NOVEL OXAZOLE DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME FOR THE PREVENTION OR TREATMENT OF ALLERGIC DISEASES

Abstract

The present invention relates to a novel oxazole derivative, a method for producing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating allergic diseases such as asthma or atopy. The novel oxazole derivative of the present invention exhibits excellent inhibitory effect on intracellular signal transduction by IL-33, and can therefore be usefully used as a pharmaceutical composition for preventing or treating allergic diseases such as asthma or atopy.

Description

Detailed Description of the Invention

[0001] [Technical Field] The present invention relates to novel oxazole derivatives, and more particularly to novel oxazole derivatives that exhibit preventive or therapeutic effects on allergic diseases.

[0002] [Background technology] Bronchodilators or anti-inflammatory drugs used to treat allergic inflammatory diseases are mainly used as popular therapies. Although they provide temporary relief of symptoms, they are unable to control the underlying causes of allergic diseases, and therefore have the disadvantage of not being able to treat the underlying cause. Environmental diseases such as bronchial asthma, atopic dermatitis, and allergic rhinitis are known as immune disorders, and Th2 cells are known to play a central role in inducing allergic responses. When CD4 T cells in lymphocytes are stimulated by antigens, they differentiate into various types of Th cells depending on the cytokines they recognize. If the cytokines they recognize are type 2 cytokines such as thymic stromal lymphoprotein (TSLP) or IL-4, these cells differentiate into Th2 cells and induce allergic responses.

[0003] Interleukin-33 (IL-33) is an innate cytokine primarily produced by mucosal epithelial cells in response to various external stimuli. It is known to play an important role in regulating immune responses, primarily Th2 cell-mediated allergic reactions such as asthma. The IL-33 receptor complex for IL-33-mediated signaling consists of the ligand IL-33, the ligand-binding component ST2 (IL-1R4), and the signal transducer IL-1 receptor accessory protein (IL-1RAcP; IL-1R3). IL-33 stimulation leads to the production of Th2 proinflammatory cytokines and chemokines, including IL-4, IL-5, IL-6, IL-13, and IL-8. Upon binding, the IL-33 receptor complex activates downstream signaling pathway molecules, such as NF-kB and AP-1, via IRAK (IL-1 receptor-associated kinase), TRAF6 (TNF receptor-associated factor 6), and / or MAPKs. In summary, TSLP and IL-33 are cytokines that play an important role in the differentiation of Th2 cells, and it is expected that controlling these cytokines will fundamentally treat allergic diseases.

[0004] Summary of the Invention [Problem to be solved by the invention] The problem to be solved by the present invention is to provide novel oxazole derivatives which can be used as therapeutic agents for allergic diseases such as asthma and atopy.

[0005] Another problem to be solved by the present invention is to provide a method for producing the novel oxazole derivative.

[0006] Another problem to be solved by the present invention is to provide a pharmaceutical composition for preventing or treating IL-33-related diseases, which contains the novel oxazole derivative as an active ingredient.

[0007] Another problem to be solved by the present invention is to provide a pharmaceutical composition for preventing or treating allergic diseases, which contains the novel oxazole derivative as an active ingredient.

[0008] Another problem to be solved by the present invention is to provide a pharmaceutical composition for the prevention or treatment of one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease, which contains the novel oxazole derivative as an active ingredient.

[0009] Another problem to be solved by the present invention is to provide a method for preventing or treating one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease, which method comprises the step of administering the novel oxazole derivative to a subject in need thereof.

[0010] Another problem to be solved by the present invention is to provide use of the novel oxazole derivatives for producing a medicament for use in the prevention or treatment of one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjögren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease.

[0011] Another problem to be solved by the present invention is to provide a functional health food composition for improving the symptoms of allergic diseases, which contains the novel oxazole derivative.

[0012] The problems to be solved by the present invention are not limited to those described above, and other technical problems will be clearly understood by those skilled in the art from the following description of the invention.

[0013] [Means for solving the problem] In order to solve the above-mentioned problems, in one aspect of the present invention, there is provided an oxazole derivative compound represented by the following chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof:

[0014] [ka]

[0015] In Formula I, R1 is hydrogen, C1-C6 straight or branched alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, halogen, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkylthio, hydroxy, cyano, nitro, NR a R b , or C5-C 12 is an aryl having one or two rings, R1 is singular or plural, each of which is an independent substituent, R2 is hydrogen, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, acetyl, hydroxy, cyano, nitro, NR a R b or a 4- to 7-membered heteroaryl containing 1-3 N; R2 is singular or plural, each of which is an independent substituent, R3 is X, which may or may not be substituted with Y; X is a C1-C4 alkoxy, amino (—NH—), C5-C7 aryl, or a 5- to 7-membered non-aromatic heterocycle containing 1 or 2 heteroatoms selected from N and O; Y is hydrogen, C1-C6 linear or branched alkyl, C3-C6 cycloalkyl, hydroxy, COO, COO-alkyl, C5-C7 aryl, alkylaryl, or a 5-7 membered aromatic or non-aromatic heterocycle containing 1-2 N; said Y being unsubstituted or substituted with Z; Z is C1-C6 straight or branched alkyl, C1-C4 alkoxy, hydroxy, C1-C4 haloalkyl, acetyl, guanidino, NR a R b , a 5-7 membered aromatic or non-aromatic heterocycle containing 1-2 heteroatoms selected from C5-C7 aryl, alkoxyaryl, N and O; At this time, the R a and R b are independently hydrogen, C1-C4 straight or branched alkyl, acetyl, C1-C4 alkylsulfonyl, or C1-C6 alkoxycarbonyl; Z is unsubstituted or substituted with Q; The Q is C1-C6 straight or branched alkyl, hydroxy, halogen, acetyl, nitro, C1-C4 alkylsulfonyl, or C1-C6 alkoxycarbonyl.

[0016] In another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating an IL-33-associated disease, comprising, as an active ingredient, an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0017] In yet another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating an allergic disease, comprising an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0018] In yet another aspect of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease, comprising an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0019] In yet another aspect of the present invention, there is provided a method for preventing or treating one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease, which method comprises administering to a subject in need thereof an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0020] In yet another aspect of the present invention, there is provided a use of the oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof for producing a medicament for use in the prevention or treatment of one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease.

[0021] In yet another aspect of the present invention, there is provided a functional health food composition for improving the symptoms of allergic diseases, comprising the oxazole derivative compound represented by the above chemical formula I, its hydrate, its solvate, or its pharmaceutically acceptable salt.

[0022] [Effects of the Invention] The novel oxazole derivative provided according to one aspect of the present invention exhibits an excellent inhibitory effect on intracellular signaling mediated by IL-33, and can therefore be usefully used as a pharmaceutical composition for the prevention or treatment of allergic diseases such as asthma or atopy.

[0023] It should be understood that the effects of the present invention are not limited to the effects described above, but include all effects that can be inferred from the configuration of the invention described in the description of the present invention or the claims.

[0024] BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows an outline of the ELISA assay for measuring inhibition of IL-33 and IL-33 receptor (ST-2) binding.

[0025] [Figure 2] IC of compound 294 50 Quantitative dose-response graphs.

[0026] [Figure 3] EC of Compound 294 in mast cell lines 50 Quantitative dose-response graphs.

[0027] [Figure 4] Results of confirming the asthma suppressing efficacy (eosinophil reducing effect) of the compound of the present invention in an animal model of HDM and ovalbumin-induced asthma.

[0028] [Mode for Carrying Out the Invention] The present invention provides an oxazole derivative compound represented by the following chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof:

[0029] [ka]

[0030] In Formula I, R1 is hydrogen, C1-C6 straight or branched alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, halogen, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkylthio, hydroxy, cyano, nitro, NR a R b , or C5-C 12 is an aryl having one or two rings, R1 is singular or plural, each of which is an independent substituent, R2 is hydrogen, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, acetyl, hydroxy, cyano, nitro, NR a R b or a 4- to 7-membered heteroaryl containing 1-3 N; R2 is singular or plural, each of which is an independent substituent, R3 is X, which may or may not be substituted with Y; X is a C1-C4 alkoxy, amino (—NH—), C5-C7 aryl, or a 5- to 7-membered non-aromatic heterocycle containing 1 or 2 heteroatoms selected from N and O; Y is hydrogen, C1-C6 linear or branched alkyl, C3-C6 cycloalkyl, hydroxy, COO, COO-alkyl, C5-C7 aryl, alkylaryl, or a 5-7 membered aromatic or non-aromatic heterocycle containing 1-2 N; said Y being unsubstituted or substituted with Z; Z is C1-C6 straight or branched alkyl, C1-C4 alkoxy, hydroxy, C1-C4 haloalkyl, acetyl, guanidino, NR a R b , a 5-7 membered aromatic or non-aromatic heterocycle containing 1-2 heteroatoms selected from C5-C7 aryl, alkoxyaryl, N and O; At this time, the R a and Rb are independently hydrogen, C1-C4 straight or branched alkyl, acetyl, C1-C4 alkylsulfonyl, or C1-C6 alkoxycarbonyl; Z is unsubstituted or substituted with Q; The Q is C1-C6 straight or branched alkyl, hydroxy, halogen, acetyl, nitro, C1-C4 alkylsulfonyl, or C1-C6 alkoxycarbonyl.

[0031] In the present specification, the following defined concepts for substituents are used in the definition of compounds of formula I:

[0032] The term "alkyl" refers to a straight or branched chain hydrocarbon, which may contain single, double or triple bonds, and is C-C 10 Alkyl is preferred, for example, including but not limited to methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, acetylene, vinyl, trifluoromethyl, and the like.

[0033] The term "cycloalkyl" refers to a partially or fully saturated single or fused ring hydrocarbon, C3-C 10 -Cycloalkyl is preferred, including, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, and the like.

[0034] The term "alkoxy", unless otherwise defined, means an alkyloxy having from 1 to 10 carbon atoms.

[0035] The term "halogen" or "halo" means fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0036] The terms "haloalkyl" and "haloalkoxy" mean an alkyl or alkoxy substituted with one or more halogen atoms.

[0037] The term "heteroatom" means N, O, or S.

[0038] The term "aryl" means an aromatic hydrocarbon, including polycyclic aromatic ring systems in which a carbocyclic aromatic ring or heteroaryl ring is fused to one or more other rings. Preferably, C5-C 12 Aryl, more preferably C5-C 10 For example, the aryl includes, but is not limited to, phenyl, naphthyl, tetrahydronaphthyl, etc.

[0039] The term "heteroaryl" or "heteroaromatic ring" refers to a 3- to 12-membered, more preferably 5- to 10-membered, aromatic hydrocarbon containing one or more heteroatoms selected from N, O, and S as ring atoms, forming a single or fused ring that can be fused to benzo or C3-C8 cycloalkyl. For example, the heteroaryl includes, but is not limited to, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrazinyl, pyrimidyl, pyridazinyl, triazinyl, oxadiazolyl, isoxadiazolyl, tetrazolyl, indolyl, indazolyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, furanyl, benzofuranyl, thiophenyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolinyl, isoquinolinyl, and the like.

[0040] The term "non-aromatic heterocycle" refers to a non-aromatic carbocyclic ring containing one or more heteroatoms selected from among N, O and S as ring atoms. The ring may be 5-, 6-, 7- or 8-membered or may be fused to other rings, such as cycloalkyl or aromatic rings.

[0041] Arylalkyl, alkylaryl, and heteroarylalkyl refer to groups formed by combining an aryl and an alkyl, or a heteroaryl and an alkyl, as defined above, and include, but are not limited to, benzyl, thiophenemethyl, pyrimidinemethyl, etc.

[0042] In one embodiment, R1 is hydrogen, butyl, cyclopropyl, methoxy, F, Cl, trifluoromethyl, trifluoromethoxy, methylthio, hydroxy, cyano, nitro, NR a R b , phenyl, or naphthyl, wherein the R a and R b may independently be hydrogen, methyl, acetyl, or butoxycarbonyl.

[0043] In one embodiment, R2 is hydrogen, methoxy, trifluoromethyl, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, acetyl, hydroxy, cyano, nitro, NR a R b or pyridinyl, wherein R a and R b may independently be hydrogen, acetyl, or methylsulfonyl.

[0044] In one embodiment, X may be ethoxy, amino (—NH—), phenyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholino. In one embodiment, Y may be hydrogen, methyl, ethyl, propyl, cyclopropyl, hydroxy, COO, COO-ethyl, phenyl, benzyl, piperidinyl, or pyridinyl.

[0045] In one embodiment, Z is ethyl, methoxy, hydroxy, trifluoromethyl, acetyl, guanidino, NR a R b , phenyl, benzyloxy, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholino, imidazolyl, or pyridinyl, wherein said R a and R b may independently be hydrogen, methyl, ethyl, propyl, acetyl, methylsulfonyl, or butoxycarbonyl.

[0046] Specific examples of the oxazole derivative compounds according to the present invention are as follows:

[0047] Ethyl 5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxylate (27), Ethyl 5-(2-nitrophenyl)-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxylate (28), Ethyl 5-phenyl-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxylate (29), Ethyl 5-(2-nitrophenyl)-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxylate (30), Ethyl 5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (31), Ethyl 5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (32), Ethyl 5-(3-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (33), Ethyl 5-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (34), Ethyl 5-(2-acetamidophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (35), Ethyl 5-(3-(methylsulfonyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (36), Ethyl 5-(4-(methylsulfonyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (37), Ethyl 5-(3-acetylphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (38), Ethyl 5-(4-acetylphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (39), Ethyl 5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (40), Ethyl 5-(4-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (41), Ethyl 5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (42), Ethyl 5-(pyridin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (43), Ethyl 5-(2-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (44), Ethyl 5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (45), Ethyl 5-(4-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (46), Ethyl 5-(3,4-dimethoxyphenyl)-2-(4-trifluoromethyl)phenyl)oxazole-4-carboxylate (47), Ethyl 5-(3,5-dimethoxyphenyl)-2-(4-trifluoromethyl)phenyl)oxazole-4-carboxylate (48), Ethyl 2-(4-trifluoromethyl)phenyl)-5-(3,4,5-trimethoxyphenyl)oxazole-4-carboxylate (49), Ethyl 5-(2-(trifluoromethyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (50), Ethyl 5-(3-(trifluoromethyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (51), Ethyl 5-(2-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (52), Ethyl 5-(3-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (53), Ethyl 5-(2-cyanophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (54) Ethyl 5-(3-cyanophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (55), Ethyl 5-phenyl-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (56), Ethyl 5-(2-nitrophenyl)-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (57), Ethyl 5-phenyl-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (58), Ethyl 5-(2-nitrophenyl)-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (59), Ethyl 2-(3-methoxyphenyl)-5-phenyloxazole-4-carboxylate (60), Ethyl 2-(3-methoxyphenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (61), Ethyl 2-(4-methoxyphenyl)-5-phenyloxazole-4-carboxylate (62), Ethyl 2-(4-methoxyphenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (63), Ethyl 2-(4-methoxyphenyl)-5-(4-nitrophenyl)oxazole-4-carboxylate (64), Ethyl 2-(3-fluorophenyl)-5-phenyloxazole-4-carboxylate (65), Ethyl 2-(3-fluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (66), Ethyl 2-(4-fluorophenyl)-5-phenyloxazole-4-carboxylate (67), Ethyl 2-(4-fluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (68), Ethyl 2-(4-fluorophenyl)-5-(4-nitrophenyl)oxazole-4-carboxylate (69), Ethyl 2-(3,4-difluorophenyl)-5-phenyloxazole-4-carboxylate (70), Ethyl 2-(3,4-difluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (71), Ethyl 2-(3,4-difluorophenyl)-5-(4-(methylthio)phenyl)oxazole-4-carboxylate (72), Ethyl 2-(3,5-difluorophenyl)-5-phenyloxazole-4-carboxylate (73), Ethyl 2-(3,5-difluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (74), Ethyl 2-(3-chlorophenyl)-5-phenyloxazole-4-carboxylate (75), Ethyl 2-(3-chlorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (76), Ethyl 2-(4-chlorophenyl)-5-phenyloxazole-4-carboxylate (77), Ethyl 2-(4-chlorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (78), Ethyl 2-(4-cyanophenyl)-5-phenyloxazole-4-carboxylate (79), Ethyl 2-(4-cyanophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (80), Ethyl 2-([1,1'-biphenyl]-4-yl)-5-phenyloxazole-4-carboxylate (81), Ethyl 2-([1,1'-biphenyl]-4-yl)-5-(2-nitrophenyl)oxazole-4-carboxylate (82), Ethyl 2-(naphthalen-2-yl)-5-phenyloxazole-4-carboxylate (83), Ethyl 2-(naphthalen-2-yl)-5-(2-nitrophenyl)oxazole-4-carboxylate (84), Ethyl 2-(4-(dimethylamino)phenyl)-5-phenyloxazole-4-carboxylate (85), Ethyl 2-(4-(dimethylamino)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (86), Ethyl 2-(4-(tert-butyl)phenyl)-5-phenyloxazole-4-carboxylate (87), Ethyl 2-(4-(tert-butyl)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (88), Ethyl 2-(4-(tert-butyl)phenyl)-5-(4-nitrophenyl)oxazole-4-carboxylate (89), Ethyl 2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxylate (90), Ethyl 2-(4-(methylthio)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (91), Ethyl 5-(3-methoxyphenyl)-2-(4-(methylthio)phenyl)oxazole-4-carboxylate (92), Ethyl 5-(4-methoxyphenyl)-2-(4-(methylthio)phenyl)oxazole-4-carboxylate (93), Ethyl 2-(4-nitrophenyl)-5-phenyloxazole-4-carboxylate (94), Ethyl 5-(2-nitrophenyl)-2-(4-nitrophenyl)oxazole-4-carboxylate (95), Ethyl 2-(4-((tert-butoxycarbonyl)amino)phenyl)-5-(3-(methylthio)phenyl)oxazole-4-carboxylate (96), Ethyl 2-(4-cyclopropylphenyl)-5-phenyloxazole-4-carboxylate (97), Ethyl 2-(4-chloro-3-(trifluoromethyl)phenyl)-5-phenyloxazole-4-carboxylate (98), Ethyl 5-(2-aminophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (99), Ethyl 5-(3-aminophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (100), Ethyl 5-(4-aminophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (101), Ethyl 5-(4-aminophenyl)-2-(4-(tert-butyl)phenyl)oxazole-4-carboxylate (102), Ethyl 5-(3-(methylsulfinyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (103), Ethyl 5-(4-(methylsulfinyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (104), Ethyl 2-(4-aminophenyl)-5-(3-(methylthio)phenyl)oxazole-4-carboxylate (105), Ethyl 5-(3-acetamidophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (106), Ethyl 5-(4-acetamidophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (107), Ethyl 5-(3-(N-acetylacetamido)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (108), Ethyl 5-(4-(N-acetylacetamido)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (109), Ethyl 5-(4-(N-acetylacetamido)phenyl)-2-(4-(tert-butyl)phenyl)oxazole-4-carboxylate (110), Ethyl 5-(4-acetamidophenyl)-2-(4-(tert-butyl)phenyl)oxazole-4-carboxylate (111), Ethyl 2-(4-acetamidophenyl)-5-(3-(methylthio)phenyl)oxazole-4-carboxylate (112), Ethyl 5-(4-(methylsulfonamido)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (113), N-(2-dimethylamino)ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (114), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (115), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (116), N-(2-(dimethylamino)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (117), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (118), N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (119), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (120), N-(2-(dimethylamino)ethyl)-5-phenyl-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide (121), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide (122), N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide (123), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide (124), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(3-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (125), N-(2-(dimethylamino)ethyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (126), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (127), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (128), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (129), N-(4-hydroxyphenethyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (130), N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (131), (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(piperazin-1-yl)methanone (132), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (133), (4-(2-methoxyphenyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (134), Ethyl 4-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carbonyl)piperazine-1-carboxylate (135), 4-Nitrophenyl 4-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carbonyl)piperazine-1-carboxylate (136), 2-(Dimethylamino)ethyl 4-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carbonyl)piperazine-1-carboxylate (137), (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(pyrrolidin-1-yl)methanone (138), 5-(2-nitrophenyl)-N-(2-(pyrrolidin-1-yl)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (139), 5-(2-nitrophenyl)-N-(3-(pyrrolidin-1-yl)propyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (140), 5-(2-nitrophenyl)-N-(pyridin-4-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (141), 5-(2-nitrophenyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (142), 5-(2-nitrophenyl)-N-(pyridin-2-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (143), (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(piperidin-1-yl)methanone (144), (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-phenylpiperidin-1-yl)methanone (145), (4-Cyclopropylpiperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (146), N-(4-acetylphenyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (147), 5-(2-nitrophenyl)-N-(4-(trifluoromethyl)benzyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (148), N-(4-fluorophenethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (149), (4-(3-(dimethylamino)propyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (150), (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-(2-(piperidin-1-yl)ethyl)piperazin-1-yl)methanone (151), (4-(2-morpholinoethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (152), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (153), (4-(2-(diethylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (154), (4-methylpiperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (155), Morpholino(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (156), N-(3-morpholinopropyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (157), N-(3-(1H-imidazol-1-yl)propyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (158), 5-(2-nitrophenyl)-N-((tetrahydrofuran-2-yl)methyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (159), N-(2-methoxyethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (160), (4-hydroxypiperidin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (161), (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-(piperidin-1-yl)phenyl)methanone (162), Ethyl 4-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carbonyl)piperazine-1-carboxylate (163), N-benzyl-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (164), N-(4-(benzyloxy)phenyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (165), N-(4-methoxybenzyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (166), (4-(2-(diisopropylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (167), (4-Isopropylpiperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (168), (4-(2-hydroxyethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (169), (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-(2-(pyrrolidin-1-yl)ethyl)piperazin-1-yl)methanone (170), N-(3-(4-methylpiperazin-1-yl)propyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (171), tert-butyl-4-(2-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamido)ethyl)piperazine-1-carboxylate (172), 5-(2-nitrophenyl)-N-(2-(piperidin-1-yl)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (173), tert-butyl(2-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamido)ethyl)covermate (174), N-(4-acetamidophenyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (175), N-(4-hydroxyphenethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (176), N-(2-(dimethylamino)ethyl)-5-(3-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (177), (5-(3-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(piperazin-1-yl)methanone (178), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(3-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (179), N-(2-(dimethylamino)ethyl)-5-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (180), (5-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(piperazin-1-yl)methanone (181), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (182), 5-(2-aminophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (183), (5-(2-aminophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-(2-(dimethylamino)ethyl)piperazin-1-yl)methanone (184), 5-(3-aminophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (185), 5-(4-aminophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (186), 5-(2-acetamidophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (187), N-(2-(4-(4-(2-(dimethylamino)ethyl)piperazine-1-carbonyl)-2-(4-(trifluoromethyl)phenyl)oxazol-5-yl)phenyl)acetamide (188), 5-(3-acetamidophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (189), N-(3-(4-(4-(2-(dimethylamino)ethyl)piperazine-1-carbonyl)-2-(4-(trifluoromethyl)phenyl)oxazol-5-yl)phenyl)acetamide (190), 5-(4-acetamidophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (191), N-(4-(4-(4-(2-(dimethylamino)ethyl)piperazine-1-carbonyl)-2-(4-(trifluoromethyl)phenyl)oxazol-5-yl)phenyl)acetamide (192), 5-(4-(methylsulfonyl)phenyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (193), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(4-(methylthio)phenyl)-2-(4-trifluoromethyl)phenyl)oxazole-4-carboxamide (194), 5-(4-(methylthio)phenyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (195), N-(2-(dimethylamino)ethyl)-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (196), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (197), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (198), N-(2-(dimethylamino)ethyl)-5-phenyl-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (199), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (200), N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (201), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (202), N-(2-(dimethylamino)ethyl)-5-phenyl-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (203), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (204), N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (205), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (206), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethoxy)phenyl)oxazol-4-yl)methanone (207), N-(2-(dimethylamino)ethyl)-2-(3-methoxyphenyl)-5-phenyloxazole-4-carboxamide (208), 2-(3-methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (209), N-(2-(dimethylamino)ethyl)-2-(3-methoxyphenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (210), 2-(3-methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (211), N-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-5-phenyloxazole-4-carboxamide (212), 2-(4-methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (213), N-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (214), 2-(4-methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (215), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(2-(4-methoxyphenyl)-5-(2-nitrophenyl)oxazol-4-yl)methanone (216), N-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-5-(4-nitrophenyl)oxazole-4-carboxamide (217), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(2-(4-methoxyphenyl)-5-(4-nitrophenyl)oxazol-4-yl)methanone (218), 2-(4-methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(4-nitrophenyl)oxazole-4-carboxamide (219), N-(2-(dimethylamino)ethyl)-2-(3-fluorophenyl)-5-phenyloxazole-4-carboxamide (220), 2-(3-fluorophenyl)N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (221), N-(2-(dimethylamino)ethyl)-2-(3-fluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (222), 2-(3-fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (223), N-(2-(dimethylamino)ethyl)-2-(4-fluorophenyl)-5-phenyloxazole-4-carboxamide (224), 2-(4-fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (225), N-(2-(dimethylamino)ethyl)-2-(4-fluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (226), 2-(4-fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (227), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(2-(4-fluorophenyl)-5-(2-nitrophenyl)oxazol-4-yl)methanone (228), N-(2-(dimethylamino)ethyl)-2-(4-fluorophenyl)-5-(4-nitrophenyl)oxazole-4-carboxamide (229), 2-(4-fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(4-nitrophenyl)oxazole-4-carboxamide (230), 2-(3,4-difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (231), 2-(3,4-difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (232), 2-(3,4-difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (233), 2-(3,4-difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (234), 2-(3,5-difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (235), 2-(3,5-difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (236), 2-(3,5-difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (237), 2-(3,5-difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (238), tert-butyl 4-(2-(2-(3,5-difluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxamido)ethyl)piperazine-1-carboxylate (239), 2-(3-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (240), 2-(3-chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (241), 2-(3-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (242), 2-(3-chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (243), 2-(4-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (244), 2-(4-chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (245), 2-(4-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (246), 2-(4-(chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (247), (2-(4-chlorophenyl)-5-(2-nitrophenyl)oxazol-4-yl)(4-(2-(dimethylamino)ethyl)piperazin-1-yl)methanone (248), 2-(4-cyanophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (249), 2-(4-cyanophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (250), 2-(4-cyanophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (251), 2-(4-cyanophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (252), 2-([1,1'-biphenyl]-4-yl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (253), 2-([1,1'-biphenyl]-4-yl)-N-2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (254), 2-([1,1'-biphenyl]-4-yl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (255), 2-([1,1'-biphenyl]-4-yl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (256), N-(2-(dimethylamino)ethyl)-2-(naphthalen-2-yl)-5-phenyloxazole-4-carboxamide (257), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(naphthalen-2-yl)-5-phenyloxazole-4-carboxamide (258), N-(2-(dimethylamino)ethyl)-2-(naphthalen-2-yl)-5-(2-nitrophenyl)oxazole-4-carboxamide (259), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(naphthalen-2-yl)-5-(2-nitrophenyl)oxazole-4-carboxamide (260), N-(2-(dimethylamino)ethyl)-2-(4-(dimethylamino)phenyl)-5-phenyloxazole-4-carboxamide (261), 2-(4-(dimethylamino)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (262), N-(2-(dimethylamino)ethyl)-2-(4-(dimethylamino)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (263), 2-(4-(dimethylamino)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (264), 2-(4-(tert-butyl)phenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (265), 2-(4-(tert-butyl)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (266), 2-(4-(tert-butyl)phenyl)-N-(2-(diethylamino)ethyl)-5-phenyloxazole-4-carboxamide (267), 2-(4-(tert-butyl)phenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (268), 2-(4-(tert-butyl)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (269), 2-(4-(tert-butyl)phenyl)-N-(2-(diethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (270), N-(2-(dimethylamino)ethyl)-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (271), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (272), N-(2-(dimethylamino)ethyl)-2-(4-(methylthio)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (273), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-(methylthio)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (274), N-(2-(dimethylamino)ethyl)-2-(4-nitrophenyl)-5-phenyloxazole-4-carboxamide (275), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-nitrophenyl)-5-phenyloxazole-4-carboxamide (276), N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(4-nitrophenyl)oxazole-4-carboxamide (277), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-nitrophenyl)oxazole-4-carboxamide (278), 2-(4-cyclopropylphenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (279), 2-(4-cyclopropylphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (280), 5-(2-nitrophenyl)-N-(2-(piperazin-1-yl)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (281), N-(2-aminoethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (282), 2-(3,5-difluorophenyl)-5-(2-nitrophenyl)-N-(2-(piperazin-1-yl)ethyl)oxazole-4-carboxamide (283), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (284), N-(2-acetamidoethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (285), N-(2-(4-acetylpiperazin-1-yl)ethyl)-2-(3,5-difluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (286), N-(2-(4-(methylsulfonyl)piperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (287), N-(2-(methylsulfonamido)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (288), N-(2-guanidinoethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (289), N-methyl-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (290), N-ethyl-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (291), 5-(3-(methylthio)phenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (292), N-(2-methoxyethyl)-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (293), N-ethyl-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (294), 5-phenyl-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (295), N-ethyl-5-(2-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (296), 5-(2-methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (297), N-ethyl-5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (298), 5-(3-methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (299), N-ethyl-5-(4-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (300), 5-(4-methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (301), 5-(3,4-dimethoxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (302), 5-(3,5-dimethoxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (303), N-ethyl-2-(4-(trifluoromethyl)phenyl)-5-(3,4,5-trimethoxyphenyl)oxazole-4-carboxamide (304), N-ethyl-5-(2-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (305), N-propyl-5-(2-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (306), N-ethyl-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (307), N-propyl-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (308), N-ethyl-5-(pyridin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (309), N-propyl-5-(pyridin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (310), 5-(3-cyanophenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (311), N-ethyl-2-(4-methoxyphenyl)-5-phenyloxazole-4-carboxamide (312), 2-(3,5-difluorophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (313), 2-(3-chlorophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (314), 2-(4-cyanophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (315), N-ethyl-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (316), 2-(4-(methylthio)phenyl)-5-phenyl-N-propyloxazole-4-carboxamide (317), N-ethyl-5-(3-hydroxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (318), 5-(3-hydroxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (319), N-ethyl-5-(4-hydroxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (320), 5-(3,4-dihydroxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (321), 5-(3,5-dihydroxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (322), N-ethyl-2-(4-(trifluoromethyl)phenyl)-5-(3,4,5-trihydroxyphenyl)oxazole-4-carboxamide (323), and N-Ethyl-2-(4-hydroxyphenyl)-5-phenyloxazole-4-carboxamide (324).

[0048] The compound represented by the above chemical formula I according to the present invention can be prepared and used in the form of a prodrug, hydrate, solvate, or pharmaceutically acceptable salt in order to enhance in vivo absorption or increase solubility. Therefore, the prodrug, hydrate, solvate, and pharmaceutically acceptable salt also fall within the scope of the present invention.

[0049] The term "prodrug" refers to a substance that is transformed into the parent drug in vivo. Prodrugs are frequently used because, in some cases, they are easier to administer than the parent drug. For example, they may be bioavailable by oral administration, whereas the parent drug may not. A prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. For example, a prodrug may be an in vivo hydrolyzable ester of a compound according to the invention and a pharmaceutically acceptable salt thereof. Another example of a prodrug may be a short peptide (polyamino acid) bonded to an acid group that is metabolically converted to reveal the active site.

[0050] The term "hydrate" means a compound of the present invention or a salt thereof that contains a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.

[0051] The term "solvate" refers to a compound of the present invention or a salt thereof that contains a stoichiometric or non-stoichiometric amount of solvent bound by non-covalent intermolecular forces, where preferred solvents are volatile, non-toxic, and / or suitable for human administration.

[0052] The term "isomer" refers to a compound of the present invention or a salt thereof that has the same chemical or molecular formula but is structurally or sterically different. Such isomers include all structural isomers such as tautomers, and stereoisomers such as R or S isomers having asymmetric carbon centers and geometric isomers (trans, cis). All of these isomers and mixtures thereof are included within the scope of the present invention.

[0053] The term "pharmaceutically acceptable salt" refers to a salt form of a compound that does not induce significant irritation to an organism to which the compound is administered and does not impair the biological activity and physical properties of the compound. The pharmaceutically acceptable salt includes acid addition salts formed with acids that form non-toxic acid addition salts containing pharmaceutically acceptable anions, for example, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, etc., organic carbonic acids such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, malic acid, salicylic acid, etc., and sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. For example, pharmaceutically acceptable carboxylic acid salts include metal salts or alkaline earth metal salts formed with lithium, sodium, potassium, calcium, magnesium, etc., amino acid salts such as lysine, arginine, guanidine, etc., organic salts such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, diethanolamine, choline, triethylamine, etc. The compound of formula I according to the present invention can also be converted into its salt by a conventional method.

[0054] The oxazole derivatives of Formula I of the present invention can be synthesized according to the following Reaction Schemes 1 to 5. Compound (2) is synthesized by substituting the amine group at the carbon number 2 of the oxazole ring with a chloride group using the Sandmeyer reaction. Then, a Suzuki-Miyaura cross-coupling reaction is used to introduce a phenyl ring substituted with various functional groups at the ortho, meta, and para positions at the carbon number 2 of the oxazole ring to synthesize compounds (3-26) (see Reaction Scheme 1). Subsequently, a Heck reaction is used to introduce a phenyl ring substituted with various functional groups at the carbon number 5 of the oxazole ring to synthesize compounds (27-113) (see Reaction Scheme 2). The ethyl carboxylate at the carbon number 4 of the oxazole ring is hydrolyzed under basic conditions, followed by amide coupling to synthesize the final compounds (114-280) (see Reaction Scheme 3).

[0055] Although Reaction Schemes 1 to 5 are shown as examples of methods for preparing the compound of Formula I of the present invention, these methods do not limit the methods for preparing the compound of Formula I of the present invention. It is obvious that the methods for preparing the compound of Formula I of the present invention are merely examples and can be easily modified by those skilled in the art depending on the specific substituents.

[0056] The present invention also provides a pharmaceutical composition for preventing or treating an IL-33-associated disease, comprising, as an active ingredient, an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0057] The present invention also provides a pharmaceutical composition for preventing or treating allergic diseases, comprising, as an active ingredient, an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0058] The present invention also provides a pharmaceutical composition for the prevention or treatment of one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease, comprising an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0059] The present invention also provides a method for preventing or treating one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease, which method comprises the step of administering to a subject in need thereof an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0060] The present invention also provides use of the oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof for producing a medicament for use in the prevention or treatment of one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease.

[0061] The present invention also provides a functional health food composition for improving the symptoms of allergic diseases, comprising an oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

[0062] The present invention also provides a pharmaceutical composition comprising the oxazole derivative compound represented by the above chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0063] The additives may contain pharmaceutically acceptable carriers or diluents, and may be formulated into oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, and sterile injection solutions by conventional methods.

[0064] The pharmaceutically acceptable carrier includes lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc. Also included are diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. Oral solid preparations include tablets, pills, powders, granules, capsules, etc., and such solid preparations may contain at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., and may contain lubricants such as magnesium stearate, talc, etc. Oral liquid preparations include suspensions, oral solutions, emulsions, syrups, etc., and may contain diluents such as water and liquid paraffin, wetting agents, sweeteners, flavorings, preservatives, etc. Parenteral preparations include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, creams, lyophilized preparations, and suppositories, and non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases that can be used include witepsol, macrogol, Tween 61, cocoa gum, laurin gum, glycerol gelatin, etc.

[0065] The dosage of the active ingredient contained in the pharmaceutical composition of the present invention varies depending on the patient's condition and weight, the severity of the disease, the form of the active ingredient, the route of administration, and the duration of administration, and can be adjusted appropriately for each patient. For example, the active ingredient can be administered at a dose of 0.0001 to 1000 mg / kg per day, preferably 0.01 to 100 mg / kg, once a day or in several divided doses. Furthermore, the pharmaceutical composition of the present invention can contain the active ingredient in an amount of 0.001 to 90% by weight based on the total weight of the composition.

[0066] The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, and humans via various routes, for example, by oral, cutaneous, peritoneal, rectal, or intravenous, intramuscular, subcutaneous, intrauterine, intradural, or intracerebroventricular injection.

[0067] The present invention will be described in more detail below through synthesis examples, examples, and experimental examples. However, the following synthesis examples, examples, and experimental examples are intended to illustrate the present invention, and the scope of the present invention is not limited thereto.

[0068] Synthesis Example 1: Synthesis of oxazole compounds (1) Summary of synthesis reactions The oxazole derivatives of the present invention were synthesized according to the following reaction schemes 1 to 5. Compound 2 was synthesized by substituting the amine group at the carbon number 2 of the oxazole ring with a chloride group using the Sandmeyer reaction. Compounds 3-26 were synthesized by introducing phenyl rings substituted with various functional groups at the ortho, meta, and para positions to the carbon number 2 of the oxazole ring using the Suzuki-Miyaura cross-coupling reaction (see reaction scheme 1).

[0069] Compounds 27-113 were synthesized by introducing a phenyl ring substituted with various functional groups to the 5th carbon of the oxazole through the Heck reaction (see Scheme 2). The ethyl carboxylate at the 4th carbon of the oxazole was hydrolyzed under basic conditions, followed by amide coupling to synthesize the final compounds 114-280 (see Scheme 3).

[0070] (2) Reagents and methods All chemicals and solvents used in the reactions were purchased from Sigma-Aldrich, TCI, and Acros and were used without further purification. 254The chromatographic analysis was performed by thin-layer chromatography (TLC) on silica gel plates pre-coated with HCl (Merck; Darmstadt, Germany) and confirmed by development with UV254 light and / or KMnO4 stain. Column chromatography was performed on silica gel (Silica gel 60; 230-400 mesh ASTM, Merck, Darmstadt, Germany). Nuclear magnetic resonance (NMR) spectra were recorded at room temperature on a Bruker UltraShield 600 MHz pulsed (1H, 600 MHz; 13C, 150 MHz) spectrometer. All chemical shifts were recorded in parts per million (ppm) from tetramethylsilane (δ = 0) and measured relative to the solvent in which the samples were analyzed (CDCl3: 1 H NMR δ 7.26, 13 C NMR δ 77.0; MeOD: 1 H NMR δ 3.31, 13 C NMR δ 49.0; DMSO-d: 1 H NMR δ 2.50, 13 δ 39.5 for C NMR). 1 H NMR shift values ​​are reported as chemical shift (δ), corresponding integral, multiplicity (s = singlet, br = broad, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets, td = triplet of doublets, qd = quartet of doublets), coupling constant (J in Hz), and assignment. High-resolution mass spectra (HRMS) were recorded on an Agilent 6530 Accurate Mass Q-TOF LCL / MS spectrometer.

[0071] [ka]

[0072] [Reagents and conditions: i) t-BuONO, CuCl2, acetonitrile, 80°C, 6 hours; ii) appropriate boronic acid, 2 M K2CO3, toluene, 90°C, 12 hours.] (3) Synthesis of ethyl 2-chlorooxazole-4-carboxylate (2) Acetonitrile (150 mL) was added to tert-butyl nitrite (5.7 mL, 48 mmol) and copper(II) oxide (6.5 g, 48 mmol) and reacted at 60 °C for 1 h. Ethyl 2-aminooxazole-4-carboxylate (5.0 g, 32 mmol) was then added portionwise, and the temperature was raised to 80 °C for an additional 6 h (until the starting material disappeared by TLC). The reaction mixture was added ice and concentrated HCl and extracted with CHCl. ​​The organic layer was washed with brine, dried over MgSO, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (eluted with hexane:EtO, 7:1 to 4:1, v / v) to give compound 2 (3.69 g, 66%) as a white solid.

[0073] 1 H NMR (300 MHz, CDCl3) δ 8.20 (s, 1H), 4.40 (q, J = 7.2 Hz, 2H), 1.39 (t, J = 6.9 Hz, 3H). LRMS (ESI) m / z 176.1 [M + H] + .

[0074] All spectroscopic data were in perfect agreement with previously reported data.

[0075] Synthesis Example 2. Synthesis of Compound by General Method of Suzuki Coupling: Ethyl 2-phenyloxazole-4-carboxylate (3) Ethyl 2-chlorooxazole-4-carboxylate (1.0 g, 5.69 mmol) (compound 2), phenylboronic acid (1.04 g, 8.54 mmol, 1.5 equiv.), and tetrakis(triphenylphosphine)palladium(0) (806 mg, 0.28 mmol, 0.05 equiv.) were dissolved in toluene (40 mL), followed by the addition of 2.0 M potassium carbonate solution (4.0 mL, 8.0 mmol) at room temperature. The reaction mixture was heated at 80 °C for 12 h under argon. The reaction mixture was cooled to room temperature, and water and 3 N HCl were added and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (eluted with hexane:EtO, 5:1 to 2:1, v / v) to give compound 3 as a white solid (1.11 g, 90%).

[0076] 1 H NMR (600 MHz, CDCl3) δ 8.28 (s, 1H), 8.12 (dd, J = 7.8 Hz and J = 1.2 Hz, 2H), 7.51-7.46 (m, 3H), 4.43 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz, 3H).

[0077] Compounds 4 to 26 were synthesized in a manner similar to that described for compound 3.

[0078] Synthesis Example 3. Ethyl 2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxylate (4) This compound was obtained as a white solid in 58% yield in a similar manner to the synthesis of compound 3, except that 3-(trifluoromethyl)phenylboronic acid was used instead of phenylboronic acid.

[0079] 1H NMR (600 MHz, CDCl3) δ 8.37 (s, 1H), 8.09 (d, J = 7.2 Hz, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.69-7.64 (m, 2H), 4.45 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H).

[0080] Synthesis Example 4. Ethyl 2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxylate (5) This compound was obtained as a white solid in 82% yield in a similar manner to the synthesis of compound 3, except that 2-(trifluoromethyl)phenylboronic acid was used instead of phenylboronic acid.

[0081] 1 H NMR (600 MHz, CDCl3) δ 8.41 (s, 1H), 8.34 (s, 1H), 8.32 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.63 (t, J = 7.8 Hz, 1H), 4.46 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0082] Synthesis Example 5. Ethyl 2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (6) This compound was obtained as a white solid in 73% yield in a similar manner to the synthesis of compound 3, except that 4-(trifluoromethyl)phenylboronic acid was used instead of phenylboronic acid.

[0083] 1 H NMR (600 MHz, CDCl3) δ 8.33 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0084] Synthesis Example 6. Ethyl 2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (7) This compound was obtained as a white solid in 86% yield in a similar manner to the synthesis of compound 3, except that 3-(trifluoromethoxy)phenylboronic acid was used instead of phenylboronic acid.

[0085] 1 H NMR (600 MHz, CDCl3) δ 8.30 (s, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.99 (s, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.38-7.37 (m, 1H), 4.45 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0086] Synthesis Example 7. Ethyl 2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (8) This compound was obtained as a white solid in 89% yield in a similar manner to the synthesis of compound 3, except that 4-(trifluoromethoxy)phenylboronic acid was used instead of phenylboronic acid.

[0087] 1 H NMR (600 MHz, CDCl3) δ 8.29 (s, 1H), 8.17 (d, J = 9.0 Hz, 2H), 7.33 (d, J = 9.0 Hz, 2H), 4.45 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H).

[0088] Synthesis Example 8. Ethyl 2-(3-methoxyphenyl)oxazole-4-carboxylate (9) This compound was obtained as white needle crystals in 96% yield by a method similar to that for compound 3, except that 3-methoxyphenylboronic acid was used instead of phenylboronic acid.

[0089] 1H NMR (600 MHz, CDCl3) δ 8.23 ​​(s, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.60 (s, 1H), 7.32 (t, J = 7.8 Hz, 1H), 6.99 (dd, J = 1.8 Hz and J = 7.8 Hz, 1H), 4.38 (q, J = 7.2 Hz, 2H), 3.81 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H).

[0090] Synthesis Example 9. Ethyl 2-(4-methoxyphenyl)oxazole-4-carboxylate (10) This compound was obtained as a white solid in 96% yield in a similar manner to the synthesis of compound 3, except that 4-methoxyphenylboronic acid was used instead of phenylboronic acid.

[0091] 1 H NMR (600 MHz, CDCl3) δ 8.23 ​​(s, 1H), 8.06 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 9.0 Hz, 2H), 4.44 (q, J = 7.2 Hz, 2H), 3.88 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H).

[0092] Synthesis Example 10. Ethyl 2-(3-fluorophenyl)oxazole-4-carboxylate (11) This compound was obtained as a white solid in 80% yield in a similar manner to the synthesis of compound 3, except that 3-fluorophenylboronic acid was used instead of phenylboronic acid.

[0093] 1H NMR (600 MHz, CDCl3) δ 8.29 (s, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.83 (d, J = 9.6 Hz, 1H), 7.50-7.46 (m, 1H), 7.20 (td, J = 8.4 Hz and J = 2.4 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H).

[0094] Synthesis Example 11. Ethyl 2-(4-fluorophenyl)oxazole-4-carboxylate (12) This compound was obtained as a white solid in 90% yield in a similar manner to the synthesis of compound 3, except that 4-fluorophenylboronic acid was used instead of phenylboronic acid.

[0095] 1 H NMR (600 MHz, CDCl3) δ 8.27 (s, 1H), 8.12 (dd, J = 5.4 Hz and J = 8.4 Hz, 2H), 7.17 (t, J = 8.4 Hz, 2H), 4.44 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2Hz, 3H).

[0096] Synthesis Example 12. Ethyl 2-(3,4-difluorophenyl)oxazole-4-carboxylate (13) This compound was obtained as a white solid in 76% yield in a similar manner to the synthesis of compound 3, except that 3,4-difluorophenylboronic acid was used instead of phenylboronic acid.

[0097] 1 H NMR (600 MHz, CDCl3) δ 8.28 (s, 1H), 7.99-7.95 (m, 1H), 7.92-7.89 (m, 1H), 7.32-7.29 (m, 1H), 4.45 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2Hz, 3H).

[0098] Synthesis Example 13. Ethyl 2-(3,5-difluorophenyl)oxazole-4-carboxylate (14) This compound was obtained as a white solid in 70% yield in the same manner as in the synthesis of compound 3, except that 3,5-difluorophenylboronic acid was used instead of phenylboronic acid.

[0099] 1 H NMR (600 MHz, CDCl3) δ 8.30 (s, 1H), 7.67-7.64 (m, 2H), 6.99-6.95 (m, 1H), 4.45 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H).

[0100] Synthesis Example 14. Ethyl 2-(3-chlorophenyl)oxazole-4-carboxylate (15) This compound was obtained as a white solid in 77% yield in a similar manner to the synthesis of compound 3, except that 3-chlorophenylboronic acid was used instead of phenylboronic acid.

[0101] 1 H NMR (600 MHz, CDCl3) δ 8.29 (s, 1H), 8.16-8.15 (m, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.50-7.48 (m, 1H), 7.43 (t, J = 7.8 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H).

[0102] Synthesis Example 15. Ethyl 2-(4-chlorophenyl)oxazole-4-carboxylate (16) This compound was obtained as a white solid in 66% yield in a similar manner to the synthesis of compound 3, except that 4-chlorophenylboronic acid was used instead of phenylboronic acid.

[0103] 1H NMR (600 MHz, CDCl3) δ 8.28 (s, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 4.45 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H).

[0104] Synthesis Example 16. Ethyl 2-(4-cyanophenyl)oxazole-4-carboxylate (17) This compound was obtained as a white solid in 47% yield in a similar manner to the synthesis of compound 3, except that 4-cyanophenylboronic acid was used instead of phenylboronic acid.

[0105] 1 H NMR (600 MHz, CDCl3) δ 8.34 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0106] Synthesis Example 17. Ethyl 2-([1,1'-biphenyl]-4-yl)oxazole-4-carboxylate (18) This compound was obtained as a white solid in 75% yield in a similar manner to the synthesis of compound 3, except that 4-biphenylboronic acid was used instead of phenylboronic acid.

[0107] 1 H NMR (600 MHz, CDCl3) δ 8.31 (s, 1H), 8.20 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.48 (t, J = 7.2 Hz, 2H), 7.43-7.40 (m, 1H), 4.46 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0108] Synthesis Example 18. Ethyl 2-(naphthalen-2-yl)oxazole-4-carboxylate (19) This compound was obtained as a white solid in 83% yield in a similar manner to the synthesis of compound 3, except that 2-naphthaleneboronic acid was used instead of phenylboronic acid.

[0109] 1 H NMR (600 MHz, CDCl3) δ 8.66 (s, 1H), 8.34 (s, 1H), 8.20 (dd, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.97-7.95 (m, 2H), 7.89-7.88 (m, 1H), 7.59-7.54 (m, 2H), 4.47 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H).

[0110] Synthesis Example 19. Ethyl 2-(4-(dimethylamino)phenyl)oxazole-4-carboxylate (20) This compound was obtained as a fluffy white solid in 92% yield in a manner similar to the synthesis of compound 3, using 4-(dimethylamino)phenylboronic acid instead of phenylboronic acid.

[0111] 1 H NMR (600 MHz, CDCl3) δ 8.19 (s, 1H), 7.98 (d, J = 9.0 Hz, 2H), 6.73 (d, J = 9.0 Hz, 2H), 4.43 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz, 3H).

[0112] Synthesis Example 20. Ethyl 2-(4-(tert-butyl)phenyl)oxazole-4-carboxylate (21) This compound was obtained as a fluffy white solid in 98% yield in a manner similar to the synthesis of compound 3, using 4-tert-butylphenylboronic acid instead of phenylboronic acid.

[0113] 1H NMR (600 MHz, CDCl3) δ 8.26 (s, 1H), 8.05 (d, J = 9.0 Hz, 2H), 7.50 (d, J = 9.0 Hz, 2H), 4.44 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz, 3H), 1.36 (s, 9H).

[0114] Synthesis Example 21. Ethyl 2-(4-(methylthio)phenyl)oxazole-4-carboxylate (22) This compound was obtained as a fluffy white solid in 87% yield by a method similar to that for the synthesis of compound 3, using 4-(methylthio)phenylboronic acid instead of phenylboronic acid.

[0115] 1 H NMR (600 MHz, CDCl3) δ 8.25 (s, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 4.44 (q, J = 7.2 Hz, 2H), 2.54 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H).

[0116] Synthesis Example 22. Ethyl 2-(4-nitrophenyl)oxazole-4-carboxylate (23) This compound was obtained as a fluffy white solid in 90% yield in a manner similar to the synthesis of compound 3, using 4-nitrophenylboronic acid instead of phenylboronic acid.

[0117] 1 H NMR (600 MHz, CDCl3) δ 8.37-8.35 (m, 3H), 8.32 (d, J = 9.0 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0118] Synthesis Example 23. Ethyl 2-(4-((tert-butoxycarbonyl)amino)phenyl)oxazole-4-carboxylate (24) This compound was obtained as a fluffy white solid in 90% yield in a similar manner to the synthesis of compound 3, except that (4-((tert-butoxycarbonyl)amino)phenyl)boronic acid was used instead of phenylboronic acid.

[0119] 1 H NMR (600 MHz, CDCl3) δ 8.24 (s, 1H), 8.05 (d, J = 9.0 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 4.43 (q, J = 7.1 Hz, 2H), 1.54 (s, 9H), 1.41 (t, J = 7.2 Hz, 3H).

[0120] Synthesis Example 24. Ethyl 2-(4-cyclopropylphenyl)oxazole-4-carboxylate (25) This compound was obtained as a fluffy white solid in 90% yield in a manner similar to the synthesis of compound 3, using 4-cyclopropyl-benzeneboronic acid instead of phenylboronic acid.

[0121] 1 H NMR (600 MHz, CDCl3) δ 8.25 (s, 1H), 8.00 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 4.44 (q, J = 7.2 Hz, 2H), 1.99-1.94 (m, 1H), 1.42 (t, J = 7.2 Hz, 3H), 1.07-1.04 (m, 2H), 0.80-0.77 (m, 2H).

[0122] Synthesis Example 25. Ethyl 2-(4-chloro-3-(trifluoromethyl)phenyl)oxazole-4-carboxylate (26) This compound was obtained as a fluffy white solid in 14% yield in a manner similar to the synthesis of compound 3, using (4-chloro-3-(trifluoromethyl)phenyl)boronic acid instead of phenylboronic acid.

[0123] 1H NMR (600 MHz, CDCl3) δ 8.45 (s, 1H), 8.33 (s, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 4.46 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0124] [ka]

[0125] [Reagents and conditions: i) appropriate iodobenzene, Cs2CO3, Pd(OAc)2, tri(o-tolyl)phosphine, toluene, 90°C, 12 hours; ii) 10% Pd / C, H2 gas, MeOH, room temperature, 12 hours; iii) m-CPBA, anhydrous CHCl2, 0°C, 4 hours; iv) 25% TFA in anhydrous CHCl2, 0°C to room temperature, 2 hours; v) acetyl chloride, DIPEA, anhydrous CHCl2, 0°C to room temperature, 6 hours; vi) methanesulfonyl chloride, DIPEA, anhydrous CHCl2, 0°C to room temperature, 6 hours.] Example 1. Synthesis of Compound by General Method of Heck Reaction: Ethyl 5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxylate (27) Compound 4 (295 mg, 1.03 mmol), iodobenzene (138.24 mL, 1.83 mmol, 1.5 eq), palladium acetate (47 mg, 0.21 mmol, 0.2 eq), tri(o-tolyl)phosphine (64 mg, 0.21 mmol, 0.2 eq), cesium carbonate (505 mg, 1.55 mmol, 1.5 eq), and toluene (15 mL) were added and stirred at 90 °C for 12 h under argon. The reaction mixture was cooled, diluted with water, and extracted three times with EtOAc. The organic layer was washed with brine, dried over MgSO, filtered, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluted with hexane:EtO = 3:1 to 1:1, v / v) to give compound 27 as a white solid (342 mg, 92%).

[0126] 1H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 7.2 Hz, 1H), 8.17 (dd, J = 1.2 Hz and J = 8.4 Hz, 2H), 7.86 (d, J = 7.2 Hz, 1H), 7.70 (t, J = 7.2 Hz, 1H), 7.65 (t, J = 7.2 Hz, 1H), 7.53-7.48 (m, 3H), 4.48 (q, J = 7.2 Hz, 2H), 1.44 (t, 3H).

[0127] Compounds 28-98 were synthesized in a manner similar to that described for compound 27.

[0128] Example 2. Ethyl 5-(2-nitrophenyl)-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxylate (28) This compound was obtained as a white solid in 64% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0129] 1 H NMR (600 MHz, CDCl3) δ 8.19 (t, J = 7.8 Hz, 2H), 7.85 (d, J = 7.8 Hz, 1H), 7.78 (t, J = 7.2 Hz, 1H), 7.75-7.69 (m, 3H), 7.66 (t, J = 7.8 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H).

[0130] Example 3. Ethyl 5-phenyl-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxylate (29) This compound was obtained in 91% yield as a white solid in the same manner as in the synthesis of compound 27.

[0131] 1H NMR (600 MHz, CDCl3) δ 8.43 (s, 1H), 8.36 (d, J = 7.8 Hz, 1H), 8.12 (dd, J = 1.8 Hz and J = 8.4 Hz, 2H), 7.77 (d, J = 8.4 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.55-7.51 (m, 3H), 4.48 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H).

[0132] Example 4. Ethyl 5-(2-nitrophenyl)-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxylate (30) This compound was obtained as a fluffy white solid in 86% yield in a manner similar to the synthesis of compound 27, using 1-iodo-2-nitrobenzene instead of iodobenzene.

[0133] 1 H NMR (600 MHz, CDCl3) δ 8.40 (s, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.80-7.71 (m, 4H), 7.63 (t, J = 7.8 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H).

[0134] Example 5. Ethyl 5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (31) This compound was obtained in 80% yield as a white solid in the same manner as in the synthesis of compound 27.

[0135] 1H NMR (600 MHz, CDCl3) δ 8.30 (d, J = 7.8 Hz, 2H), 8.12 (dd, J = 1.8 Hz and J = 7.8 Hz, 2H), 7.77 (d, J = 7.8 Hz, 2H), 7.54-7.50 (m, 3H), 4.49 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H).

[0136] Example 6. Ethyl 5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (32) This compound was obtained as a white solid in 83% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0137] 1 H NMR (600 MHz, CDCl3) δ 8.24 (d, J = 8.1 Hz, 2H), 8.21 (d, J = 10.5 Hz, 1H), 7.86-7.68 (m, 5H), 4.32 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H); 13 C NMR (75 MHz, CDCl3) δ 166.1, 159.9, 151.7, 148.5, 133.0, 132.6, 131.5, 130.5, 129.3, 127.3, 126.0, 125.9, 124.9, 122.4, 61.8, 14.0. LRMS (ESI) m / z 407.0 [M + H] + , 428.7 [M + Na] + and 445.3 [M + K] + .HRMS (ESI) m / z calculated for C 19 H 14 F3N2O5 + [M + H] + : 407.0849; found: 407.0809.

[0138] Example 7. Ethyl 5-(3-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (33) This compound was obtained as a fluffy white solid in 91% yield in a manner similar to the synthesis of compound 27, using 1-iodo-3-nitrobenzene instead of iodobenzene.

[0139] 1 H NMR (600 MHz, CDCl3) δ 9.07 (s, 1H), 8.55 (d, J = 7.8 Hz, 1H), 8.39-8.37 (m, 1H), 8.34 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.75 (t, J = 8.4 Hz, 1H), 4.54 (q, J = 7.2 Hz, 2H), 1.48 (t, J = 7.2 Hz, 3H).

[0140] Example 8. Ethyl 5-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (34) This compound was obtained as a white solid in 52% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-4-nitrobenzene was used instead of iodobenzene.

[0141] 1 H NMR (600 MHz, CDCl3) δ 8.68 (td, J = 8.8 Hz and J = 1.9 Hz, 4H), 8.31 (d, J = 8.1 Hz, 2H), 7.79 (d, J = 8.1 Hz, 2H), 4.51 (q, J = 7.1 Hz, 2H), 1.46 (t, J = 7.1 Hz, 3H).

[0142] Example 9. Ethyl 5-(2-acetamidophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (35) This compound was obtained in 5% yield by the same method as in the synthesis of compound 27, except that 1-iodo-4-nitrobenzene was used instead of iodobenzene.

[0143] 1 H NMR (600 MHz, CDCl3) δ 8.61 (brs, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.96(d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.33 (t, J = 7.2 Hz, 1H), 4.48 (q, J = 6.6 Hz, 2H), 2.09 (s, 3H), 1.43 (t, J = 7.2 Hz, 3H).

[0144] Example 10. Ethyl 5-(3-(methylsulfonyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (36) This compound was obtained as a fluffy white solid in 77% yield in a manner similar to the synthesis of compound 27, using 3-bromophenylmethylsulfone instead of iodobenzene.

[0145] 1 H NMR (600 MHz, CDCl3) δ 8.73 (s, 1H), 8.47 (d, J = 7.9 Hz, 1H), 8.31 (d, J = 8.1 Hz, 2H), 8.07 (d, J = 7.9 Hz, 1H), 7.78 (d, J = 8.3 Hz, 2H), 7.75 (t, J = 7.8 Hz, 1H), 4.50 (q, J = 7.1 Hz, 2H), 3.15 (s, 3H), 1.46 (t, J = 7.1 Hz, 3H). HRMS m / z: calcd for C 20 H 16 F3NO5S [M + H] + : 440.0735; found: 440.0809.

[0146] Example 11. Ethyl 5-(4-(methylsulfonyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (37) This compound was obtained as a fluffy white solid in 82% yield in a manner similar to the synthesis of compound 27, using 4-bromophenylmethylsulfone instead of iodobenzene.

[0147] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 8.3 Hz, 2H), 8.30 (d, J = 7.8 Hz, 2H), 8.09 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 7.9 Hz, 2H), 4.50 (q, J = 7.1 Hz, 2H), 3.11 (s, 3H), 1.46 (t, J = 7.1 Hz, 3H). 20 H 16 F3NO5S [M + H] + : 440.0735; found: 440.0784.

[0148] Example 12. Ethyl 5-(3-acetylphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (38) This compound was obtained as a white solid in 73% yield in a similar manner to the synthesis of compound 27, except that 3'-iodoacetophenone was used instead of iodobenzene.

[0149] 1 H NMR (600 MHz, CDCl3) δ 8.76 (s, 1H), 8.34-8.31 (m, 3H), 8.09 (d, J = 7.8 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 4.50 (q, J = 7.2 Hz, 2H), 2.71 (s, 3H), 1.45 (t, J = 7.2 Hz, 3H). HRMS m / z: calcd for C 21 H 16 F3NO4[M + H] +: 404.1065; found: 404.1123.

[0150] Example 13. Ethyl 5-(4-acetylphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (39) This compound was obtained as a white solid in 68% yield in a similar manner to the synthesis of compound 27, except that 4'-iodoacetophenone was used instead of iodobenzene.

[0151] 1 H NMR (600 MHz, CDCl3) δ 8.31 (d, J = 8.4 Hz, 2H), 8.26 (d, J = 8.4 Hz, 2H), 8.11 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 4.50 (q, J = 7.2 Hz, 2H), 2.68 (s, 3H), 1.46 (t, J = 7.2 Hz, 3H). HRMS m / z : calcd for C 21 H 16 F3NO4[M + H] + : 404.1065; found: 404.1122.

[0152] Example 14. Ethyl 5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (40) This compound was obtained as a fluffy white solid in 59% yield in a manner similar to the synthesis of compound 27, using 3-bromothioanisole instead of iodobenzene.

[0153] 1H NMR (600 MHz, CDCl3) δ 8.31 (d, J = 8.1 Hz, 2H), 8.07 (s, 1H), 7.87 (d, J = 7.7 Hz, 1H), 7.79 (d, J = 8.2 Hz, 2H), 7.46 (t, J = 7.8 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 4.69 (q, J = 7.1 Hz, 2H), 2.60 (s, 3H), 1.46 (t, J = 7.1 Hz, 3H).

[0154] Example 15. Ethyl 5-(4-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (41) This compound was obtained as a fluffy white solid in 76% yield in a manner similar to the synthesis of compound 27, using 4-bromothioanisole instead of iodobenzene.

[0155] 1 H NMR (600 MHz, CDCl3) δ 8.27 (d, J = 8.2 Hz, 2H), 8.07 (dd, J = 1.7 Hz and J = 6.8 Hz, 2H), 7.75 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.6 Hz, 2H), 4.47 (q, J = 7.1 Hz, 2H), 2.55 (s, 3H), 1.44 (t, J = 7.1 Hz, 3H). HRMS m / z: calcd for C 20 H 16 F3NO3S [M + H] + : 408.0837; found: 408.0888.

[0156] Example 16. Ethyl 5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (42) This compound was obtained as a white solid in 85% yield in a similar manner to the synthesis of compound 27, except that 3-iodopyridine was used instead of iodobenzene.

[0157] 1 H NMR (600 MHz, CDCl3) δ 9.26 (d, J = 1.8 Hz, 1H), 8.73 (dd, J = 1.8 Hz and J = 4.8 Hz, 1H), 8.53 (td, J = 8.1 Hz and J = 1.8 Hz, 1H), 8.30 (d, J = 7.8 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.47 (dd, J = 4.8 Hz and J = 7.8 Hz, 1H), 4.49 (q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H).

[0158] Example 17. Ethyl 5-(pyridin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (43) This compound was obtained as a white solid in 82% yield in a similar manner to the synthesis of compound 27, except that 4-iodopyridine was used instead of iodobenzene.

[0159] 1 H NMR (600 MHz, CDCl3) δ 8.81-8.80 (m, 2H), 8.31 (d, J = 8.4 Hz, 2H), 8.08-8.07 (m, 2H), 7.79 (d, J = 8.4 Hz, 2H), 4.52 (q, J = 7.2 Hz, 2H), 1.47 (t, J = 7.2 Hz, 3H).

[0160] Example 18. Ethyl 5-(2-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (44) This compound was obtained as a pale yellow solid in 84% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-methoxybenzene was used instead of iodobenzene.

[0161] 1H NMR (600 MHz, CDCl3) δ 8.28 (d, J = 7.8 Hz, 2H), 7.76 (d, J = 7.8 Hz, 2H), 7.58 (dd, J = 1.8 Hz and J = 8.2 Hz, 1H), 7.53-7.50 (m, 1H), 7.11 (td, J = 7.5 Hz and J = 1.2 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 4.37 (q, J = 7.2 Hz, 2H), 1.30 (t, J = 6.9 Hz, 3H).

[0162] Example 19. Ethyl 5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (45) This compound was obtained as a pale yellow solid in 94% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-3-methoxybenzene was used instead of iodobenzene.

[0163] 1 H NMR (600 MHz, CDCl3) δ 8.29 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 8.4 Hz, 3H), 7.69 (d, J = 7.8 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 7.06 (dd, J = 2.4 Hz and J = 8.4 Hz, 1H), 4.48 (q, J = 7.2 Hz, 2H), 3.91 (s, 3H), 1.44 (t, J = 7.2 Hz, 3H).

[0164] Example 20. Ethyl 5-(4-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (46) This compound was obtained as a white solid in 84% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-4-methoxybenzene was used instead of iodobenzene.

[0165] 1H NMR (600 MHz, CDCl3) δ 8.27 (d, J = 8.4 Hz, 2H), 8.12 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 4.48 (q, J = 6.6 Hz, 2H), 3.91 (s, 3H), 1.45 (t, J = 7.2 Hz, 3H).

[0166] Example 21. Ethyl 5-(3,4-dimethoxyphenyl)-2-(4-trifluoromethyl)phenyl)oxazole-4-carboxylate (47) This compound was obtained as a white solid in 80% yield in a similar manner to the synthesis of compound 27, except that 4-bromo-1,2-dimethoxybenzene was used instead of iodobenzene.

[0167] 1 H NMR (600 MHz, CDCl3) δ 8.28 (d, J = 7.8 Hz, 2H), 7.90 (d, J = 1.8 Hz, 1H), 7.77-7.75 (m, 3H), 7.00 (d, J = 8.4 Hz, 1H), 4.49 (q, J = 7.2 Hz, 2H), 4.01 (s, 3H), 3.98 (s, 3H), 1.46 (t, J = 7.2 Hz, 3H).

[0168] Example 22. Ethyl 5-(3,5-dimethoxyphenyl)-2-(4-trifluoromethyl)phenyl)oxazole-4-carboxylate (48) This compound was obtained as a white solid in 76% yield in a similar manner to the synthesis of compound 27, except that 1-bromo-3,5-dimethoxybenzene was used instead of iodobenzene.

[0169] 1H NMR (600 MHz, CDCl3) δ 8.28 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 9.0 Hz, 2H), 7.36 (d, J = 1.8 Hz, 2H), 4.48 (q, J = 7.2 Hz, 2H), 3.89 (s, 6H), 1.45 (t, J = 7.2 Hz, 3H).

[0170] Example 23. Ethyl 2-(4-trifluoromethyl)phenyl)-5-(3,4,5-trimethoxyphenyl)oxazole-4-carboxylate (49) This compound was obtained as a white solid in 67% yield in a similar manner to the synthesis of compound 27, except that 5-bromo-1,2,3-trimethoxybenzene was used instead of iodobenzene.

[0171] 1 H NMR (600 MHz, CDCl3) δ 8.28 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.52 (s, 2H), 4.49 (q, J = 7.2 Hz, 2H), 3.99 (s, 6H), 3.95 (s, 3H), 1.46 (t, J = 7.2 Hz, 3H).

[0172] Example 24. Ethyl 5-(2-(trifluoromethyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (50) This compound was obtained as a pink solid in 77% yield in a similar manner to the synthesis of compound 27, except that 2-iodobenzotrifluoride was used instead of iodobenzene.

[0173] 1H NMR (600 MHz, CDCl3) δ 8.28 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.52 (s, 2H), 4.49 (q, J = 7.2 Hz, 2H), 3.99 (s, 6H), 3.95 (s, 3H), 1.46 (t, J = 7.2 Hz, 3H).

[0174] Example 25. Ethyl 5-(3-(trifluoromethyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (51) This compound was obtained as a white solid in 82% yield in a similar manner to the synthesis of compound 27, except that 3-iodobenzotrifluoride was used instead of iodobenzene.

[0175] 1 H NMR (600 MHz, CDCl3) δ 8.41 (s, 1H), 8.35 (d, J = 7.8 Hz, 1H), 8.31 (d, J = 7.8 Hz, 2H), 7.79 (d, J = 7.8 Hz, 2H), 7.77 (d, J = 7.8 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 4.50 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 2H).

[0176] Example 26. Ethyl 5-(2-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (52) This compound was obtained as a white solid in 66% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-(trifluoromethoxy)benzene was used instead of iodobenzene.

[0177] 1H NMR (600 MHz, CDCl3) δ 8.29 (d, J = 7.8 Hz, 2H), 7.80-7.78 (m, 3H), 7.63-7.60 (m, 1H), 7.49-7.45 (m, 2H), 4.39 (q, J = 7.2 Hz, 2H), 1.32 (t, J = 6.6 Hz, 2H).

[0178] Example 27. Ethyl 5-(3-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (53) This compound was obtained as a white solid in 66% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-3-(trifluoromethoxy)benzene was used instead of iodobenzene.

[0179] 1 H NMR (600 MHz, CDCl3) δ 8.31 (d, J = 7.8 Hz, 2H), 8.12 (d, J = 7.8 Hz, 1H), 8.08 (s, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.58 (t, J = 8.4 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 4.52 (q, J = 7.8 Hz, 2H), 1.47 (t, J = 7.2 Hz, 3H).

[0180] Example 28. Ethyl 5-(2-cyanophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (54) This compound was obtained as a yellow solid in 83% yield in a similar manner to the synthesis of compound 27, except that 2-iodobenzonitrile was used instead of iodobenzene.

[0181] 1H NMR (600 MHz, CDCl3) δ 8.35 (d, J = 8.4 Hz, 2H), 8.06 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 7.8 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 4.46 (q, J = 4.8 Hz, 2H), 1.40 (t, J = 5.4 Hz, 3H).

[0182] Example 29. Ethyl 5-(3-cyanophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (55) This compound was obtained as a white solid in 53% yield in a similar manner to the synthesis of compound 27, except that 3-iodobenzonitrile was used instead of iodobenzene.

[0183] 1 H NMR (600 MHz, CDCl3) δ 8.50 (s, 1H), 8.45 (d, J = 7.8 Hz, 1H), 8.32 (d, J = 7.8 Hz, 2H), 7.80 (t, J = 7.8 Hz, 3H), 7.68 (t, J = 8.4 Hz, 1H), 4.52 (q, J = 4.8 Hz, 2H), 1.40 (t, J = 5.4 Hz, 3H).

[0184] Example 30. Ethyl 5-phenyl-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (56) This compound was obtained as a white solid in 88% yield by the same method as in the synthesis of compound 27.

[0185] 1H NMR (600 MHz, CDCl3) δ 8.13-8.10 (m, 3H), 8.02 (s, 1H), 7.56-7.51 (m, 4H), 7.37 (d, J = 8.4 Hz, 1H), 4.48 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H).

[0186] Example 31. Ethyl 5-(2-nitrophenyl)-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (57) This compound was obtained as a white solid in 88% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0187] 1 H NMR (600 MHz, CDCl3) δ 8.21 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.99 (s, 1H), 7.80-7.71 (m, 3H), 7.54 (t, J = 7.8 Hz, 1H), 7.40-7.38 (m, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H).

[0188] Example 32. Ethyl 5-phenyl-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (58) This compound was obtained in 85% yield as a white solid in the same manner as in the synthesis of compound 27.

[0189] 1H NMR (600 MHz, CDCl3) δ 8.22 (d, J = 8.4 Hz, 2H), 8.11 (dd, J = 1.8 Hz and J = 7.8 Hz, 2H), 7.54-7.50 (m, 3H), 7.35 (d, J = 8.4 Hz, 2H), 4.48 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0190] Example 33. Ethyl 5-(2-nitrophenyl)-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxylate (59) This compound was obtained as a white solid in 78% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0191] 1 H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.4 Hz, 2H), 7.80-7.71 (m, 3H), 7.34 (d, J = 8.4 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H).

[0192] Example 34. Ethyl 2-(3-methoxyphenyl)-5-phenyloxazole-4-carboxylate (60) This compound was obtained in 79% yield as a fluffy white solid in a manner similar to that of compound 27.

[0193] 1H NMR (600 MHz, CDCl3) δ 8.12 (d, J = 6.6 Hz, 2H), 7.76 (d, J = 6.6 Hz, 1H), 7.69 (s, 1H), 7.53-7.50 (m, 3H), 7.44-7.41 (m, 1H), 7.06 (d, J = 7.8 Hz, 1H), 4.47 (q, J = 7.2 Hz, 2H), 3.91 (s, 3H), 1.44 (t, J = 7.2 Hz, 3H).

[0194] Example 35. Ethyl 2-(3-methoxyphenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (61) This compound was obtained as a fluffy white solid in 57% yield in a manner similar to the synthesis of compound 27, using 1-iodo-2-nitrobenzene instead of iodobenzene.

[0195] 1 H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 1H), 7.79-7.77 (m, 2H), 7.72-7.69 (m, 2H), 7.66 (s, 1H), 7.39 (t, J = 7.8 Hz, 1H), 7.07 (ddd, J = 0.6 Hz, J = 2.4 Hz and J = 8.4 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 3.90 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H).

[0196] Example 36. Ethyl 2-(4-methoxyphenyl)-5-phenyloxazole-4-carboxylate (62) This compound was obtained in 90% yield as a fluffy white solid in a manner similar to that of compound 27.

[0197] 1H NMR (600 MHz, CDCl3) δ 8.12-8.10 (m, 4H), 7.52-7.47 (m, 3H), 7.01 (d, J = 8.4 Hz, 2H), 4.47 (q, J = 7.2 Hz, 2H), 3.89 (s, 3H), 1.43 (t, J = 7.2 Hz, 3H).

[0198] Example 37. Ethyl 2-(4-methoxyphenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (63) This compound was obtained as a fluffy white solid in 90% yield in a manner similar to the synthesis of compound 27, using 1-iodo-2-nitrobenzene instead of iodobenzene.

[0199] 1 H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.78-7.74 (m, 2H), 7.69 (s, 1H), 6.99 (d, J = 8.4 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 3.88 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H).

[0200] Example 38. Ethyl 2-(4-methoxyphenyl)-5-(4-nitrophenyl)oxazole-4-carboxylate (64) This compound was obtained as a fluffy white solid in 90% yield in a manner similar to the synthesis of compound 27, using 1-iodo-4-nitrobenzene instead of iodobenzene.

[0201] 1H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 9.0 Hz, 2H), 8.35 (d, J = 9.0 Hz, 2H), 8.13 (d, J = 9.0 Hz, 2H), 7.03 (d, J = 9.0 Hz, 2H), 4.50 (q, J = 7.2 Hz, 2H), 3.91 (s, 3H), 1.47 (t, J = 7.2 Hz, 3H).

[0202] Example 39. Ethyl 2-(3-fluorophenyl)-5-phenyloxazole-4-carboxylate (65) This compound was obtained as a white solid in 89% yield by the same method as in the synthesis of compound 27.

[0203] 1 H NMR (600 MHz, CDCl3) δ 8.12-8.11 (m, 2H), 7.97 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 9.0 Hz, 1H), 7.54-7.46 (m, 4H), 7.21 (td, J = 8.4 Hz and J = 2.4 Hz, 1H), 4.47 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H).

[0204] Example 40. Ethyl 2-(3-fluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (66) This compound was obtained as a yellow solid in 81% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0205] 1H NMR (600 MHz, CDCl3) δ 8.21 (dd, J = 0.6 Hz and J = 9.6 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.83 (td, J = 9.6 Hz and J = 1.8 Hz, 1H), 7.80-7.75 (m, 2H), 7.75-7.72 (m, 1H), 7.50-7.47 (m, 1H), 7.25-7.22 (m, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H).

[0206] Example 41. Ethyl 2-(4-fluorophenyl)-5-phenyloxazole-4-carboxylate (67) This compound was obtained in 59% yield as a white solid in the same manner as in the synthesis of compound 27.

[0207] 1 H NMR (600 MHz, CDCl3) δ 8.17 (dd, J = 5.4 Hz and J = 8.4 Hz, 2H), 8.10 (d, J = 6.6 Hz, 2H), 7.53-7.48 (m, 3H), 7.19 (t, J = 8.4 Hz, 2H), 4.47 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0208] Example 42. Ethyl 2-(4-fluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (68) This compound was obtained as a white solid in 88% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0209] 1H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 1H), 8.13 (dd, J = 5.4 Hz and J = 9.0 Hz, 2H), 7.78-7.76 (m, 2H), 7.73-7.69 (m, 1H), 7.18 (t, J = 9.0 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H).

[0210] Example 43. Ethyl 2-(4-fluorophenyl)-5-(4-nitrophenyl)oxazole-4-carboxylate (69) This compound was obtained as a fluffy white solid in 20% yield in a manner similar to the synthesis of compound 27, using 1-iodo-4-nitrobenzene instead of iodobenzene.

[0211] 1 H NMR (600 MHz, CDCl3) δ 8.39-8.35 (m, 4H), 8.20 (dd, J = 5.4 Hz and J = 9.0 Hz, 2H), 7.22 (t, J = 9.0 Hz, 2H), 4.51 (q, J = 7.2 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H).

[0212] Example 44. Ethyl 2-(3,4-difluorophenyl)-5-phenyloxazole-4-carboxylate (70) This compound was obtained in 86% yield as a fluffy white solid in a manner similar to that of compound 27.

[0213] 1H NMR (600 MHz, CDCl3) δ 8.10 (dd, J = 1.2 Hz and J = 7.8 Hz, 2H), 8.01-7.98 (m, 1H), 7.94-7.92 (m, 1H), 7.54-7.50 (m, 3H), 7.32-7.28 (m, 1H), 4.47 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0214] Example 45. Ethyl 2-(3,4-difluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (71) This compound was obtained as a yellow solid in 86% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0215] 1 H NMR (600 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 1H), 7.98-7.96 (m, 1H), 7.90-7.88 (m, 1H), 7.80-7.71 (m, 3H), 7.31-7.28 (m, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H).

[0216] Example 46. Ethyl 2-(3,4-difluorophenyl)-5-(4-(methylthio)phenyl)oxazole-4-carboxylate (72) This compound was obtained as a yellow solid in 86% yield in a similar manner to the synthesis of compound 27, except that 4-bromothioanisole was used instead of iodobenzene.

[0217] 1H NMR (600 MHz, CDCl3) δ 8.04 (d, J = 8.5 Hz, 2H), 7.97 (t, J = 8.3 Hz, 1H), 7.96-7.85 (m, 1H), 7.34 (d, J = 8.5 Hz, 2H), 7.29 (q, J = 8.5 Hz, 1H), 4.49 (q, J = 7.1 Hz, 2H), 2.54 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H).

[0218] Example 47. Ethyl 2-(3,5-difluorophenyl)-5-phenyloxazole-4-carboxylate (73) This compound was obtained as a white solid in 76% yield by the same method as in the synthesis of compound 27.

[0219] 1 H NMR (600 MHz, CDCl3) δ 8.10 (dd, J = 1.8 Hz and J = 7.8 Hz, 2H), 7.71-7.68 (m, 2H), 7.53-7.50 (m, 3H), 6.98-6.94 (m, 1H), 4.48 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0220] Example 48. Ethyl 2-(3,5-difluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (74) This compound was obtained as a white solid in 76% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0221] 1 H NMR (600 MHz, CDCl3) δ 8.22-8.20 (m, 1H), 7.81-7.78 (m, 1H), 7.74-7.71 (m, 2H), 7.64-7.62 (m, 2H), 6.98-6.95 (m, 1H), 4.30 (q, J = 7.2 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H).

[0222] Example 49. Ethyl 2-(3-chlorophenyl)-5-phenyloxazole-4-carboxylate (75) This compound was obtained in 94% yield as a white solid in the same manner as in the synthesis of compound 27.

[0223] 1 H NMR (600 MHz, CDCl3) δ 8.17 (t, J = 1.8 Hz, 1H), 8.12 (dd, J = 1.8 Hz and J = 8.4 Hz, 2H), 8.06 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.54-7.47 (m, 4H), 7.44 (t, J = 7.8 Hz, 1H), 4.48 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H).

[0224] Example 50. Ethyl 2-(3-chlorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (76) This compound was obtained as a white solid in quantitative yield by a method similar to that for compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0225] 1 H NMR (600 MHz, CDCl3) δ 8.19 (dd, J = 2.4 Hz and J = 8.4 Hz, 1H), 8.12 (t, J = 1.8 Hz, 1H), 8.00 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.78-7.74 (m, 2H), 7.73-7.70 (m, 1H), 7.48-7.46 (m, 1H), 7.42 (t, J = 7.8 Hz, 1H), 4.31 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H).

[0226] Example 51. Ethyl 2-(4-chlorophenyl)-5-phenyloxazole-4-carboxylate (77) This compound was obtained in 98% yield as a white solid in the same manner as in the synthesis of compound 27.

[0227] 1 H NMR (600 MHz, CDCl3) δ 8.12-8.10 (m, 4H), 7.53-7.47 (m, 5H), 4.47 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0228] Example 52. Ethyl 2-(4-chlorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (78) This compound was obtained as a white solid in 75% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0229] 1 H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 7.8 Hz, 1H), 8.07 (d, J = 8.4 Hz, 2H), 7.79-7.76 (m, 2H), 7.73-7.71 (m, 1H), 7.48 (d, J = 8.4 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H).

[0230] Example 53. Ethyl 2-(4-cyanophenyl)-5-phenyloxazole-4-carboxylate (79) This compound was obtained in 77% yield as a white solid in the same manner as in the synthesis of compound 27.

[0231] 1H NMR (600 MHz, CDCl3) δ 8.29 (d, J = 8.4 Hz, 2H), 8.12-8.10 (m, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.54-7.52 (m, 3H), 4.48 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H).

[0232] Example 54. Ethyl 2-(4-cyanophenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (80) This compound was obtained as a white solid in 72% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0233] 1 H NMR (600 MHz, CDCl3) δ 8.24-8.21 (m, 3H), 7.81-7.73 (m, 5H), 4.33 (q, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz, 3H).

[0234] Example 55. Ethyl 2-([1,1'-biphenyl]-4-yl)-5-phenyloxazole-4-carboxylate (81) This compound was obtained as a white solid in 70% yield by the same method as in the synthesis of compound 27.

[0235] 1 H NMR (600 MHz, CDCl3) δ 8.25 (d, J = 8.4 Hz, 2H), 8.15 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.54-7.48 (m, 5H), 7.42-7.40 (m, 1H), 4.49 (q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H).

[0236] Example 56. Ethyl 2-([1,1'-biphenyl]-4-yl)-5-(2-nitrophenyl)oxazole-4-carboxylate (82) This compound was obtained as a white solid in 88% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0237] 1 H NMR (600 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 3H), 7.80-7.77 (m, 2H), 7.73-7.71 (m, 3H), 7.66 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 8.4 Hz, 2H), 7.41 (t, J = 7.2 Hz, 1H), 4.35 (q, J = 7.2 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H).

[0238] Example 57. Ethyl 2-(naphthalen-2-yl)-5-phenyloxazole-4-carboxylate (83) This compound was obtained as a white solid in 86% yield by the same method as in the synthesis of compound 27.

[0239] 1 H NMR (600 MHz, CDCl3) δ 8.69 (s, 1H), 8.25 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.20-8.18 (m, 2H), 7.99-7.96 (m, 2H), 7.92-7.90 (m, 1H), 7.59-7.50 (m, 5H), 4.50 (q, J = 7.2 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H).

[0240] Example 58. Ethyl 2-(naphthalen-2-yl)-5-(2-nitrophenyl)oxazole-4-carboxylate (84) This compound was obtained as a white solid in 64% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0241] 1 H NMR (600 MHz, CDCl3) δ 8.85 (s, 1H), 8.21 (t, J = 8.4 Hz, 2H), 7.96 (d, J = 9.0 Hz, 2H), 7.90 (d, J = 7.8 Hz, 1H), 7.83-7.76 (m, 2H), 7.74-7.71(m, 1H), 7.60-7.55 (m, 2H), 4.36 (q, J = 7.2 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H).

[0242] Example 59. Ethyl 2-(4-(dimethylamino)phenyl)-5-phenyloxazole-4-carboxylate (85) This compound was obtained as a white solid in 76% yield by the same method as in the synthesis of compound 27.

[0243] 1 H NMR (600 MHz, CDCl3) δ 8.12 (d, J = 7.2 Hz, 2H), 8.03 (d, J = 9.0 Hz, 2H), 7.49 (t, J = 7.2 Hz, 2H), 7.46-7.44 (m, 1H), 6.75 (d, J = 9.0 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 3.06 (s, 6H), 1.43 (t, J = 7.2 Hz, 3H).

[0244] Example 60. Ethyl 2-(4-(dimethylamino)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (86) This compound was obtained as a white solid in 33% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0245] 1H NMR (600 MHz, CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 9.0 Hz, 2H), 7.79 (d, J = 7.8 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H), 7.66 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 6.73 (d, J = 9.0 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 3.06 (s, 6H), 1.28 (t, J = 7.2 Hz, 3H).

[0246] Example 61. Ethyl 2-(4-(tert-butyl)phenyl)-5-phenyloxazole-4-carboxylate (87) This compound was obtained as a white solid in 64% yield by the same method as in the synthesis of compound 27.

[0247] 1 H NMR (600 MHz, CDCl3) δ 8.12 (d, J = 7.8 Hz, 2H), 8.10 (d, J = 7.8 Hz, 2H), 7.52-7.48 (m, 5H), 4.47 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H), 1.37 (s, 9H).

[0248] Example 62. Ethyl 2-(4-(tert-butyl)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (88) This compound was obtained as a white solid in 31% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0249] 1H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 2H), 7.78-7.77 (m, 2H), 7.73-7.68 (m, 1H), 7.52 (d, J = 8.4 Hz, 2H), 4.34 (q, J = 7.2 Hz, 2H), 1.38 (s, 9H), 1.29 (t, J = 7.2 Hz, 3H).

[0250] Example 63. Ethyl 2-(4-(tert-butyl)phenyl)-5-(4-nitrophenyl)oxazole-4-carboxylate (89) This compound was obtained as a white solid in quantitative yield by a method similar to that for compound 27, except that 1-iodo-4-nitrobenzene was used instead of iodobenzene.

[0251] 1 H NMR (600 MHz, CDCl3) δ 8.38-8.37 (m, 2H), 8.34-8.33 (m, 2H), 8.10 (d, J = 7.2 Hz, 2H), 7.54 (d, J = 7.0 Hz, 2H), 4.49 (q, J = 7.2 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H), 1.38 (s, 9H).

[0252] Example 64. Ethyl 2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxylate (90) This compound was obtained as a white solid in 70% yield by the same method as in the synthesis of compound 27.

[0253] 1H NMR (600 MHz, CDCl3) δ 8.11 (dd, J = 1.2 Hz and J = 8.4 Hz, 2H), 8.06 (d, J = 8.4 Hz, 2H), 7.51-7.47 (m, 3H), 7.31 (d, J = 8.4 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 2.53 (s, 3H), 1.43 (t, J = 7.2 Hz, 3H).

[0254] Example 65. Ethyl 2-(4-(methylthio)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxylate (91) This compound was obtained as a white solid in 65% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0255] 1 H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 7.8 Hz, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.77-7.76 (m, 2H), 7.71-7.68 (m, 1H), 7.31 (d, J = 8.4 Hz, 2H), 4.32 (q, J = 7.2 Hz, 2H), 2.54 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H).

[0256] Example 66. Ethyl 5-(3-methoxyphenyl)-2-(4-(methylthio)phenyl)oxazole-4-carboxylate (92) This compound was obtained as a fluffy white solid in 54% yield in a manner similar to the synthesis of compound 27, using 1-iodo-3-methoxybenzene instead of iodobenzene.

[0257] 1H NMR (600 MHz, CDCl3) δ 8.08 (d, J = 9.0 Hz, 2H), 7.77 (s, 1H), 7.72-7.70 (m, 1H), 7.43 (t, J = 8.4 Hz, 2H), 7.05-7.04 (m, 1H), 4.48 (q, J = 7.2 Hz, 2H), 3.92 (s, 3H), 2.57 (s, 3H), 1.45 (t, J = 7.2 Hz, 3H).

[0258] Example 67. Ethyl 5-(4-methoxyphenyl)-2-(4-(methylthio)phenyl)oxazole-4-carboxylate (93) This compound was obtained as a fluffy white solid in 54% yield in a manner similar to the synthesis of compound 27, using 1-iodo-4-methoxybenzene instead of iodobenzene.

[0259] 1 H NMR (600 MHz, CDCl3) δ 8.12 (d, J = 9.0 Hz, 2H), 8.07 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 9.0 Hz, 2H), 7.04 (d, J = 9.0 Hz, 2H), 4.48 (q, J = 7.2 Hz, 2H), 3.91 (s, 3H), 2.56 (s, 3H), 1.46 (t, J = 6.6 Hz, 3H).

[0260] Example 68. Ethyl 2-(4-nitrophenyl)-5-phenyloxazole-4-carboxylate (94) This compound was obtained in 57% yield as a white solid in the same manner as in the synthesis of compound 27.

[0261] 1H NMR (600 MHz, MeOD) δ 8.41 (d, J = 9.0 Hz, 1H), 8.37 (d, J = 9.0 Hz, 2H), 8.13-8.11 (m, 2H), 7.55-7.53 (m, 3H), 4.41 (q, J = 7.2 Hz, 2H), 1.38 (t, J = 7.2 Hz, 3H).

[0262] Example 69. Ethyl 5-(2-nitrophenyl)-2-(4-nitrophenyl)oxazole-4-carboxylate (95) This compound was obtained as a white solid in 70% yield in a similar manner to the synthesis of compound 27, except that 1-iodo-2-nitrobenzene was used instead of iodobenzene.

[0263] 1 H NMR (600 MHz, MeOD) δ 8.43 (d, J = 8.4 Hz, 2H), 8.35 (d, J = 8.4 Hz, 2H), 8.27 (d, J = 7.8 Hz, 1H), 7.92-7.89 (m, 2H), 7.89-7.86 (m, 1H), 4.24 (q, J = 7.2 Hz, 2H), 1.18 (t, J = 7.2 Hz, 3H).

[0264] Example 70. Ethyl 2-(4-((tert-butoxycarbonyl)amino)phenyl)-5-(3-(methylthio)phenyl)oxazole-4-carboxylate (96) This compound was obtained as a white solid in 57% yield in a similar manner to the synthesis of compound 27, except that 3-bromothioanisole was used instead of iodobenzene.

[0265] 1H NMR (600 MHz, CDCl3) δ 8.09 (d, J = 9.0 Hz, 2H), 8.06-8.05 (m, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.51 (d, J = 9.0 Hz, 2H), 7.42 (t, J = 7.8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 6.66 (s, 1H), 4.46 (q, J = 7.2 Hz, 2H), 2.57 (s, 3H), 1.54 (s, 9H), 1.43 (t, J = 7.2 Hz, 3H).

[0266] Example 71. Ethyl 2-(4-cyclopropylphenyl)-5-phenyloxazole-4-carboxylate (97) This compound was obtained in quantitative yield as a white solid in a similar manner to the synthesis of compound 27.

[0267] 1 H NMR (600 MHz, CDCl3) δ 8.14-8.12 (m, 2H), 8.05 (d, J = 8.4 Hz, 2H), 7.52-7.48 (m, 3H), 7.17 (d, J = 8.4 Hz, 2H), 4.47 (q, J = 7.2 Hz, 2H), 1.98-1.95 (m, 1H), 1.43 (t, J = 7.2 Hz, 3H), 1.08-1.05 (m, 2H), 0.81-0.78 (m, 2H).

[0268] Example 72. Ethyl 2-(4-chloro-3-(trifluoromethyl)phenyl)-5-phenyloxazole-4-carboxylate (98) This compound was obtained in 11% yield as a fluffy white solid in a manner similar to that of compound 27.

[0269] 1H NMR (600 MHz, CDCl3) δ 8.49 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.12-8.11 (m, 2H), 7.67 (d, J = 6.0 Hz, 1H), 7.56-7.53 (m, 3H), 4.49 (q, J = 7.2 Hz, 2H), 1.45 (t, J = 6.6 Hz, 3H).

[0270] Example 73. Ethyl 5-(2-aminophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (99) To a solution of compound 32 (100 mg, 0.25 mmol) in MeOH (7.0 mL) was added 10% Pd / C (52.3 mg, 0.49 mmol). The reaction mixture was purged with H (hydrogen-filled balloon) and stirred for 18 h. After adding additional MeOH (10 mL), the reaction mixture was briefly heated with a heat gun and filtered through a Celite pad. The volatiles were removed by evaporation to give compound 99 (91.6 mg, 99%) as a gray powder.

[0271] 1 H NMR (600 MHz, CDCl3) δ 8.26 (d, J = 7.8 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.52-7.31 (m, 4H), 4.47 (q, J = 7.2 Hz, 2H), 3.89 (brs, 2H), 1.45 (t, J = 7.2 Hz, 3H).

[0272] Example 74. Ethyl 5-(3-aminophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (100) To a solution of compound 33 (200 mg, 0.49 mmol) in MeOH (14 mL) was added 10% Pd / C (105 mg, 0.098 mmol). The reaction mixture was irradiated with H (hydrogen-filled balloon) and stirred for 12 h. After adding additional MeOH (10 mL), the reaction mixture was briefly heated with a heat gun and filtered through a Celite pad. The volatiles were removed by evaporation, and the residue was purified by silica gel column chromatography (eluted with hexane:EtOAc = 4:1 to 2:1, v / v) to give compound 100 as a gray powder (125 mg, 67%).

[0273] 1 H NMR (600 MHz, CDCl3) δ 8.27 (d, J = 7.8 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.50-7.48 (m, 2H), 7.30 (t, J = 7.2 Hz, 1H), 6.83-6.82 (m, 1H), 4.48 (q, J = 7.2 Hz, 2H), 3.89 (brs, 2H), 1.45 (t, J = 7.2 Hz, 3H).

[0274] Example 75. Ethyl 5-(4-aminophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (101) To a solution of compound 34 (200 mg, 0.49 mmol) in MeOH (14 mL) was added 10% Pd / C (105 mg, 0.098 mmol). The reaction mixture was irradiated with H (hydrogen-filled balloon) and stirred for 12 h. After the addition of additional MeOH (10 mL), the reaction mixture was briefly heated with a heat gun and filtered through a Celite pad. The volatiles were removed by evaporation, and the residue was purified by silica gel column chromatography (eluted with hexane:EtOAc = 4:1 to 2:1, v / v) to give pure compound 101 as a gray powder (132 mg, 52%).

[0275] 1H NMR (600 MHz, CDCl3) δ 8.25 (d, J = 7.9 Hz, 2H), 8.01 (d, J = 8.3 Hz, 2H), 7.74 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 8.3 Hz, 2H), 4.46 (q, J = 7.0 Hz, 2H), 4.10-3.94 (m, 2H), 1.44 (t, J = 7.0 Hz, 3H).

[0276] Example 76. Ethyl 5-(4-aminophenyl)-2-(4-(tert-butyl)phenyl)oxazole-4-carboxylate (102) To a solution of compound 89 (270 mg, 0.68 mmol) in MeOH (20 mL) was added 10% Pd / C (146 mg, 0.069 mmol). The reaction mixture was irradiated with H2 (hydrogen-filled balloon) and stirred for 12 h. After adding more MeOH (10 mL), the reaction mixture was briefly heated with a heat gun and filtered through a Celite pad. The volatiles were removed by evaporation, and the residue was purified by silica gel column chromatography (eluted with hexane:ether = 3:1 to 1:1, v / v) to give pure compound 102 as a gray powder (149 mg, 60%).

[0277] 1 H NMR (600 MHz, CDCl3) δ 8.07 (d, J = 8.4 Hz, 2H), 8.00 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 9.0 Hz, 2H), 6.77 (d, J = 8.4 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 4.00 (brs, 2H), 1.44 (t, J = 7.2 Hz, 3H), 1.36 (s, 9H).

[0278] Example 77. Ethyl 5-(3-(methylsulfinyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (103) A solution of compound 36 (120 mg, 0.29 mmol) in anhydrous CHCl (8.0 mL) was added dropwise to a solution of m-CPBA (51 mg, 0.29 mmol, 1.0 eq) in anhydrous CHCl (2.0 mL) at 0 °C under an argon atmosphere, and the mixture was stirred at room temperature for 4 h. The reaction mixture was quenched with water and extracted three times with CHCl. ​​The organic layer was dried over MgSO, filtered, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluted with hexane:EtOAc = 2:1 to 1:3, v / v) to give compound 103 (93 mg, 76%).

[0279] 1 H NMR (600 MHz, CDCl3) δ 8.47 (s, 1H), 8.33 (d, J = 8.1 Hz, 3H), 7.80 (d, J = 8.3 Hz, 3H), 7.72 (t, J = 7.8 Hz, 1H), 4.51 (q, J = 7.1 Hz, 2H), 2.85 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H). HRMS m / z: calcd for C 20 H 16 F3NO4S [M + H] + : 424.0786; found: 424.0830.

[0280] Example 78. Ethyl 5-(4-(methylsulfinyl)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (104) A solution of compound 37 (154 mg, 0.38 mmol) in anhydrous CHCl (8.0 mL) was added dropwise to a solution of m-CPBA (65 mg, 0.38 mmol, 1.0 eq) in anhydrous CHCl (2.0 mL) at 0 °C under an argon atmosphere, and the mixture was stirred at room temperature for 4 h. The reaction mixture was quenched with water and extracted three times with CHCl. ​​The organic layer was dried over MgSO, filtered, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluted with hexane:EtOAc = 2:1 to 1:3, v / v) to give compound 104 (116 mg, 72%).

[0281] 1H NMR (600 MHz, CDCl3) δ 8.30-8.37 (m, 4H), 7.79-7.85 (m, 4H), 4.52 (q, J = 7.1 Hz, 2H), 2.82 (s, 3H), 1.48 (t, J = 7.08 Hz, 3H). HRMS m / z: calcd for C 20 H 16 F3NO4S [M + H] + : 424.0786; found: 424.0835.

[0282] Example 79. Ethyl 2-(4-aminophenyl)-5-(3-(methylthio)phenyl)oxazole-4-carboxylate (105) Compound 96 (240 mg, 0.53 mmol) was dissolved in anhydrous CHCl (10 mL) and trifluoroacetic acid (16 equivalents per amine functional group) was added at 0 °C. The mixture was then stirred at room temperature for 2 hours. The volatile components were evaporated and replaced with anhydrous toluene, which was then evaporated to azeotrope excess trifluoroacetic acid. This process was repeated three times to obtain an oil, which was dried in vacuo and used in the next step without further purification.

[0283] 1 H NMR (600 MHz, DMSO-d6) δ 7.98 (m, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.47 (t, J = 7.8 Hz, 2H), 7.41-7.37 (m, 1H), 6.67 (d, J = 8.4 Hz, 2H), 5.88 (s, 2H), 4.31 (q, J = 7.2 Hz, 2H), 2.54 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H).

[0284] Example 80. Ethyl 5-(3-acetamidophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (106) Under an argon atmosphere, DIPEA (97 μL, 0.59 mmol) was added to a solution of compound 100 (70 mg, 0.19 mmol) in anhydrous CHCl (4.0 mL). Acetyl chloride (27 μL, 0.37 mmol) was slowly added dropwise to the mixture at 0 °C, followed by stirring at room temperature for 6 h. The volatile components were evaporated, and the residue was purified by silica gel column chromatography (eluted with hexane: EtOAc = 4:1 v / v) to give compound 106 (55 mg, 70%).

[0285] 1 H NMR (600 MHz, CDCl3) δ 8.36 (s, 1H), 8.25 (d, J = 7.8 Hz, 2H), 7.83 (d, J = 7.2 Hz, 2H), 7.74 (d, J = 8.4 Hz, 3H), 7.45 (t, J = 7.8 Hz, 1H), 4.47 (q, J = 7.2 Hz, 2H), 2.23 (s, 3H), 1.44 (t, J = 7.2 Hz, 3H).

[0286] Compounds 107-112 were synthesized in a manner similar to that described for compound 106.

[0287] Example 81. Ethyl 5-(4-acetamidophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (107) This compound was obtained in 73% yield as a fluffy white solid in a manner similar to that of compound 106.

[0288] 1 H NMR (600 MHz, CDCl3) δ 8.28 (d, J = 8.4 Hz, 2H), 8.14 (d, J = 9.0 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.62 (brs, 1H), 4.48 (q, J = 7.2 Hz, 2H), 2.25 (s, 3H), 1.45 (t, J = 7.2 Hz, 3H).

[0289] Example 82. Ethyl 5-(3-(N-acetylacetamido)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (108) This compound was obtained in 26% yield as a fluffy white solid in a manner similar to that of compound 106.

[0290] 1 H NMR (600 MHz, CDCl3) δ 8.30 (d, J = 8.4 Hz, 2H), 8.22 (d, J = 7.8 Hz, 1H), 8.03 (s, 1H), 7.79 (d, J = 7.8 Hz, 2H), 7.65 (t, J = 8.4 Hz, 1H), 7.31 (d, J = 0.6 Hz, 1H), 4.50 (q, J = 7.2 Hz, 2H), 2.39 (s, 6H), 1.47 (t, J = 7.8 Hz, 3H).

[0291] Example 83. Ethyl 5-(4-(N-acetylacetamido)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (109) This compound was obtained in 15% yield as a fluffy white solid in a manner similar to that of compound 106.

[0292] 1 H NMR (600 MHz, CDCl3) δ 8.31 (d, J = 8.4 Hz, 4H), 7.80 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 4.51 (q, J = 7.2 Hz, 2H), 2.37 (s, 6H), 1.47 (t, J = 7.8 Hz, 3H).

[0293] Example 84. Ethyl 5-(4-(N-acetylacetamido)phenyl)-2-(4-(tert-butyl)phenyl)oxazole-4-carboxylate (110) This compound was obtained in quantitative yield as a fluffy white solid in a manner similar to that of compound 106.

[0294] 1 H NMR (600 MHz, CDCl3) δ 8.31 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 9.0 Hz, 2H), 4.50 (q, J = 7.2 Hz, 2H), 2.37 (s, 6H), 1.47 (t, J = 7.2 Hz, 3H), 1.39 (s, 9H).

[0295] Example 85. Ethyl 5-(4-acetamidophenyl)-2-(4-(tert-butyl)phenyl)oxazole-4-carboxylate (111) This compound was obtained in 54% yield as a fluffy white solid in a manner similar to that of compound 106.

[0296] 1 H NMR (600 MHz, CDCl3) δ 8.15 (d, J = 9.0 Hz, 2H), 8.09 (d, J = 7.8 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.47 (s, 1H), 4.48 (q, J = 7.2 Hz, 2H), 2.45 (s, 3H), 1.45 (t, J = 7.2 Hz, 3H), 1.38 (s, 9H).

[0297] Example 86. Ethyl 2-(4-acetamidophenyl)-5-(3-(methylthio)phenyl)oxazole-4-carboxylate (112) This compound was obtained in 74% yield as a white solid in a similar manner to the synthesis of compound 106.

[0298] 1H NMR (600 MHz, CDCl3) δ 8.11 (d, J = 8.4 Hz, 2H), 8.04 (s, 1H), 7.86 (d, J = 7.2 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.52 (s, 1H), 7.42 (t, J = 7.2 Hz, 1H), 7.37-7.35 (m, 1H), 4.45 (q, J = 6.6 Hz, 2H), 2.57 (s, 3H), 2.22 (s, 3H), 1.43 (t, J = 7.2 Hz, 3H).

[0299] Example 87. Ethyl 5-(4-(methylsulfonamido)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate (113) Pyridine (90 μL, 0.46 mmol) was added to a solution of compound 101 (87 mg, 0.23 mmol) in anhydrous CHCl (5.0 mL) under an argon atmosphere. Methanesulfonyl chloride (20 μL, 0.28 mmol) was slowly added dropwise to the reaction mixture at 0 °C, and the mixture was stirred for 16 h after warming to room temperature. The reaction mixture was distilled under reduced pressure, and the residue was purified by silica gel column chromatography (eluted with hexane:EtOAc = 5:1 to 1:1, v / v) to give compound 113 (72 mg, 69%).

[0300] 1 H NMR (600 MHz, CDCl3) δ 8.27 (d, J = 8.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 2H), 7.76 (d, J = 8.7 Hz, 2H), 6.58 (s, 1H), 4.48 (q, J = 7.1 Hz, 2H), 3.11 (s, 3H), 1.45 (t, J = 7.14 Hz, 3H). HRMS m / z: calcd for C 20 H 17 F3N2O5S [M + H] + : 455.0844; found: 455.0908.

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[0315] Example 88. Synthesis by general method of hydrolysis and amide coupling reaction: N-(2-dimethylamino)ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (114) Ethyl 5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxylate (150 mg, 0.53 mmol) was dissolved in EtOH (10 mL). 3N NaOH (1.5 mL) was added, and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was evaporated under reduced pressure, acidified with 3N HCl, and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO, filtered, and evaporated under reduced pressure to give the carboxylic acid compound as a white solid, which was used in the next step without further purification. To a solution of the carboxylic acid compound (132 mg, 0.51 mmol) in DMF (5 mL) was added N,N-dimethylethylenediamine (67 μL, 0.61 mmol), 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (117 mg, 0.61 mmol), 1-hydroxybenzotriazole (82 mg, 0.61 mmol), and DIPEA (178 μL, 1.0 mmol). After stirring at room temperature for 15 h, the reaction was confirmed to be complete by TLC. The reaction mixture was evaporated, and then toluene was added and distilled under reduced pressure (repeated three times) to completely remove DMF. The concentrated reaction mixture was added to water and extracted three times with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and distilled under reduced pressure. The residue was purified by silica gel column chromatography (eluted with CH2Cl2:MeOH=20:1 to 10:1, v / v) to give compound 114 as a pale yellow solid (66 mg, 40%).

[0316] 1 H NMR (600 MHz, CDCl3) δ 8.29 (s, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.44 (br s, 1H), 3.57 (t, J = 6.0 Hz, 2H), 2.57 (t, J = 6.0 Hz, 2H), 2.34 (s, 6H).

[0317] Compounds 115-280 were synthesized in a manner similar to that described for compound 114.

[0318] Example 89. N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (115) This compound was obtained in 91% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0319] 1 H NMR (600 MHz, MeOD) δ 8.48 (s, 1H), 8.24 (d, J = 8,4 Hz, 2H), 7.83 (d, J = 8,4 Hz, 2H), 3.55 (t, J = 6.6 Hz, 2H), 2.63 (t, J = 6.6 Hz, 2H), 2.53 (br s, 8H), 2.29 (s, 3H).

[0320] Example 90. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (116) This compound was obtained in 59% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0321] 1 H NMR (600 MHz, MeOD) δ 8.47 (s, 1H), 8.25 (d, J = 7.8 Hz, 2H), 7.85 (d, J = 7.8 Hz, 2H), 4.14 (br s, 2H), 3.79 (br s, 2H), 2.61 (br s, 8H), 2.36 (s, 6H).

[0322] Example 91. Synthesis by general method of hydrolysis and amide coupling reaction: N-(2-(dimethylamino)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (117) This compound was obtained in 59% yield (75 mg, 25%) by a general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 114.

[0323] 1 H NMR (600 MHz, CDCl3) δ 8.42 (d, J = 7.2 Hz, 2H), 8.17 (d, J = 7.8 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.73-7.70 (m, 2H), 7.65 (t, J = 7.8 Hz, 1H), 7.49 (t, J = 7.2 Hz, 2H), 7.45-7.42 (m, 1H), 3.58 (q, J = 6.0 Hz, 2H), 2.57 (t, J = 6.0 Hz, 2H), 2.32 (s, 6H).

[0324] Example 92. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (118) This compound was obtained in 41% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0325] 1 H NMR (600 MHz, CDCl3) δ 8.42 (d, J = 7.2 Hz, 2H), 8.17 (d, J = 7.2 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.83 (t, J = 4.8 Hz, 1H), 7.72 (t, J = 7.8 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.47-7.44 (m, 1H), 3.59 (q, J = 6.0 Hz, 2H), 2.65 (t, J = 6.0 Hz, 2H), 2.64-2.45 (brs, 8H), 2.33 (s, 3H).

[0326] Example 93. N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (119) This compound was obtained in 51% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0327] 1 H NMR (600 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 7.8 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.86 (d, J = 7.2 Hz, 1H), 7.75-7.70 (m, 2H), 7.65 (q, J = 8.4 Hz, 2H), 7.55 (brs, 1H), 3.49 (q, J = 6.0 Hz, 2H), 2.51 (t, J = 6.0 Hz, 2H), 2.29 (s, 6H).

[0328] Example 94. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (120) This compound was obtained in 49% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0329] 1 H NMR (600 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.75-7.63 (m, 5H), 3.50 (q, J = 6.0 Hz, 2H), 2.60 (t, J = 6.0 Hz, 2H), 2.52 (brs, 8H), 2.32 (s, 3H).

[0330] Example 95. N-(2-(dimethylamino)ethyl)-5-phenyl-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide (121) This compound was obtained in 42% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0331] 1 H NMR (600 MHz, CDCl3) δ 8.39-8.37 (m, 3H), 8.32 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.69 (brs, 1H), 7.66 (t, J = 7.8 Hz, 1H), 7.53-7.45 (m, 3H), 3.60 (q, J = 6.0 Hz, 2H), 2.59 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0332] Example 96. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide (122) This compound was obtained in 74% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0333] 1 H NMR (600 MHz, CDCl3) δ 8.42-8.40 (m, 3H), 8.30 (d, J = 8.4 Hz, 1H), 7.88 (t, J = 4.8 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.48-7.46 (m, 1H), 3.60 (q, J = 6.0 Hz, 2H), 2.67 (t, J = 6.0 Hz, 2H), 2.65-2.45 (brs, 8H), 2.33 (s, 3H).

[0334] Example 97. N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide (123) This compound was obtained in 56% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0335] 1 H NMR (600 MHz, CDCl3) δ 8.33 (s, 1H), 8.24 (d, J = 7.8 Hz, 1H), 8.15 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.93 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.77-7.74 (m, 2H), 7.68-7.63 (m, 2H), 7.52 (t, J = 4.8 Hz, 1H), 3.51 (q, J = 6.0 Hz, 2H), 2.54 (t, J = 6.0 Hz, 2H), 2.31 (s, 6H).

[0336] Example 98. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(3-(trifluoromethyl)phenyl)oxazole-4-carboxamide (124) This compound was obtained in 28% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0337] 1H NMR (600 MHz, CDCl3) δ 8.35 (s, 1H), 8.21 (d, J = 7.8 Hz, 1H), 8.14 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.94 (dd, J = 1.2 and J = 7.8 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.75 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.70-7.64 (m, 3H), 3.51 (q, J = 6.0 Hz, 2H), 2.63 (t, J = 6.0 Hz, 2H), 2.60 (brs, 8H), 2.34 (s, 3H).

[0338] Example 99. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(3-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (125) This compound was obtained in 56% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0339] 1 H NMR (600 MHz, CDCl3) δ 8.31 (s, 1H), 8.23 ​​(d, J = 7.8 Hz, 1H), 8.10 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 7.2 Hz, 1H), 7.77-7.73 (m, 2H), 7.67-7.62 (m, 2H), 3.87 (brs, 2H), 3.73 (brs, 2H), 2.58-2.51 (m, 8H), 2.37 (s, 6H).

[0340] Example 100. N-(2-(dimethylamino)ethyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (126) This compound was obtained in 50% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0341] 1 H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 7.2 Hz, 2H), 8.23 ​​(d, J = 7.8 Hz, 2H), 7.76-7.73 (m, 3H), 7.51 (t, J = 7.2 Hz, 2H), 7.49-7.46 (m, 1H), 3.61 (q, J = 6.6 Hz, 2H), 2.62 (t, J = 6.6 Hz, 2H), 2.36 (s, 6H).

[0342] Example 101. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (127) This compound was obtained in 81% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0343] 1 H NMR (600 MHz, MeOD) δ 8.28-8.24 (m, 4H), 7.82 (d, J = 8.4 Hz, 2H), 7.49-7.43 (m, 3H), 3.59 (t, J = 6.6 Hz, 2H), 2.63 (t, J = 6.6 Hz, 2H), 2.57 (brs, 8H), 2.29 (s, 3H).

[0344] Example 102. N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (128) This compound was obtained in 60% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0345] 1H NMR (600 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.75-7.63 (m, 5H), 3.50 (q, J = 6.0 Hz, 2H), 2.60 (t, J = 6.0 Hz, 2H), 2.52 (brs, 8H), 2.32 (s, 3H).

[0346] Example 103 (4-(2-(dimethylamino)ethyl)piperazin-1-yl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (129) This compound was obtained in 34% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0347] 1 H NMR (600 MHz, CDCl3) δ 8.24 (d, J = 7.8 Hz, 2H), 7.86 (d, J = 7.8 Hz, 2H), 7.76 (d, J = 7.8 Hz, 2H), 7.48 (t, J = 7.2 Hz, 2H), 7.43-7.41 (m, 1H), 3.89 (brs, 2H), 3.57 (brs, 2H), 2.61 (brs, 2H), 2.52-2.51 (m, 2H), 2.47-2.46 (m, 2H), 2.43 (brs, 2H), 2.28 (s, 6H).

[0348] Example 104. N-(4-hydroxyphenethyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (130) This compound was obtained in 34% yield by a method similar to the synthesis of compound 114, which is a general method of hydrolysis and amide coupling reaction.

[0349] 1H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 7.8 Hz, 2H), 8.21 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 7.8 Hz, 2H), 7.52 (t, J = 7.2 Hz, 3H), 7.15 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.4 Hz, 2H), 3.71 (q, J = 7.2 Hz, 2H), 2.92 (t, J = 7.2 Hz, 2H).

[0350] Example 105. N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (131) This compound was obtained in 92% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0351] 1 H NMR (600 MHz, CDCl3) δ 8.19 (t, J = 7.8 Hz, 2H), 7.85 (d, J = 7.8 Hz, 1H), 7.78 (t, J = 7.2 Hz, 1H), 7.75-7.69 (m, 3H), 7.66 (t, J = 7.8 Hz, 1H), 3.59 (q, J = 6.6 Hz, 2H), 2.61 (t, J = 6.6 Hz, 2H), 2.53 (s, 6H).

[0352] Example 106 (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(piperazin-1-yl)methanone (132) This compound was obtained in 100% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0353] 1H NMR (600 MHz, MeOD) δ 8.31 (d, J = 8.4 Hz, 2H), 8.19 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 7.8 Hz, 1H), 7.90 (d, J = 8.4 Hz, 3H), 7.91-7.88 (m, 1H), 7.80 (t, J = 8.4 Hz, 1H), 4.30 (s, 2H), 3.92 (s, 2H), 3.34 (s, 4H).

[0354] Example 107. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (133) This compound was obtained in 91% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0355] 1 H NMR (600 MHz, CDCl3) δ 8.25 (d, J = 8.1 Hz, 2H), 8.15 (d, J = 6 Hz, 1H), 7.91-7.81 (m, 4H), 7.80-7.72 (m, 1H), 3.88 (brs, 2H), 3.71 (brs, 2H), 2.61-2.45 (m, 8H), 2.29 (s, 6H).

[0356] Example 108 (4-(2-Methoxyphenyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (134) This compound was obtained in 27% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0357] 1H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 2H), 8.09 (d, J = 7.8 Hz, 1H), 7.91 (d, J =7.8 Hz, 1H), 7.79-7.71 (m, 3H), 7.64 (t, J = 7.8 Hz, 1H), 7.05 (t, J = 7.8 Hz, 1H), 6.97-6.89 (m, 2H), 6.88 (d, J = 8.4 Hz, 1H), 4.03 (s, 2H), 3.92 (s, 2H), 3.88 (s, 3H), 3.11 (s, 2H), 3.07 (s, 2H).

[0358] Example 109. Ethyl 4-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carbonyl)piperazine-1-carboxylate (135) This compound was obtained in 91% yield as a yellow solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0359] 1 H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.76-7.74 (m, 3H), 7.65 (t, J = 7.8 Hz, 1H), 4.17 (q, J = 7.2 Hz, 2H), 3.90 (brs, 2H), 3.70 (brs, 2H), 3.56 (brs, 4H), 1.28 (t, J = 7.2 Hz, 3H).

[0360] Example 110. 4-Nitrophenyl 4-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carbonyl)piperazine-1-carboxylate (136) This compound was obtained in 73% yield as a yellow solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0361] 1 H NMR (600 MHz, CDCl3) δ 8.28 (d, J = 9.0 Hz, 2H), 8.20 (d, J = 8.4 Hz, 2H), 8.13 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.90 (brs, 1H), 7.80-7.77 (m, 3H), 7.70-7.68 (m, 1H), 7.34 (d, J = 8.4 Hz, 2H), 4.09 (brs, 2H), 3.82 (brs, 4H), 3.72 (brs, 2H).

[0362] Example 111. 2-(Dimethylamino)ethyl 4-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carbonyl)piperazine-1-carboxylate (137) This compound was obtained in 34% yield as a yellow solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0363] 1 H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 7.8 Hz, 2H), 8.11 (d, J = 7.8 Hz, 1H), 7.89 (d, J = 7.2 Hz, 1H), 7.77-7.74 (m, 3H), 7.66 (t, J = 7.8 Hz, 1H), 4.23 (t, J = 6.0 Hz, 2H), 3.91 (brs, 2H), 3.70 (brs, 2H), 3.57 (brs, 4H), 2.61 (brs, 2H), 2.31 (s, 6H).

[0364] Example 112 (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(pyrrolidin-1-yl)methanone (138) This compound was obtained in 96% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0365] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 7.8 Hz, 2H), 8.10 (dd, J = 0.6 Hz and J = 8.1 Hz, 1H), 7.95 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.74-7.71 (m, 3H), 7.63 (t, J = 8.4 Hz, 1H), 3.95 (t, J = 6.9 Hz, 2H), 3.60 (t, J = 6.9 Hz, 2H), 2.00-1.96 (m, 2H), 1.93-1.88 (m, 2H).

[0366] Example 113. 5-(2-Nitrophenyl)-N-(2-(pyrrolidin-1-yl)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (139) This compound was obtained in 90% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0367] 1H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 8.4 Hz, 2H), 8.12 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.94 (dd, J = 1.8 Hz and J = 7.5 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.73 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 7.60 (brs, 1H), 3.56 (dd, J = 6.0 Hz and J = 12.0 Hz, 2H), 2.75 (t, J = 6.0 Hz, 2H), 2.63 (brs, 4H), 1.84 (brs, 6H).

[0368] Example 114. 5-(2-Nitrophenyl)-N-(3-(pyrrolidin-1-yl)propyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (140) This compound was obtained in 90% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0369] 1 H NMR (600 MHz, CDCl3) δ 8.33 (brs, 1H), 8.17 (d, J = 8.4 Hz, 2H), 8.14 (dd, J = 0.6 Hz and J = 8.4 Hz, 1H), 7.96 (dd, J = 1.2 Hz and J = 7.5 Hz, 1H), 7.78-7.74 (m, 3H), 7.68 (t, J = 8.7 Hz, 1H), 3.55 (q, J = 9.0 Hz, 2H), 2.72-2.68 (m, 6H), 1.91-1.87 (m, 6H).

[0370] Example 115. 5-(2-Nitrophenyl)-N-(pyridin-4-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (141) This compound was obtained in 90% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0371] 1 H NMR (600 MHz, CDCl3) δ 8.58 (dd, J = 1.2 Hz and J = 4.8 Hz, 2H), 8.16-8.14 (m, 3H), 7.94 (dd, J = 1.2 Hz and J = 7.8 Hz, 2H), 7.78-7.75 (m, 3H), 7.71-7.67 (m, 2H), 7.29 (d, J = 6.0 Hz, 2H), 4.63 (d, J = 6.0 Hz, 2H).

[0372] Example 116. 5-(2-Nitrophenyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (142) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0373] 1 H NMR (600 MHz, CDCl3) δ 8.64 (d, J = 1.2 Hz, 1H), 8.57 (dd, J = 1.2 Hz and J = 4.8 Hz, 1H), 8.16 (t, J = 6.9 Hz, 3H), 7.96 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.79-7.68 (m, 5H), 7.61 (t, J = 6.0 Hz, 1H), 7.31-7.28 (m, 1H), 4.65 (d, J = 6.0 Hz, 2H).

[0374] Example 117. 5-(2-Nitrophenyl)-N-(pyridin-2-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (143) This compound was obtained in 47% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0375] 1 H NMR (600 MHz, CDCl3) δ 9.58 (s, 1H), 8.37 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.22 (d, J = 8.2 Hz, 2H), 8.19 (dd, J = 1.2 Hz and J = 8.2 Hz, 1H), 7.94 (dd, J = 1.3 Hz and J = 7.8 Hz, 1H), 7.81-7.78 (m, 3H), 7.73-7.69 (m, 2H), 7.09 (ddd, J = 1.0 Hz, J = 4.9 Hz and J = 7.3 Hz, 1H).

[0376] Example 118 (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(piperidin-1-yl)methanone (144) This compound was obtained in 93% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0377] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.2 Hz, 2H), 8.07 (dd, J = 0.9 Hz and J = 8.2 Hz, 1H), 7.91 (dd, J = 1.2 Hz and J = 7.6 Hz, 1H), 7.75-7.22 (m, 3H), 7.63 (t, J = 6.0 Hz, 1H), 3.69-3.65 (m, 4H), 1.67-1.60 (m, 4H), 1.55 (brs, 2H).

[0378] Example 119. (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-phenylpiperidin-1-yl)methanone (145) This compound was obtained in 85% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0379] 1 H NMR (600 MHz, CDCl3) δ 8.18 (d, J = 8.4 Hz, 2H), 8.09 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.94 (dd, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.78-7.75 (m, 3H), 7.68-7.65 (m, 1H), 7.32 (t, J = 7.2 Hz, 2H), 7.24-7.21 (m, 3H), 4.80 (d, J = 12.6 Hz, 1H), 4.57 (d, J = 13.2 Hz, 1H), 3.23 (t, J = 12.6 Hz, 1H), 2.86-2.77 (m, 2H), 1.96 (d, J = 12.6 Hz, 1H), 1.88 (d, J = 12.6 Hz, 1H), 1.80-1.73 (m, 2H).

[0380] Example 120 (4-Cyclopropylpiperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (146) This compound was obtained in 98% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0381] 1H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.4 Hz, 2H), 8.08 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.74 (t, J = 8.4 Hz, 3H), 7.65 (t, J = 7.8 Hz, 1H), 3.79 (s, 2H), 3.69 (s, 2H), 2.66 (s, 2H), 2.60 (s, 2H), 1.65-1.60 (m, 1H), 1.31-1.22 (m, 2H), 1.30-1.23 (m, 1H), 0.91-0.41 (m, 4H).

[0382] Example 121. N-(4-acetylphenyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (147) This compound was obtained in 78% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0383] 1 H NMR (600 MHz, CDCl3) δ 9.12 (s, 1H), 8.23-8.29 (m, 3H), 7.98-7.94 (m, 3H), 7.82-7.79 (m, 5H), 7.73 (t, J = 12.0 Hz, 1H), 2.59 (s, 3H).

[0384] Example 122. 5-(2-Nitrophenyl)-N-(4-(trifluoromethyl)benzyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (148) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0385] 1H NMR (600 MHz, CDCl3) δ 8.15 (d, J = 7.8 Hz, 3H), 7.95 (d, J = 7.8 Hz, 1H), 7.78-7.74 (m, 3H), 7.68 (t, J = 7.8 Hz, 1H), 7.61 (d, J = 7.8 Hz, 3H), 7.48 (d, J = 7.8 Hz, 2H), 4.67(d, J = 6.6 Hz, 2H).

[0386] Example 123. N-(4-fluorophenethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (149) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0387] 1 H NMR (600 MHz, CDCl3) δ 8.12 (t, J = 8.4 Hz, 3H), 7.92 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.76-7.73 (m, 3H), 7.66 (td, J = 8.1 Hz and J = 1.8 Hz, 1H), 7.28-7.26 (m, 1H), 7.21-7.18 (m, 2H), 7.00 (t, J = 8.7 Hz, 2H), 3.63 (q, J = 6.6 Hz, 2H), 2.89 (t, J = 7.2 Hz, 2H).

[0388] Example 124 (4-(3-(dimethylamino)propyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (150) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0389] 1H NMR (600 MHz, MeOD) δ 8.23 ​​(d, J = 8.4 Hz, 2H), 8.13 (d, J = 7.8 Hz, 1H), 7.87-7.84 (m, 3H), 7.70-7.74 (m, 1H), 7.68 (dd, J = 7.8 Hz and J = 19.8 Hz, 1H), 7.29-7.24 (m, 1H), 3.86 (brs, 2H), 3.69 (brs, 2H), 3.19 (t, J = 7.2 Hz, 2H), 2.88 (s, 6H), 2.52-2.48 (m, 6H), 1.93-1.88 (m, 2H).

[0390] Example 125. (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-(2-(piperidin-1-yl)ethyl)piperazin-1-yl)methanone (151) This compound was obtained in 92% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0391] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.3 Hz, 2H), 8.08 (d, J = 8.3 Hz, 1H), 7.87 (d, J = 7.7 Hz, 1H), 7.75-7.73 (m, 3H), 7.65 (t, J = 8.4 Hz, 1H), 3.85 (brs, 2H), 3.73 (brs, 2H), 2.49-2.60 (m, 12H), 1.62 (t, J = 6.0 Hz, 4H), 1.45 (brs, 2H).

[0392] Example 126 (4-(2-morpholinoethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (152) This compound was obtained in 31% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0393] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 7.8 Hz, 2H), 8.09 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.88 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.76-7.73 (m, 3H), 7.67-7.64 (m, 1H), 3.86 (brs, 2H), 3.73-3.70 (m, 6H), 2.55-2.49 (m, 12H).

[0394] Example 127. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (153) This compound was obtained in 90% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0395] 1 H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 8.3 Hz, 2H), 8.12 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 7.7 Hz, 1H), 7.77-7.73 (m, 3H), 7.66 (t, J = 7.7 Hz, 1H), 7.62 (t, J = 5.0 Hz, 1H), 3.51 (q, J = 6.0 Hz, 2H), 2.63-2.46 (m, 10H), 2.35 (s, 3H).

[0396] Example 128 (4-(2-(diethylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (154) This compound was obtained in 82% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0397] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.4 Hz, 2H), 8.09 (d, J = 7.8 Hz, 1H), 7.86 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.74 (t, J = 7.8 Hz, 3H), 7.65 (t, J = 8.4 Hz, 1H), 3.92 (brs, 2H), 3.75 (brs, 2H), 3.05 (brs, 4H), 2.97 (brs, 2H), 2.82 (brs, 2H), 2.57 (d, J = 4.2 Hz, 4H), 1.32 (t, J = 6.6 Hz, 6H).

[0398] Example 129 (4-Methylpiperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (155) This compound was obtained in 42% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0399] 1 H NMR (600 MHz, CDCl3) δ 8.17 (s, 1H), 8.16 (s, 1H), 8.09 (d, J = 8.3 Hz, 1H), 7.89 (dd, J = 1.1 Hz and J = 7.7 Hz, 1H), 7.75-7.73 (m, 3H), 7.65 (t, J = 8.4 Hz, 1H), 3.87 (brs, 2H), 3.74 (brs, 2H), 2.46 (brs, 2H), 2.41 (brs, 2H), 2.31 (s, 3H).

[0400] Example 130. Morpholino(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (156) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0401] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 7.8 Hz, 2H), 8.10 (dd, J = 0.6 Hz and J = 8.1 Hz, 1H), 7.88 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.79-7.72 (m, 3H), 7.66 (t, J = 9.0 Hz, 1H), 3.93 (s, 2H), 3.83-3.62 (m, 6H).

[0402] Example 131. N-(3-morpholinopropyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (157) This compound was obtained in 27% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0403] 1 H NMR (600 MHz, CDCl3) δ 8.38 (t, J = 5.4 Hz, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.12 (d, J = 8.4 Hz, 1H), 7.92 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.77 (d, J = 8.4, 2H), 7.74 (t, J = 7.2 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 3.87 (t, J = 4.8 Hz, 4H), 3.52 (dd, J = 6.0 Hz and J = 12.0 Hz, 2H), 2.54 (t, J = 6.6 Hz, 6H), 1.91-1.76 (m, 2H).

[0404] Example 132. N-(3-(1H-imidazol-1-yl)propyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (158) This compound was obtained in 46% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0405] 1 H NMR (600 MHz, CDCl3) δ 8.17-8.14 (m, 3H), 7.91 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.78-7.75 (m, 3H), 7.70-7.66 (m, 2H), 7.29 (t, J = 6.0 Hz, 1H), 7.07 (s, 1H), 6.99 (s, 1H), 4.06 (t, J = 7.2 Hz, 2H), 3.47-3.43 (m, 2H), 2.14-2.10 (m, 2H).

[0406] Example 133. 5-(2-Nitrophenyl)-N-((tetrahydrofuran-2-yl)methyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (159) This compound was obtained in 96% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0407] 1H NMR (600 MHz, CDCl3) δ 8.18 (d, J = 8.4 Hz, 2H), 8.13 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.94 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.77-7.73 (m, 3H), 7.67-7.65 (m, 1H), 7.51 (t, J = 6.0 Hz, 1H), 4.10-4.06 (m, 1H), 3.96-3.93 (m, 1H), 3.84-3.80 (m, 1H), 3.73-3.69 (m, 1H), 3.37-3.33 (m, 1H), 2.05-1.99 (m, 1H), 1.98-1.90 (m, 2H), 1.64-1.60 (m, 1H).

[0408] Example 134. N-(2-Methoxyethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (160) This compound was obtained in 53% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0409] 1 H NMR (600 MHz, CDCl3) δ 8.15 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 8.4 Hz, 1H), 7.91 (dd, J = 1.2 Hz and J = 7.2 Hz, 1H), 7.74-7.71 (m, 3H), 7.65-7.62 (m, 1H), 7.50 (t, J = 5.4 Hz, 1H), 3.59 (q, J = 4.8 Hz, 2H), 3.54 (t, J = 4.8 Hz, 2H), 3.40 (s, 3H).

[0410] Example 135 (4-Hydroxypiperidin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (161) This compound was obtained in 95% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0411] 1 H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 7.8 Hz, 2H), 8.08 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.90 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.76-7.73 (m, 3H), 7.66-7.63 (m, 1H), 4.13 (brs, 2H), 3.99-3.98 (m, 1H), 3.52 (t, J = 9.0 Hz, 1H), 3.37 (t, J = 9.6 Hz, 1H), 1.94 (brs, 2H), 1.61-1.59 (m, 2H).

[0412] Example 136 (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-(piperidin-1-yl)phenyl)methanone (162) This compound was obtained in 32% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0413] 1 H NMR (600 MHz, CDCl3) δ 8.85 (s, 1H), 8.21 (d, J = 8.4 Hz, 2H), 8.15 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.00 (dd, J = 1.2 Hz and J = 7.2 Hz, 1H), 7.79-7.75 (m, 3H), 7.70-7.67 (m, 1H), 7.55 (d, J = 9.0 Hz, 2H), 6.92 (d, J = 9.0 Hz, 2H), 3.14 (t, J = 6.0 Hz, 4H), 1.74-1.70 (m, 4H), 1.60-1.56 (m, 2H).

[0414] Example 137. Ethyl 4-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carbonyl)piperazine-1-carboxylate (163) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0415] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.4 Hz, 2H), 8.10 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.75 (t, J = 8.4 Hz, 3H), 7.66 (t, J = 8.4 Hz, 1H), 4.17 (dd, J = 7.2 Hz and J = 13.8 Hz, 2H), 3.90 (s, 2H), 3.70 (s, 2H), 3.56 (s, 4H), 1.27 (dd, J = 6.6 Hz and J = 14.1 Hz, 3H).

[0416] Example 138. N-benzyl-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (164) This compound was obtained in 99% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0417] 1 H NMR (600 MHz, CDCl3) δ 8.14 (dd, J = 1.2 Hz and J = 8.4 Hz, 3H), 7.97 (dd, J = 1.2 Hz and J = 7.5 Hz, 1H), 7.76-7.72 (m, 3H), 7.67 (t, J = 6.0 Hz, 1H), 7.49 (t, J = 5.4 Hz, 5H), 7.36 (d, J = 7.2 Hz, 4H), 7.31-7.28 (m, 1H), 4.61 (d, J = 6.0 Hz, 2H).

[0418] Example 139. N-(4-(benzyloxy)phenyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (165) This compound was obtained in 82% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0419] 1 H NMR (600 MHz, CDCl3) δ 8.89 (s, 1H), 8.20 (d, J = 8.4 Hz, 2H), 8.16 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.98 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.80-7.75 (m, 3H), 7.70-7.67 (m, 1H), 7.59 (d, J = 9.0 Hz, 2H), 7.44 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.2 Hz, 2H), 7.35-7.33 (m, 1H), 6.98 (d, J = 9.0 Hz, 2H), 5.07 (s, 2H).

[0420] Example 140. N-(4-Methoxybenzyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (166) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0421] 1H NMR (600 MHz, CDCl3) δ 8.16-8.13 (m, 3H), 7.98 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.78-7.74 (m, 3H), 7.70-7.67 (m, 1H), 7.42 (t, J = 5.4 Hz, 1H), 7.31 (d, J = 9.0 Hz, 2H), 4.55 (d, J = 6.0 Hz, 2H), 3.82 (s, 3H).

[0422] Example 141. (4-(2-(diisopropylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (167) This compound was obtained in 43% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0423] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.4 Hz, 2H), 8.09 (d, J = 7.8 Hz, 1H), 7.87 (dd, J = 1.2 Hz and J =7.8 Hz, 1H), 7.74 (t, J = 7.8 Hz, 3H), 7.65 (t, J = 8.4 Hz, 1H), 3.68 (brs, 2H), 3.73 (brs, 2H), 3.56 (brs, 3H), 2.53 (brs, 2H), 1.17 (brs, 12H).

[0424] Example 142. (4-Isopropylpiperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (168) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0425] 1H NMR (600 MHz, CDCl3) δ 8.18 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 7.8 Hz, 1H), 7.84 (t, J = 7.8 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.74 (t, J = 7.8 Hz, 1H), 7.64 (t, J = 7.8 Hz, 1H), 4.17 (s, 2H), 3.91 (s, 2H), 3.21-3.11 (m, 1H), 2.92 (s, 4H), 1.19 (s, 3H), 1.18 (s, 3H).

[0426] Example 143 (4-(2-hydroxyethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (169) This compound was obtained in 64% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0427] 1 H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.1 Hz, 2H), 8.09 (dd, J = 0.8 Hz and J = 8.2 Hz, 1H), 7.88 (dd, J = 1.3 Hz and J = 7.7 Hz, 1H), 7.76-7.74 (m, 3H), 7.65 (t, J = 8.4 Hz, 1H), 3.9 (brs, 2H), 3.75 (brs, 2H), 3.65 (t, J = 6.0 Hz, 2H), 1.19-1.18 (m, 6H).

[0428] Example 144. (5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-(2-(pyrrolidin-1-yl)ethyl)piperazin-1-yl)methanone (170) This compound was obtained in 90% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0429] 1 H NMR (600 MHz, CDCl3) δ 8.14 (d, J = 8.3 Hz, 2H), 8.06 (dd, J = 1.1 Hz and J = 8.1 Hz, 1H), 7.76-7.73 (m, 2H), 7.67-7.64 (m, 2H), 7.31 (t, J = 8.4 Hz, 1H), 3.82 (brs, 2H), 3.66 (brs, 2H), 3.37 (brs, 4H), 3.20 (t, J = 6.0 Hz, 2H), 2.83 (t, J = 6.0 Hz, 2H), 2.51 (t, J = 4.4 Hz, 4H), 2.09 (brs, 4H).

[0430] Example 145. N-(3-(4-methylpiperazin-1-yl)propyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (171) This compound was obtained in 51% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0431] 1 H NMR (600 MHz, MeOD) δ 8.32 (d, J = 8.2 Hz, 2H), 8.22-8.20 (m, 1H), 7.92-7.86(m, 4H), 7.81-7.78 (m, 1H), 7.74-7.69 (m, 1H), 7.33-7.29 (m, 1H), 3.44 (t, J = 6.6 Hz, 2H), 3.04 (s, 4H), 2.83 (s, 2H), 2.78 (s, 1H), 2.67-2.65 (m, 6H), 1.87-1.83 (m, 4H).

[0432] Example 146. tert-Butyl-4-(2-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamido)ethyl)piperazine-1-carboxylate (172) This compound was obtained in 87% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0433] 1 H NMR (600 MHz, CDCl3) δ 8.18 (d, J = 8.2 Hz, 2H), 8.14 (dd, J = 1.2 Hz and J = 8.2 Hz, 1H), 7.95 (dd, J = 1.3 Hz and J = 7.8 Hz, 1H), 7.79 (d, J = 8.5 Hz, 2H), 7.76-7.74 (m, 1H), 7.69-7.66 (m, 1H), 7.61 (t, J = 5.3 Hz, 1H), 3.55-3.50 (m, 7H), 2.64 (t, J = 6.2 Hz, 2H), 2.64 (t, J = 6.2 Hz, 2H), 1.49 (s, 9H).

[0434] Example 147. 5-(2-Nitrophenyl)-N-(2-(piperidin-1-yl)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (173) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0435] 1 H NMR (600 MHz, CDCl3) δ 8.11 (d, J = 7.9 Hz, 1H), 7.93-7.92 (m, 1H), 7.84 (d, J = 8.2 Hz, 2H), 7.74 (d, J = 7.3 Hz, 2H), 7.66-7.64 (m, 1H), 7.58 (d, J = 7.9 Hz, 3H), 3.90 (q, J = 5.9 Hz, 2H), 3.25 (t, J = 5.6 Hz, 3H), 2.17 (s, 6H), 1.88 (s, 3H).

[0436] Example 148. tert-Butyl(2-(5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamido)ethyl)cabarmate (174) This compound was obtained in 93% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0437] 1 H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 2.4 Hz, 2H), 8.15 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.95 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.78-7.77 (m, 3H), 7.70-7.67 (m, 1H), 7.62 (brs, 1H), 3.55 (q, J = 5.4 Hz, 2H), 3.41 (d, J = 5.4 Hz, 2H), 1.48 (s, 9H).

[0438] Example 149. N-(4-acetamidophenyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (175) This compound was obtained in quantitative yield as a fluffy white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0439] 1 H NMR (600 MHz, CDCl3) δ 8.23 ​​(d, J = 8.4 Hz, 2H), 8.19 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.2 Hz, 1H), 7.81-7.79 (m, 3H), 7.72 (t, J = 7.8 Hz, 1H), 7.67-7.65 (m, 2H), 7.53-7.51 (m, 2H), 2.19 (s, 3H).

[0440] Example 150. N-(4-hydroxyphenethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (176) This compound was obtained in quantitative yield as a fluffy white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0441] 1 H NMR (600 MHz, CDCl3) δ 8.13 (dd, J = 1.8 Hz and J = 8.4 Hz, 3H), 7.91 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.75-7.72 (m, 3H), 7.66-7.63(m, 1H), 7.38 (t, J = 5.4 Hz, 1H), 7.04 (d, J = 8.4 Hz, 2H), 6.74 (d, J = 8.4 Hz, 2H), 6.43 (brs, 1H), 3.62 (q, J = 6.6 Hz, 2H), 2.84 (t, J = 7.2 Hz, 2H).

[0442] Example 151. N-(2-(dimethylamino)ethyl)-5-(3-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (177) This compound was obtained in 65% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0443] 1 H NMR (600 MHz, CDCl3) δ 9.24 (s, 1H), 8.92 (d, J = 8.4 Hz, 1H), 8.28 (t, J = 9.0 Hz, 3H), 7.80 (d, J = 7.8 Hz, 2H), 7.78 (s, 1H), 7.69 (t, J = 7.8 Hz, 1H), 3.60 (dd, J = 5.4 Hz and J = 11.7 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0444] Example 152. (5-(3-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(piperazin-1-yl)methanone (178) This compound was obtained in 97% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0445] 1 H NMR (600 MHz, MeOD) δ 8.92 (s, 1H), 8.49-8.31 (m, 4H), 7.90 (d, J =8.4 Hz, 2H), 7.80 (t, J = 8.4 Hz, 1H), 4.09 (s, 4H), 3.41 (s, 2H), 3.37 (s, 2H).

[0446] Example 153. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(3-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (179) This compound was obtained in 36% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0447] 1 H NMR (600 MHz, MeOD) δ 8.76 (s, 1H), 8.38 (d, J = 7.8 Hz, 2H), 8.35 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.31 (d, J = 7.8 Hz, 1H), 7.92 (d, J = 8.4 Hz, 2H), 7.83 (t, J = 7.8 Hz, 1H), 3.91 (t, J = 9.6 Hz, 2H), 3.70 (t, J = 9.6 Hz, 2H), 2.69 (t, J = 10.2 Hz, 2H), 2.58-2.51 (m, 6H), 2.30 (s, 6H).

[0448] Example 154. N-(2-(dimethylamino)ethyl)-5-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (180) This compound was obtained in 52% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0449] 1 H NMR (600 MHz, CDCl3) δ 8.53 (d, J = 8.4 Hz, 2H), 8.33 (d, J = 8.4 Hz, 2H), 8.26 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 3.59 (dd, J = 6.0 Hz and J = 12.0 Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.34 (s, 6H).

[0450] Example 155. (5-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(piperazin-1-yl)methanone (181) This compound was obtained in 99% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0451] 1 H NMR (600 MHz, MeOD) δ 8.40 (d, J = 6.6 Hz, 2H), 8.39 (d, J = 5.4 Hz, 2H), 8.26 (d, J = 9.0 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 4.11 (s, 2H), 4.04 (s, 2H), 3.44 (s, 2H), 3.38 (s, 2H), 3.37 (s, 6H).

[0452] Example 156. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (182) This compound was obtained in 30% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0453] 1 H NMR (600 MHz, MeOD) δ 8.39 (t, J = 4.8 Hz, 4H), 8.15 (d, J = 9.0 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 3.90 (t, J = 4.2 Hz, 2H), 3.66 (t, J = 5.4 Hz, 2H), 2.67 (t, J = 4.8 Hz, 2H), 2.63-2.41 (m, 6H), 2.31 (s, 6H).

[0454] Example 157. 5-(2-aminophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (183) This compound was obtained in 71% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0455] 1 H NMR (600 MHz, CDCl3) δ 8.23 ​​(d, J = 7.2 Hz, 2H), 7.98 (s, 1H), 7.74 (d, J = 7.2 Hz, 2H), 7.50 (d, J = 7.8 Hz, 1H), 7.29-7.26 (m, 1H), 6.88-6.83 (m, 3H), 3.64 (t, J = 4.2 Hz, 2H), 2.77 (t, J = 4.2 Hz, 2H), 2.43 (s, 6H).

[0456] Example 158. (5-(2-aminophenyl)-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)(4-(2-(dimethylamino)ethyl)piperazin-1-yl)methanone (184) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0457] 1 H NMR (600 MHz, CDCl3)δ 8.19 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 9.0 Hz, 1H), 7.29-7.21 (m, 1H), 6.83 (t, J = 7.2 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 3.81 (s, 2H), 3.53 (s, 2H), 2.59-2.32 (m, 6H), 2.31-2.25 (m, 2H), 2.23 (s, 6H).

[0458] Example 159. 5-(3-aminophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (185) This compound was obtained in 43% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0459] 1 H NMR (600 MHz, CDCl3)δ 8.61 (brs, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.96(d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.33 (t, J = 7.2 Hz, 1H), 3.59 (q, J = 6.6 Hz, 2H), 2.61 (t, J = 6.6 Hz, 2H), 2.53 (s, 6H).

[0460] Example 160. 5-(4-aminophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (186) This compound was obtained in 59% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0461] 1 H NMR (600 MHz, CDCl3)δ 8.25 (d, J = 8.4 Hz, 2H), 8.21 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.69 (brs, 1H), 6.76 (d, J = 8.4 Hz, 2H), 3.59 (q, J = 6.6 Hz, 2H), 2.61 (t, J = 6.6 Hz, 2H), 2.53 (s, 6H).

[0462] Example 161. 5-(2-acetamidophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (187) This compound was obtained in 69% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0463] 1 H NMR (600 MHz, MeOD) δ 8.31 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 7.8 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H), 3.61 (t, J = 6.0 Hz, 2H), 2.72 (t, J = 6.6 Hz, 2H), 2.43 (s, 6H), 2.05 (s, 3H).

[0464] Example 162. N-(2-(4-(4-(2-(dimethylamino)ethyl)piperazine-1-carbonyl)-2-(4-(trifluoromethyl)phenyl)oxazol-5-yl)phenyl)acetamide (188) This compound was obtained in 78% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0465] 1 H NMR (600 MHz, MeOD) δ 8.29 (d, J = 7.8 Hz, 2H), 7.89 (d, J = 7.8 Hz, 2H), 7.67 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 7.2 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 3.72 (s, 2H), 3.53 (s, 2H), 2.53 (s, 2H), 2.48 (s, 4H), 2.28 (s, 6H), 2.17 (s, 2H), 2.07 (s, 3H).

[0466] Example 163. 5-(3-acetamidophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (189) This compound was obtained in 91% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0467] 1 H NMR (600 MHz, MeOD) δ 8.45 (s, 1H), 8.29 (d, J = 7.8 Hz, 2H), 8.07 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 8.4 Hz, 2H), 7.68 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 3.58 (t, J = 6.6 Hz, 2H), 2.69 (t, J = 6.6 Hz, 2H), 2.41 (s, 6H), 2.18 (s, 3H).

[0468] Example 164. N-(3-(4-(4-(2-(dimethylamino)ethyl)piperazine-1-carbonyl)-2-(4-(trifluoromethyl)phenyl)oxazol-5-yl)phenyl)acetamide (190) This compound was obtained in 83% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0469] 1 H NMR (600 MHz, MeOD) δ 8.33 (d, J = 6.0 Hz, 2H), 8.24 (s, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.47 (t, J = 7.8 Hz, 1H), 3.90 (t, J = 4.8 Hz, 2H), 3.57 (t, J = 4.8 Hz, 2H), 2.66 (t, J = 5.4 Hz, 2H), 2.61-2.51 (m, 4H), 2.45 (t, J = 4.8 Hz, 2H), 2.29 (s, 6H), 2.17 (s, 3H).

[0470] Example 165. 5-(4-acetamidophenyl)-N-(2-(dimethylamino)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (191) This compound was obtained in 71% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0471] 1H NMR (600 MHz, MeOD) δ 8.27 (d, J = 8.4 Hz, 2H), 8.26 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 9.0 Hz, 2H), 3.61 (t, J = 6.6 Hz, 2H), 2.81 (t, J = 6.6 Hz, 2H), 2.51 (s, 6H), 2.17 (s, 3H).

[0472] Example 166. N-(4-(4-(4-(2-(dimethylamino)ethyl)piperazine-1-carbonyl)-2-(4-(trifluoromethyl)phenyl)oxazol-5-yl)phenyl)acetamide (192) This compound was obtained in 81% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0473] 1 H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 7.8 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 3.61-3.43 (m, 12H), 2.61 (s, 6H), 2.05 (s, 3H).

[0474] Example 167. 5-(4-(methylsulfonyl)phenyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (193) This compound was obtained in 87% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0475] 1H NMR (600 MHz, CDCl3) δ 8.68 (s, 1H), 8.63 (d, J = 8.5 Hz, 2H), 8.58 (d, J = 4.3 Hz, 1H), 8.24 (d, J = 8.2 Hz, 2H), 8.08 (d, J = 8.5 Hz, 2H), 7.82 (t, J = 5.7 Hz, 1H), 7.79 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 7.9 Hz, 1H), 7.31 (q, J = 4.9 Hz, 1H), 4.72 (d, J = 6.1 Hz, 2H), 3.10 (s, 3H). HRMS m / z: calcd for C 24 H 18 F3N3O4S [M + H] + : 502.1004; found: 502.1059.

[0476] Example 168. N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(4-(methylthio)phenyl)-2-(4-trifluoromethyl)phenyl)oxazole-4-carboxamide (194) This compound was obtained in 48% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0477] 1H NMR (600 MHz, CDCl3) δ 8.36 (t, J = 1.5 Hz, 1H), 8.22 (d, J= 8.4 Hz, 2H), 8.17 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 7.8 Hz, 2H), 7.75 (d, J = 5.1 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 3.69 (t, J = 4.8 Hz, 2H), 3.61 (q, J = 6.2 Hz, 2H), 3.52 (t, J = 5.1 Hz, 2H), 2.67 (t, J = 6.0 Hz, 2H), 2.59 (s, 3H), 2.56 (t, J = 4.8 Hz, 2H), 2.53 (t, J = 5.1 Hz, 2H), 2.12 (s, 3H).

[0478] Example 169. 5-(4-(methylthio)phenyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (195) This compound was obtained in 89% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0479] 1 H NMR (600 MHz, CDCl3) δ 8.67 (s, 1H), 8.56 (d, J = 4.4 Hz, 1H), 8.33 (d, J = 8.3 Hz, 2H), 8.20 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.1 Hz, 4 H), 7.35 (d, J = 8.3 Hz, 2H), 7.30 (q, J = 4.9 Hz, 1H), 4.70 (d, J = 6.1 Hz, 2H), 2.54 (s, 3H).

[0480] Example 170. N-(2-(dimethylamino)ethyl)-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (196) This compound was obtained in 19% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0481] 1 H NMR (600 MHz, CDCl3) δ 9.35 (d, J = 1.8 Hz, 1H), 8.97 (td, J = 1.8 Hz and J = 7.8 Hz, 1H), 8.67 (dd, J = 1.8 Hz and J = 4.8 Hz, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.80 (brs, 1H), 7.46-7.42 (m, 1H), 3.59 (q, J = 6.0 Hz, 2H), 2.60 (t, J = 6.0 Hz, 2H), 2.34 (s, 6H).

[0482] Example 171. N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (197) This compound was obtained in 49% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0483] 1H NMR (600 MHz, CDCl3) δ 9.36 (d, J = 1.2, 1H), 8.96 (d, J= 7.8 Hz, 1H), 8.68 (d, J = 3.6 Hz, 1H), 8.24 (d, J = 7.8 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.76 (t, J = 5.1 Hz, 1H), 7.45 (dd, J = 4.8 Hz and J = 7.8 Hz, 1H), 3.69 (t, J = 4.8 Hz, 2H), 3.62 (q, J = 6.0 Hz, 2H), 3.53 (t, J = 4.8 Hz, 2H), 2.68 (t, J = 6.3 Hz, 2H), 2.57 (t, J = 5.1 Hz, 2H), 2.54 (t, J = 5.1 Hz, 2H), 2.12 (s, 3H).

[0484] Example 172. N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (198) This compound was obtained in 72% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0485] 1H NMR (600 MHz, CDCl3) δ 8.22 (d, J= 7.8 Hz, 2H), 8.14 (d, J = 3.6 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.76 (t, J = 5.1 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.02 (dd, J = 2.4 Hz and J = 7.8 Hz, 1H), 3.92 (s, 3H), 3.69 (t, J = 5.1 Hz, 2H), 3.62 (q, J = 6.0 Hz, 2H), 3.52 (t, J = 4.2 Hz, 2H), 2.68 (t, J = 6.3 Hz, 2H), 2.56 (t, J = 4.8 Hz, 2H), 2.53 (t, J = 4.8 Hz, 2H), 2.12 (s, 3H).

[0486] Example 173. N-(2-(dimethylamino)ethyl)-5-phenyl-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (199) This compound was obtained in 42% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0487] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 7.3 Hz, 2H), 8.07 (d, J = 7.6 Hz, 1H), 7.97 (s, 1H), 7.71 (brs, 1H), 7.56 (t, J = 7.9 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 7.45 (t, J = 7.2 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H), 3.59 (q, J = 6.1 Hz, 2H), 2.60 (t, J = 6.2 Hz, 2H), 2.35 (s, 6H).

[0488] Example 174. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (200) This compound was obtained in 60% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0489] 1 H NMR (600 MHz, MeOD) δ 8.25 (dd, J = 1.2 Hz and J = 7.8 Hz, 2H), 8.03 (d, J = 7.8 Hz, 1H), 7.93 (s, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.47-7.41 (m, 4H), 3.51 (t, J = 6.6 Hz, 2H), 2.62 (t, J = 6.6 Hz, 2H), 2.57 (brs, 8H), 2.28 (s, 3H).

[0490] Example 175. N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (201) This compound was obtained in 82% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0491] 1H NMR (600 MHz, MeOD) δ 8.17 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.98 (s, 1H), 7.91 (dd, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.82 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.8 Hz and J =1.2 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.48-7.47 (m, 1H), 3.46 (t, J = 7.2 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.30 (s, 6H).

[0492] Example 176. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (202) This compound was obtained in 80% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0493] 1 H NMR (600 MHz, MeOD) δ 8.16 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.04 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.97 (s, 1H), 7.90 (dd, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.82 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.8 Hz and J = 1.8 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.51-7.49 (m, 1H), 3.46 (t, J = 6.6Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.54 (brs, 8H), 2.28 (s, 3H).

[0494] Example 177. N-(2-(dimethylamino)ethyl)-5-phenyl-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (203) This compound was obtained in 83% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0495] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 7.2 Hz, 2H), 8.17 (d, J = 8.4 Hz, 2H), 7.70 (brs, 1H), 7.51-7.43 (m, 3H), 7.36 (d, J = 8.4 Hz, 2H), 3.58 (q, J = 6.0 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0496] Example 178. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (204) This compound was obtained in 39% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0497] 1 H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 7.2 Hz, 2H), 8.17 (d, J = 9.0 Hz, 2H), 7.78 (brt, J = 4.8 Hz, 1H), 7.50 (t, J = 7.2 Hz, 2H), 7.48-7.45 (m, 1H), 7.38 (d, J = 9.0 Hz, 2H), 3.60 (q, J = 6.0 Hz, 2H), 2.66 (t, J = 6.0 Hz, 2H), 2.61-2.54 (brs, 8H), 2.34 (s, 3H).

[0498] Example 179. N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (205) This compound was obtained in 58% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0499] 1 H NMR (600 MHz, CDCl3) δ 8.12-8.09 (m, 3H), 7.96 (dd, J = 1.2 Hz and J = 7.2 Hz, 1H), 7.74 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.65 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.55 (brs, 1H), 7.34 (d, J = 8.4 Hz, 2H), 3.50 (q, J = 6.0 Hz, 2H), 2.54 (t, J = 6.0 Hz, 2H), 2.31 (s, 6H).

[0500] Example 180. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (206) This compound was obtained in 39% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0501] 1H NMR (600 MHz, MeOD) δ 8.18-8.15 (m, 3H), 7.89 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.81 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.74 (td, J = 8.4 Hz and J = 1.8 Hz, 1H), 7.46 (d, J = 7.8 Hz, 2H), 3.47 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.56 (brs, 8H), 2.28 (s, 3H).

[0502] Example 181. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(5-(2-nitrophenyl)-2-(4-(trifluoromethoxy)phenyl)oxazol-4-yl)methanone (207) This compound was obtained in 39% yield as a yellow solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0503] 1 H NMR (600 MHz, CDCl3) δ 8.09-8.07 (m, 3H), 7.87 (d, J = 7.8 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 3.88 (brs, 2H), 3.75 (brs, 2H), 2.64-2.51 (m, 8H), 2.46 (s, 6H).

[0504] Example 182. N-(2-(dimethylamino)ethyl)-2-(3-methoxyphenyl)-5-phenyloxazole-4-carboxamide (208) This compound was obtained in 25% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0505] 1H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 7.8 Hz, 2H), 7.74 (brs, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.65 (s, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.45-7.41(m, 2H), 7.06 (dd, J = 1.8 Hz and J = 8.4 Hz, 1H), 3.93 (s, 3H), 3.61 (q, J = 6.0 Hz, 2H), 2.62 (t, J = 6.0 Hz, 2H), 2.35 (s, 6H).

[0506] Example 183. 2-(3-Methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (209) This compound was obtained in 46% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0507] 1 H NMR (600 MHz, CDCl3) δ 8.39 (d, J = 7.8 Hz, 2H), 7.82 (brs, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.65 (s, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.43 (t, J = 7.8 Hz, 2H), 7.08- 7.06 (m, 1H), 3.93 (s, 3H), 3.60 (q, J = 6.0 Hz, 2H), 2.66 (t, J = 6.0 Hz, 2H), 2.60-2.50 (m, 8H), 2.32 (s, 3H).

[0508] Example 184. N-(2-(dimethylamino)ethyl)-2-(3-methoxyphenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (210) This compound was obtained in 61% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0509] 1 H NMR (600 MHz, MeOD) δ 8.15 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.90 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.82 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.61-7.60 (m, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.14 (ddd, J = 0.6 Hz, J = 2.4 Hz and J = 8.4 Hz, 1H), 3.86 (s, 3H), 3.46 (t, J = 6.6 Hz, 2H), 2.55 (t, J = 6.6 Hz, 2H), 2.29 (s, 6H).

[0510] Example 185. 2-(3-Methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (211) This compound was obtained in 73% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0511] 1H NMR (600 MHz, MeOD) δ 8.12 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.88 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.79 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.71 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.61 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.57-7.56 (m, 1H), 7.41 (t, J = 7.8 Hz, 1H), 7.09 (ddd, J = 0.6 Hz, J = 2.4 and J = 8.4 Hz, 1H), 3.85 (s, 3H), 3.45 (t, J = 6.6 Hz, 2H), 2.57 (t, J = 6.6 Hz, 2H), 2.51 (brs, 8H), 2.27 (s, 6H).

[0512] Example 186. N-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-5-phenyloxazole-4-carboxamide (212) This compound was obtained in 45% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0513] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 7.8 Hz, 2H), 7.70 (brs, 1H), 7.48 (t, J = 8.4 Hz, 2H), 7.43-7.40 (m, 1H), 7.02 (d, J = 8.4 Hz, 2H), 3.90 (s, 3H), 3.59 (q, J = 6.0 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0514] Example 187. 2-(4-Methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (213) This compound was obtained in 77% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0515] 1 H NMR (600 MHz, MeOD) δ 8.21 (dd, J = 1.2 Hz and J = 8.4 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 7.44-7.38 (m, 3H), 6.96 (d, J = 8.4 Hz, 2H), 3.79 (s, 3H), 3.49 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.50 (brs, 8H), 2.26 (s, 3H).

[0516] Example 188. N-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (214) This compound was obtained in 69% yield as a yellow solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0517] 1 H NMR (600 MHz, MeOD) δ 8.14 (d, J = 7.8 Hz, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 7.8 Hz, 1H), 7.81 (t, J = 7.2 Hz, 1H), 7.73 (t, J = 7.2 Hz, 1H), 7.08 (d, J = 8.4 Hz, 2H), 3.88 (s, 3H), 3.47 (t, J = 6.6 Hz, 2H), 2.56 (t, J = 6.6 Hz, 2H), 2.31 (s, 6H).

[0518] Example 189. 2-(4-Methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (215) This compound was obtained in 82% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0519] 1 H NMR (600 MHz, MeOD) δ 8.14 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.01 (d, J = 9.0 Hz, 2H), 7.90 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.81 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.73 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.07 (t, J = 9.0 Hz, 2H), 3.88 (s, 3H), 3.47 (t, J = 6.6 Hz, 2H), 2.60 (t, J = 6.6 Hz, 2H), 2.58 (brs, 1H), 2.30 (s, 3H).

[0520] Example 190. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(2-(4-methoxyphenyl)-5-(2-nitrophenyl)oxazol-4-yl)methanone (216) This compound was obtained in 67% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0521] 1H NMR (600 MHz, MeOD) δ 8.11 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 9.0 Hz, 2H), 7.85-7.82 (m, 2H), 7.75-7.72 (m, 1H), 7.09 (d, J = 9.0 Hz, 2H), 3.89 (s, 3H), 3.73 (brs, 2H), 3.20 (brs, 2H), 2.84 (s, 6H), 2.73-2.70 (m, 2H), 2.60-2.55 (m, 6H).

[0522] Example 191. N-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-5-(4-nitrophenyl)oxazole-4-carboxamide (217) This compound was obtained in 54% yield as a yellow solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0523] 1 H NMR (600 MHz, DMSO-d6) δ 8.68 (d, J = 9.0 Hz, 2H), 8.44 (t, J = 6.6 Hz, 1H), 8.35 (d, J = 9.0 Hz, 2H), 8.12 (d, J = 9.0 Hz, 2H), 7.17 (d, J = 9.0 Hz, 2H), 3.87 (s, 3H), 3.42 (q, J = 6.6 Hz, 2H), 2.44 (t, J = 6.6 Hz, 2H), 2.20 (s, 6H).

[0524] Example 192. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(2-(4-methoxyphenyl)-5-(4-nitrophenyl)oxazol-4-yl)methanone (218) This compound was obtained in 65% yield as a yellow solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0525] 1H NMR (600 MHz, DMSO-d6) δ 8.38 (d, J = 9.0 Hz, 2H), 8.09 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 9.0 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 3.87 (s, 3H), 3.71 (brs, 2H), 3.46 (brs, 2H), 2.53-2.52 (m, 2H), 2.42-2.35 (m, 6H), 2.16 (s, 6H).

[0526] Example 193. 2-(4-Methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(4-nitrophenyl)oxazole-4-carboxamide (219) This compound was obtained in 76% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0527] 1 H NMR (600 MHz, MeOD) δ 8.52 (dd, J = 9.0 Hz and J = 1.8 Hz, 2H), 8.25 (dd, J = 9.0 Hz and J = 1.8 Hz, 2H), 8.02 (dd, J = 9.0 Hz and J = 1.8 Hz, 2H), 7.05 (dd, J = 9.0 Hz and J = 1.8 Hz, 2H), 3.86 (s, 3H), 3.53 (t, J = 6.6 Hz, 2H), 2.64 (t, J = 6.6 Hz, 2H), 2.61 (brs, 8H), 2.30 (s, 3H).

[0528] Example 194. N-(2-(dimethylamino)ethyl)-2-(3-fluorophenyl)-5-phenyloxazole-4-carboxamide (220) This compound was obtained in 48% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0529] 1 H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 7.2 Hz, 2H), 7.92 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 9.0 Hz, 1H), 7.70 (brs, 1H), 7.51-7.43 (m, 4H), 7.22 (td, J = 8.4 Hz and J = 1.8 Hz, 1H), 3.59 (q, J = 6.0 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0530] Example 195. 2-(3-fluorophenyl)N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (221) This compound was obtained in 48% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0531] 1 H NMR (600 MHz, MeOD) δ 8.24 (d, J = 7.2 Hz, 2H), 7.86 (d, J = 7.8 Hz, 1H), 7.76-7.74 (m, 1H), 7.53-7.49 (m, 1H), 7.47-7.41 (m, 3H) 7.26-7.23 (m, 1H), 3.51 (t, J = 6.6 Hz, 2H), 2.61 (t, J = 6.6 Hz, 2H), 2.58 (brs, 8H), 2.28 (s, 3H).

[0532] Example 196. N-(2-(dimethylamino)ethyl)-2-(3-fluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (222) This compound was obtained in 51% yield as a pale yellow solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0533] 1H NMR (600 MHz, CDCl3) δ 8.12 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.94 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.77 (td, J = 9.0 Hz and J = 1.8 Hz, 1H), 7.74 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.65 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.54 (brs, 1H), 7.49-7.46 (m, 1H), 7.22 (td, J = 7.8 Hz and J = 2.4 Hz, 1H), 3.50 (q, J = 6.0 Hz, 2H), 2.53 (t, J = 6.0 Hz, 2H), 2.31 (s, 6H).

[0534] Example 197. 2-(3-fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (223) This compound was obtained in 87% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0535] 1 H NMR (600 MHz, MeOD) δ 8.14 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.88-7.85 (m, 2H), 7.80 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.77-7.75 (m, 1H), 7.74-7.71 (m, 1H), 7.55 (td, J = 8.0 Hz and J = 5.7 Hz, 1H), 7.30-7.27 (m, 1H), 3.46 (t, J = 6.6 Hz, 2H), 2.58 (t, J = 6.6 Hz, 2H), 2.55 (brs, 8H), 2.27 (s, 3H).

[0536] Example 198. N-(2-(dimethylamino)ethyl)-2-(4-fluorophenyl)-5-phenyloxazole-4-carboxamide (224) This compound was obtained in 25% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0537] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 7.2 Hz, 2H), 8.13 (dd, J = 5.4 Hz and J = 8.4 Hz, 2H), 7.68 (brs, 1H), 7.49 (t, J = 7.2 Hz, 2H), 7.45-7.42 (m, 1H), 7.21 (t, J = 8.4 Hz, 2H), 3.58 (q, J = 6.0 Hz, 2H), 2.57 (t, J = 6.0 Hz, 2H), 2.32 (s, 6H).

[0538] Example 199. 2-(4-Fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (225) This compound was obtained in 15% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0539] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 7.2 Hz, 2H), 8.13 (dd, J = 4.4 Hz and J = 8.8 Hz, 2H), 7.78 (brs, 1H), 7.51-7.42 (m, 3H), 7.22 (t, J = 8.4 Hz, 2H), 3.59 (q, J = 6.6 Hz, 2H), 2.66 (t, J = 6.6 Hz, 2H), 2.60 (brs, 8H), 2.33 (s, 3H).

[0540] Example 200. N-(2-(dimethylamino)ethyl)-2-(4-fluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (226) This compound was obtained in 82% yield as a pale yellow solid by a method similar to the synthesis of compound 114, which is a general method of hydrolysis and amide coupling reaction.

[0541] 1 H NMR (600 MHz, MeOD) δ 8.17 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 8.15-8.12 (m, 2H), 7.91 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.83 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.76 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.30 (t, J = 8.4 Hz, 2H), 3.47 (t, J = 6.6 Hz, 2H), 2.56 (t, J = 6.6 Hz, 2H), 2.30 (s, 6H).

[0542] Example 201. 2-(4-Fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (227) This compound was obtained in 50% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0543] 1H NMR (600 MHz, MeOD) δ 8.00 (dd, J = 0.6 Hz and J = 8.4 Hz, 1H), 7.96-7.93 (m, 2H), 7.73 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.65 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.58 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.13 (t, J = 9.0, 2H), 3.31 (t, J = 6.6 Hz, 2H), 2.43 (t, J = 6.6 Hz, 2H), 2.41 (brs, 1H), 2.13 (s, 3H).

[0544] Example 202. (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(2-(4-fluorophenyl)-5-(2-nitrophenyl)oxazol-4-yl)methanone (228) This compound was obtained in 47% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0545] 1 H NMR (600 MHz, MeOD) δ 8.13 (d, J = 8.4 Hz, 1H), 8.11 (dd, J = 5.4 Hz and J = 9.0 Hz, 2H), 7.85-7.84 (m, 2H), 7.77-7.74 (m, 1H), 7.30 (t, J = 9.0 Hz, 2H), 3.86 (brs, 2H), 3.70 (brs, 2H), 2.79 (brs, 2H), 2.61-2.58 (m, 6H), 2.50 (s, 6H).

[0546] Example 203. N-(2-(dimethylamino)ethyl)-2-(4-fluorophenyl)-5-(4-nitrophenyl)oxazole-4-carboxamide (229) This compound was obtained in 36% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0547] 1 H NMR (600 MHz, CDCl3) δ 8.66 (d, J = 9.0 Hz, 2H), 8.32 (d, J = 9.0 Hz, 2H), 8.16 (dd, J = 5.4 Hz and J = 8.4 Hz, 2H), 7.80 (brs, 1H), 7.24 (t, J = 8.4 Hz, 2H), 3.59 (q, J = 6.0 Hz, 2H), 2.59 (t, J = 6.0 Hz, 2H), 2.34 (s, 6H).

[0548] Example 204. 2-(4-fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(4-nitrophenyl)oxazole-4-carboxamide (230) This compound was obtained in 90% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0549] 1 H NMR (600 MHz, MeOD) δ 8.62 (d, J = 9.0 Hz, 2H), 8.35 (d, J = 9.0 Hz, 2H), 8.24 (dd, J = 5.4 Hz and J = 9.0 Hz, 2H), 7.33 (t, J = 9.0 Hz, 2H), 3.58 (d, J = 6.6 Hz, 2H), 2.66 (d, J = 6.6 Hz, 2H), 2.55 (brs, 8H), 2.30 (s, 3H).

[0550] Example 205. 2-(3,4-Difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (231) This compound was obtained in 50% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0551] 1 H NMR (600 MHz, CDCl3) δ 8.36 (d, J = 7.2 Hz, 2H), 7.96-7.94 (m, 1H), 7.90-7.87 (m, 1H), 7.67 (brs, 1H), 7.50 (t, J = 7.2 Hz, 2H), 7.46 (d, J = 7.2 Hz, 1H), 7.33-7.29 (m, 1H), 3.58 (q, J = 6.0 Hz, 2H), 2.57 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0552] Example 206. 2-(3,4-Difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (232) This compound was obtained in 81% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0553] 1 H NMR (600 MHz, MeOD) δ 8.27 (dd, J = 1.8 Hz and J =8.4 Hz, 2H), 8.04-8.02 (m, 1H), 7.96-7.94 (m, 1H), 7.51-7.44 (m, 4H), 3.55 (t, J = 6.6 Hz, 2H), 2.64 (t, J = 6.6 Hz, 2H), 2.60 (brs, 8H), 2.29 (s, 3H).

[0554] Example 207. 2-(3,4-Difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (233) This compound was obtained in 52% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0555] 1 H NMR (600 MHz, CDCl3) δ 8.12 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.91-7.89 (m, 1H), 7.82-7.80 (m, 1H), 7.74 (td, J = 7.8 Hz and J = 0.6 Hz, 1H), 7.65 (td, J = 7.8 Hz and J = 0.6 Hz, 1H), 7.52 (brs, 1H), 7.32-7.29 (m, 1H), 3.50 (q, J = 6.0 Hz, 2H), 2.53 (t, J = 6.0 Hz, 2H), 2.31 (s, 6H).

[0556] Example 208. 2-(3,4-Difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (234) This compound was obtained in 89% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0557] 1 H NMR (600 MHz, MeOD) δ 8.16 (dd, J = 0.6 Hz and J = 7.8 Hz, 1H), 7.99-7.96 (m, 1H), 7.90-7.87 (m, 2H), 7.81 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.48-7.44 (m, 1H), 3.46 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.55 (brs, 8H), 2.28 (s, 3H).

[0558] Example 209. 2-(3,5-difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (235) This compound was obtained in 41% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0559] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 7.8 Hz, 2H), 7.67-7.64 (m, 3H), 7.52-7.44 (m, 3H), 6.98-6.95 (m, 1H), 3.58 (q, J = 6.0 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0560] Example 210. 2-(3,5-difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (236) This compound was obtained in quantitative yield as a white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0561] 1 H NMR (600 MHz, MeOD) δ 8.29 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.68-7.62 (m, 2H), 7.52-7.48 (m, 3H), 7.17-7.11 (m, 1H), 3.56 (t, J = 6.6 Hz, 2H), 2.65 (t, J = 6.6 Hz, 2H), 2.55 (s, 3H), 2.30 (s, 3H).

[0562] Example 211. 2-(3,5-difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (237) This compound was obtained in 60% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0563] 1 H NMR (600 MHz, MeOD) δ 8.18 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.90 (dd, J = 1.2 Hz and J = 7.2 Hz, 1H), 7.83 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.76 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.68-7.66 (m, 2H), 7.21-7.17 (m, 1H), 3.46 (t, J = 6.6 Hz, 2H), 2.55 (t, J = 6.6 Hz, 2H), 2.30 (s, 6H).

[0564] Example 212. 2-(3,5-difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (238) This compound was obtained in quantitative yield as a white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0565] 1 H NMR (600 MHz, MeOD) δ 8.17 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.88 (dd, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.82 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.8 Hz and J = 1.8 Hz, 1H), 7.66-7.64 (m, 2H), 7.23-7.19 (m, 1H), 3.46 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.54 (brs, 8H), 2.82 (s, 3H).

[0566] Example 213. tert-Butyl 4-(2-(2-(3,5-difluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxamido)ethyl)piperazine-1-carboxylate (239) This compound was obtained in quantitative yield as a white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0567] 1 H NMR (600 MHz, CDCl3) δ 8.12 (dd, J = 0.6 Hz and J = 7.8 Hz, 1H), 7.88 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.76-7.70 (m, 1H), 7.68-7.63 (m, 1H), 7.58-7.50 (m, 3H), 6.99-6.93 (m, 1H), 3.53-3.45 (m, 1H), 2.59 (t, J = 6.6 Hz, 2H), 2.45 (brs, 4H), 1.46 (brs, 9H).

[0568] Example 214. 2-(3-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (240) This compound was obtained in 26% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0569] 1 H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 7.2 Hz, 2H), 8.11 (s, 1H), 8.02 (d, J = 7.2 Hz, 1H), 7.68 (brs, 1H), 7.51-7.43 (m, 5H), 3.59 (q, J = 6.0 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0570] Example 215. 2-(3-chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (241) This compound was obtained in quantitative yield as a white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0571] 1 H NMR (600 MHz, MeOD) δ 8.27-8.25 (m, 2H), 8.08- 8.07 (m, 1H), 8.01-7.99 (m, 1H), 7.54-7.44 (m, 5H), 3.53 (t, J = 6.6 Hz, 2H), 2.64 (t, J = 6.6 Hz, 2H), 2.54 (brs, 8H), 2.29 (s, 3H).

[0572] Example 216. 2-(3-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (242) This compound was obtained in 48% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0573] 1H NMR (600 MHz, MeOD) δ 8.15 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.05 (t, J = 1.8 Hz, 1H), 7.95 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.88 (dd, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.80 (td, J = 7.8 Hz and J = 1.8 Hz, 1H), 7.73 (td, J = 7.8 Hz and J =1.8 Hz, 1H), 7.54-7.53 (m, 1H), 7.50 (t, J = 7.8 Hz, 1H), 3.45 (t, J = 6.6 Hz, 2H), 2.54 (t, J = 6.6 Hz, 2H), 2.29 (s, 6H).

[0574] Example 217. 2-(3-chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (243) This compound was obtained in 77% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0575] 1H NMR (600 MHz, MeOD) δ 8.16 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.08 (t, J = 1.8 Hz, 1H), 7.98 (td, J = 8.4 Hz and J = 1.8 Hz, 1H), 7.89 (dd, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.81 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.57-7.56 (m, 1H), 7.53 (t, J = 7.8 Hz, 1H), 3.46 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.56 (brs, 8H), 2.29 (s, 3H).

[0576] Example 218. 2-(4-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (244) This compound was obtained in 38% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0577] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 7.2 Hz, 2H), 8.07 (d, J = 8.4 Hz, 2H), 7.69 (brs, 1H), 7.51-7.43 (m, 5H), 3.59 (q, J = 6.0 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0578] Example 219. 2-(4-chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (245) This compound was obtained in 75% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0579] 1 H NMR (600 MHz, MeOD) δ 8.30 (dd, J = 1.2 Hz and J = 8.4 Hz, 2H), 8.16 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 7.54-7.48 (m, 3H), 3.58 (t, J = 6.6 Hz, 2H), 2.67 (t, J = 6.6 Hz, 2H), 2.56 (brs, 8H), 2.32 (s, 3H).

[0580] Example 220. 2-(4-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (246) This compound was obtained in quantitative yield as a white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0581] 1 H NMR (600 MHz, MeOD) δ 8.17 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 8.06 (d, J = 9.0 Hz, 2H), 7.90 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.82 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.56 (d, J = 9.0 Hz, 2H), 3.46 (t, J = 6.6 Hz, 2H), 2.55 (t, J = 6.6 Hz, 2H), 2.30 (s, 6H).

[0582] Example 221. 2-(4-(chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (247) This compound was obtained in 86% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0583] 1 H NMR (600 MHz, MeOD) δ 8.16 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 7.2 Hz, 1H), 7.82 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 3.48 (t, J = 6.6 Hz, 2H), 2.60 (t, J = 6.6 Hz, 2H), 2.54 (brs, 8H), 2.29 (s, 3H).

[0584] Example 222. (2-(4-chlorophenyl)-5-(2-nitrophenyl)oxazol-4-yl)(4-(2-(dimethylamino)ethyl)piperazin-1-yl)methanone (248) This compound was obtained in 38% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0585] 1 H NMR (600 MHz, CDCl3) δ 8.07 (d, J = 7.2 Hz, 1H), 7.98 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 7.2 Hz, 1H), 7.72 (t, J = 7.2 Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 3.88 (brs, 2H), 3.75 (brs, 2H), 2.60-2.51 (m, 8H), 2.41 (s, 6H).

[0586] Example 223. 2-(4-cyanophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (249) This compound was obtained in quantitative yield as a white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0587] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 7.2 Hz, 2H), 8.24 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.69 (brs, 1H), 7.52-7.49 (m, 3H), 3.59 (q, J = 6.0 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0588] Example 224. 2-(4-cyanophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (250) This compound was obtained in 22% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0589] 1 H NMR (600 MHz, CDCl3) δ 8.38-8.36 (m, 2H), 8.23 ​​(d, J = 9.0 Hz, 2H), 7.83 (d, J = 9.0 Hz, 2H), 7.77 (brt, J = 4.8 Hz, 1H), 7.52-7.45 (m, 3H), 3.60 (q, J = 6.0 Hz, 2H), 2.66 (t, J = 6.0 Hz, 2H), 2.64-2.45 (brs, 8H), 2.33 (s, 3H).

[0590] Example 225. 2-(4-cyanophenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (251) This compound was obtained in 50% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0591] 1 H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 8.4 Hz, 2H), 8.15 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.94 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.75 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.67 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.54 (brt, J = 4.8 Hz, 1H), 3.50 (q, J = 6.0 Hz, 2H), 2.53 (t, J = 6.0 Hz, 2H), 2.31 (s, 6H).

[0592] Example 226. 2-(4-cyanophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (252) This compound was obtained in 68% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0593] 1H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 9.0 Hz, 2H), 8.14 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.94 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.81 (d, J = 9.0 Hz, 2H), 7.75 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.68 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.60 (brt, J = 4.8 Hz, 1H), 3.52 (q, J = 6.0 Hz, 2H), 2.62 (t, J = 6.0 Hz, 2H), 2.61-2.45 (brs, 8H), 2.34 (s, 3H).

[0594] Example 227. 2-([1,1'-biphenyl]-4-yl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (253) This compound was obtained in 12% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0595] 1 H NMR (600 MHz, CDCl3) δ 8.41 (d, J = 7.8 Hz, 2H), 8.20 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 7.2 Hz, 2H), 7.52-7.49 (m, 4H), 7.45-7.41 (m, 2H), 3.61 (q, J = 6.0 Hz, 2H), 2.60 (t, J = 6.0 Hz, 2H), 2.35 (s, 6H).

[0596] Example 228. 2-([1,1'-biphenyl]-4-yl)-N-2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (254) This compound was obtained in 64% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0597] 1 H NMR (600 MHz, MeOD) δ 8.24 (dd, J = 1.2 Hz and J = 8.4 Hz, 2H), 8.06 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.62 (dd, J = 1.2 Hz and J = 8.4 Hz, 2H), 7.46-7.40 (m, 5H), 7.37-7.34 (m, 1H), 3.49 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.51(brs, 8H), 2.27 (s, 3H).

[0598] Example 229. 2-([1,1'-biphenyl]-4-yl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (255) This compound was obtained in quantitative yield as a white solid by a general method of hydrolysis and amide coupling reaction similar to the synthesis of compound 114.

[0599] 1H NMR (600 MHz, MeOD) δ 8.15 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 8.11 (d, J = 8.4 Hz, 2H), 7.89 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.80 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.77 (d, J = 8.4 Hz, 2H), 7.73 (td, J = 7.8 Hz and J = 1.8 Hz, 1H), 7.67-7.66 (m, 2H), 7.46 (t, J = 7.8 Hz, 2H), 7.39-7.36 (m, 1H), 3.46 (t, J = 6.6 Hz, 2H), 2.55 (t, J = 6.6 Hz, 2H), 2.30 (s, 3H).

[0600] Example 230. 2-([1,1'-biphenyl]-4-yl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (256) This compound was obtained in 46% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0601] 1 H NMR (600 MHz, MeOD) δ 8.13 (d, J = 7.8 Hz, 1H), 8.10-8.07 (m, 2H), 7.87-7.86 (m, 1H), 7.80-7.70 (m, 4H), 7.66-7.65 (m, 2H), 7.46-7.43 (m, 2H), 7.38-7.35 (m, 1H), 3.46-3.44 (m, 2H), 2.59-2.56 (m, 2H), 2.51-2.30 (brs, 8H), 2.27 (s, 3H).

[0602] Example 231. N-(2-(dimethylamino)ethyl)-2-(naphthalen-2-yl)-5-phenyloxazole-4-carboxamide (257) This compound was obtained in 44% yield as a white solid by a method similar to the synthesis of compound 114, using the general method of hydrolysis and amide coupling reaction.

[0603] 1 H NMR (600 MHz, CDCl3) δ 8.62 (s, 1H), 8.45 (d, J = 7.2 Hz, 2H), 8.21 (dd, J = 1.8 Hz and J = 9.0 Hz, 1H), 8.00-7.99 (m, 1H), 7.98 (d, J = 9.0 Hz, 1H), 7.92-7.90 (m, 1H), 7.76 (brt, J = 4.8 H, 1H), 7.60-7.57 (m, 2H), 7.52 (t, J = 7.2 Hz, 2H), 7.47-7.44 (m, 1H), 3.61 (q, J = 6.0 Hz, 2H), 2.60 (t, J = 6.0 Hz, 2H), 2.35 (s, 6H).

[0604] Example 232. N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(naphthalen-2-yl)-5-phenyloxazole-4-carboxamide (258) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0605] 1 H NMR (600 MHz, MeOD) δ 8.61 (s, 1H), 8.32-8.31 (m, 2H), 8.17 (dd, J = 1.8 Hz and J = 8.4 Hz, 1H), 8.01-7.98 (m, 2H), 7.92-7.91 (m 1H), 7.59-7.56 (m, 2H), 7.52-7.50 (m, 2H), 7.50-7.46 (m, 1H), 3.56 (t, J = 6.6 Hz, 2H), 2.66 (t, J = 6.6 Hz, 2H), 2.56 (brs, 8H), 2.30 (s, 3H).

[0606] Example 233. N-(2-(dimethylamino)ethyl)-2-(naphthalen-2-yl)-5-(2-nitrophenyl)oxazole-4-carboxamide (259) This compound was obtained in 55% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0607] 1 H NMR (600 MHz, CDCl3) δ 8.55 (s, 1H), 8.15-8.13 (m, 2H), 7.99 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.97-7.95 (m, 2H), 7.90 (d, J = 7.8 Hz, 1H), 7.75 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.65 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.60-7.55 (m, 3H), 3.53 (q, J = 6.0 Hz, 2H), 2.55 (t, J = 6.0 Hz, 2H), 2.33 (s, 6H).

[0608] Example 234. N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(naphthalen-2-yl)-5-(2-nitrophenyl)oxazole-4-carboxamide (260) This compound was obtained in 29% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0609] 1H NMR (600 MHz, CDCl3) δ 8.54 (s, 1H), 8.15-8.13 (m, 2H), 8.00 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.98-7.95 (m, 2H), 7.91-7.90 (m, 1H), 7.74 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.69 (t, J = 4.8 Hz, 1H), 7.66 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.60-7.55 (m, 2H), 3.54 (q, J = 6.0 Hz, 2H), 2.64 (t, J = 6.0 Hz, 2H), 2.63-2.45 (brs, 8H), 2.35 (s, 3H).

[0610] Example 235. N-(2-(dimethylamino)ethyl)-2-(4-(dimethylamino)phenyl)-5-phenyloxazole-4-carboxamide (261) This compound was obtained in 59% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0611] 1 H NMR (600 MHz, MeOD) δ 8.26 (d, J = 7.2 Hz, 2H), 7.95 (d, J = 9.0 Hz, 2H), 7.49 (t, J = 7.2 Hz, 2H), 7.44 (d, J = 7.2 Hz, 1H), 6.83 (d, J = 9.0 Hz, 2H), 3.57 (t, J = 6.6 Hz, 2H), 3.05 (s, 6H), 2.63 (t, J = 6.6 Hz, 2H), 2.36 (s, 6H).

[0612] Example 236. 2-(4-(dimethylamino)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (262) This compound was obtained in 37% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0613] 1 H NMR (600 MHz, MeOD) δ 8.25 (d, J = 7.2 Hz, 2H), 7.91 (d, J = 9.0 Hz, 2H), 7.48 (t, J = 7.2 Hz, 2H), 7.43 (d, J = 7.2 Hz, 1H), 6.79 (d, J = 9.0 Hz, 2H), 3.55 (t, J = 6.6 Hz, 2H), 3.03 (s, 6H), 2.65 (t, J = 6.6 Hz, 2H), 2.76-2.47 (m, 8H), 2.30 (s, 3H).

[0614] Example 237. N-(2-(dimethylamino)ethyl)-2-(4-(dimethylamino)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (263) This compound was obtained in 72% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0615] 1 H NMR (600 MHz, MeOD) δ 8.13 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.92-7.89 (m, 3H), 7.80 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.72-7.69 (m, 1H), 6.83 (d, J = 9.0 Hz, 2H), 3.48 (t, J = 6.6 Hz, 2H), 3.06 (s, 6H), 2.57 (t, J = 6.6 Hz, 2H), 2.32 (s, 6H).

[0616] Example 238. 2-(4-(dimethylamino)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (264) This compound was obtained in 67% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0617] 1 H NMR (600 MHz, MeOD) δ 8.13 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.91-7,90 (m, 3H), 7.81 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.72-7.69 (m, 1H), 6.84 (d, J = 9.0 Hz, 2H), 3.48 (t, J = 6.6 Hz, 2H), 3,07 (s, 6H), 2,62 (t, J = 6.6 Hz, 2H), 2.55 (brs, 8H), 2.31 (s, 3H).

[0618] Example 239. 2-(4-(tert-butyl)phenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (265) This compound was obtained in 49% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0619] 1 H NMR (600 MHz, MeOD) δ 8.25 (d, J = 8.4 Hz, 2H), 8.03 (d, J = 9.0 Hz, 2H), 7.56 (t, J = 8.4 Hz, 2H), 7.48 (t, J = 7.2 Hz, 2H), 7.45 (d, J = 7.2 Hz, 1H), 3.55 (t, J = 6.6 Hz, 2H), 2.60 (t, J = 6.6 Hz, 2H), 2.34 (s, 6H), 1.36 (s, 9H).

[0620] Example 240. 2-(4-(tert-butyl)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (266) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0621] 1 H NMR (600 MHz, MeOD) δ 8.29 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 9.0 Hz, 2H), 7.65-7.57 (m, 2H), 7.55-7.43 (m, 3H), 3.60 (t, J = 6.6 Hz, 2H), 2.66 (t, J = 6.6 Hz, 2H), 2.93-2.39 (m, 8H), 2.31 (s, 3H), 1.39 (s, 9H).

[0622] Example 241. 2-(4-(tert-butyl)phenyl)-N-(2-(diethylamino)ethyl)-5-phenyloxazole-4-carboxamide (267) This compound was obtained in 60% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0623] 1 H NMR (600 MHz, MeOD) δ 8.27 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 6.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.47 (t, J = 8.4 Hz, 2H), 7.46-7.41 (m, 1H), 3.51 (t, J = 6.6 Hz, 2H), 2.75 (t, J = 6.6 Hz, 2H), 2.67 (dd, J = 7.8 Hz and J = 14.1 Hz, 4H), 1.35 (s, 9H), 1.11 (t, J = 7.2 Hz, 6H).

[0624] Example 242. 2-(4-(tert-butyl)phenyl)-N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (268) This compound was obtained in 76% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0625] 1 H NMR (600 MHz, MeOD) δ 8.18 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.75 (t, J = 7.8 Hz, 1H), 7.92 (dd, J = 1.8 Hz and J = 8.4 Hz, 1H), 7.84 (td, J = 8.4 Hz and J = 1.8 Hz, 1H), 7.77 (td, J = 8.4 Hz and J = 1.8 Hz, 1H), 7.62 (t, J = 8.4 Hz, 2H), 3.49 (t, J = 6.6 Hz, 2H), 2.58 (t, J = 6.6 Hz, 2H), 2.33 (s, 6H).

[0626] Example 243. 2-(4-(tert-butyl)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (269) This compound was obtained in 86% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0627] 1 H NMR (600 MHz, MeOD) δ 8.15 (d, J = 8.4 Hz, 4H), 8.01 (d, J = 8.4 Hz, 2H), 7.90 (t, J = 7.8 Hz, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.74 (t, J = 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 3.48 (t, J = 6.6 Hz, 2H), 2.61 (t, J = 6.6 Hz, 2H), 2.30 (s, 3H), 1.38 (s, 9H).

[0628] Example 244. 2-(4-(tert-butyl)phenyl)-N-(2-(diethylamino)ethyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (270) This compound was obtained in 70% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0629] 1 H NMR (600 MHz, MeOD) δ 8.18 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.93 (dd, J = 1.2 Hz and J =7.8 Hz, 1H), 7.84 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.76-7.74 (m, 1H), 7.62 (d, J = 8.4 Hz, 2H), 3.46 (t, J = 6.6 Hz, 2H), 2.74 (t, J = 6.6 Hz, 2H), 2.68 (q, J = 7.2 Hz, 4H), 1.40 (s, 9H), 1.12 (t, J = 7.2 Hz, 6H).

[0630] Example 245. N-(2-(dimethylamino)ethyl)-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (271) This compound was obtained in 58% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0631] 1 H NMR (600 MHz, MeOD) δ 8.28 (d, J = 8.4 Hz, 2H), 8.04 (d, J = 9.0 Hz, 2H), 7.54-7.49 (m, 3H), 7.39 (d, J = 8.4 Hz, 2H), 3.57 (t, J = 6.6 Hz, 2H), 2.63 (t, J = 6.6 Hz, 2H), 2.56 (s, 3H), 2.36 (s, 6H).

[0632] Example 246. N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (272) This compound was obtained in 69% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0633] 1 H NMR (600 MHz, MeOD) δ 8.23 ​​(d, J = 8.4 Hz, 2H), 7.90 (d, J = 9.0 Hz, 2H), 7.49-7.40 (m, 3H), 7.29 (d, J = 9.0 Hz, 2H), 3.51 (t, J = 6.6 Hz, 2H), 2.61 (t, J = 6.6 Hz, 2H), 2.49 (s, 3H), 2.29 (s, 3H).

[0634] Example 247. N-(2-(dimethylamino)ethyl)-2-(4-(methylthio)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (273) This compound was obtained in 35% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0635] 1H NMR (600 MHz, MeOD) δ 8.16 (dd, J = 1.2 Hz and J = 7.8 Hz, 4H), 7.98 (d, J = 9.0 Hz, 2H), 7.90 (dd, J = 1.2 Hz and J = 9.0 Hz, 1H), 7.83 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.75 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.39 (d, J = 9.0 Hz, 2H), 3.48 (t, J = 6.6 Hz, 2H), 2.57 (t, J = 6.6 Hz, 2H), 2.56 (s, 3H), 2.32 (s, 6H).

[0636] Example 248. N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-(methylthio)phenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (274) This compound was obtained in 76% yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0637] 1 H NMR (600 MHz, MeOD) δ 8.13 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.95 (d, J = 9.0 Hz, 2H), 7.88 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.80 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.73 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 3.47 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 6.6 Hz, 2H), 2.53 (s, 3H), 2.74-2.32 (m, 8H), 2.29 (s, 3H).

[0638] Example 249. N-(2-(dimethylamino)ethyl)-2-(4-nitrophenyl)-5-phenyloxazole-4-carboxamide (275) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0639] 1 H NMR (600 MHz, DMSO-d6) δ 8.37 (d, J = 7.8 Hz, 2H), 8.33 (d, J = 7.8 Hz, 2H), 8.23 ​​(d, J = 7.2 Hz, 2H), 7.51-7.44 (m, 3H), 3.39 (t, J = 6.6 Hz, 2H), 2.45 (t, J = 6.6 Hz, 2H), 2.17 (s, 6H).

[0640] Example 250. N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-nitrophenyl)-5-phenyloxazole-4-carboxamide (276) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0641] 1 H NMR (600 MHz, MeOD) δ 8.31 (d, J = 9.0 Hz, 2H), 8.25 (dd, J = 1.8 Hz and J =7.8 Hz, 2H), 8.22 (d, J = 9.0 Hz, 2H), 7.48-7.44 (m, 3H), 3.52 (t, J = 6.6 Hz, 2H), 2,63 (t, J = 6.6 Hz, 2H), 2.60 (brs, 8H), 2.29 (s, 3H).

[0642] Example 251. N-(2-(dimethylamino)ethyl)-5-(2-nitrophenyl)-2-(4-nitrophenyl)oxazole-4-carboxamide (277) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0643] 1 H NMR (600 MHz, DMSO-d6) δ 8.41 (d, J = 8.4 Hz, 2H), 8.28 (d, J = 8.4 Hz, 2H), 8.18 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.91 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.87 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.80 (td, J = 7.8 Hz and J = 1.8 Hz, 1H), 3.27 (t, J = 6.6 Hz, 2H), 2.36 (t, J = 6.6 Hz, 2H), 2.13 (s, 6H).

[0644] Example 252. N-(2-(4-methylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-nitrophenyl)oxazole-4-carboxamide (278) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0645] 1 H NMR (600 MHz, DMSO-d6) δ 8.45 (d, J = 8.4 Hz, 2H), 8.29 (d, J = 8.4 Hz, 2H), 8.20 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.96 (dd, J = 1.2 Hz and J =7.8 Hz, 1H), 7.90 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 7.82 (td, J = 7.8 Hz and J = 1.2 Hz, 1H), 3.29 (t, J = 6.6 Hz, 2H), 2.41 (t, J = 6.6 Hz, 2H), 2.39 (brs, 8H), 2.12 (s, 6H).

[0646] Example 253. 2-(4-Cyclopropylphenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (279) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0647] 1 H NMR (600 MHz, MeOD) δ 8.23 ​​(dd, J = 1.2 Hz and J = 8.4 Hz, 2H), 7.89 (d, J = 7.8, Hz, 2H), 7.45-7.39 (m, 3H), 7.14 (d, J = 7.8, Hz, 2H), 3.50 (t, J = 6.6 Hz, 2H), 2.60 (t, J = 6.6 Hz, 2H), 2.50 (brs, 8H), 2.26 (s, 3H), 1.93-1.89 (m, 1H), 1.03-1.00 (m, 2H), 0.74-0.71 (m, 2H).

[0648] Example 254. 2-(4-Cyclopropylphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (280) This compound was obtained in quantitative yield by a method similar to the synthesis of compound 114, which involves general hydrolysis and amide coupling reactions.

[0649] 1H NMR (600 MHz, MeOD) δ 8.24 (dd, J = 1.8 Hz and J = 9.0 Hz, 2H), 7.94 (d, J = 7.8 Hz, 2H), 7.47-7.42 (m, 3H), 7.17 (d, J = 7.8 Hz, 2H), 3.52 (t, J = 6.6 Hz, 2H), 2.58 (t, J = 6.6 Hz, 2H), 2.32 (s, 6H), 1.97-1.92 (m, 1H), 1.05-1.02 (m, 2H), 0.76-0.74 (m, 2H).

[0650] [ka]

[0651] Reagents and conditions: i) 25% TFA in anhydrous CHCl, 0° C. to room temperature, 1 to 4 hours, quantitative yield for compound 281, 45% yield for compound 282, quantitative yield for compound 283; ii) acetyl chloride, DIPEA, anhydrous CHCl, 0° C. to room temperature, 12 hours, 53% yield for compound 284, 49% yield for compound 285, 41% yield for compound 286; iii) methanesulfonyl chloride, DIPEA, anhydrous CHCl, 0° C. to room temperature, 1 hour, 45% yield for compound 287, 62% yield for compound 288; iv) 1-[N,N'-(di-Boc)amidino]pyrazole, EtN, MeOH, room temperature, 20 hours, 50% yield for compound 289. Example 255. Synthesis by general method of Boc deprotection reaction: 5-(2-nitrophenyl)-N-(2-(piperazin-1-yl)ethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (281) Trifluoroacetic acid (2 mL) was added to a solution of the N-Boc-protected amine (217 mg, 0.37 mmol) in anhydrous CHCl (6 mL) at 0 °C, and the reaction mixture was stirred at 25 °C for 4 h. The volatile components were evaporated and replaced with anhydrous toluene, followed by evaporation to azeotrope excess trifluoroacetic acid. This process was repeated three times to obtain an oil, which was then dried in vacuo. The residue was purified by silica gel column chromatography (eluted with CHCl:MeOH = 20:1 to 10:1, v / v) to give compound 281 as a yellow solid (230 mg, quantitative yield).

[0652] 1 H NMR (600 MHz, CDCl3) δ 8.15 (d, J = 8.2 Hz, 1H), 8.12 (d, J = 7.9 Hz, 1H), 7.88-7.87 (m, 1H), 7.76 (d, J = 8.8 Hz, 3H), 7.68-7.65 (m, 1H), 7.57 (t, J = 5.4 Hz, 1H), 3.58 (q, J = 5.6 Hz, 2H), 3.31 (s, 4H), 2.95 (s, 4H), 2.80 (s, 2H).

[0653] Compounds 282 and 283 were synthesized in a manner similar to that described for compound 281.

[0654] Example 256. N-(2-aminoethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (282) This compound was obtained in 45% yield by a method similar to the synthesis of compound 281, which is a general method for Boc deprotection reaction.

[0655] 1H NMR (600 MHz, CDCl3) δ 8.18 (brs, 2H), 8.08 (d, J = 7.8 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.90 (s, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.8 Hz, 1H), 7.67 (d, J = 7.8 Hz, 2H), 7.63 (t, J = 7.8 Hz, 1H), 3.55 (brs, 2H), 3.08 (brs, 2H).

[0656] Example 257. 2-(3,5-difluorophenyl)-5-(2-nitrophenyl)-N-(2-(piperazin-1-yl)ethyl)oxazole-4-carboxamide (283) This compound was obtained in quantitative yield by a general method for Boc deprotection reaction, similar to the synthesis of compound 281.

[0657] 1 H NMR (600 MHz, CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.75 (t, J = 7.8 Hz, 1H), 7.67 (t, J = 7.2 Hz, 1H), 7.59-7.49 (m, 3H), 6.96 (t, J = 9.0 Hz, 1H), 3.57 (brs, 2H), 3.32 (brs, 3H), 3.01 (brs, 3H), 2.85 (brs, 2H).

[0658] Example 258. Synthesis by general method of acetylation: N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (284) To a solution of compound 281 (70 mg, 0.14 mmol) in anhydrous CHCl (5.0 mL) was added DIPEA (50 μL, 0.29 mmol) under an argon atmosphere. Acetyl chloride (20 μL, 0.29 mmol) was slowly added dropwise to the mixture at 0 °C, followed by stirring at room temperature for 12 h. The volatile components were evaporated, and the residue was purified by silica gel column chromatography (eluted with CHCl:MeOH = 20:1 to 10:1, v / v) to give compound 284 (41 mg, 53%) as a yellow solid.

[0659] 1 H NMR (600 MHz, CDCl3) δ 8.19-8.15 (m, 3H), 7.95 (d, J = 8.4 Hz, 1H), 7.80-7.76 (m, 3H), 7.70-7.68 (m, 1H), 7.57 (brs, 1H), 3.70 (brs, 2H), 3.57-3.53 (m, 4H), 2.65 (t, J = 6.0 Hz, 2H), 2.56-2.53 (m, 4H), 2.13 (s, 3H).

[0660] Compounds 285 and 286 were synthesized in a manner similar to that described for compound 284.

[0661] Example 259. N-(2-acetamidoethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (285) This compound was obtained in 49% yield by a method similar to the synthesis of compound 284, which is a general method for acetylation reaction.

[0662] 1H NMR (600 MHz, CDCl3) δ 8.32 (d, J = 8.4 Hz, 2H), 8.21 (dd, J = 0.6 Hz and J = 8.4 Hz, 1H), 7.93 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.88-7.85 (m, 1H), 7.81-7.78 (m, 1H), 3.46 (t, J = 5.4 Hz, 2H), 3.39 (t, J = 6.0 Hz, 2H), 1.97(s, 3H).

[0663] Example 260. N-(2-(4-acetylpiperazin-1-yl)ethyl)-2-(3,5-difluorophenyl)-5-(2-nitrophenyl)oxazole-4-carboxamide (286) This compound was obtained in 41% yield by a method similar to the synthesis of compound 284, which is a general method for acetylation reaction.

[0664] 1 H NMR (600 MHz, CDCl3) δ 8.18 (dd, J = 0.6 Hz and J = 7.8 Hz, 1H), 7.89 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.76 (td, J = 7.2 Hz and J = 1.2 Hz, 1H), 7.68 (td, J = 8.4 Hz and J = 1.2 Hz, 1H), 7.61-7.54 (m, 2H), 7.51 (t, J = 5.4 Hz, 1H), 7.02-6.94 (m, 1H), 3.68 (t, J = 4.8 Hz, 2H), 3.57-3.49 (m, 4H), 2.63 (t, J = 6.0 Hz, 2H), 2.54 (t, J = 4.8 Hz, 2H), 2.50 (t, J = 4.8 Hz, 2H), 2.12 (s, 3H).

[0665] Example 261. Synthesis by general method of sulfonylation: N-(2-(4-(methylsulfonyl)piperazin-1-yl)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (287) To a solution of compound 281 (70 mg, 0.14 mmol) in anhydrous CHCl (5.0 mL) was added DIPEA (50 μL, 0.29 mmol), and the solution was cooled to 0 °C. Methanesulfonyl chloride (22 μL, 0.29 mmol) was added dropwise, and the mixture was stirred for 5 min and then at room temperature for 1 h. The volatile components were evaporated, and the residue was purified by silica gel column chromatography (eluted with CHCl:MeOH = 20:1 to 10:1, v / v) to give compound 287 (37 mg, 45%) as a yellow solid.

[0666] 1 H NMR (600 MHz, CDCl3) δ 8.19-8.15 (m, 3H), 7.94-7.92 (m, 1H), 7.79-7.76 (m, 3H), 7.71-7.68 (m, 1H), 7.43 (t, J = 5.4 Hz, 1H), 3.55 (q, J = 6.0 Hz, 2H), 3.32-3.30 (m, 4H), 2.83 (s, 3H), 2.68-2.65 (m, 6H).

[0667] Compound 288 was synthesized in a manner similar to that described for compound 287.

[0668] Example 262. N-(2-(methylsulfonamido)ethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (288) This compound was obtained in 62% yield as a fluffy white solid by a general sulfonylation reaction similar to the synthesis of compound 287.

[0669] 1H NMR (600 MHz, CDCl3) δ 8.31 (d, J = 7.8 Hz, 2H), 8.21 (dd, J = 1.2 Hz and J = 8.4 Hz, 1H), 7.94 (dd, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.90-7.85 (m, 3H), 7.81-7.79 (m, 1H), 3.50 (t, J = 6.0 Hz, 2H), 3.37 (s, 1H), 3.29 (t, J = 6.0 Hz, 2H).

[0670] Example 263. N-(2-guanidinoethyl)-5-(2-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (289) To a solution of compound 282 (200 mg, 0.48 mmol) in anhydrous MeOH (5.0 mL), N,N'-bis(tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine (243 mg, 0.78 mmol) and EtN (0.3 mL, 1.6 mmol) were added under argon atmosphere and stirred at room temperature for 20 h. The reaction mixture was distilled under reduced pressure and redissolved in anhydrous CHCl (3.0 mL). Trifluoroacetic acid (1 mL) was added at 0 °C and stirred at room temperature for 6 h. CHCl was evaporated and replaced with anhydrous toluene, which was then evaporated to azeotrope excess trifluoroacetic acid. This process was repeated three times. The residue was purified by silica gel column chromatography (eluted with CHCl:MeOH = 20:1 to 10:1, v / v) to give compound 289 (111 mg, 50%).

[0671] 11H NMR (600 MHz, DMSO-d6) δ 10.8 (s, 1H), 8.66 (s, 1H), 8.41 (s, 1H), 8.27 (d, J = 6.0 Hz, 1H), 8.21 (dd, J = 0.9 Hz and J = 8.2 Hz, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.99 (dd, J = 1.3 Hz and J = 7.8 Hz, 1H), 7.93 - 7.90 (m, 1H), 7.85 - 7.83 (m, 1H), 3.46 (t, J = 6.0 Hz, 2H), 3.43 (t, J = 5.4 Hz, 2H).

[0672] [Chemical formula]

[0673] [Reagents and conditions: i) CH3NH2·HCl, CH3CH2NH2·HCl or CH3(CH2)2NH2·HBr, EDC·HCl, HOBt, DIPEA, DMF, room temperature, 15 hours, 61% yield for compound 290, 74% yield for compound 291, 79% yield for compound 292, 38% yield for compound 293, 67% yield for compound 294, 70% yield for compound 295, 85% yield for compound 296, 85% yield for compound 297, 71% yield for compound 298, 78% yield for compound 299, 80% yield for compound 300, 72% yield for compound 301] Yields: quantitative for compound 302, 82% for compound 303, 40% for compound 304, 73% for compound 305, 77% for compound 306, 35% for compound 307, 18% for compound 308, 39% for compound 309, 12% for compound 310, 61% for compound 311, 100% for compound 312, 85% for compound 313, 85% for compound 314, 68% for compound 315, 65% for compound 316, 69% for compound 317; ii) 1M in DCM BBr3 solution, DCM, 0 °C to room temperature, 15 hours, 58% yield for compound 318, 85% yield for compound 319, 87% yield for compound 320, 43% yield for compound 321, 84% yield for compound 322, 62% yield for compound 323, 54% yield for compound 324. Example 264. Synthesis by general method of hydrolysis and amide coupling reaction: N-methyl-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (290) To a solution of ethyl 5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxylate 40 (900 mg, 2.21 mmol) in a 1:1 mixture of THF and EtOH (20 mL, 3.70 mL, 11.1 mmol) was added 3N NaOH (3.70 mL, 11.1 mmol) and stirred at room temperature for 1 h. The reaction mixture was evaporated under reduced pressure, diluted with water, acidified with 3N HCl, and extracted three times with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting carboxylic acid compound was used in the next step without further purification.

[0674] The carboxylic acid compound (190 mg, 0.50 mmol), methylamine hydrochloride (66 mg, 0.75 mmol), EDC·HCl (144 mg, 0.75 mmol), HOBt (101 mg, 0.75 mmol), and DIPEA (435 μL, 2.50 mmol) were dissolved in DMF (5 mL) and stirred at room temperature for 15 h. The reaction mixture was evaporated under reduced pressure, followed by addition of water and extraction with EtOAc three times. The organic layer was washed with brine, dried over MgSO, filtered, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluted with hexane:EtOAc = 4:1, v / v) to give pure compound 290 (119 mg, 61%).

[0675] 1 H NMR (600 MHz, CDCl3) δ 8.39 (s, 1H), 8.22 (d, J = 7.8 Hz, 2H), 8.17 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 7.8 Hz, 2H), 7.41 (brs, 1H), 7.35 (d, J = 7.8 Hz, 1H), 3.06 (d, J = 4.8 Hz, 3H), 2.60 (s, 3H).

[0676] Compounds 291-317 were synthesized in a manner similar to that described for compound 290.

[0677] Example 265. N-Ethyl-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (291) This compound was obtained as a white solid in 74% yield by reacting compound 40 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0678] 1 H NMR (600 MHz, CDCl3) δ 8.36 (s, 1H), 8.24 (d, J = 7.8 Hz, 2H), 8.18 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.42 (t, J = 7.2 Hz, 1H), 7.39 (brs, 1H), 7.35 (d, J = 8.4 Hz, 1H), 3.57-3.49 (m, 2H), 2.59 (s, 3H), 1.31 (t, J = 7.2 Hz, 3H).

[0679] Example 266. 5-(3-(methylthio)phenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (292) This compound was obtained as a white solid in 79% yield by reacting compound 40 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0680] 1 H NMR (600 MHz, CDCl3) δ 8.35 (s, 1H), 8.24 (d, J = 7.8 Hz, 2H), 8.18 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.43 (brs, 1H), 7.42 (t, J = 7.2 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 3.47 (q, J = 7.2 Hz, 2H), 2.59 (s, 3H), 1.75-1.59 (m, 2H), 1.03 (t, J = 7.2 Hz, 3H).

[0681] Example 267. N-(2-Methoxyethyl)-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (293) This compound was obtained as a white solid in 38% yield by reacting compound 40 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 293.

[0682] 1 H NMR (600 MHz, CDCl3) δ 8.36 (s, 1H), 8.24 (d, J = 7.8 Hz, 2H), 8.17 (d, J = 7.8 Hz, 1H), 7.19 (d, J = 8.4 Hz, 2H), 7.70 (brs, 1H), 7.42 (t, J = 7.2 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 3.70 (q, J = 4.8 Hz, 2H), 3.62 (t, J = 5.4 Hz, 2H), 3.44 (s, 3H), 2.59 (s, 3H).

[0683] Example 268. N-Ethyl-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (294) This compound was obtained as a white solid in 67% yield by reacting compound 31 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0684] 1 H NMR (600 MHz, CDCl3) δ 8.41 (d, J = 7.8 Hz, 2H), 8.25 (d, J = 7.8 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.52 (t, J = 7.2 Hz, 2H), 7.47 (t, J = 7.2 Hz, 1H), 7.40 (brs, 1H), 3.56 (q, J = 6.6 Hz, 2H), 1.33 (t, J = 7.8 Hz, 3H).

[0685] Example 269. 5-Phenyl-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (295) This compound was obtained as a white solid in 70% yield by reacting compound 31 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0686] 1 H NMR (600 MHz, CDCl3) δ 8.41 (d, J = 7.8 Hz, 2H), 8.25 (d, J = 7.8 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.52 (t, J = 7.2 Hz, 2H), 7.47 (t, J = 7.2 Hz, 1H), 7.40 (brs, 1H), 3.56 (q, J = 6.6 Hz, 2H), 1.78-1.68 (m, 2H), 1.05 (t, J = 7.8 Hz, 3H).

[0687] Example 270. N-Ethyl-5-(2-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (296) This compound was obtained as a white solid in 85% yield by reacting compound 44 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0688] 1 H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 7.8 Hz, 2H), 7.73 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 8.4 Hz, 1H), 7.14 (brs, 1H), 7.08 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 3.88 (s, 3H), 3.51-3.41 (m, 2H), 1.27 (t, J = 7.2 Hz, 3H).

[0689] Example 271. 5-(2-Methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (297) This compound was obtained as a white solid in 85% yield by reacting compound 44 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0690] 1 H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 7.8 Hz, 2H), 7.73 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 8.4 Hz, 1H), 7.18 (brs, 1H), 7.08 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 3.88 (s, 3H), 3.40 (q, J = 6.6 Hz, 2H), 1.71-1.59 (m, 2H), 1.00 (t, J = 7.2 Hz, 3H).

[0691] Example 272. N-Ethyl-5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (298) This compound was obtained as a white solid in 71% yield by reacting compound 45 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0692] 1H NMR (600 MHz, CDCl3) δ 8.23 ​​(d, J = 7.8 Hz, 2H), 8.17 (d, J = 1.2 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.41 (t, J = 7.8 Hz, 1H), 7.40 (brs, 1H), 7.01 (dd, J = 2.4 Hz and J = 6.0 Hz, 1H), 3.97 (s, 3H), 3.59-3.50 (m, 2H), 1.32 (t, J = 7.2 Hz, 3H).

[0693] Example 273. 5-(3-Methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (299) This compound was obtained as a white solid in 78% yield by reacting compound 45 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0694] 1 H NMR (600 MHz, CDCl3) δ 8.23 ​​(d, J = 7.8 Hz, 2H), 8.17 (d, J = 1.2 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.44 (brs, 1H), 7.41 (t, J = 7.8 Hz, 1H), 7.01 (dd, J = 2.4 Hz and J = 6.0 Hz, 1H), 3.98 (s, 3H), 3.47 (q, J = 7.2 Hz, 2H), 1.75-1.64 (m, 2H), 1.04 (t, J = 7.2 Hz, 3H).

[0695] Example 274. N-Ethyl-5-(4-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (300) This compound was obtained as a white solid in 80% yield by reacting compound 46 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0696] 1 H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 9.0 Hz, 2H), 8.22 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.63 (brs, 1H), 7.02 (d, J = 9.0 Hz, 2H), 3.89 (s, 3H), 3.58-3.49 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H).

[0697] Example 275. 5-(4-Methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (301) This compound was obtained as a white solid in 72% yield by reacting compound 46 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0698] 1 H NMR (600 MHz, CDCl3) δ 8.38 (d, J = 9.0 Hz, 2H), 8.22 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.41 (brs, 1H), 7.02 (d, J = 9.0 Hz, 2H), 3.89 (s, 3H), 3.45 (q, J = 6.6 Hz, 2H), 1.75-1.65 (m, 2H), 1.03 (t, J = 7.2 Hz, 3H).

[0699] Example 276. 5-(3,4-Dimethoxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (302) This compound was obtained as a white solid in 79% yield by reacting compound 47 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0700] 1 H NMR (600 MHz, CDCl3) δ 8.37 (d, J = 1.8 Hz, 1H), 8.22 (d, J = 8.4 Hz, 2H), 7.91 (dd, J = 2.4 Hz and J = 8.4 Hz, 1H), 7.78 (d, J = 7.8 Hz, 2H), 7.40 (brs, 1H), 6.98 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 3.97 (s, 3H), 3.58-3.51 (m, 2H), 1.32 (t, J = 7.5 Hz, 3H).

[0701] Example 277. 5-(3,5-dimethoxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (303) This compound was obtained as a white solid in 82% yield by reacting compound 48 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0702] 1 H NMR (600 MHz, CDCl3) δ 8.23 ​​(d, J = 8.4 Hz, 2H), 7.78 (d, J = 7.8 Hz, 2H), 7.73 (d, J = 2.4 Hz, 2H), 7.42 (brs, 1H), 6.58 (t, J = 2.4 Hz, 1H), 3.91 (s, 6H), 3.57-3.51 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H).

[0703] Example 278. N-Ethyl-2-(4-(trifluoromethyl)phenyl)-5-(3,4,5-trimethoxyphenyl)oxazole-4-carboxamide (304) This compound was obtained as a white solid in 40% yield by reacting compound 49 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0704] 1 H NMR (600 MHz, CDCl3) δ 8.23 ​​(d, J = 8.4 Hz, 2H), 7.84 (s, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.42 (brt, J = 5.4 Hz, 1H), 4.00 (s, 6H), 3.96 (s, 3H), 3.57-3.51 (m, 2H), 1.32 (t, J = 7.2 Hz, 3H).

[0705] Example 279. N-Ethyl-5-(2-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (305) This compound was obtained as a white solid in 73% yield by reacting compound 50 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0706] 1 H NMR (600 MHz, CDCl3) δ 8.22 (d, J = 8.4 Hz, 2H), 8.07 (dd, J = 1.8 Hz and J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.54 (td, J = 1.2 Hz and J = 7.2 Hz, 1H), 7.44 (td, J = 1.2 Hz and J = 7.2 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.25 (brs, 1H), 3.52-3.47 (m, 2H), 1.29 (t, J = 7.2 Hz, 3H).

[0707] Example 280. N-Propyl-5-(2-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (306) This compound was obtained as a white solid in 77% yield by reacting compound 50 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0708] 1 H NMR (600 MHz, CDCl3) δ 8.22 (d, J = 7.8 Hz, 2H), 8.07 (dd, J = 1.8 Hz and J = 7.2 Hz, 1H), 7.78 (d, J = 7.8 Hz, J = 2H), 7.54 (td, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.44 (td, J = 1.2 Hz and J = 7.8 Hz, 1H), 7.41 (d, J = 7.2 Hz, 1H), 7.29 (br s, 1H), 3.42 (q, J = 7.2 Hz, 2H), 1.71-1.65 (m, 2H), 1.01 (t, J = 7.2 Hz, 3H).

[0709] Example 281. N-Ethyl-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (307) This compound was obtained as a white solid in 76% yield by reacting compound 42 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0710] 1 H NMR (600 MHz, CDCl3) δ 9.35 (d, J = 1.8 Hz, 1H), 9.00 (td, J = 1.8 Hz and J = 8.4 Hz, 1H), 8.67 (dd, J = 1.2 Hz and J = 5.1 Hz, 1H), 8.25 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.44 (q, J = 4.8 Hz, 1H), 7.40 (brs, 1H), 3.59-3.50 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H).

[0711] Example 282. N-Propyl-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (308) This compound was obtained as a white solid in 18% yield by reacting compound 42 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0712] 1 H NMR (600 MHz, CDCl3) δ 9.35 (d, J = 1.8 Hz, 1H), 9.00 (td, J = 1.8 Hz and J = 8.4 Hz, 1H), 8.67 (dd, J = 1.2 Hz and J = 5.1 Hz, 1H), 8.25 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.44 (q, J = 4.8 Hz, 1H), 3.47 (q, J = 6.6 Hz, 2H), 1.75-1.66 (m, 2H), 1.04 (t, J = 7.2 Hz, 3H).

[0713] Example 283. N-Ethyl-5-(pyridin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (309) This compound was obtained as a white solid in 39% yield by reacting compound 43 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0714] 1 H NMR (600 MHz, CDCl3) δ 8.78 (d, J = 6.0 Hz, 2H), 8.35 (d, J = 6.0 Hz, 2H), 8.26 (d, J = 7.8 Hz, 2H), 7.80 (d, J = 9.0 Hz, 2H), 7.44 (brs, 1H), 3.60-3.51 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H).

[0715] Example 284. N-Propyl-5-(pyridin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (310) This compound was obtained in 12% yield by reacting compound 43 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0716] 1 H NMR (600 MHz, CDCl3) δ 8.78 (dd, J = 1.8 Hz and J = 6.6 Hz, 2H), 8.36 (dd, J = 1.8 Hz and J = 6.0 Hz, 2H), 8.27 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.84 (brs, 1H), 3.48 (q, J = 6.6 Hz, 2H), 1.76-1.69 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H).

[0717] Example 285. 5-(3-cyanophenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (311) This compound was obtained as a white solid in 61% yield by reacting compound 55 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0718] 1H NMR (600 MHz, CDCl3) δ 8.82-8.80 (m, 1H), 8.68 (t, J = 1.8 Hz, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.73 (dt, J = 1.8 Hz and J = 7.8 Hz, 1H), 7.63 (t, J = 7.8 Hz, 1H), 7.42 (br s, 1H), 3.57-3.53 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H).

[0719] Example 286. N-Ethyl-2-(4-methoxyphenyl)-5-phenyloxazole-4-carboxamide (312) This compound was obtained as a white solid in 73% yield by reacting compound 62 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0720] 1 H NMR (600 MHz, CDCl3) δ 8.39 (d, J = 7.2 Hz, 2H), 8.06 (d, J = 9.0 Hz, 2H), 7.49 (t, J = 7.8 Hz, 2H), 7.42 (td, J = 1.2 Hz and J = 7.5 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 3.90 (s, 3H), 3.57-3.49 (m, 2H), 1.30 (t, J = 7.2 Hz, 3H).

[0721] Example 287. 2-(3,5-difluorophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (313) This compound was obtained as a white solid in 85% yield by reacting compound 70 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0722] 1H NMR (600 MHz, CDCl3) δ 8.40-8.36 (m, 2H), 7.66-7.62 (m, 2H), 7.53-7.49 (m, 2H), 7.48-7.44 (m, 1H), 7.35 (brs, 1H), 6.79 (tt, J = 2.4 Hz and J = 8.7 Hz, 1H), 3.57-3.50 (m, 2H), 1.31 (t, J = 6.9 Hz, 3H).

[0723] Example 288. 2-(3-chlorophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (314) This compound was obtained as a white solid in 85% yield by reacting compound 75 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0724] 1 H NMR (600 MHz, CDCl3) δ 8.41-8.38 (m, 2H), 8.11 (t, J = 1.8 H, 1H), 8.00 (td, J = 1.5 Hz and J = 7.2 Hz, 1H), 7.52-7.48 (m, 3H), 7.47-7.43 (m, 2H), 7.39 (brs, 1H), 3.56-3.50 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H).

[0725] Example 289. 2-(4-cyanophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (315) This compound was obtained as a white solid in 68% yield by reacting compound 79 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0726] 1H NMR (600 MHz, CDCl3) δ 8.42-8.37 (m, 2H), 8.23 ​​(d, J = 9.0 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.53-7.49 (m, 2H), 7.48-7.44 (m, 1H), 7.36 (brs, 1H), 3.57-3.50 (m, 2H), 1.31 (t, J = 7.2H, 3H).

[0727] Example 290. N-Ethyl-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (316) This compound was obtained as a white solid in 65% yield by reacting compound 87 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0728] 1 H NMR (600 MHz, CDCl3) δ 8.40 (d, J = 7.2 Hz, 2H), 8.03 (d, J = 8.4 Hz, 2H), 7.51 (t, J = 7.2 Hz, 2H), 7.44 (t, J = 7.2 Hz, 1H), 7.43 (brs, 1H), 7.36 (d, J = 8.4 Hz, 2H), 3.58-3.49 (m, 2H), 1.32 (t, J = 6.6 Hz, 3H).

[0729] Example 291. 2-(4-(methylthio)phenyl)-5-phenyl-N-propyloxazole-4-carboxamide (317) This compound was obtained as a white solid in 69% yield by reacting compound 87 with the general method of hydrolysis and amide coupling reaction, similar to the synthesis of compound 290.

[0730] 1H NMR (600 MHz, CDCl3) δ 8.40 (d, J = 7.2 Hz, 2H), 8.03 (d, J = 9.0 Hz, 2H), 7.50 (t, J = 7.8 Hz, 2H), 7.51-7.41 (m, 2H), 7.36 (d, J = 8.4 Hz, 2H), 3.46 (q, J = 6.6 Hz, 2H), 1.76-1.67 (m, 2H), 1.04 (t, J = 7.2 Hz, 3H).

[0731] Example 292. Synthesis by general method of methoxy deprotection reaction: N-ethyl-5-(3-hydroxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (318) To a solution of compound 298 (310 mg, 0.79 mmol) in anhydrous CHCl (10 mL) was added boron tribromide solution (2.37 mL, 1.0 M in CHCl) at 0 °C and stirred at room temperature for 15 h. The reaction mixture was added with water and extracted three times with CHCl. ​​The organic layer was dried over NaSO, filtered, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluted with hexane:EtOAc = 3:1 v / v) to give compound 318 (172 mg, 58%) as a white solid.

[0732] 1 H NMR (600 MHz, DMSO-d6) δ 9.74 (brs, 1H), 8.53. 1H), 7.79-7.76 (m, 1H), 7.33 (t, J = 5.4 Hz, 1H), 6.90 (ddd, J = 0.6 Hz, J = 2.4 Hz and J = 8.4 Hz, 1H), 1.16 (t, J = 7.2 Hz, 3H).

[0733] Compounds 319-324 were synthesized in a manner similar to that described for compound 318.

[0734] Example 293. 5-(3-hydroxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (319) This compound was obtained as a white solid in 85% yield by a general method for methoxy deprotection, similar to the synthesis of compound 318.

[0735] 1 H NMR (600 MHz, CDCl3) δ 8.23 ​​(d, J = 8.4 Hz, 2H), 8.15 (t, J = 1.8 Hz, 1H), 7.81-7.79 (m, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.49 (brs, 1H), 7.36 (t, J = 8.4 Hz, 1H), 6.96 (ddd, J = 0.6 Hz, J = 2.4 Hz and J = 8.4Hz, 1H), 3.47-3.44 (m, 2H), 1.73-1.67 (m, 2H), 1.02 (t, J = 7.2 Hz, 2H).

[0736] Example 294. N-Ethyl-5-(4-hydroxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (320) This compound was obtained as a white solid in 87% yield by a general method of methoxy deprotection reaction, similar to the synthesis of compound 318.

[0737] 1 H NMR (600 MHz, MeOD) δ 8.31 (d, J = 8.4 Hz, 2H), 8.18 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H), 3.44 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H).

[0738] Example 295. 5-(3,4-dihydroxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (321) This compound was obtained as a white solid in 43% yield by a method similar to the synthesis of compound 318, which is a general method for methoxy deprotection reaction.

[0739] 1 H NMR (600 MHz, MeOD) δ 8.30 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 2.4 Hz, 1H), 7.72 (dd, J = 2.4 Hz and J = 8.4 Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), 3.45 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H).

[0740] Example 296. 5-(3,5-dihydroxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (322) This compound was obtained as a white solid in 84% yield by a general method of methoxy deprotection reaction, similar to the synthesis of compound 318.

[0741] 1 H NMR (600 MHz, MeOD) δ 8.31 (d, J = 8.4 Hz, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 1.8 Hz, 2H), 6.39 (t, J = 1.8 Hz, 1H), 3.45 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H).

[0742] Example 297. N-Ethyl-2-(4-(trifluoromethyl)phenyl)-5-(3,4,5-trihydroxyphenyl)oxazole-4-carboxamide (323) This compound was obtained as a white solid in 62% yield by a method similar to the synthesis of compound 318, which is a general method for methoxy deprotection reaction.

[0743] 1 H NMR (600 MHz, MeOD)δ 8.29 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 7.38 (s, 2H), 3.45 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H).

[0744] Example 298. N-Ethyl-2-(4-hydroxyphenyl)-5-phenyloxazole-4-carboxamide (324) This compound was obtained in 54% yield by a method similar to the synthesis of compound 318, which is a general method for methoxy deprotection reaction.

[0745] 1 H NMR (600 MHz, MeOD) δ 8.23 ​​(d, J = 7.8 Hz, 2H), 7.99 (d, J = 9.0 Hz, 2H), 7.48 (t, J = 7.5 HZ, 2H), 7.46-7.43 (m, 1H), 6.93 (d, J = 9.0 Hz, 2H), 3.44 (q, J = 7.4 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H).

[0746] Experimental Example 1. ELISA Analysis 1.1. Coating 100 nM of Flag-tagged human recombinant IL-33 protein was prepared in 1X coating buffer solution (BioLegend), then transferred to a 96-well microplate (Corning) using a multichannel pipette (Gilson) and coated at 4°C for 12 hours or more.

[0747] 1.2.Blocking After washing three times with PBST (1X PBS (Welgene) and 1% Tween 20 (Sikma)), the cells were incubated with a 1% BSA (Bovogen) blocking buffer solution at room temperature for 1 hour.

[0748] 1.3.Binding Samples containing 200 nM of His-tagged ST2 human recombinant protein and 60 μM or 200 μM of the synthetic compounds of the Examples were prepared and added in equal volumes, and then reacted at room temperature for 2 hours or more.

[0749] 1.4.Detection After washing three times with PBST (1X PBS (Welgene), 1% Tween 20 (Sikma)), anti-His HRP (BioLegend) antibody was diluted 5000:1 and reacted at room temperature for at least 1 hour.

[0750] 1.5.Reaction After washing three times with PBST (1X PBS (Welgene) and 1% Tween 20 (Sikma)), TMB substrate solution (Thermo) was added and reacted for at least 5 minutes. The reaction was stopped by adding 1N HCl (Samchun), and the plate was orbitally shaken for 5 seconds using a microplate reader (Tecan, Spark®), after which the absorbance was measured at 450 nm.

[0751] 1.6.Analysis method The results obtained from the program linked to the microplate reader were analyzed using an Excel program. The average of three values ​​obtained from triplicate runs was calculated, and the positive control value was subtracted. The negative control value was then converted to 100% to determine the IL33-ST2 binding rate (%). The IL33-ST2 binding rate (%) was subtracted from 100% to determine the inhibition rate (inhibition%) for each compound. The error range of the triplicate runs was also calculated and reflected in the derivation of the compound inhibition graph.

[0752] 1.7.Results The inhibition rates of IL33 and ST2 binding are shown in Tables 1 to 8 below.

[0753] [Table 1]

[0754] [Table 2]

[0755] [Table 3]

[0756] [Table 4]

[0757] [Table 5]

[0758] [Table 6]

[0759] [Table 7]

[0760] [Table 8]

[0761] Experimental Example 2: Method for evaluating IL-6 production inhibition 2.1.Cell culture Human mast cell line HMC1.1 cells were cultured in a medium (Iscove's modified Dulbecco's medium, IMDM, HyClone) supplemented with 10% fetal bovine serum (FBS, HyClone®) and 1% antibiotics in an incubator maintained at 5% CO2 and 37°C.

[0762] 2.2. Treatment of Example Compounds For non-adherent HMC1.1 cells, 5 × 10 cells were collected from a culture flask filled to about 80% capacity by centrifugation. 5 The cells were cultured in 0.5 mL of culture medium containing 200 nM of wild-type human recombinant IL-33 protein, treated with 5 μM, 10 μM, 25 μM, 30 μM, or 50 μM of an example compound, and cultured for 24 hours.

[0763] 2.3. Cell culture medium harvest The medium was collected by centrifugation (2,000 × g, 5 minutes) and then stored at −80°C until ELISA analysis.

[0764] 2.4.IL-6ELISA analysis The experiment was carried out using a human IL-6 ELISA kit (Abcam) according to the protocol.

[0765] 2.5.Analysis method The results obtained from the program linked to the microplate reader were analyzed using an Excel program. The average of three values ​​obtained from triplicate runs was calculated, and IL-6 secretion was measured using a standard curve. The measured IL-6 secretion was converted to 100% based on the vehicle-treated sample value to calculate vehicle %. The inhibition rate value for each compound was calculated by subtracting vehicle % from 100%, and the error range of the triplicate runs was also calculated and reflected in the derivation of a compound inhibition rate graph.

[0766] 2.6.Results The inhibition rates of IL-6 secretion in the human mast cell line HMC1.1 are shown in Tables 9 to 11 below.

[0767] [Table 9]

[0768] [Table 10]

[0769] [Table 11]

[0770] Experimental Example 3: Measurement of cell viability 3.1.Cell culture Human liver cancer cell line HepG2 cells were cultured in a medium (Dulbecco's modified Eagle's medium (high glucose), DMEM, HyClone) supplemented with 10% fetal bovine serum (FBS, HyClone) and 1% antibiotics in an incubator maintained at 5% CO2 and 37°C.

[0771] 3.2. Treatment of Example Compounds HepG2 cells, which are adherent cells, were cultured at 1 × 10 4 The cells were cultured in 100 μM culture medium for 18 hours, and the culture medium in the absence or presence of human liver microsomes (Gibco®) and an NADPH regenerating system was treated with 25 μM, 30 μM or 50 μM of an example compound for 24 hours.

[0772] 3.3.Changing the cell culture medium The medium was replaced with 100 μM medium (Dulbecco's modified Eagle's medium (high glucose), DMEM, HyClone), and the cells were cultured for 24 hours.

[0773] Analysis of WST-8 10 μL of WST-8 (Abcam) was added, and after 2 hours, the plate was orbitally shaken for 5 seconds using a microplate reader (Tecan, Spark (registered trademark)), and the absorbance value was determined at 460 nm.

[0774] 3.5.Analysis method The results obtained from the program linked to the microplate reader were analyzed using an Excel program. Three values ​​obtained from triplicate runs were averaged and converted into a percentage of cell viability compared to the vehicle-treated group.

[0775] 3.6.Results The stability results in human and mouse liver S9 fractions are shown in Table 12 below.

[0776] [Table 12]

[0777] Experimental Example 4: Confirmation of efficacy in HDM and ovalbumin-induced asthma animal models 4.1. Experimental animals The animals used in the experiment were 6-week-old specific pathogen-free (SPF) BALB / C female mice purchased from Orientbio (Seongnam, Korea).

[0778] 4.2. Test Substances 4.2.1.Name 1) House dust mites (HDM), Dermatophagoides farinae (XPB81D3A25, Greer Labs) 2) House dust mites (HDM), Dermatophagoides pteronyssinus (XPB82D3A25, Greer Labs) 3) Chicken egg white albumin (A5503, Sigma) 4) Phosphate buffer solution (SH30256.01, manufactured by CYTIVA) 4.2.2. Storage conditions: frozen 4.3. Experimental method overview Before HDM and ovalbumin administration, DO11.10 CD4 T cells 1 × 10 6The mice were injected into the tail vein. The naive group consisted of 5–6 mice, while the HDM-OVA acute asthma mouse model group consisted of 20–24 mice. HDM (50 μg / mouse of Dermatophagoides farinae and Dermatophagoides pteronyssinus) and OVA (100 μg / mouse) were dissolved in PBS and administered intranasally at 40 μL per mouse for 3 days to create the model. The example compounds (vehicle [DMSO:Labrafil = 10:90 (vol%), 10 mg / kg]) were orally administered at 5 mL / kg. The naive group received 40 μL of saline instead of HDM-OVA. Whenever possible, the test substances and HDM were administered at consistent times. Care was taken to maintain sterility during intratracheal instillation and SC administration. On day 7 after the first reduction, mice were sacrificed to obtain alveolar lavage fluid and excise the lungs.

[0779] 4.4. Analysis of eosinophils in bronchial lavage fluid Mice were sacrificed by cervical dislocation, and the lungs were lavaged three times with 0.8 ml of PBS injected into the trachea (BAL fluid). Total cell counts were performed using a hemocytometer, and BAL fluid smears were prepared using Cytospin (TXT3, Korea). For cellular differentiation, eosinophils were counted after staining with Diff-Quick solution (Dade Diagnostics of Princ. Aguada, Puerto Rico).

[0780] The above description of the present invention is for illustrative purposes only, and those skilled in the art will understand that the present invention can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. Therefore, it should be understood that the above-described embodiments are illustrative in all respects and are not limiting. For example, each component described as a single type can be implemented separately, and similarly, the separated components can be implemented in a combined form.

[0781] The scope of the present invention is defined by the claims that follow, and it is to be understood that the scope of the present invention encompasses all modifications and variations that fall within the meaning and scope of the claims and their equivalents. [Brief explanation of the drawings]

[0782] [Figure 1] FIG. 1 shows an outline of an ELISA assay for measuring inhibition of IL-33 and IL-33 receptor (ST-2) binding. [Figure 2] 1 is a dose-response graph measuring IC50 values ​​for Compound 294. [Figure 3] 1 is a dose-response graph measuring the EC50 value of Compound 294 in a mast cell line. [Figure 4] 1 shows the results of confirming the asthma suppressing efficacy (eosinophil reducing effect) of the compound of the present invention in an animal model of HDM and ovalbumin-induced asthma.

Claims

1. An oxazole derivative compound represented by the following chemical formula I, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof: 【Chemistry 1】 In Formula I, R １ is C １ -C ６ Straight or branched chain alkyl, C ３ -C ６ Cycloalkyl, C １ -C ４ Alkoxy, halogen, C １ -C ４ Haloalkyl, C １ -C ４ Haloalkoxy, C １ -C ４ Alkylthio, hydroxy, cyano, nitro, NR ａ R ｂ , or C ５ -C １２ is an aryl having one or two rings, The R １ is singular or plural, and R １ If there are multiple １ are each independently a substituent, R ２ is hydrogen, C １ -C ４ Alkoxy, C １ -C ４ Haloalkoxy, C １ -C ４ Alkylthio, C １ -C ４ alkylsulfonyl, hydroxy, cyano, or 4- to 7-membered heteroaryl containing 1-3 N; The R ２ is singular or plural, and R ２ If there are multiple R ２ are each independently a substituent, R ３ is a single X unsubstituted or substituted with a single Y; X is —NH—Y or piperazinyl-Y; The Y is C １ -C ６ is a straight or branched chain alkyl; said Y being unsubstituted or substituted with a single Z; The Z is C １ -C ４ Alkoxy, NR ａ R ｂ , C ５ -C ７ aryl or a 5-7 membered aromatic or non-aromatic heterocycle containing 1-2 N; At this time, the R ａ and R ｂ are independently hydrogen or C １ -C ４ is a straight or branched chain alkyl; Z is unsubstituted or substituted with Q; The Q is C １ -C ６ is a straight or branched chain alkyl, hydroxy, or acetyl; Excluding the cases where R 1 is 4-trifluoromethyl, R 2 is hydrogen, and R 3 is butylamino; where R 1 is 2,6-difluoro, R 2 is hydrogen, and R 3 is pentylamino; where R 1 is 2,6-difluoro, R 2 is hydrogen, and R 3 is benzylamino; and where R 1 is 3-trifluoromethyl, R 2 is 4-trifluoromethoxy, and R 3 is butylamino.

2. The R １ is butyl, cyclopropyl, methoxy, F, Cl, trifluoromethyl, trifluoromethoxy, methylthio, hydroxy, cyano, nitro, NR ａ R ｂ , phenyl, or naphthyl, or a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, according to claim 1 .

3. The R ａ and R ｂ The oxazole derivative compound, its hydrate, its solvate, or its pharmaceutically acceptable salt according to claim 2, wherein is methyl.

4. The R ２ 2. The oxazole derivative compound, its hydrate, its solvate, or its pharmaceutically acceptable salt according to claim 1, wherein is hydrogen, methoxy, trifluoromethoxy, methylthio, methylsulfonyl, hydroxy, cyano, or pyridinyl.

5. 2. The oxazole derivative compound, its hydrate, its solvate, or its pharmaceutically acceptable salt according to claim 1, wherein Y is methyl, ethyl, or propyl.

6. The Z is methoxy, NR ａ R ｂ , phenyl, piperazinyl, or pyridinyl, or a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, according to claim 1 .

7. The R ａ and R ｂ The oxazole derivative compound, its hydrate, its solvate, or its pharmaceutically acceptable salt according to claim 6, wherein is independently methyl or ethyl.

8. The oxazole derivative compound, its hydrate, its solvate, or its pharmaceutically acceptable salt according to claim 1, wherein the oxazole derivative compound represented by the above chemical formula I is any one selected from the group consisting of the following compounds: N-(2-(dimethylamino)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (117), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (118), N-(2-(dimethylamino)ethyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (126), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-phenyl-2-(2-(trifluoromethyl)phenyl)oxazole-4-carboxamide (128), (4-(2-(dimethylamino)ethyl)piperazin-1-yl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl)methanone (129), N-(4-hydroxyphenethyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (130), 5-(4-(methylsulfonyl)phenyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (193), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(4-(methylthio)phenyl)-2-(4-trifluoromethyl)phenyl)oxazole-4-carboxamide (194), 5-(4-(methylthio)phenyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (195), N-(2-(dimethylamino)ethyl)-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (196), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (197), N-(2-(4-acetylpiperazin-1-yl)ethyl)-5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (198), N-(2-(dimethylamino)ethyl)-5-phenyl-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (199), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(3-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (200), N-(2-(dimethylamino)ethyl)-5-phenyl-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (203), N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-2-(4-(trifluoromethoxy)phenyl)oxazole-4-carboxamide (204), N-(2-(dimethylamino)ethyl)-2-(3-methoxyphenyl)-5-phenyloxazole-4-carboxamide (208), 2-(3-methoxyphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (209), 2-(4-fluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (225), 2-(3,4-difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (231), 2-(3,4-difluorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (232), 2-(3,5-difluorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (235), 2-(3-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (240), 2-(3-chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (241), 2-(4-chlorophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (244), 2-(4-chlorophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (245), 2-(4-cyanophenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (249), 2-(4-cyanophenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (250), 2-([1,1′-biphenyl]-4-yl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (253), 2-([1,1′-biphenyl]-4-yl)-N-2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (254), N-(2-(dimethylamino)ethyl)-2-(naphthalen-2-yl)-5-phenyloxazole-4-carboxamide (257), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(naphthalen-2-yl)-5-phenyloxazole-4-carboxamide (258), N-(2-(dimethylamino)ethyl)-2-(4-(dimethylamino)phenyl)-5-phenyloxazole-4-carboxamide (261), 2-(4-(dimethylamino)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (262), 2-(4-(tert-butyl)phenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (265), 2-(4-(tert-butyl)phenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (266), 2-(4-(tert-butyl)phenyl)-N-(2-(diethylamino)ethyl)-5-phenyloxazole-4-carboxamide (267), N-(2-(dimethylamino)ethyl)-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (271), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (272), N-(2-(4-methylpiperazin-1-yl)ethyl)-2-(4-nitrophenyl)-5-phenyloxazole-4-carboxamide (276), 2-(4-cyclopropylphenyl)-N-(2-(dimethylamino)ethyl)-5-phenyloxazole-4-carboxamide (279), 2-(4-cyclopropylphenyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyloxazole-4-carboxamide (280), N-methyl-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (290), N-ethyl-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (291), 5-(3-(methylthio)phenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (292), N-(2-methoxyethyl)-5-(3-(methylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (293), N-ethyl-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (294), 5-phenyl-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (295), N-ethyl-5-(2-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (296), 5-(2-methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (297), N-ethyl-5-(3-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (298), 5-(3-methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (299), N-ethyl-5-(4-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (300), 5-(4-methoxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (301), 5-(3,4-dimethoxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (302), 5-(3,5-dimethoxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (303), N-ethyl-2-(4-(trifluoromethyl)phenyl)-5-(3,4,5-trimethoxyphenyl)oxazole-4-carboxamide (304), N-ethyl-5-(2-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (305), N-propyl-5-(2-(trifluoromethoxy)phenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (306), N-ethyl-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (307), N-propyl-5-(pyridin-3-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (308), N-ethyl-5-(pyridin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (309), N-propyl-5-(pyridin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (310), 5-(3-cyanophenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (311), N-ethyl-2-(4-methoxyphenyl)-5-phenyloxazole-4-carboxamide (312), 2-(3,5-difluorophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (313), 2-(3-chlorophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (314), 2-(4-cyanophenyl)-N-ethyl-5-phenyloxazole-4-carboxamide (315), N-ethyl-2-(4-(methylthio)phenyl)-5-phenyloxazole-4-carboxamide (316), 2-(4-(methylthio)phenyl)-5-phenyl-N-propyloxazole-4-carboxamide (317), N-ethyl-5-(3-hydroxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (318), 5-(3-hydroxyphenyl)-N-propyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (319), N-ethyl-5-(4-hydroxyphenyl)-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (320), 5-(3,4-dihydroxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (321), 5-(3,5-dihydroxyphenyl)-N-ethyl-2-(4-(trifluoromethyl)phenyl)oxazole-4-carboxamide (322), N-ethyl-2-(4-(trifluoromethyl)phenyl)-5-(3,4,5-trihydroxyphenyl)oxazole-4-carboxamide (323), and N-Ethyl-2-(4-hydroxyphenyl)-5-phenyloxazole-4-carboxamide (324).

9. A pharmaceutical composition for preventing or treating an allergic disease, comprising the oxazole derivative compound, its hydrate, its solvate, or its pharmaceutically acceptable salt according to any one of claims 1 to 8 as an active ingredient.

10. A pharmaceutical composition for the prevention or treatment of one or more diseases selected from the group consisting of one or more allergic diseases selected from asthma, allergic rhinitis, chronic sinusitis, allergic contact dermatitis, atopic dermatitis, chronic idiopathic urticaria, and anaphylaxis; one or more autoimmune diseases selected from Graves' disease, Sjogren's syndrome, immune thrombocytopenia, autoimmune hemolytic anemia, inflammatory bowel disease, and primary biliary cholangitis; and chronic obstructive pulmonary disease, comprising the oxazole derivative compound, its hydrate, its solvate, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 8 as an active ingredient.

11. A pharmaceutical composition for preventing or treating an allergic disease, comprising the oxazole derivative compound, its hydrate, its solvate, or its pharmaceutically acceptable salt according to any one of claims 1 to 8, and a pharmaceutically acceptable additive.

12. A food composition for improving symptoms of an allergic disease, comprising the oxazole derivative compound according to any one of claims 1 to 8, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

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