydroxy-C1-C7 alkyl, hydroxy-C3-C 12 Cycloalkyl, halo-C1-C7alkyl, cyano-C1-C7alkyl, halo-C1-C7alkoxy, C1-C7alkoxy-C1-C7alkyl, C1-C7alkoxy-C1-C7alkoxy, C1-C7alkyl-phosphine oxide, di(C1-C7alkyl)amino, di(C1-C7alkyl)amino-C1-C7alkoxy, di(C1-C7alkyl)amino-C1-C7alkoxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkoxy-C1-C7alkyl, C1-C7alkylsulfonyl, C1-C7alkylsulfonylamino, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy, 3 to 10-membered Heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkylcarbonyl substituted with C1-C7 alkyl, C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy, C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy, C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkyl, di(C1-C7 alkyl)amino-C1-C7 alkylcarbonyloxy-C1-C7 alkyl, phosphono-C1-C7 alkylcarbonyl-C1-C7 alkoxy-C1-C7 alkyl, dihydrogen phosphate-C1-C7 alkylcarbonyloxy-C1-C7 alkyl, dihydrogen phosphate-C1-C7 alkoxy-C1-C7 alkyl, diaminooxyphosphoryloxy-C1-C7 alkoxycarbonyloxy-C1-C7 alkyl, disodium oxyphosphoryloxy-C1-C7 alkoxycarbonyloxy-C1-C7 alkyl and 5 to 10 It can be optionally substituted with 1 to 4 substituents selected from the heteroaryl group;The above heterocycloalkyl and partially unsaturated heterocyclyl are hydroxy, halo, amino, carboxy, oxo, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C1-C7 alkoxy, C1-C7 alkylthio, hydroxy-C1-C7 alkyl, hydroxy-C3-C; 12 Cycloalkyl, halo-C1-C7alkyl, cyano-C1-C7alkyl, halo-C1-C7alkoxy, C1-C7alkoxy-C1-C7alkyl, C1-C7alkoxy-C1-C7alkoxy, C1-C7alkyl-phosphine oxide, di(C1-C7alkyl)amino, di(C1-C7alkyl)amino-C1-C7alkoxy, di(C1-C7alkyl)amino-C1-C7alkoxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkoxy-C1-C7alkyl, C1-C7alkylsulfonyl, C1-C7alkylsulfonylamino, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy, 3 to 10-membered Heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl substituted with C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy substituted with C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with C1-C7alkyl, C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy, C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkoxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkylcarbonyloxy-C1-C7alkyl, It may optionally be substituted with one to four substituents selected from the group consisting of dihydrogen phosphate-C1-C7alkyl, dihydrogen phosphate-C1-C7alkylcarbonyloxy-C1-C7alkyl, and 5 to 10-membered heteroaryls; R2 is hydrogen, C1-C7 alkyl, C2-C7 alkynyl, C3-C 12 Cycloalkyl, C6-C 10 Aryl, 5 to 10-membered heteroaryl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl or C6-C 10 It is an aryl-C1-C7 alkyl; Herein, the cycloalkyl, aryl, heteroaryl, and heterocycloalkyl are 3 to 10-membered heterocycloalkyls substituted with hydroxy, halo, amino, carboxyl, C1-C7 alkyl, C1-C7 alkoxy, C1-C7 deuterium alkoxy, hydroxy-C1-C7 alkyl, halo-C1-C7 alkyl, halo-C1-C7 alkoxy, di(C1-C7 alkyl)amino, di(C1-C7 alkyl)amino-C1-C7 alkyl, azide, amide, C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkoxy, 3 to 10-membered heterocycloalkyl-amino, 3 to 10-membered heterocycloalkyl-amino-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-oxy-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-amino-C1-C7alkyl substituted with oxo, 3 to 10-membered heterocycloalkyl-amino-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with carboxyl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl substituted with C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkyl substituted with C1-C7 alkylsulfonyl It may optionally be substituted with 1 to 4 substituents selected from the group consisting of heterocycloalkyl-C1-C7alkyl, 5 to 10-membered heteroaryl, and 5 to 10-membered heteroaryl-C1-C7alkylamino-C1-C7alkyl substituted with C1-C7alkyl; R3 is hydroxy, cyano, nitro, C1-C7 alkyl, C1-C7 alkoxy, halo-C1-C7 alkyl, amino, C1-C7 alkylamino, di(C1-C7 alkyl)amino, carboxy, or C1-C7 alkoxycarbonyl; L is a direct bond, C1-C7 alkylene, halo-C1-C7 alkylene, -C(=O)-, -C(=O)O-, -CH2NRa-, -C(=O)NRa-, or -NRaC(=O)-; where Ra is hydrogen, C1-C7 alkyl, or di(C1-C7 alkyl)amino-C1-C7 alkyl; R4 is hydroxy, halo, cyano, amino, carboxy, C1-C7 alkyl, hydroxy-C1-C7 alkyl, halo-C1-C7 alkyl, carboxy-C1-C7 alkyl, C1-C7 alkoxy, C3-C 12 Cycloalkyl, C3-C 12 Cycloalkyl-C1-C7alkyl, 3 to 10-membered heterocycloalkyl, C1-C7alkyl-substituted phosphonate, dihydrogen phosphite, C6-C 10 Aryl, 5 to 10-membered heteroaryl, partially unsaturated 3 to 10-membered heterocyclil, C6-C 10 Aryl-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkyl, 5 to 10-membered heteroaryl-C1-C7 alkyl, C1-C7 alkylamino, di(C1-C7 alkyl)amino, di(C1-C7 alkyl)amino-C1-C7 alkyl, C6-C 10 Arylamino, C1-C7 alkylcarbonylamino, C6-C 10 Arylcarbonylamino, C1-C7 alkylsulfonylamino, C6-C 10 It is arylsulfonylamino or -BR6R7; wherein R6 and R7 are each independently hydroxyl, or R6 and R7 may form a 3 to 10-membered heterocycloalkyl group substituted with a C1-C7 alkyl together with a boron (B) atom to which they are linked; and the alkyl, cycloalkyl, heterocycloalkyl and unsaturated heterocycloyl are hydroxyl, halo, amino, oxo, oxide, carboxyl, C1-C7 alkyl, C3-C 12 C3-C substituted with cycloalkyl, hydroxy-C1-C7alkyl 12 Cycloalkyl, 3 to 10-membered heterocycloalkyl, C1-C7 alkoxy, hydroxy-C1-C7 alkyl, halo-C1-C7 alkyl, carboxy-C1-C7 alkyl, amino-C1-C7 alkyl, halo-C1-C7 alkoxy, di(C1-C7 alkyl)amino, aminocarbonyl, C6-C 10 Aryl, C6-C 10 Aryl-C1-C7 alkylcarbonyl, amino-substituted C1-C7 alkyl-carbonyloxy, C1-C7 alkylaminocarbonyloxy, amino-C1-C7 alkylcarbonyloxy, amino-C1-C7 alkylcarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkylcarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkoxycarbonyloxy-C1-C7alkyl, amino-substituted C1-C7 alkylcarbonyloxy-C1-C7alkyl, guanidino and amino-substituted C1-C7 alkylcarbonyloxy-C1-C7alkyl, aminocarbonyl and amino-substituted C1-C7 alkylcarbonyloxy-C1-C7alkyl, carboxy-C1-C7 alkylcarbonyloxy-C1-C7alkyl, Carboxy-C1-C7 alkoxycarbonyloxy-C1-C7 alkyl, carboxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkoxy-C1-C7 alkylcarbonyloxy-C1-C7 alkyl, 5 to 10-membered heteroaryl-carbonyloxy-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7 alkyl, dihydrogen phosphate-C1-C7 alkyl, C1-C7 alkoxycarbonyl-C1-C7 alkylaminocarbonyloxy-C1-C7 alkyl, (C1-C7 alkylamino-C1-C7 alkyl)(C1-C7 alkyl)aminocarbonyloxy-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7 alkyl substituted with C1-C7 alkyl, Aminosulfonyloxy-C1-C7alkyl, C1-C7alkoxy-C1-C7alkoxycarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkoxycarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)aminothiocarbonyloxy-C1-C7alkyl, C1-C7alkylaminothiocarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)aminocarbonyloxy-C1-C7alkyl, sodium oxycarbonyl-C1-C7alkoxycarbonyloxy-C1-C7alkyl, phosphono-C1-C7alkylcarbonyloxy-C1-C7alkyl, dihydrogenphosphate-C1-C7alkylcarbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7alkyl, 3 to 10 heterocycloalkyl-carbonyloxy-C1-C7alkyl substituted with C1-C7 alkoxycarbonyl,3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-C1-C7alkyl substituted with C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-carbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkoxy-carbonyloxy-C1-C7alkyl substituted with C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkylaminocarbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkylaminocarbonyloxy-C1-C7alkyl substituted with C1-C7alkyl, (3 to 10 members substituted with C1-C7alkyl The aryl and heteroaryl may optionally be substituted with one to four substituents selected from the group consisting of heterocycloalkyl-C1-C7alkyl)(C1-C7alkyl)aminocarbonyloxy-C1-C7alkyl, and 3 to 10 heterocycloalkyl-oxy-C1-C7alkyl substituted with carboxy and hydroxyl; said aryl and heteroaryl may be optionally substituted with hydroxy, halo, amino, oxide, carboxy, C1-C7alkyl, C1-C7 alkoxy, hydroxy-C1-C7alkyl, halo-C1-C7alkyl, carboxy-C1-C7alkyl, amino-C1-C7alkyl, halo-C1-C7 alkoxy, di(C1-C7alkyl)amino, aminocarbonyl, C6-C, 10 Aryl, C6-C 10 Aryl-C1-C7 alkylcarbonyl, amino-substituted C1-C7 alkyl-carbonyloxy, C1-C7 alkylaminocarbonyloxy, amino-C1-C7 alkylcarbonyloxy, di(C1-C7 alkyl)amino-C1-C7 alkylcarbonyloxy-C1-C7 alkyl, amino-substituted C1-C7 alkylcarbonyloxy-C1-C7 alkyl, 5 to 10-membered heteroaryl-carbonyloxy-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7 alkyl, dihydrogenphosphate-C1-C7 alkyl, C1-C7 alkoxycarbonyl-C1-C7 alkylaminocarbonyloxy-C1-C7 alkyl, (C1-C7 alkylamino-C1-C7 alkyl)(C1-C7 alkyl)aminocarbonyloxy-C1-C7 alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7alkyl substituted with C1-C7 alkyl, aminosulfonyloxy-C1-C7alkyl, C1-C7 alkoxy-C1-C7 alkoxycarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)aminothiocarbonyloxy-C1-C7alkyl, C1-C7 alkylaminothiocarbonyloxy-C1-C7alkyl, di(C1-C7alkyl)aminocarbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-carbonyloxy-C1-C7alkyl substituted with C1-C7 alkoxycarbonyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkoxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7 alkoxy-C1-C7alkyl, 3 to It may optionally be substituted with one to four substituents selected from the group consisting of 10-membered heterocycloalkyl-C1-C7alkoxy-carbonyloxy-C1-C7alkyl, 3 to 10-membered heterocycloalkyl-C1-C7alkylaminocarbonyloxy-C1-C7alkyl, and 3 to 10-membered heterocycloalkyl-oxy-C1-C7alkyl substituted with carboxy and hydroxy. n is 1 or 2, and; R5 is -H, C1-C7alkyl, hydroxy-C1-C7alkyl, C3-C 12 Cycloalkyl, C3-C 12 Cycloalkyl-C1-C7alkyl or C6-C 10 It is an aryl-C1-C7 alkyl; and when m is 2, two R5s are connected to each other with a carbon atom bonded to C3-C 10 A cycloalkyl group can be formed, wherein the aryl group may optionally be substituted with one to four substituents selected from the group consisting of halos, C1-C7 alkyls, and C1-C7 alkoxys; m is 1 or 2, and; The above heterocycloalkyl, partially unsaturated heterocyclil, and heteroaryl have 1 to 4 heteroatoms selected from N, O, and S; A compound characterized in that, where R1 is a benzyl substituted with a single hydroxyl and R3 is a nitro, R4 is not a C1-C7 alkyl and a 3 to 10-membered heterocycloalkyl-C1-C7 alkyl, or a pharmaceutically acceptable salt or isomer thereof.

3. The compound of claim 1, characterized in that the compound of Formula 1 is selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt or isomer thereof: 1) 4-((R)-5-benzyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 2) (R)-N-(2,3-dihydrobenzofuran-5-yl)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 3) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-hydroxypyridine-2-yl)methyl)-3-nitrobenzamide; 4) 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((1r,4R)-4-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 5) (R)-N-(3-carbamoylcyclobutyl)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 6) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxycyclobutyl)-3-nitrobenzamide; 7) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((3-hydroxycyclobutyl) methyl)-3-nitrobenzamide; 8) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 9) (R)-3-cyano-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 9-1) 3-cyano-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 10) (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-nitrobenzamide; 11) (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl) methyl)-3-nitrobenzamide; 12) 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 13) (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide; 14) (R)-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 15) 4-((R)-5-cyclopentyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 16) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-morpholino-3-(trifluoromethyl)benzamide; 17) 3-cyano-4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 18) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 19) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 19-1) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 20) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 21) 4-((S)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 22) (4-((S)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 23) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-methylfuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 24) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1r,4R)-4-hydroxycyclohexyl)-3-(trifluoromethyl)benzamide; 25) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 26) (S)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 27) (R)-2-(4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)pyridine 1-oxide; 28) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-morpholinoethyl)-3-(trifluoromethyl)benzamide; 29) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methylpiperidine-4-yl)methyl)-3-(trifluoromethyl)benzamide; 30) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-ethylpiperidine-4-yl)methyl)-3-(trifluoromethyl)benzamide; 31) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1,1-deoxydothiomophorino)-3-(trifluoromethyl)benzamide; 32) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-(1,1-deoxydothiomophorino)ethyl)-3-(trifluoromethyl)benzamide; 33) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(trifluoromethyl)benzamide; 34) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((5-fluoropyridine-2-yl)methyl)-3-(trifluoromethyl)benzamide; 35) (R)-2-((4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)-5-fluoropyridine 1-oxide; 36) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)benzamide; 37) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-methyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 38) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-ethyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 39) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methoxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 40) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methylcyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 41) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 42) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)-3-(trifluoromethyl)benzamide; 43) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3-(trifluoromethyl)benzamide; 44) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-3-yl)methyl)-3-(trifluoromethyl)benzamide; 45) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxetane-3-ylmethyl)-3-(trifluoromethyl)benzamide; 46) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-tetrahydrofuran-3-yl)-3-(trifluoromethyl)benzamide; 47) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-tetrahydrofuran-3-yl)-3-(trifluoromethyl)benzamide; 48) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide; 49) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide; 50) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-3-ylmethyl)-3-(trifluoromethyl)benzamide; 51) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide; 52) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1-methylazetidine-3-yl)-3-(trifluoromethyl)benzamide; 53) (R)-N-((1H-imidazole-4-yl)methyl)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 54) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methyl-1H-imidazole-4-yl)methyl)-3-(trifluoromethyl)benzamide; 55) 4-[(2R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-5-[(4-methoxyphenyl)methyl]-2-(1-methylethyl)-3-oxo-2H-pyrazine-1-yl]-N-[[1-(hydroxymethyl)cyclohexyl]methyl]-3-(trifluoromethyl)benzamide; 56) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 57) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 58) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 59) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 60) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 61) (R)-4-(5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 62) 4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-methyl-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 63) N-((3S,5S,7S)-adamantan-1-yl)-4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 64) N-(((3R,5R,7R)-adamantan-1-yl)methyl)-4-((R)-5-benzyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 65) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 66) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 67) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclopentyl)methyl)-3-(trifluoromethyl)benzamide; 68) 4-((R)-5-cyclopropyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 69) (R)-4-(5-cyclopropyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 70) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 71) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 72) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 73) 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 74) (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 75) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 76) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 77) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(thiophene-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 78) 3-cyano-4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 79) 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 80) 4-((R)-4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 81) (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 82) (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 83) (R)-4-(4-(3,4-dimethoxybenzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 84) 4-((R)-5-(4-fluorobenzyl)-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 85) 4-((R)-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 86) 4-((R)-5-benzyl-4-((5-fluoropyridine-2-yl)methyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 87) 4-((R)-4-(4-(dimethylamino)benzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 88) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-((1-methylpiperidine-4-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 89) 4-((R)-4-((1-ethylpiperidine-4-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 90) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 91) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-(4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 92) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-(4-(3-morpholinopropoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 93) (R)-4-(4-(3-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 94) (R)-4-(4-(3-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 95) 4-((R)-4-(3-hydroxy-4-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 96) 4-((R)-5-benzyl-2-isopropyl-3-oxo-4-(pyridine-2-ylmethyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 97) 4-((R)-5-benzyl-2-isopropyl-3-oxo-4-(pyridine-2-ylmethyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 98) (R)-4-(4-benzyl-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 98-1) 4-((R)-4-benzyl-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 99) 4-((R)-4-benzyl-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 100) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 100-1) 4-((R)-5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 101) (R)-4-(4-(4-fluorobenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 102) 3-cyano-4-((R)-4-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 103) (R)-3-cyano-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 103-1) 3-cyano-4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 104) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 105) 4-((R)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-4-((5-(trifluoromethyl)pyridine-2-yl)methyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 106) 4-((R)-5-benzyl-2-isopropyl-3-oxo-4-((5-(trifluoromethyl)pyridine-2-yl)methyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 107) (R)-N-isobutyl-4-(2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 108) (R)-N,N-diethyl-4-(2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 109) Hydroxycyclohexyl)-4-((R)-2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 110) (R)-4-(2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 110-1) 4-((R)-2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 111) 3-cyano-4-((R)-5-(4-fluorobenzyl)-2-isopropyl-4-((5-methylfuran-2-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 112) 4-((R)-5-(4-fluorobenzyl)-2-isopropyl-4-((5-methylfuran-2-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 113) 4-((R)-4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 114) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzoic acid; 114-1) 4-((R)-4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 115) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 115-1) 4-((R)-4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 116) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 116-1) 4-((R)-4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 117) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 117-1) 4-((R)-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)-3-(trifluoromethyl)benzamide; 118) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 119) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-nitrobenzamide; 120) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4-(3-(trifluoromethoxy)benzyl)-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 121) (R)-4-(2-isopropyl-3-oxo-4,5-bis(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 121-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4,5-bis(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 122) (R)-N-((1-(dimethylamino)cyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4,5-bis(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 123) (R)-1-((4-(2-isopropyl-3-oxo-4,5-bis(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexane-1-carboxylic acid; 124) (R)-4-(2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 124-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 125) (R)-4-(2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methoxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 126) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-(4-(methylsulfonamido)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 127) (R)-4-(4-(4-(dimethylamino)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 128) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 129) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 130) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(dimethylamino)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 131) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 132) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methyl-1H-imidazole-4-yl)methyl)-3-(trifluoromethyl)benzamide; 133) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxazole-2-ylmethyl)-3-(trifluoromethyl)benzamide; 134) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide; 135) (R)-4-(5-cyclopropyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide; 136) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 137) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 138) (R)-4-(5-cyclopropyl-2-isopropyl-4-(4-(3-morpholinopropoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 139) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-(4-(3-morpholinopropoxy)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 140) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxazole-2-ylmethyl)-3-(trifluoromethyl)benzamide; 141) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(thiazole-2-ylmethyl)-3-(trifluoromethyl)benzamide; 142) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide; 143) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide; 144) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(oxazole-2-ylmethyl)-3-(trifluoromethyl)benzamide; 145) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(thiazole-2-ylmethyl)-3-(trifluoromethyl)benzamide; 146) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-2-ylmethyl)-3-(trifluoromethyl)benzamide; 147) (R)-4-(5-cyclopentyl-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(pyridine-4-ylmethyl)-3-(trifluoromethyl)benzamide; 148) 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-((3S,4S,5R,6S)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)benzamide; 149) (R)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 150) N-((1r,3S,5R,7S)-3-hydroxyadamantan-1-yl)-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 151) (S)-4-(4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(2-(4-(2-phenylacetyl)piperazine-1-yl)ethyl)benzamide; 152) (R)-4-(5-cyclopentyl-4-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 153) 4-((R)-5-(4-(dimethylamino)benzyl)-4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 154) 4-((R)-5-(4-bromobenzyl)-4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 155) 4-((R)-4-(3,4-dihydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 156) 4-((R)-4-(4-hydroxy-3-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 157) 4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 158) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 159) 4-((R)-4-(2-hydroxyethyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 160) 4-((R)-2-isopropyl-4-methyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 161) 4-((R)-2-isopropyl-5-(4-methoxybenzyl)-4-methyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 162) 4-((R)-4-(2-hydroxyethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 163) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 164) Methyl (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzoate; 165) 4-((R)-5-cyclopentyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 166) (R)-4-(5-cyclopentyl-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-nitrobenzamide; 167) 3-amino-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 168) 4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(methylamino)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 169) 3-(dimethylamino)-4-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 170) 3-amino-4-((2R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxopiperazine-1-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 171) Ethyl 2-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-((((S)-tetrahydrofuran-2-yl)methyl)carbamoyl)benzoate; 172) Methyl 2-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-((((S)-tetrahydrofuran-2-yl)methyl)carbamoyl)benzoate; 173) 2-((R)-4-(4-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-((((S)-tetrahydrofuran-2-yl)methyl)carbamoyl)benzoic acid; 174) 4-(((R)-6-(4-(dimethylamino)benzyl)-3-isopropyl-4-(2-nitro-4-((((S)-tetrahydrofuran-2-yl)methyl)carbamoyl)phenyl)-2-oxo-3,4-dihydropyrazine-1(2H)-yl)methyl)benzoic acid; 175) 4-((R)-5-(4-azidobenzyl)-4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 176) 4-((R)-5-(4-azidobenzyl)-4-(4-ethynylbenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 177) 4-((R)-4-(4-(hydroxymethyl)benzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-nitro-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 178) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 179) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 180) (R)-4-(4-(3-fluoro-4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 181) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 182) (R)-4-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 183) 4-[2-(1-methylethyl)-3-oxydanylidene-4,5-bis[[4-[tris(fluoranyl)methoxy]phenyl]methyl]-2H-pyrazine-1-yl]-N-[[1-(oxydanylmethyl)cyclohexyl]methyl]-3-[tris(fluoranyl)methyl]benzamide; 184) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(5-(4-(hydroxymethyl)phenyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 185) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(5-(4-(hydroxymethyl)phenyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 186) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-5-(4-(piperidine-1-ylmethyl)phenyl)-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 187) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-5-(4-(morpholinomethyl)phenyl)-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 188) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-5-(4-((4-methylpiperazine-1-yl)methyl)phenyl)-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 189) (4-((R)-4-(4-(((1-hydroxycyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-5-isopropyl-6-oxo-1-(4-(trifluoromethoxy)benzyl)-1,4,5,6-tetrahydropyrazine-2-yl)benzyl)-L-proline; 190) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 191) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)benzamide; 192) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 193) (R)-N-((1H-1,2,4-triazole-3-yl)methyl)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 194) (R)-N-((1H-tetrazole-5-yl)methyl)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 195) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(1H-tetrazole-5-yl)-3-(trifluoromethyl)benzamide; 196) (R)-N-(2-(1H-imidazole-4-yl)ethyl)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 197) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(2-(pyridine-4-yl)ethyl)-3-(trifluoromethyl)benzamide; 198) (R)-4-(4-(3,4-difluorobenzyl)-5-(4-(dimethylamino)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 199) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(pyridine-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 200) (R)-3-cyano-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(pyridine-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)benzamide; 201) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 201-1) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 202) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 203) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 204) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclopropyl)methyl)-3-(trifluoromethyl)benzamide; 205) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((4-hydroxy-1,1-deoxydotetrahydro-2H-thiopyran-4-yl)methyl)-3-(trifluoromethyl)benzamide; 206) (R)-4-(4-(3-fluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((4-(hydroxymethyl)-1,1-deoxydotetrahydro-2H-thiopyran-4-yl)methyl)-3-(trifluoromethyl)benzamide; 207) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 208) (R)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 209) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-5-(4-(hydroxymethyl)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 210) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(piperidine-1-ylmethyl)phenyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 211) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-5-(4-(morpholinomethyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 212) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethyl)benzyl)-2-isopropyl-5-(4-((4-methylpiperazine-1-yl)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 213) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-nitrobenzamide; 214) (R)-3-cyano-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzamide; 215) 3-cyano-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)benzamide; 216) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 216-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 217) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 218) (R)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 219) (R)-1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexane-1-carboxylic acid; 220) (R)-2-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)acetic acid; 221) N-((1-(aminomethyl)cyclohexyl)methyl)-4-((2R)-4-((4-(hydroxymethyl)-3-methoxycyclohexa-1,5-diene-1-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 222) 4-[[(2R,4R)-1-[4-[[1-(hydroxymethyl)cyclohexyl]methylcarbamoyl]-2-(trifluoromethyl)phenyl]-2-(1-methylethyl)-3-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2H-pyrazine-4-yl]methyl]-2-methoxy-benzoic acid; 223) (R)-4-(4-(4-((2-(dimethylamino)ethoxy)methyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 224) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-((3-morpholinopropoxy)methyl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 225) (R)-4-(4-(4-((3-(dimethylamino)propoxy)methyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 226) (R)-4-(4-(4-((3-(dimethylamino)propoxy)methyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 227) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-((3-(4-methylpiperazine-1-yl)propoxy)methyl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 228) (R)-4-(4-(3-fluoro-4-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(pyridine-2-yl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 229) (R)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 229-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 230) (R)-4-(4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 231) (R)-4-(4-(4-bromobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 232) (R)-4-(4-(4-bromobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 233) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-(4-(4-methylpiperazine-1-yl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 234) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(4-(4-methylpiperazine-1-yl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 235) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-(4-(methylsulfonamido)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 236) (R)-4-(2-isopropyl-4-(4-(methylsulfonamido)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 236-1) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(4-(methylsulfonamido)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 237) (R)-4-(4-((1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 238) (R)-4-(4-((1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 239) 4-((2R)-4-((4-hydroxycroman-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 240) 4-((2R)-4-((4-hydroxycroman-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 241) 4-((2R)-4-((4-hydroxycroman-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 242) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 243) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 244) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 245) (R)-4-(4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 245-1) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 246) (R)-4-(4-(4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 247) (R)-4-(4-((4H-benzo[d][1,3]dioxin-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 247-1) (R)-4-(4-((4H-benzo[d][1,3]dioxin-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 248) (R)-4-(4-((4H-benzo[d][1,3]dioxin-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 249) (R)-4-(4-((4H-benzo[d][1,3]dioxin-7-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 250) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(2-hydroxypropane-2-yl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 251) (R)-4-(4-(4-(2-hydroxypropane-2-yl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-methylcyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 252) (R)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-4-(4-(4-(2-hydroxypropane-2-yl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 253) (R)-4-(4-(3-fluoro-4-(2-hydroxypropane-2-yl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 254) (R)-4-(4-(3,5-difluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 255) (R)-4-(4-(3,5-difluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 256) (R)-4-(4-(3,5-difluoro-4-(hydroxymethyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 257) (R)-4-(4-(4-(1-hydroxycyclobutyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 258) (R)-4-(4-(4-(1-hydroxycyclobutyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 259) (R)-4-(4-(4-(1-hydroxycyclobutyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 260) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(methylthio)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 261) (R)-4-(4-(4-(hydroxymethyl)-3-(methylthio)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 262) (R)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-(methylthio)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 263) (R)-4-(4-(3-fluoro-4-(methylsulfonyl)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 264) (R)-4-(4-(3-fluoro-4-isopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 265) (R)-4-(4-(3-fluoro-4-isopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 266) (R)-4-(4-(3-fluoro-4-isopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 267) (R)-4-(4-(3,4-diisopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 268) (R)-4-(4-(3,4-diisopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 269) (R)-4-(4-(3,4-diisopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 270) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 271) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 272) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(2-hydroxyethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 273) (R)-4-(4-(3-fluoro-4-hydroxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 274) (R)-4-(4-(3-fluoro-4-(3-morpholinopropoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 275) (R)-4-(4-(4-(3-(dimethylamino)propoxy)-3-fluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 276) (R)-4-(4-(3-fluoro-4-(3-(4-methylpiperazine-1-yl)propoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 277) (R)-4-(4-(3,4-diisopropoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 278) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-5-(4-(hydroxymethyl)phenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 279) (R)-4-(5-(4-(chloromethyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 280) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((4-methylpiperazine-1-yl)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 281) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(piperidine-1-ylmethyl)phenyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 282) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(morpholinomethyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 283) (R)-4-(5-(4-((dimethylamino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 284) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((((1-methyl-1H-imidazole-5-yl)methyl)amino)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 285) (R)-4-(5-cyclopropyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 286) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(4-methylpiperazine-1-yl)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 287) (4-((R)-1-(3-fluoro-4-methoxybenzyl)-4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-5-isopropyl-6-oxo-1,4,5,6-tetrahydropyrazine-2-yl)benzyl)-L-proline; 288) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((morpholinoamino)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 289) (R)-4-(5-(4-(((1,1-deoxydothiomorpholino)amino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 290) (R)-4-(5-(4-((3-(dimethylamino)propoxy)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 291) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((3-morpholinopropoxy)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 292) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((3-(4-methylpiperazine-1-yl)propoxy)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 293) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((4-(methylsulfonyl)piperazine-1-yl)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 294) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(((1-methylazetidin-3-yl)amino)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 295) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(((1-methylpiperidin-4-yl)oxy)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 296) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(pyridine-2-yl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 297) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(pyridine-4-yl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 298) (R)-4-(5-((1,3-dioxolane-2-yl)methyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 299) (R)-4-(5-((1,3-dioxolane-2-yl)methyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 300) (R)-4-(4-((1H-indazole-5-yl)methyl)-2-isopropyl-3-ox7so-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 301) (R)-4-(4-((1H-indazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 302) (R)-4-(4-((1H-benzo[d][1,2,3]triazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 303) (R)-4-(4-((1H-benzo[d][1,2,3]triazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 304) (R)-4-(4-((5-fluoro-6-methoxypyridine-3-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 305) (R)-4-(4-((5-fluoro-6-methoxypyridine-3-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 306) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(3-morpholinopropoxy)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 307) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(morpholinoamino)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 308) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4-(quinoxalin-6-ylmethyl)-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 309) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-3-oxo-4-(quinoxalin-6-ylmethyl)-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 310) (R)-4-(4-(3-fluoro-4-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 311) (R)-4-(4-(3-fluoro-4-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 312) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(((3aR,6aS)-tetrahydro-1H-puro[3,4-c]pyrrole-5(3H)-yl)methyl)phenyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 313) (R)-4-(5-(4-((2-oxa-6-azaspiro[3.3]heptane-6-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 314) 4-((2R)-5-(4-((3-oxa-7-azabicyclo[3.3.1]nonan-7-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 315) 4-((R)-5-(4-(((2S,6R)-2,6-dimethylmorpholino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 316) (R)-4-(5-(4-((2,2-dimethylmorpholino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 317) (R)-4-(5-(4-((3,3-dimethylmorpholino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 318) (R)-4-(5-(4-((7-oxa-2-azaspiro[3.5]nonan-2-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 319) 4-((R)-5-(4-(((3S,5R)-3,5-dimethylmorpholino)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 320) (R)-4-(4-(3-fluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 321) (R)-4-(5-(4-((4-oxa-7-azaspiro[2.5]octane-7-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 322) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-((4-isopropylpiperazine-1-yl)methyl)phenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 323) (R)-4-(5-(4-((4-(tert-butyl)piperazine-1-yl)methyl)phenyl)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 324) (R)-4-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 325) (R)-4-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 326) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-(methoxymethyl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 327) (R)-4-(4-(4-(dimethylphosphoryl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 328) (R)-4-(4-(4-(dimethylphosphoryl)-3-fluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 329) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((1-methyl-1H-indazole-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 330) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((1-methyl-1H-benzo[d][1,2,3]triazole-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 331) (R)-4-(4-((1-(cyanomethyl)-1H-indazole-5-yl)methyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 332) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-(pyridine-2-yl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 333) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 334) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 335) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((2-methoxypyrimidine-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 336) (R)-N-((1-hydroxycyclohexyl)methyl)-4-(2-isopropyl-4-((2-methoxypyrimidine-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 337) (R)-4-(5-benzyl-2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 338) (R)-4-(5-benzyl-2-isopropyl-4-((2-methoxypyrimidine-5-yl))methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-hydroxycyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 339) (R)-4-(4-((1H-indazole-5-yl)methyl)-5-benzyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 340) 4-((R)-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide; 341) (R)-4-(5-benzyl-4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 342) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 343) (R)-3-cyano-4-(5-(4-fluorophenyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 344) (R)-3-cyano-4-(2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 345) (R)-3-cyano-4-(2-isopropyl-5-methyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 346) (R)-3-cyano-4-(2-isopropyl-3-oxo-5-(prop-2-fin-1-yl)-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 347) (R)-4-(5-(2-bromobenzyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 348) (R)-3-cyano-4-(5-(2,6-difluorobenzyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 349) (R)-3-cyano-4-(2-isopropyl-3-oxo-5-phenethyl-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 350) (R)-3-cyano-4-(2-isopropyl-5-(2-methylbenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 351) (R)-3-cyano-4-(5-(2,5-difluorobenzyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 352) (R)-3-cyano-4-(2-isopropyl-5-(3-methylbenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 353) (R)-3-cyano-4-(5-(3,5-difluorobenzyl)-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 354) (R)-3-cyano-4-(2-isopropyl-5-(3-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 355) (R)-3-cyano-4-(2,5-dibenzyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 356) 4-(5-benzyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 357) tert-butyl (R)-4-(5-benzyl-2-methyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate; 358) (R)-4-(5-benzyl-2-methyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 359) 4-(5-benzyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide; 360) (R)-4-(5-benzyl-2-methyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide; 361) (R)-3-cyano-4-(2,5-dibenzyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N,N-dimethylbenzamide; 362) 4-(6-benzyl-8-oxo-7-(4-(trifluoromethyl)benzyl)-4,7-diazaspiro[2.5]oc-5-ten-4-yl)-3-cyanobenzoic acid; 363) 4-(5-benzyl-2,2-dimethyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 364) 4-((R)-5-benzyl-2-((S)-1-hydroxyethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 365) 4-((S)-5-benzyl-2-((R)-1-hydroxyethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 366) (R)-4-(5-benzyl-2-(hydroxymethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid 367) (S)-4-(5-benzyl-2-(hydroxymethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 368) (R)-4-(5-benzyl-2-isobutyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 369) (S)-4-(5-benzyl-2-isobutyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 370) (R)-4-(5-benzyl-2-(cyclohexylmethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 371) (S)-4-(5-benzyl-2-(cyclohexylmethyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 372) (S)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 373) (S)-3-cyano-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 374) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 375) (R)-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 376) (R)-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 377) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N,N-dimethyl-3-nitrobenzamide; 378) tert-butyl (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate; 379) Methyl (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate; 380) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N,N-dimethyl-3-nitrobenzamide; 381) (R)-2-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(morpholine-4-carbonyl)benzonitrile; 382) (R)-2-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(4-methylpiperazine-1-carbonyl)benzonitrile; 383) (R)-3-cyano-N,N-diethyl-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzamide; 384) (R)-5-(3-ethyl-1,2,4-oxadiazole-5-yl)-2-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzonitrile; 385) (3-cyano-4-((R)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoyl)proline; 386) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-bromobenzonitrile; 387) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-chlorobenzonitrile; 388) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N,3-dicyanobenzamide; 389) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(2,2,2-trifluoroethyl)benzamide; 390) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(2,2,2-trifluoroethyl)benzamide; 391) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N'-phenylbenzohydrazide; 392) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N'-methylbenzohydrazide; 393) (R)-N'-benzoyl-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzohydrazide; 394) (R)-N'-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoyl)benzenesulfonohydrazide; 395) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(5-methyl-1,3,4-oxadiazole-2-yl)benzonitrile; 396) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(5-phenyl-1,3,4-oxadiazole-2-yl)benzonitrile; 397) Diethyl (R)-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)phosphonate; 398) (R)-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)phosphorous acid; 399) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(dimethylamino)benzonitrile; 400) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(isooxazole-4-yl)benzonitrile; 401) (R)-N'-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoyl)methanesulfonohydrazide; 402) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzohydrazide; 403) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-hydroxybenzamide; 404) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile; 405) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(hydroxymethyl)benzonitrile; 406) (R)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-5-(1H-pyrazol-4-yl)benzonitrile; 407) (R)-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)boronic acid; 408) (R)-5-(azetidine-1-yl)-2-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzonitrile; 409) (R)-2-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)-2-methylpropionic acid; 410) (R)-2-(4-(5-benzyl-2-isopropyl-3-oxo-4-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanophenyl)acetic acid; 411) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(3-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 412) (R)-4-(5-benzyl-2-isopropyl-3-oxo-4-(2-(trifluoromethyl)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 413) (R)-4-(5-benzyl-4-(3-fluoro-4-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 414) (R)-4-(5-benzyl-4-(2-fluoro-4-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 415) (S)-4-(5-benzyl-4-(3-fluoro-4-(trifluoromethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 416) (R)-3-cyano-4-(2-isopropyl-5-(4-methoxybenzyl)-3-oxo-4-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 417) (S)-4-(5-benzyl-4-(4-(difluoromethyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 418) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide; 419) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-benzyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 420) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 421) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 422) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(3-chloro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 423) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(3,5-difluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 424) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 425) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-(difluoromethoxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 426) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-hydroxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 427) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-ethoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 428) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-(4-isopropoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 429) (R)-4-(4-(benzo[d][1,3]dioxol-5-ylmethyl)-2-isopropyl-5-(4-(methoxy-d3)benzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 430) (R)-4-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 431) (R)-4-(4-(benzo[d]oxazole-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 432) (R)-4-(4-(benzofuran-5-ylmethyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 433) (R)-4-(4-((2,3-dihydrobenzofuran-5-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 434) (R)-4-(4-((1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-yl)methyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 435) (R)-4-(4-(4-(tert-butyl)benzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 436) (R)-4-(4-(4-(tert-butyl)benzyl)-5-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 437) (R)-4-(4-(4-(tert-butyl)benzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 438) (R)-4-(4-(4-(tert-butyl)benzyl)-5-(4-fluorophenyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide; 439) (S)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 440) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 441) Methyl (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoate; 442) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-dimethylbenzamide; 443) (R)-2-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-(morpholine-4-carbonyl)benzonitrile; 444) (R)-2-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-(4-methylpiperazine-1-carbonyl)benzonitrile formate; 445) (R)-2-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-5-(3-ethyl-1,2,4-oxadiazole-5-yl)benzonitrile; 446) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N-(2-(dimethylamino)ethyl)-N-methylbenzamide; 447) (R)-4-(5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyano-N,N-diethylbenzamide; 448) (4-((R)-5-benzyl-4-(4-(tert-butyl)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoyl)-L-proline; 449) (R)-3-cyano-4-(5-cyclopentyl-4-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 450) (R)-3-cyano-4-(2-isopropyl-4,5-bis(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 451) (R)-3-cyano-4-(4-(4-fluorobenzyl)-2-isopropyl-5-methyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 452) (R)-3-cyano-4-(5-cyclobutyl-4-(4-fluorobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 453) (R)-3-cyano-4-(4-(4-fluorobenzyl)-5-isobutyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 454) (R)-3-cyano-4-(4-(4-fluorobenzyl)-5-(furan-2-yl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 455) (R)-3-cyano-4-(4-(4-fluorobenzyl)-5-(furan-3-yl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 456) (R)-4-(5-benzyl-2-isopropyl-4-(4-methylbenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 457) (R)-4-(5-benzyl-4-(3-fluoro-4-methylbenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 458) (R)-4-(5-benzyl-4-(2-fluoro-4-methylbenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 459) (R)-4-(5-benzyl-4-(4-bromobenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 460) (R)-4-(4-(3-hydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 461) (R)-4-(4-(3,4-dihydroxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzoic acid; 462) (R)-3-cyano-4-(2-isopropyl-4-(4-methoxybenzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)benzoic acid; 463) (R)-4-(5-benzyl-2-isopropyl-4-((5-methylfuran-2-yl)methyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 464) (R)-4-(5-benzyl-2-isopropyl-4-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-cyanobenzoic acid; 465) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-(3-methoxy-4-(2,5,8,11,14-pentaoxapentadecyl)benzyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 466) (R)-4-(4-(4-((2,5,8,11-tetraoxatridecan-13-yl)oxy)-3-fluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 467) [1-[[[4-[(1S,2R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-5-[(4-methoxyphenyl)methyl]-2-(1-methylethyl)-3-oxo-2H-pyrazine-1-yl]-3-(trifluoromethyl)benzoyl]amino]methyl]cyclohexyl] 2-amino-3-methyl-butanoate; 468) (R)-1-((4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl glycinate; 469) 1-((4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-5-(4-methoxybenzyl)-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl D-alaninate; 470) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate; 471) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl L-leucinate; 472) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate; 473) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl picolinate; 474) (1-((4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl prolinate; 475) [1-[[[4-[(1S,2R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-5-[(4-methoxyphenyl)methyl]-2-(1-methylethyl)-3-oxo-2H-pyrazine-1-yl]-3-(trifluoromethyl)benzoyl]amino]methyl]cyclohexyl] 2-amino-3-methyl-butanoate; 476) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate; 477) (1-((4-((R)-4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl L-leucinate formate; 478) 1-((4-((R)-4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl L-leucinate formate; 479) (R)-(1-((4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate; 480) (R)-2-(1-((4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)ethyl dimethylglycinate; 481) (R)-1-((4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl 3-aminopropanoate; 482) (R)-4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl dimethylglycinate; 483) (R)-4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl dihydrogen phosphate; 484) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dihydrogen phosphate; 485) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dihydrogen phosphate; 486) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl phosphate; 487) (R)-(1-((4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dihydrogen phosphate; 488) (R)-4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl 2-(phosphonooxy)acetate; 489) Methyl (2S)-2-[[1-[[[4-[(2R)-4-[(3-fluoro-4-methoxy-phenyl)methyl]-2-isopropyl-3-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2H-pyrazine-1-yl]-3-(trifluoromethyl)benzoyl]amino]methyl]cyclohexyl]methoxycarbonylamino]-3-methyl-butanoate; 490) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl methyl(2-(methylamino)ethyl)carbamate; 491) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl methyl(2-(methylamino)ethyl)carbamate; 492) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methylsulfamate; 493) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-methoxyethyl) carbonate; 494) (R)-O-((1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) dimethylcarbamothioate; 495) (R)-O-((1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) ethylcarbamothioate; 496) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl diethylcarbamate; 497) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl methyl(2-(methylamino)ethyl)carbamate; 498) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methylmorpholine-4-carboxylate; 499) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate; 500) 1-((1-((4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) 2-methyl (S)-pyrrolidine-1,2-dicarboxylate; 501) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-((2-morpholinoethoxy)methyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide formate; 502) (R)-4-(5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 503) (R)-(1-((4-(5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate formate; 504) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl methyl(2-(methylamino)ethyl)carbamate formate; 505) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate; 506) (R)-4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-5-benzyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 507) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-5-benzyl-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate formate; 508) (R)-(1-((4-(5-benzyl-4-(4-(hydroxymethyl)-3-(trifluoromethoxy)benzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate; 509) (R)-(1-((4-(2-isopropyl-4-((2-methoxypyrimidine-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate; 510) (R)-(1-((4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate formate; 511) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate; 512) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl)carbamate; 513) (2S,3S,4S,5R)-6-((1-((4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid; 514) (R)-N-(1,3-dihydroxy-2-(hydroxymethyl)propane-2-yl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 515) N-((2R,3R)-1,3-dihydroxybutane-2-yl)-4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 516) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide; 517) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-1-hydroxy-3-methylbutane-2-yl)-3-(trifluoromethyl)benzamide; 518) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide; 519) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide; 520) N-((R)-2,3-dihydroxypropyl)-4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 521) N-(3-(dimethylamino)-2-hydroxypropyl)-4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 522) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(2-((2-hydroxyethyl)(methyl)amino)ethyl)-3-(trifluoromethyl)benzamide; 523) (R)-N-(3-(bis(2-hydroxyethyl)amino)propyl)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 524) N-((R)-1-hydroxybutane-2-yl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 525) N-((R)-1-hydroxy-3-methylbutane-2-yl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 526) N-((R)-1-hydroxy-4-methylpentane-2-yl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 527) N-((2R,3R)-1,3-dihydroxybutane-2-yl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 528) N-((R)-2,3-dihydroxypropyl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 529) (R)-N-(3-hydroxy-2,2-dimethylpropyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 530) (R)-N-(1,3-dihydroxy-2-(hydroxymethyl)propane-2-yl)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 531) N-(3-amino-2-hydroxypropyl)-4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 532) (R)-N-(2-(bis(2-hydroxyethyl)amino)ethyl)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 533) 4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)-N-((3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)benzamide; 534) (R)-4-(4-(4,4-bis(hydroxymethyl)peperidin-1-carbonyl)-2-(trifluoromethyl)phenyl)-1-(3-fluoro-4-methoxybenzyl)-3-isopropyl-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-2(1H)-one; 535) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide; 536) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-1-hydroxy-3-methylbutane-2-yl)-3-(trifluoromethyl)benzamide; 537) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((S)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide; 538) (R)-4-(5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide; 539) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((2R,3R)-1,3-dihydroxybutane-2-yl)-3-(trifluoromethyl)benzamide; 540) 4-((R)-5-benzyl-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-2,3-dihydroxypropyl)-3-(trifluoromethyl)benzamide; 541) N-(3-(dimethylamino)-2-hydroxypropyl)-4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 542) (R)-N-(2-((2-hydroxyethyl)(methyl)amino)ethyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 543) (R)-N-(3-(bis(2-hydroxyethyl)amino)propyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 544) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide; 545) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-3-methylbutane-2-yl)-3-(trifluoromethyl)benzamide; 546) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide; 547) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((2R,3R)-1,3-dihydroxybutane-2-yl)-3-(trifluoromethyl)benzamide; 548) 4-((R)-5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-2,3-dihydroxypropyl)-3-(trifluoromethyl)benzamide; 549) (R)-4-(5-benzyl-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide; 550) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide; 551) 4-((R)-4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-4-methylpentane-2-yl)-3-(trifluoromethyl)benzamide; 552) (R)-4-(4-(3,4-dimethoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide; 553) 4-((R)-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxybutane-2-yl)-3-(trifluoromethyl)benzamide; 554) 4-((R)-4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((R)-1-hydroxy-3-methylbutane-2-yl)-3-(trifluoromethyl)benzamide; 555) (R)-4-(4-(3,4-difluorobenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)benzamide; 556) (R)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((1-(4-methylpiperazine-1-carbonyl)-1H-indazole-5-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 557) (R)-4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-N-(2-morpholinoethyl)-3-(trifluoromethyl)benzamide; 558) (R)-N-(4-(hydroxymethyl)-3-methoxybenzyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide 559) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((6-methoxypyridine-3-yl)methyl)-3-(trifluoromethyl)benzamide; 560) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((6-methoxypyridine-3-yl)methyl)-3-(trifluoromethyl)benzamide; 561) (R)-N-(4-(hydroxymethyl)-3-methoxybenzyl)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 562) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 4-methylpiperazine-1-carboxylate; 563) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate; 564) (R)-(1-((4-(4-(benzo[c][1,2,5]oxadiazole-5-ylmethyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl)carbamate; 565) (R)-(1-((4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl)carbamate; 566) (R)-(1-((4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate; 567) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,3-dimethylmorpholino)ethyl)carbamate; 568) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(4-methylpiperazine-1-yl)ethyl) carbonate; 569) (R)-2-(dimethylamino)ethyl ((1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) carbonate; 570) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate; 571) (R)-(1-((4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl dimethylglycinate; 572) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,3-dimethylmorpholino)ethyl)carbamate; 573) (1-((4-((R)-4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,5-dimethylmorpholino)ethyl)carbamate; 574) (R)-(1-((4-(4-(3-fluoro-4-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(7-oxa-4-azaspiro[2.5]octane-4-yl)ethyl)carbamate; 575) (R)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-((2-morpholinoethoxy)methyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 576) (R)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-N-((1-((2-morpholinoethoxy)methyl)cyclohexyl)methyl)-3-(trifluoromethyl)benzamide; 577) (R)-N-((1-((2-(3,3-dimethylmorpholino)ethoxy)methyl)cyclohexyl)methyl)-4-(2-isopropyl-4-((6-methoxypyridine-3-yl)methyl)-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 578) (R)-N-((1-((2-(3,3-dimethylmorpholino)ethoxy)methyl)cyclohexyl)methyl)-4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamide; 579) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,3-dimethylmorpholino)ethyl)(methyl)carbamate; 580) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-((2R,6S)-2,6-dimethylmorpholino)ethyl)(methyl)carbamate; 581) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(3,3-dimethylmorpholino)ethyl)(ethyl)carbamate; 582) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-((2R,6S)-2,6-dimethylmorpholino)ethyl)(ethyl)carbamate; 583) (R)-2-(dimethylamino)ethyl ((1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl) carbonate; 584) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-(4-methylpiperazine-1-yl)ethyl) carbonate; 585) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate; 586) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl glycinate; 587) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl L-arginine; 588) (1-((4-((R)-4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl L-glutaminate; 589) (R)-3-((((1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)carbonyl)oxy)propionic acid; 590) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl (2-morpholinoethyl) carbonate; 591) Sodium (R)-3-((((1-((4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)carbonyl)oxy)propanoate; 592) (R)-(3-((1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)-3-oxopropyl)phosphorous acid; 593) (R)-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methyl 3-(phosphonooxy)propanoate; 594) (R)-1-(1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)-3-oxo-2,6,9,12-tetraoxapentadeca-15-noic acid; 595) (R)-4-((1-((4-(4-(4-(hydroxymethyl)-3-methoxybenzyl)-2-isopropyl-3-oxo-5-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)-3-(trifluoromethyl)benzamido)methyl)cyclohexyl)methoxy)-4-oxobutanoic acid; 596) (R)-(3-((4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl)oxy)-3-oxopropyl)phosphorous acid; 597) (R)-4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl 2-(phosphonooxy)acetate; 598) (R)-((4-((4-(4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl)oxy)methyl dihydrogen phosphate; 599) (R)-2-((bis((λ5-azaneyl)oxy)phosphoryl)oxy)ethyl (4-((4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl) carbonate; and 600) Sodium (R)-2-((((4-((4-(((1-(hydroxymethyl)cyclohexyl)methyl)carbamoyl)-2-(trifluoromethyl)phenyl)-3-isopropyl-2-oxo-6-(4-(trifluoromethoxy)benzyl)-3,4-dihydropyrazine-1(2H)-yl)methyl)-2-methoxybenzyl)oxy)carbonyl)oxy)ethyl phosphate.

4. A pharmaceutical composition for immuno-oncology comprising, as an active ingredient, a therapeutically effective amount of a compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt or isomer thereof, together with a pharmaceutically acceptable carrier.

5. A pharmaceutical composition according to claim 4, characterized by inhibiting the interaction between STING (stimulator of interferon genes) protein and TRIM29 (tripartitemotif-containing protein 29).

6. In paragraph 4, the above cancer is pseudomyxoma, intrahepatic cholangiocarcinoma, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, mycosis fungoides, acute myeloid leukemia, acute lymphoblastic leukemia, basal cell carcinoma, ovarian epithelial carcinoma, ovarian germ cell carcinoma, male breast cancer, brain cancer, pituitary adenoma, multiple myeloma, gallbladder cancer, biliary tract cancer, colorectal cancer, chronic myeloid leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal melanoma, ampulla of Vater (AOV) cancer, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, paranasal sinus cancer, non-small cell lung cancer, tongue cancer, astrocytoma, small cell lung cancer, pediatric brain cancer, pediatric lymphoma, pediatric leukemia, small intestine cancer, meningioma, esophageal cancer, Glioma, renal pelvis cancer, kidney cancer, heart cancer, duodenal cancer, malignant soft tissue cancer, malignant bone cancer, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye cancer, vulvar cancer, ureteral cancer, urethral cancer, cancer of unknown primary site, gastric lymphoma, gastric cancer, gastric carcinoid tumor, gastrointestinal stromal cancer, Wilms tumor, breast cancer, triple-negative breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational trophoblastic disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, rectal cancer, rectal carcinoid tumor, vaginal cancer, spinal cord cancer, acoustic neuroma (vestibular schwannoma), pancreatic cancer, salivary gland cancer, Kaposi sarcoma, Paget's disease, tonsil cancer, squamous cell carcinoma, lung adenocarcinoma, lung cancer, pulmonary squamous cell carcinoma, skin cancer, anal cancer, rhabdomyosarcoma, A pharmaceutical composition characterized by being selected from the group consisting of laryngeal cancer, pleural cancer, hematological cancer, and thymic cancer.

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