Pde4 inhibitor compounds and medical uses thereof

Abstract

A class of PDE4 inhibitor compounds, isomers, solvates, deuterated derivatives or pharmaceutically acceptable salts thereof. Medicaments comprising the compounds, isomers, solvates, deuterated derivatives and pharmaceutically acceptable salts thereof, and their use in the preparation of a medicament for the treatment of diseases associated with PDE4 inhibition, such as autoimmune diseases, cancer.

Description

[0001] Related applications

[0002] This application claims priority to Chinese Patent Application No. 202010114076.2, filed on February 24, 2020, entitled "PDE4 Inhibitor Compound and Its Pharmaceutical Use Thereof", filed on July 28, 2020, entitled "PDE4 Inhibitor Compound and Its Pharmaceutical Use Thereof", and Chinese Patent Application No. 202010748673.0, filed on August 28, 2020, entitled "PDE4 Inhibitor Compound and Its Pharmaceutical Use Thereof", the entire contents of which are incorporated herein by reference. Technical Field

[0003] This invention relates to a class of PDE4 inhibitor compounds, their isomers, solvates, deuterated derivatives or pharmaceutically acceptable salts of such compounds, and medicaments in which such compounds or their salts are active ingredients, and their use in the preparation of drugs for PDE4-related diseases such as autoimmune diseases and cancer. Background Technology

[0004] Tumor necrosis factor (TNFα) is a cytokine primarily released by mononuclear phages in response to immune stressors. TNFα promotes most processes, including cell differentiation, recruitment, proliferation, and protein degradation. At low levels, TNFα has a protective effect against infectious agents, tumors, and tissue damage. Excessive release of TNFα can also cause disease; for example, administration of TNFα to mammals or humans can cause or exacerbate inflammation, fever, cardiovascular effects, hemorrhage, coagulation, and acute reactions similar to acute infection and shock. Long-term excessive or uncontrolled production of TNFα in animals and adults can lead to the following diseases: endotoxemia and / or poisoning shock syndrome, cachexia, adult respiratory stress syndrome, cancer (such as solid tumors and hematologic malignancies), heart disease (such as congestive heart failure), viral infections, genetic diseases, inflammatory diseases, allergic diseases, or autoimmune diseases.

[0005] Cancer is a particularly destructive disease, and elevated levels of TNFα in the blood indicate a risk of developing or spreading cancer. Normally, cancer cells cannot survive in the circulatory system of a healthy individual, partly because the inner walls of blood vessels act as a barrier against their extravasation. Studies have shown that ELAM-1 on endothelial cells can mediate the adhesion of colon cancer cells to endothelial cells treated with cytokines.

[0006] Cyclic adenosine monophosphate (cAMP) plays a role in many diseases and conditions. During inflammation, increased cAMP concentration in leukocytes inhibits leukocyte activation, subsequently releasing inflammatory regulatory factors including TNFα and NF-κB. Elevated cAMP levels also lead to relaxation of airway smooth muscle.

[0007] The primary cellular mechanism of cAMP inactivation is the destruction of cAMP by a family of isoenzymes called cyclic nucleotide phosphodiesters (PDEs). Eleven members of the PDE family are known. To date, inhibition of PDE4 enzymes has been shown to be particularly effective in suppressing the release of inflammatory mediators and relaxing respiratory smooth muscle, making PDE4 an attractive drug target. Based on different gene encodings, the PDE-4 family can be divided into four subtypes (PDE-4A, B, C, and D). Among them, PDE-4A, PDE-4B, and PDE-4D are expressed more strongly than PDE-4C in inflammatory cells (such as B cells, T cells, and neutrophils). Inhibition of PDE4 enzymes leads to an increase in cAMP levels, thereby regulating TNFα levels and achieving the goal of treating diseases.

[0008] Inhibiting PDE4 enzymes leads to an increase in cAMP levels, thereby regulating TNFα levels and achieving therapeutic effects on inflammatory, infectious, immune, or other malignant diseases such as septic shock, sepsis, endotoxin shock, hemorrhagic shock, sepsis syndrome, post-ischemia-reperfusion injury, Mycobacterium malaria infection, meningitis, psoriasis, congestive heart failure, fibrotic diseases, cachexia, transplant rejection, tumors, autoimmune disorders, opportunistic infections in AIDS patients, rheumatoid arthritis, rheumatic spondylitis, osteoarthritis, other inflammatory diseases, Crohn's disease, ulcerative colitis, multiple sclerosis, systemic lupus erythematosus, atopic dermatitis, erythema nodosum leprosy, radiation injury, and hyperoxia-induced lung injury. Summary of the Invention

[0009] One object of the present invention is to provide a compound of formula (I), and its isomers, solvates, deuterated derivatives, or pharmaceutically acceptable salts:

[0010]

[0011] Its features are:

[0012] X 1 Selected from N or CH;

[0013] X 2 X 3 X 4 One of them is selected from N, and the others are CH;

[0014] X is selected from O, -N(R) 6 ), -CH(R6 )-;

[0015] R is selected from hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl, and may be substituted with halogens;

[0016] R 1 R 2 R 3 Each of the following is independently selected from hydrogen, halogen, hydroxyl, -CN, -NH2, C1-C6 alkyl, C1-6 alkoxy, C1-C6 alkylamino, C2-6 alkylenyl, C3-6 cycloalkenyl, 3-6 heterocyclic alkenyl, C3-C6 cycloalkyl, 3-6 heterocyclic alkyl, phenyl, 5-6 heteroaryl, and -COOR. 8 These groups can be substituted with halogens, C1-C6 alkyl groups, any halogenated C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or any halogenated C3-C6 cycloalkyl groups.

[0017] R 4 R 5 It is independently selected from C1-C6 alkyl and C3-C6 cycloalkyl groups, and can be substituted with deuterium, tritium or halogen in any way;

[0018] R 6 Selected from H, halogen, hydroxyl, -CN, -NH2, -COOH, R 7 -L 1 -or selected from C1-6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 3-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -COOR 9 -SO2R 10 -SO2NHR 11 -NHCONHR 12 These groups can be substituted with halogens, C1-C6 alkyl groups, any halogenated C1-C6 alkyl groups, C3-C6 cycloalkyl groups, or any halogenated C3-C6 cycloalkyl groups.

[0019] R 7 Selected from C3-C6 cycloalkyl, 3-6 heterocyclic alkyl, 3-6 heterocyclic alkenyl, phenyl, 5-6 heteroaryl, -COOR 8 It can be substituted by halogens, C1-C6 alkyl groups, and C3-C6 cycloalkyl groups;

[0020] L 1 Selected from -CH2-, -CH2CH2-, O, S, NH;

[0021] R 8 R 9 R 10 R 11 R 12It can be C1-C6 alkyl, halogenated C1-C6 alkyl, or C3-C6 cycloalkyl.

[0022] Preferably, the compound of formula (I), and its isomers, solvates, deuterated derivatives, or pharmaceutically acceptable salts, are characterized in that X is selected from:

[0023]

[0024] Preferably, the compound of formula (I), and its isomers, solvates, deuterated derivatives, or pharmaceutically acceptable salts, are characterized by R 1 R 2 R 3 Independently selected from the following groups:

[0025]

[0026] These groups can be substituted with halogens, -OH, -NH2, -CN, C1-C6 alkyl, any halogenated C1-C6 alkyl, C3-C6 cycloalkyl, or any halogenated C3-C6 cycloalkyl.

[0027] Preferably, the compound of formula (I), and its isomers, solvates, deuterated derivatives, or pharmaceutically acceptable salts, are characterized in that the compound comprises the following structures:

[0028] 3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0029] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0030] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0031] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0032] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0033] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0034] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0035] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5b]pyridin-2(3H)-one;

[0036] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5b]pyridin-2(3H)-one;

[0037] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-ethylphenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0038] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-isopropylphenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0039] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-methoxyphenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0040] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-methoxyphenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0041] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(2-(trifluoromethyl)phenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0042] (S)-2-(3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)benzyl nitrile;

[0043] (R)-2-(3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)benzyl nitrile;

[0044] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0045] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0046] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1,7-dimethyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0047] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-(2-methoxyethyl)-7-methyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0048] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0049] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0050] (S)-6-(2,6-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0051] (R)-6-(2,6-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0052] (S)-6-(2,3-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0053] (R)-6-(2,3-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0054] (S)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0055] (S)-6-(2,4-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0056] (S)-6-(2,4,5-trifluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0057] (R)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0058] (S)-6-(2,4-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0059] (S)-6-(2,5-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0060] (S)-6-(2,3-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0061] (S)-6-(2,6-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0062] (S)-6-(4-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0063] (S)-6-(5-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0064] (S)-6-(2-fluoro-5-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0065] (S)-6-(2-fluoro-3-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0066] (S)-6-(2-fluoro-4-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0067] (S)-6-(2-fluoro-5-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0068] (S)-6-(2-fluoro-3-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0069] (S)-6-(2-fluoro-4-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0070] (S)-6-(5-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0071] (S)-6-(4-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0072] (S)-6-(6-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0073] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0074] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0075] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0076] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-7-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0077] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0078] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0079] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0080] (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0081] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0082] (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0083] (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0084] (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0085] (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0086] (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0087] (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0088] (R)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0089] (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0090] (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0091] (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0092] (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1,7-dimethyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0093] (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-1,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0094] (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1,7-dimethyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0095] (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-isopropoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0096] (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-isopropoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0097] (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-isopropoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0098] (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-isopropoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0099] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-bromo-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0100] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0101] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0102] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0103] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-phenyl-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0104] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0105] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0106] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0107] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-ethylphenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0108] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-ethylphenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0109] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0110] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-methoxyphenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0111] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-(trifluoromethyl)phenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0112] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-(trifluoromethyl)phenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0113] (S)-6-(2-Cyclopropylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0114] (S)-6-(2,6-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0115] (S)-6-(2,6-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0116] (S)-6-(2,3-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0117] (S)-6-(2,3-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0118] (S)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0119] (S)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0120] (S)-6-(2,4-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0121] (S)-6-(2,4-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0122] (S)-6-(2,4,5-trifluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0123] (S)-6-(2,4,5-trifluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0124] (R)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0125] (S)-6-(2,4-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0126] (S)-6-(2,4-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0127] (S)-6-(2,5-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0128] (S)-6-(2,5-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0129] (S)-6-(2,3-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0130] (S)-6-(2,3-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0131] (S)-6-(2,6-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0132] (S)-6-(2,6-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0133] (S)-6-(4-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0134] (S)-6-(4-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0135] (S)-6-(5-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0136] (S)-6-(5-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0137] (S)-6-(3-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0138] (S)-6-(3-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0139] (S)-6-(2-fluoro-5-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0140] (S)-6-(2-fluoro-5-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0141] (S)-6-(2-fluoro-4-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0142] (S)-6-(2-fluoro-4-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0143] (S)-6-(5-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0144] (S)-6-(5-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0145] (S)-6-(4-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0146] (S)-6-(4-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0147] (S)-6-(6-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0148] (S)-6-(pyridin-2-yl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0149] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0150] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0151] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-(2-methoxyethyl)-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0152] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0153] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0154] (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one;

[0155] (S)-5-bromo-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0156] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-phenyl-1H-benzo[d]imidazol-2(3H)-one;

[0157] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-phenyl-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0158] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0159] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0160] (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0161] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(4-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0162] (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(4-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0163] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-5-(4-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0164] (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-5-(4-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0165] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(o-tolyl)-1H-benzo[d]imidazol-2(3H)-one;

[0166] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(o-tolyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0167] (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(o-tolyl)-1H-benzo[d]imidazol-2(3H)-one;

[0168] (S)-5-(2-chlorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0169] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-methoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0170] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-methoxyphenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0171] (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-methoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0172] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0173] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-(trifluoromethyl)phenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0174] (S)-5-(2-Cyclopropylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0175] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-isopropylphenyl)-4-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0176] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-ethylphenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0177] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-ethylphenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0178] (S)-5-(2,3-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0179] (S)-5-(2,3-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0180] (S)-5-(2,6-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0181] (S)-5-(2,6-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0182] (S)-5-(2,4-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0183] (S)-5-(2,4-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0184] (S)-5-(2,4,5-trifluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0185] (S)-5-(2,4,5-trifluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0186] (S)-5-(2,5-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0187] (S)-5-(2,5-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0188] (S)-5-(2,4-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0189] (S)-5-(2,4-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0190] (S)-5-(2,5-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0191] (S)-5-(2,5-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0192] (S)-5-(2,3-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0193] (S)-5-(2,3-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0194] (S)-5-(2,6-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0195] (S)-5-(4-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0196] (S)-5-(4-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0197] (S)-5-(5-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0198] (S)-5-(5-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0199] (S)-5-(3-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0200] (S)-5-(3-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0201] (S)-5-(2-fluoro-5-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0202] (S)-5-(2-fluoro-5-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0203] (S)-5-(2-fluoro-3-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0204] (S)-5-(2-fluoro-3-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0205] (S)-5-(2-fluoro-4-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0206] (S)-5-(2-fluoro-4-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0207] (S)-5-(2-fluoro-5-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0208] (S)-5-(2-fluoro-5-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0209] (S)-5-(2-fluoro-3-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0210] (S)-5-(2-fluoro-4-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0211] (S)-5-(2-fluoro-4-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0212] (S)-5-(5-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0213] (S)-5-(5-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0214] (S)-5-(4-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0215] (S)-5-(4-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0216] (S)-5-(6-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0217] (S)-5-(6-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0218] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-ethoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0219] (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-ethoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0220] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one;

[0221] (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one;

[0222] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one;

[0223] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-ethyl-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one;

[0224] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-(2-methoxyethyl)-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one;

[0225] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(4-fluoro-2-methylphenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0226] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(4-fluoro-2-methylphenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0227] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluoro-5-methylphenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0228] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluoro-5-methylphenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0229] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-(2-methoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0230] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-(o-tolyl)-1H-benzo[d]imidazol-2(3H)-one;

[0231] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-(2-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0232] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-phenyl-1H-benzo[d]imidazol-2(3H)-one;

[0233] (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-(2-fluorobenzyl)-1H-benzo[d]imidazol-2(3H)-one;

[0234] (S)-3-Cyclopropyl-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one;

[0235] (S)-3-Cyclopropyl-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-methyl-1H-benzo[d]imidazol-2(3H)-one;

[0236] (S)-5-bromo-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-(2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0237] (S)-3-Cyclopropyl-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-2(3H)-one;

[0238] (S)-Ethyl 1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylic acid ester;

[0239] (S)-Isopropyl 1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylic acid ester; and

[0240] (S)-2,2,2-trifluoroethyl 1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylic acid ester.

[0241] Another object of the present invention is to provide compounds of formula (II), and isomers, solvates, deuterated derivatives or pharmaceutically acceptable salts thereof:

[0242]

[0243] Its features are:

[0244] Y 1 Selected from N or CH;

[0245] Y 2 Y 3 Y 4 One of them is selected from N, and the others are CH;

[0246] R 13 Selected from C1-C3 alkyl and C1-C6 cycloalkyl groups, and may be substituted with halogens;

[0247] R 14 R 15 R 16 The group is independently selected from hydrogen, halogen, hydroxyl, CN, -NO2, -NH2, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 alkanoylamino, C3-C6 cycloalkanoylamino, C2-C6 alkylenyl, C3-C6 cycloenyl, 3-6 membered heterocyclic alkenyl, C3-C6 cycloalkyl, 3-6 membered heterocyclic, phenyl, 5-6 membered heteroaryl. These groups may be substituted by halogen, C3-C6 cycloalkyl, C1-C8 alkoxy, C3-C8 cycloalkoxy, 3-12 membered heterocyclic, C1-C8 alkylamino, di(C1-C8 alkyl) substituted amino, phenyl, 5-6 membered heteroaryl in any way.

[0248] R 17 R 18 It is independently selected from C1-C6 alkyl, C3-C6 cycloalkyl, and can be substituted by deuterium, tritium or halogen in any way.

[0249] Preferably, the compound of formula (II), and its isomers, solvates, deuterated derivatives, or pharmaceutically acceptable salts, are characterized in that the compound comprises the following structures:

[0250] (S)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)acetamide;

[0251] (R)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)acetamide;

[0252] (S)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)cyclopropaneformamide;

[0253] (R)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)cyclopropaneformamide;

[0254] (S)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)propionamide; or

[0255] (R)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-3-oxoisoindol-4-yl)propionamide.

[0256] Another object of the present invention is a compound of formula (III), and its isomers, solvates, deuterated derivatives, and pharmaceutically acceptable salts thereof:

[0257]

[0258] Its features are:

[0259] R 19 Selected from C1-C3 alkyl and C3-C6 cycloalkyl groups, and may be substituted with halogens;

[0260] R 20 R 21 Selected from hydrogen, halogen, C1-C8 alkyl, C1-C8 alkoxy, hydroxyl, cyano, nitro, and -NHC(O)R respectively. 26 -NHSO2R 26 or -NR 24 R 25 ;

[0261] R 22 R 23 It is independently selected from C1-C6 alkyl groups and can be substituted with deuterium, tritium or halogen in any way;

[0262] R 24 R 25 Selected from hydrogen, C1-C8 alkyl, C6-C12 aryl, C(O)R 26 SO2R 26 Or R 24 R 25 Together with the N-membered ring it is attached to, they form a 4-8 membered ring or -CH2CH2ZCH2CH2-;

[0263] Z is selected from O, S, NR 26 ;

[0264] R 26It can be hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, or C1-C8 alkylamino, and can be substituted by halogen, C1-C8 alkoxy, C3-C8 cycloalkoxy, 3-12 membered heterocyclic group, C1-C8 alkylamino, or di(C1-C8 alkyl) substituted amino groups in any way.

[0265] Preferably, the compound of formula (III), and its isomers, solvates, deuterated derivatives, or pharmaceutically acceptable salts, are characterized in that the compound includes, but is not limited to, the following structures:

[0266] 5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-nitro-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione;

[0267] (S)-5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-nitro-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione;

[0268] (S)-1-amino-5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione;

[0269] N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)acetamide;

[0270] (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)acetamide;

[0271] (R)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)acetamide;

[0272] (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)propionamide;

[0273] (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)cyclopropaneformamide;

[0274] (S)-2-(dimethylamino)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)acetamide;

[0275] (S)-2-(diethylamino)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)acetamide;

[0276] (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)-2-(piperidin-1-yl)acetamide;

[0277] (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)-2-(pyrrolidin-1-yl)acetamide; or

[0278] (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)-2-morpholinoacetamide.

[0279] technical terms

[0280] The term "alkyl" refers to a straight-chain or branched alkyl group having 1 to 12 carbon atoms in the chain. Examples of alkyl groups include methyl (Me), ethyl (Et), n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl (t-Bu), pentyl, isopentyl, tert-pentyl, hexyl, isohexyl, and any group that is considered equivalent to any of the foregoing examples in accordance with the teachings of a person skilled in the art and the present text.

[0281] The term "alkoxy group" refers to an alkyl group as defined above that is bonded to an oxygen atom. Alkoxy groups are attached to the parent structure via an oxygen atom.

[0282] The term "alkenyl" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon double bond, such as vinyl, 1-propenyl, 2-propenyl, etc. C2-10 alkenyl groups are preferred, C2-6 alkenyl groups are more preferred, C2-4 alkenyl groups are most preferred, and vinyl groups are the most desirable. Alkenyl groups can be substituted or unsubstituted; when substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkoxy, alkylamino, halogen, hydroxyl, cycloalkyl, heterocycloalkyl, and heterocycloalkoxy groups.

[0283] The term "amino" refers to a -NH2 group or a mono- or dialkylamino group.

[0284] The term cycloalkyl refers to a saturated or partially saturated, monocyclic, fused polycyclic, bridged polycyclic, or burst polycyclic carbon ring, with each carbon atom having 3 to 12 ring atoms. Illustrative examples of cycloalkyl groups include entities in the following suitable bonded molar forms:

[0285]

[0286] The term "heteroaryl" refers to a monocyclic, fused bicyclic, or fused polycyclic aromatic heterocycle (the ring structure having 3 to 12 ring atoms selected from carbon atoms and up to four heteroatoms selected from nitrogen, oxygen, and sulfur). Illustrative examples of heteroaryls include the following entities in appropriate bonded form:

[0287]

[0288] The term "aryl" refers to an aromatic ring containing C5-C20 monocyclic, fused bicyclic, or fused polycyclic rings, without heteroatoms such as nitrogen, oxygen, or sulfur. Common aromatic groups include, but are not limited to, residues derived from benzene, substituted benzene, naphthalene, anthracene, biphenyl, etc.

[0289] The term "heterocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent comprising 3 to 20 ring atoms, wherein one or more ring atoms are selected from nitrogen, oxygen, or S(O)m (where m is an integer from 0 to 2), and the remaining ring atoms are carbon. Preferably, it comprises 3 to 12 ring atoms, wherein 1 to 4 are heteroatoms; more preferably, heterocyclic alkyl rings comprise 3 to 10 ring atoms, and even more preferably, they comprise 5 to 6 ring atoms. Non-limiting examples of monocyclic heterocyclic alkyl groups include pyrrolidinyl, piperidinyl, morpholinyltetrahydrofuranyl, etc. Polycyclic heterocyclic alkyl groups include spirocyclic, fused-ring, and bridged-ring heterocyclic alkyl groups. The heterocycle can be substituted or unsubstituted; when substituted, the substituent is preferably one or more of the following groups independently selected from alkyl, haloalkyl, alkoxy, alkylamino, halogen, hydroxy, amino, oxo, alkylamino, cycloalkyl, heterocyclic alkyl, heterocyclic alkoxy, hydroxyalkyl, carboxyl, or carboxylic acid ester groups.

[0290] The term "halogen" refers to chlorine, fluorine, bromine, or iodine. The term "halogenated" represents chlorination, fluorination, bromination, or iodination. The term "halogenated alkyl" refers to an alkyl group as defined above, which is substituted with one or more halogen atoms.

[0291] "Acceptable carriers, diluents, or excipients for pharmaceuticals include, but are not limited to, any adjuvants, carriers, excipients, glidants, sweeteners, diluents, preservatives, dyes / colorants, flavor enhancers, surfactants, wetting agents, dispersants, suspending agents, stabilizers, isotonic agents, solvents, or emulsifiers that have been approved by the U.S. Food and Drug Administration for use in humans or animals and have no adverse effects on the composition of the pharmaceutical composition."

[0292] "Drug-acceptable salts" include "drug-acceptable acid adduct salts" and "drug-acceptable base adduct salts".

[0293] "Pharmaceutical-acceptable acid adducts" refer to those salts that retain the biological effectiveness and properties of a free base, wherein the acid adduct is biologically or otherwise suitable and is formed using inorganic or organic acids, such as, but not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc., and such organic acids as, but not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, phenylcarboxylic acid, 4-acetamidophenylcarboxylic acid, camphoric acid, camphor-10-sulfonic acid, decanoic acid, hexanoic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclohexylaminosulfonic acid, dodecyl sulfate, ethane-1,2-disulfonic acid, ethanesulfonic acid, etc. Acids, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, viscous acid, gentian acid, glucoheponic acid, gluconic acid, glucuronic acid, glutamic acid, glutamate, 2-oxoglutamate, glycerophosphate, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lacturonic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, viscous acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, dihydroxynaphthalic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanate, p-methyltheanosulfonic acid, trifluoroacetic acid, undecenoic acid, etc.

[0294] "Pharmaceutical-acceptable base addition salts" refer to those salts that retain the biological effectiveness and properties of free acids, wherein the base addition salts are suitable in a biological or other respectable manner. These salts are prepared by adding an inorganic or organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum salts. Preferred inorganic salts are ammonium, sodium, potassium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and salts of basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, dimethylaminoethanol, 2-dimethylethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, heparin, choline, betaine, benzylamine, phenylethylenediamine, ethylenediamine, glucosamine, methylglucosamine, theobromine, triethanolamine, aminobutanetriol, purine, piperazine, piperidine, N-hexylpiperidine, polyamine resins, etc. Particularly preferred organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

[0295] "Pharmaceutical combination" refers to a formulation formed by combining the compounds of this application with a medium generally accepted in the art for delivering bioactive compounds to mammals such as humans. Such a medium includes carriers, diluents, or excipients acceptable to all pharmaceuticals.

[0296] Secondly, the present invention provides methods for preparing compounds of formula (I), formula (II) or formula (III) and their isomers and deuterated derivatives, as detailed in the embodiments.

[0297] In the embodiments provided by this invention, if the compound of this invention contains a basic group, it can form a salt with an acid, and the salt of acyclic nucleoside derivatives or isomers can be prepared using methods well known to those skilled in the art.

[0298] Common acid salts include organic acid salts and inorganic acid salts. Commonly used organic acid salts include citrates, fumarates, oxalates, malates, lactates, and sulfonates (such as camphor sulfonate, p-toluenesulfonate, and methanesulfonate). Inorganic acid salts include hydrohalides, sulfates, phosphates, and nitrates. For example, they can form methanesulfonates and trifluoromethanesulfonates with lower alkyl sulfonic acids, such as methanesulfonic acid and trifluoromethanesulfonic acid; they can form p-toluenesulfonates and benzenesulfonates with aryl sulfonic acids, such as benzenesulfonic acid or p-toluenesulfonic acid; they can form corresponding salts with organic carboxylic acids, such as acetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid, or citric acid; and they can form glutamate or aspartate with amino acids, such as glutamic acid or aspartic acid. They can also form corresponding salts with inorganic acids, such as hydrohalides (such as hydrofluoric acid, hydrobromic acid, hydroiodic acid, and hydrochloric acid), nitric acid, carbonic acid, sulfuric acid, or phosphoric acid.

[0299] Thirdly, this invention provides a medicament using a compound of formula (I), formula (II), or formula (III), isomer, solvate, deuterated derivative, or a pharmaceutically acceptable salt or solvate thereof as an active ingredient. The medicament may also contain one or more pharmaceutically acceptable carriers, including conventional pharmaceutical diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, adsorbents, lubricants, etc., and flavoring agents, sweeteners, etc., may be added if necessary. The medicament of this invention can be formulated into various forms such as tablets, powders, granules, capsules, oral liquids, and injectable drugs, and all of the above dosage forms can be prepared according to conventional pharmaceutical methods.

[0300] Fourthly, the present invention provides compounds of formula (I), formula (II), or formula (III), isomers, solvates, deuterated derivatives, or pharmaceutically acceptable salts thereof, and provides a method for inhibiting PDE4, comprising administering a therapeutically effective amount of at least one compound of the present invention to a host in need of such treatment.

[0301] One preferred embodiment is the use of a medicament for treating inflammatory and autoimmune diseases. For this purpose of the invention, inflammatory and autoimmune diseases or conditions include systemic lupus erythematosus (SLE), lupus nephritis, cutaneous lupus, Crohn's disease, ulcerative colitis, type 1 diabetes, psoriasis, rheumatoid arthritis, systemic paroxysmal juvenile idiopathic arthritis, ankylosing spondylitis, or multiple sclerosis, etc. Detailed Implementation

[0302] The feasibility of the present invention will be illustrated below through examples. Those skilled in the art should understand that modifications or substitutions to the corresponding technical features based on the teachings of the prior art still fall within the scope of protection claimed by the present invention.

[0303] Example 1: 3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0304]

[0305] Step 1: 5-Bromo-N-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-methyl-3-nitropyridin-2-amine

[0306] At room temperature, 30.0 g of 5-bromo-2-chloro-4-methyl-3-nitropyridine, 29.4 g of 1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethylamine (synthesized according to the method disclosed in WO2018157779) and 30 g of diisopropylamine were dissolved in 150.0 mL of N,N-dimethylformamide. Under nitrogen protection, the mixture was reacted at 120 °C for 2 hours. 1000 mL of water was added to the mixture, and the mixture was extracted with ethyl acetate (250 mL × 3). The combined organic phases were washed with saturated brine (100 mL × 3), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and the residue was subjected to column chromatography to give 36.8 g of the target compound.

[0307] ESI MS m / z: 489.04 [M+1] +

[0308] Step 2: N-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-4-methyl-3-nitropyridin-2-amine

[0309]

[0310] At room temperature, 24.1 g of the product from step 2 and 10.40 g of o-fluorophenylboronic acid were dissolved in 300 mL of dioxane and 100 mL of water. Under nitrogen protection, 20 g of potassium carbonate and 4 g of the [1,1,-bis(diphenylphosphine)ferrocene]palladium dichloromethane complex were added. The reaction mixture was heated to 80 °C and stirred for 14 hours under nitrogen protection. After the reaction was complete, the mixture was cooled to room temperature, and 600 mL of water was added to the reaction mixture. The mixture was extracted with ethyl acetate (300 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the drying agent, concentrated under reduced pressure, and the residue was subjected to column chromatography to give 16.4 g of the target compound.

[0311] ESI MS m / z: 505.15 [M+1] +

[0312] Step 3: N2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-4-methylpyridin-2,3-diamine

[0313]

[0314] At room temperature, ethanol (200 mL) was added to 12.0 g of the product from step 3 and 13 g of ammonium chloride. Then, 15 g of zinc powder was added in 20 portions at 0 °C. The reaction mixture was stirred at 0 °C for 16 hours. After the reaction was complete, the reaction mixture was filtered to remove the zinc powder, and the filtrate was concentrated under reduced pressure to obtain the residue. The residue was dissolved in 300 mL of dichloromethane, and the suspension was filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to obtain 8.7 g of the compound.

[0315] ESI MS m / z: 475.17 [M+1] +

[0316] Step 4: 3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazol[4,5-b]pyridin-2(3H)-one

[0317] At room temperature, 4.65 g of the product from step 3 and 10 g of triethylamine were dissolved in 50.0 mL of tetrahydrofuran. The mixture was cooled to 0 °C, and 1.17 g of triphosgene and 10.0 mL of tetrahydrofuran solution were added dropwise to the reaction mixture. After the addition was complete, the reaction mixture was stirred at 0 °C for 2 hours under nitrogen protection. After the reaction was complete, 100 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and the residue was subjected to column chromatography to obtain the target compound.

[0318] ESI MS m / z: 501.15 [M+1] +

[0319] Example 2, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0320]

[0321] Step 1, (S)-5-bromo-N-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-methyl-3-nitropyridin-2-amine

[0322]

[0323] (S)-1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethylamine (1.43 g, 5.23 mmol) (prepared from the racemic mixture via SFC resolution) was dissolved in 10 mL of N,N-dimethylformamide, followed by the addition of (5-bromo-2-chloro-4-methyl-3-nitropyridine) (1.93 g, 8.16 mmol) and 3 mL of triethylamine. The mixture was heated to 100 °C for 16 hours under nitrogen protection. After cooling to room temperature, the reaction was quenched with water, extracted with ethyl acetate (50 mL x 3), and the organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The mixture was then filtered, concentrated, and column filtered. The eluent was concentrated to give 1.3 g of the target compound.

[0324] Step 2, (S)-N-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-4-methyl-3-nitropyridin-2-amine

[0325]

[0326] The product from step 1 (121 mg, 0.25 mmol) was dissolved in 8 mL of a mixed solvent (1,4-dioxane:water = 3:1), and (2-fluorophenyl)boric acid (52 mg, 0.37 mmol), (dppf)PdCl2 (110 mmg), and potassium carbonate (102 mg, 0.74 mmol) were added. The mixture was refluxed at 85 °C for 8 hours under nitrogen vacuum. After cooling to room temperature, the mixture was quenched with water, filtered through diatomaceous earth, and extracted with ethyl acetate (50 mL * 3). The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The product was filtered, concentrated, and dried to obtain 1.3 g of the target compound.

[0327] Step 3, (S)-N 2 -(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-4-methylpyridin-2,3-diamine

[0328]

[0329] At room temperature, ethanol (200 mL) was added to 1.2 g of the product from step 2 and 2.3 g of ammonium chloride. Then, 2.8 g of zinc powder was added in 20 portions at 0 °C. The reaction mixture was stirred at 0 °C for 4 hours. After the reaction was complete, the reaction mixture was filtered to remove the zinc powder. The filtrate was concentrated under reduced pressure to obtain the residue. The residue was dissolved in 300 mL of dichloromethane, washed twice with sodium carbonate aqueous solution, and the ethyl acetate layer was dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, 0.8 g of the compound was obtained.

[0330] ESI MS m / z: 475.17 [M+1] +

[0331] Step 4: (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazol[4,5-b]pyridin-2(3H)-one

[0332] At room temperature, 0.6 g of the product from step 3 and 0.8 g of triethylamine were dissolved in 50.0 mL of tetrahydrofuran. The mixture was cooled to 0 °C, and 0.3 g of triphosgene and 10.0 mL of tetrahydrofuran solution were added dropwise to the reaction mixture. After the addition was complete, the reaction mixture was stirred at 0 °C for 2 hours under nitrogen protection. After the reaction was complete, 20 mL of saturated sodium carbonate aqueous solution was added to the reaction mixture, and the mixture was extracted with 100 mL of ethyl acetate. The mixture was washed twice with 2 M sodium carbonate aqueous solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 0.4 g of the compound.

[0333] 1 H NMR (400MHz, DMSO-D6) δ11.52(s,1H),7.75(s,1H),7.50-7.46(m,1H),7.39-7.29(m,3H),7.26-7.24(d,1H),6.85-6.83(d,1H), 6.09-6.05(q,1H),4.58(m,1H),4.35-4.30(q,1H),4.28-4.17(m,2H),3.75(s,3H),3.08(s,3H),2.14(s,3H),1.23-1.18(q,3H).

[0334] ESI MS m / z: 501.15 [M+1] +

[0335] Example 3, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0336]

[0337] Synthesized according to the method in Example 2.

[0338] 1H NMR (400MHz, DMSO-D6) δ11.50(s,1H),7.75(s,1H),7.50-7.46(m,1H),7.39-7.29(m,3H),7.26-7.24(d,1H),6.85-6.83(d,1H),6.0 9-6.05(q,1H),4.65-4.59(q,1H),4.34-4.30(q,1H),4.27-4.19(m,2H),3.75(s,3H),3.08(s,3H),2.14(s,3H),1.28-1.20(m,3H).

[0339] ESI MS m / z: 501.15 [M+1] +

[0340] Example 4: (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0341]

[0342] Synthesized according to the method in Example 2.

[0343] 1 H NMR (400MHz, DMSO-D6) δ11.47(s,1H),7.76(s1H),7.48-7.37(m,5H),7.25-7.23(d,1H),6.82-6.79(d ,1H),4.65-4.59(q,1H),4.34-4.22(m,3H),3.75(s,3H),3.07(s,3H),2.24(s,3H),1.28-1.24(m,3H).

[0344] ESI MS m / z: 483.16 [M+1] +

[0345] Example 5: (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0346]

[0347] Synthesized according to the method in Example 2.

[0348] 1H NMR (400MHz, DMSO-D6) δ11.47(s,1H),7.76(s1H),7.48-7.37(m,5H),7.25-7.23(d,1H),6.82-6.79(d ,1H),4.65-4.59(q,1H),4.34-4.22(m,3H),3.75(s,3H),3.07(s,3H),2.24(s,3H),1.28-1.24(m,3H).

[0349] ESI MS m / z: 483.16 [M+1] +

[0350] Example 6: (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0351]

[0352] Synthesized according to the method in Example 2.

[0353] ESI MS m / z: 501.15 [M+1] +

[0354] Example 7, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0355]

[0356] Synthesized according to the method in Example 2.

[0357] ESI MS m / z: 501.15 [M+1] +

[0358] Example 8, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5b]pyridin-2(3H)-one

[0359]

[0360] Synthesized according to the method in Example 2.

[0361] 1H NMR (400MHz, DMSO-D6) δ11.44(s,1H),7.63-7.62(d,1H),7.33-7.24(m,4H),7.13-7.11(q,1H),6.89-6.86-(t,3H),6.09-6.04(m,1 H),4.68-4.60(m,1H),4.34-4.29(q,1H),4.23-4.16(m,2H),4.06-4.01(q,1H),3.07(d,3H),2.02-2.00(t,6H),1.22-1.16(m,3H).

[0362] ESI MS m / z: 497.18 [M+1] +

[0363] Example 9, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5b]pyridin-2(3H)-one

[0364]

[0365] Synthesized according to the method in Example 2.

[0366] 1 H NMR (400MHz, DMSO-D6) δ11.44(s,1H),7.63-7.62(d,1H),7.32-7.24(m,4H),7.13-7.11(q,1H),6.89-6.86-(t,3H),6.09-6.04(m,1 H),4.68-4.60(m,1H),4.34-4.29(q,1H),4.23-4.16(m,2H),4.06-4.01(q,1H),3.06(d,3H),2.02-2.00(m,6H),1.22-1.16(m,3H).

[0367] ESI MS m / z: 497.18 [M+1] +

[0368] Example 10, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-ethylphenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0369]

[0370] Synthesized according to the method in Example 2.

[0371] 1 H NMR(400MHz,DMSO-D6)δ11.43(s,1H),7.64-7.63(d,1H),7.37-7.33(m,2H), 7.28-7.23(m,2H),7.09-7.07(d,1H),6.92-6.88(t,1H),6.09-6.04(m,1H), 4.66-4.63(q,1H),4.33-4.29(t,1H),4.22-4.18(m,2H),3.75(s,3H),3.06( s,3H),2.49-1.99(m,2H),2.05(s,3H),1.28-1.16(m,3H),1.00-0.94(m,3H).

[0372] ESI MS m / z: 511.19 [M+1] +

[0373] Example 11, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-isopropylphenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0374]

[0375] Synthesized according to the method in Example 2.

[0376] ESI MS m / z: 525.218 [M+1] +

[0377] Example 12, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-methoxyphenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0378]

[0379] Synthesized according to the method in Example 2.

[0380] 1H NMR (400MHz, DMSO-D6) δ11.39(s,1H),7.63(s,1H),7.42-7.38(m,1H),7.26-7.24(d,1H),7.15-7.10(m,2H),7.04-7.00(m,1H),6.84- 6.82(d,1H),6.08-6.04(q,1H),4.63-4.60(t,1H),4.33-4.21(m,3H),3.75-3.73(d,6H),3.08(s,3H),2.05(s,3H),1.25-1.21(t,3H).

[0381] ESI MS m / z: 513.17 [M+1] +

[0382] Example 13, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-methoxyphenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0383]

[0384] Synthesized according to the method in Example 2.

[0385] 1 H NMR (400MHz, DMSO-D6) δ11.39(s,1H),7.63(s,1H),7.42-7.38(m,1H),7.26-7.24(d,1H),7.15-7.10(m,2H),7.04-7.00(m,1H),6.84- 6.82(d,1H),6.08-6.04(q,1H),4.66-4.59(q,1H),4.34-4.21(m,3H),3.75-3.73(d,6H),3.08(s,3H),2.05(s,3H),1.25-1.21(t,3H).

[0386] ESI MS m / z: 513.17 [M+1] +

[0387] Example 14, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(2-(trifluoromethyl)phenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0388]

[0389] Synthesized according to the method in Example 2.

[0390] ESI MS m / z: 551.15 [M+1] +

[0391] Example 15, (S)-2-(3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)benzylnitrile

[0392]

[0393] Synthesized according to the method in Example 2.

[0394] 1 H NMR(400MHz, DMSO-D6)δ11.36(s,1H),7.89-7.86(m,1H),7.79-7.77(d,1H),7.47-7.43(m,1H),7.23-7.21(d,1H),6.87-6.86(d,1H),6.77-6.7 5(d,1H),6.04-6.01(q,1H),4.62-4.55(q,1H),4.30-4.20(m,2H),3.74 (s,2H),3.02(s,3H),2.52-2.50(m,3H),2.32(s,3H),1.24-1.21(t,3H).

[0395] ESI MS m / z: 508.16 [M+1] +

[0396] Example 16: (R)-2-(3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)benzylnitrile

[0397]

[0398] Synthesized according to the method in Example 2.

[0399] 1H NMR (400MHz, DMSO-D6) δ11.36(s,1H),7.89-7.86(m,1H),7.79-7.77(d,1H),7.46-7.43(m,1H),7.23-7.21(d,1H),6.87-6.86(d,1H),6.77-6.7 5(d,1H),6.04-6.01(q,1H),4.62-4.55(q,1H),4.30-4.20(m,2H),3.74 (s,2H),3.02(s,3H),2.51-2.50(m,3H),2.32(s,3H),1.24-1.21(t,3H).

[0400] ESI MS m / z: 508.16 [M+1] +

[0401] Example 17, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0402]

[0403] Synthesized according to the method in Example 2.

[0404] ESI MS m / z: 484.16 [M+1] +

[0405] Example 18, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0406]

[0407] Synthesized according to the method in Example 2.

[0408] ESI MS m / z: 484.16 [M+1] +

[0409] Example 19, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1,7-dimethyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0410]

[0411] Example 17: 100 mg of compound was dissolved in 1 mL of N,N-dimethylformamide, 100 mg of iodomethane and 0.1 mL of triethylamine were added, and the mixture was heated to 0 °C for 16 hours under nitrogen protection. After cooling to room temperature, the mixture was quenched with water, extracted with ethyl acetate (10 mL * 3), and the organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated, and then passed through a column chromatography. The eluent was concentrated to give 53 mg of the target compound.

[0412] ESI MS m / z: 498.17 [M+1] +

[0413] Example 20: (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-(2-methoxyethyl)-7-methyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0414]

[0415] Synthesized according to the method in Example 19.

[0416] ESI MS m / z: 542.208 [M+1] +

[0417] Example 21, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0418]

[0419] Synthesized according to the method in Example 2.

[0420] ESI MS m / z: 519.14 [M+1] +

[0421] Example 22, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0422]

[0423] Synthesized according to the method in Example 19.

[0424] ESI MS m / z: 515.17 [M+1] +

[0425] Example 23, (S)-6-(2,6-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0426]

[0427] Synthesized according to the method in Example 2.

[0428] 1 H NMR (400MHz, DMSO-D6) δ11.38(s,1H),7.79-7.77(d,1H),7.73-7.68(m,1H),7.23-7.21(d,1H),6.87-6.86(t,1H),6.77-6.74(t,1H), 6.04-6.01(q,1H),4.61-4.55(q,1H),4.30-4.19(m,3H),4.15-4.13(q,1H),3.74(s,3H),3.03(s,3H),2.32(s,3H),1.24-1.20(t,3H).

[0429] ESI MS m / z: 519.14 [M+1] +

[0430] Example 24, (R)-6-(2,6-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0431]

[0432] Synthesized according to the method in Example 2.

[0433] ESI MS m / z: 519.14 [M+1] +

[0434] Example 25: (S)-6-(2,3-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0435]

[0436] Synthesized according to the method in Example 2.

[0437] 1H NMR (400MHz, DMSO-D6) δ11.38(s,1H),7.78(s,1H),7.74-7.67(m,1H),7.23-7.21(d,1H),6.87-6.86(t,1H),6.77-6.74(q,1H),6.0 4-6.01(q,1H),4.64-4.55(q,1H),4.30-4.18(m,3H),4.15-4.13(q,1H),3.74(s,3H),3.03(s,3H),2.33(s,3H),1.24-1.20(t,3H).

[0438] ESI MS m / z: 519.14 [M+1] +

[0439] Example 26: (R)-6-(2,3-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0440]

[0441] Synthesized according to the method in Example 2.

[0442] ESI MS m / z: 519.14 [M+1] +

[0443] Example 27, (S)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0444]

[0445] Synthesized according to the method in Example 2.

[0446] 1 H NMR (400MHz, DMSO-D6) δ11.53(s,1H),7.78(s,1H),7.69-7.67(q,1H),7.42-7.24(m,2H),6.85-6.83(q,1H),6.09-6.06(q,1H),4.6 4-4.58(q,1H),4.27-4.18(m,2H),4.15-4.13(m,1H),4.04-4.03(d,1H),3.75(s,3H),3.08(s,3H),2.16(d,3H),1.29-1.16(m,3H).

[0447] ESI MS m / z: 519.14 [M+1] +

[0448] Example 28, (S)-6-(2,4-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0449]

[0450] Synthesized according to the method in Example 2.

[0451] 1 HNMR(400MHz,DMSO-D6)δ11.51(s,1H),7.74(s,1H),7.46-7.36(m,2H),7.26-7.18(m,2H),6.84(d,1 H),6.06(q,1H),4.61(q,1H),4.34-4.18(m,3H),3.75(s,3H),3.07(s,3H),2.13(s,3H),1.21(t,3H)

[0452] ESI MS m / z: 519.14 [M+1] +

[0453] Example 29, (S)-6-(2,4,5-trifluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0454]

[0455] Synthesized according to the method in Example 2.

[0456] ESI MS m / z: 537.13 [M+1] +

[0457] Example 30: (R)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0458]

[0459] Synthesized according to the method in Example 2.

[0460] ESI MS m / z: 519.14 [M+1]+

[0461] Example 31, (S)-6-(2,4-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0462]

[0463] Synthesized according to the method in Example 2.

[0464] 1 H NMR (400MHz, DMSO-D6) δ11.41(s,1H),7.59(d,1H),7.27-7.24(q,1H),7. 13(s,1H),7.07-7.05(d,1H),7.00-6.97(q,1H),6.89-6.85(d,1H),6.08- 6.04(m,1H),4.64-4.59(q,1H),4.33-4.29(t,1H),4.23-4.16(m,2H),3.7 5(s,3H),3.06(s,3H),2.32(s,3H),2.01-1.97(q,6H),1.22-1.17(m,3H).

[0465] ESI MS m / z: 511.19 [M+1]+

[0466] Example 32, (S)-6-(2,5-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0467]

[0468] Synthesized according to the method in Example 2.

[0469] 1 H NMR (400MHz, DMSO-D6) δ11.42(s,1H),7.61(s,1H),7.60-7.13(m,2H),7.11(t,1H),6.93-6.85(m,2H),6.09-6.05(m,1H),4.66-4.5 9(m,1H),4.33-4.23(m,1H),4.22-4.15(m,2H),3.75(s,3H),3.06(s,3H),2.29(s,3H),2.00(d,3H),1.96(d,3H),1.40-1.18(m,3H).

[0470] ESI MS m / z: 511.19 [M+1] +

[0471] Example 33: (S)-6-(2,3-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0472]

[0473] Synthesized according to the method in Example 2.

[0474] 1 H NMR (400MHz, DMSO-D6) δ11.42(s,1H),7.60(s,1H),7.27-7.12(m,3H),6.96-6.85(m,2H),6.09-6.04(m,1H),4.66-4.62(t,1H) ),4.33-4.30(m,1H),4.23-4.17(m,2H),3.75(s,3H),3.07(s,3H),2.31(d,3H),1.99(s,3H),1.91(d,3H),1.26-1.18(m,3H).

[0475] ESI MS m / z: 511.19 [M+1] +

[0476] Example 34: (S)-6-(2,6-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0477]

[0478] Synthesized according to the method in Example 2.

[0479] ESI MS m / z: 511.19 [M+1] +

[0480] Example 35, (S)-6-(4-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0481]

[0482] Synthesized according to the method in Example 2.

[0483] 1 H NMR (400MHz, DMSO-D6) δ11.45(s,1H),7.62(d,1H),7.27-7.06(m,4H),6.89-6.85(d,1H),6.08-6.04(m,1H),4.64- 4.59(q,1H),4.33-4.29(t,1H),4.23-4.15(m,2H),3.75(s,3H),3.06(s,3H)2.02-1.99(q,6H),1.22-1.18(m,3H).

[0484] ESI MS m / z: 515.17 [M+1] +

[0485] Example 36, (S)-6-(5-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0486]

[0487] Synthesized according to the method in Example 2.

[0488] 1 HNMR(400MHz,DMSO-D6)δ11.47(d,1H),7.65(s,1H),7.64-7.35(m,1H),7.34-7.24(m,1H),7.18-7.13(m,1H),7.02-6.99(m,1H),6.98-6.85(m,1 H),6.09-6.05(m,1H),4.60(d,1H),4.34-4.23(m,1H),4.22-4.16(m,2H ),3.75(s,3H),3.07(d,3H),2.03(d,3H),1.98(t,3H),1.40-1.17(m,3H)

[0489] ESI MS m / z: 515.17 [M+1] +

[0490] Example 37, (S)-6-(3-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0491]

[0492] Synthesized according to the method in Example 2.

[0493] 1 H NMR (400MHz, DMSO-D6) δ11.49(s,1H),7.65(s,1H),7.33-7.19(m,3H),7.02-6.99(q,1H),6.89-6.85(q,1H),6.09-6.04(m,1H), 4.65-4.59(m,1H),4.34-4.30(m,1H),4.23-4.18(m,2H),3.75(s,3H),3.08(s,3H),2.03(s,3H),1.93(s,3H),1.21-1.19(t,3H).

[0494] ESI MS m / z: 515.17 [M+1] +

[0495] Example 38, (S)-6-(2-fluoro-5-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0496]

[0497] Synthesized according to the method in Example 2.

[0498] 1 H NMR (400MHz, DMSO-D6) δ11.51(s,1H),7.74(s,1H),7.27-7.15(m,4H),6.84-6.82(t,1H),6.08-6.05(q,1H), 4.64-4.57(q,1H),4.34-4.20(m,3H),3.75(s,3H),3.08(s,3H),2.33(s,3H),2.14(s,3H),1.24-1.20(t,3H).

[0499] ESI MS m / z: 515.17 [M+1] +

[0500] Example 39, (S)-6-(2-fluoro-3-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0501]

[0502] Synthesized according to the method in Example 2.

[0503] 1 H NMR (400MHz, DMSO-D6) δ11.50(s,1H),7.73(s,1H),7.36-7.33(q,1H),7.26-7.16(m,3H),6.85-6.83(q,1H),6.08-6.05(q,1H), 4.64-4.58(q,1H),4.34-4.30(m,1H),4.25-4.19(m,2H),3.75(s,3H),3.08(s,3H),2.30(s,3H),2.13(s,3H),1.24-1.19(t,3H).

[0504] ESI MS m / z: 515.17 [M+1]+

[0505] Example 40: (S)-6-(2-fluoro-4-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0506]

[0507] Synthesized according to the method in Example 2.

[0508] 1 H NMR (400MHz, DMSO-D6) δ11.50(s,1H),7.72(s,1H),7.26-7.21(t,2H),7.17-7.11(q,2H),6.84-6.82(t,1H),6.08-6.05(q,1H), 4.64-4.57(q,1H),4.34-4.30(q,1H),4.27-4.18(m,2H),3.75(s,3H),3.08(s,3H),2.38(s,3H),2.13(s,3H),1.23-1.18(t,3H).

[0509] ESI MS m / z: 515.17 [M+1] +

[0510] Example 41, (S)-6-(2-fluoro-5-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0511]

[0512] Synthesized according to the method in Example 2.

[0513] 1 HNMR(400MHz,DMSO-D6)δ11.50(s,1H),7.77(d,1H),7.27-7.20(m,2H),7.00-6.99(m,1H),7.98-6.82(m,2H),6.07(m, 1H),4.62-4.58(m,1H),4.34-4.19(m,3H),3.77(s,3H),3.73(d,3H),3.05(s,3H),2.51-2.50(m,3H),1.20-1.09(m,3H)

[0514] ESI MS m / z: 531.16 [M+1] +

[0515] Example 42, (S)-6-(2-fluoro-3-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0516]

[0517] Synthesized according to the method in Example 2.

[0518] ESI MS m / z: 531.16 [M+1] +

[0519] Example 43, (S)-6-(2-fluoro-4-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0520]

[0521] Synthesized according to the method in Example 2.

[0522] 1HNMR(400MHz,DMSO-D6)δ11.49(s,1H),7.71(s,1H),7.29-7.23(m,2H),6.96(q,1H),6.88(q,1H),6.82(q,1H),6.06 (q,1H),4.64-4.58(m,1H),4.34-4.18(m,3H),3.82(s,3H),3.74(d,3H),3.05(d,3H),2.14(d,3H),1.28-1.19(m,3H)

[0523] ESI MS m / z: 531.16 [M+1] +

[0524] Example 44, (S)-6-(5-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0525]

[0526] Synthesized according to the method in Example 2.

[0527] 1 HNMR(400MHz,DMSO-D6)δ11.40(d,1H),7.70(d,1H),7.26-7.21(m,2H),7.20-7.11(m,1H),7.10-6.99(m,1H),6.98-6.84(m,1 H),6.07(t,1H),4.62-4.59(m,1H),4.33-4.03(m,3H),3.76(d,3H),3.72(d,3H),3.05(d,3H),2.07(s,3H),1.40-1.21(m,3H)

[0528] ESI MS m / z: 531.16 [M+1] +

[0529] Example 45, (S)-6-(4-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0530]

[0531] Synthesized according to the method in Example 2.

[0532] 1HNMR(400MHz,DMSO-D6)δ11.40(s,1H),7.70(d,1H),7.26-7.16(m,2H),7.15-7.01(m,1H),6.87-6.81(m,2H),6.05( q,1H),4.65-4.59(m,1H),4.33-4.21(m,3H),4.74(s,3H),3.73(s,3H),3.03(s,3H),2.01(d,3H),1.28-1.16(m,3H)

[0533] ESI MS m / z: 531.16 [M+1] +

[0534] Example 46, (S)-6-(6-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0535]

[0536] Synthesized according to the method in Example 2.

[0537] 1 HNMR(400MHz,DMSO-D6)δ11.36(s,1H),7.78(d,1H),7.21(d,1H),6.87-6.85(q,2H),6.77-6.75(q,1H),6.04- 6.01(q,1H),4.62-4.55(m,1H),4.30-4.19(m,3H),3.74(d,3H),3.06(t,3H),2.32(s,3H),1.28-1.19(m,3H).

[0538] ESI MS m / z: 531.16 [M+1] +

[0539] Example 47, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0540]

[0541] Synthesized according to the method in Example 19.

[0542] ESI MS m / z: 511.19 [M+1] +

[0543] Example 48, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0544]

[0545] Synthesized according to the method in Example 19.

[0546] ESI MS m / z: 529.18 [M+1] +

[0547] Example 49, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0548]

[0549] Synthesized according to the method in Example 19.

[0550] ESI MS m / z: 529.18 [M+1] +

[0551] Example 50, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-7-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0552]

[0553] Synthesized according to the method in Example 19.

[0554] ESI MS m / z: 525.21 [M+1] +

[0555] Example 51, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0556]

[0557] Synthesized according to the method in Example 19.

[0558] ESI MS m / z: 583.16 [M+1]+

[0559] Example 52, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0560]

[0561] Synthesized according to the method in Example 19.

[0562] ESI MS m / z: 583.16 [M+1] +

[0563] Example 53, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0564]

[0565] Synthesized according to the method in Example 19.

[0566] SI MS m / z: 565.17 [M+1] +

[0567] Example 54, (R)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0568]

[0569] Synthesized according to the method in Example 19.

[0570] SI MS m / z: 565.17 [M+1] +

[0571] Example 55, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0572]

[0573] Synthesized according to the method in Example 19.

[0574] ESI MS m / z: 579.18 [M+1] +

[0575] Example 56: (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0576]

[0577] Synthesized according to the method in Example 19.

[0578] ESI MS m / z: 565.17 [M+1] +

[0579] Example 57: (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0580]

[0581] Synthesized according to the method in Example 19.

[0582] ESI MS m / z: 547.17 [M+1] +

[0583] Example 58, (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0584]

[0585] Synthesized according to the method in Example 19.

[0586] ESI MS m / z: 565.17 [M+1] +

[0587] Example 59: (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0588]

[0589] Synthesized according to the method in Example 19.

[0590] ESI MS m / z: 561.19 [M+1] +

[0591] Example 60, (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0592]

[0593] Synthesized according to the method in Example 19.

[0594] ESI MS m / z: 537.13 [M+1] +

[0595] Example 61, (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0596]

[0597] Synthesized according to the method in Example 2.

[0598] ESI MS m / z: 519.14 [M+1] +

[0599] Example 62, (R)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0600]

[0601] Synthesized according to the method in Example 2.

[0602] ESI MS m / z: 519.14 [M+1] +

[0603] Example 63, (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0604]

[0605] Synthesized according to the method in Example 2.

[0606] ESI MS m / z: 537.13 [M+1] +

[0607] Example 64, (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0608]

[0609] Synthesized according to the method in Example 2.

[0610] ESI MS m / z: 533.16 [M+1] +

[0611] Example 65, (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0612]

[0613] Synthesized according to the method in Example 19.

[0614] ESI MS m / z: 551.15 [M+1] +

[0615] Example 66: (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1,7-dimethyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0616]

[0617] Synthesized according to the method in Example 19.

[0618] ESI MS m / z: 533.16 [M+1] +

[0619] Example 67, (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-1,7-dimethyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0620]

[0621] Synthesized according to the method in Example 19.

[0622] ESI MS m / z: 551.15 [M+1] +

[0623] Example 68, (S)-3-(1-(5-(difluoromethoxy)-6-ethoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1,7-dimethyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0624]

[0625] Synthesized according to the method in Example 19.

[0626] ESI MS m / z: 547.17 [M+1] +

[0627] Example 69: (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-isopropoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0628]

[0629] Synthesized according to the method in Example 19.

[0630] ESI MS m / z: 593.20 [M+1] +

[0631] Example 70: (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-isopropoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0632]

[0633] Synthesized according to the method in Example 19.

[0634] ESI MS m / z: 575.21 [M+1] +

[0635] Example 71, (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-isopropoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0636]

[0637] Synthesized according to the method in Example 19.

[0638] ESI MS m / z: 593.20 [M+1] +

[0639] Example 72, (S)-1-(2,2-difluoroethyl)-3-(1-(6-ethoxy-5-isopropoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-7-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0640]

[0641] Synthesized according to the method in Example 19.

[0642] ESI MS m / z: 589.22 [M+1] +

[0643] Example 73, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-bromo-7-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0644]

[0645] Synthesized according to the method in Example 2.

[0646] ESI MS m / z: 485.04 [M+1] +

[0647] Example 74, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0648]

[0649] Synthesized according to the method in Example 2.

[0650] 1H NMR (400MHz, DMSO-D6) δ11.39(s,1H),8.06(t,1H),7.57-7.59(m,1H),7.41-7.55(m,2H),7.31-7.36(m,2H),7.23-7.31(m,1H), 6.86(d,1H),6.07(q,1H),4.36-4.62(m,1H),4.21-4.32(m,1H),4.17-4.21(m,2H),3.74(s,3H),3.07(s,3H),1.15-1.23(m,3H).

[0651] ESI MS m / z: 487.14 [M+1] +

[0652] Example 75, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0653]

[0654] Synthesized according to the method in Example 2.

[0655] 1 H NMR (400MHz, DMSO-D6) δ8.11(m,1H),7.77(t,1H),7.58-7.62(m,1H),7.43-7.47(m,1H),7.32--7.38(m,2H),6.12(d d,1H),4.58-4.64(m,1H),4.16-4.22(m,2H),4.32-437(m,1H),3.74(s,3H),3.43(s,3H),2.96(s,3H),1.21(t,3H).

[0656] ESI MS m / z: 501.15 [M+1] +

[0657] Example 76, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0658]

[0659] Synthesized according to the method in Example 2.

[0660] 1H NMR (400MHz, DMSO-D6) δ11.39(s,1H),8.19(d,1H),7.66(d,2H),7.55(d,1H),7.47(t,2H),7.37(t,1H),7.24(d,1 H),7.84(d,1H),6.07(q,1H),4.60(q,1H),4.32(q,1H),4.25-4.20(m,2H),3.74(s,3H),3.06(s,3H),1.22(t,3H).

[0661] ESI MS m / z: 469.15 [M+1] +

[0662] Example 77, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-phenyl-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0663]

[0664] Synthesized according to the method in Example 19.

[0665] 1 HNMR(400MHz,DMSO-D6)δ8.25(d,1H),7.89(d,1H),7.72(d,2H),7.49(t,2H),7.39(t,1H),7.23(d,1H),6.86(d,1 H),6.10(q,1H),4.60(q,1H),4.34(q,1H),4.23-4.18(m,2H),3.74(s,3H),3.45(s,3H),3.06(s,3H),1.21(t,3H)

[0666] ESI MS m / z: 483.16 [M+1] +

[0667] Example 78, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0668]

[0669] Synthesized according to the method in Example 2.

[0670] ESI MS m / z: 487.14 [M+1] +

[0671] Example 79, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0672]

[0673] Synthesized according to the method in Example 2.

[0674] 1 H NMR (400MHz, DMSO-D6) δ11.31(s,1H),7.71(s,1H),7.22-7.32(m,6H),6.88-6.91(m,1H),6.06-6.09(dd,1H), 4.59-4.65(q,1H),4.31-4.35(m,1H),4.19(m,2H),3.75(s,3H),3.08(s,3H),2.24(s,3H),1.16-1.19(q,3H).

[0675] ESI MS m / z: 483.16 [M+1] +

[0676] Example 80, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-6-(o-tolyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0677]

[0678] Synthesized according to the method in Example 19.

[0679] 1 H NMR (400MHz, DMSO-D6) δ7.90(d,1H),7.62(t,1H),7.24-7.35(m,5H),6.91(t,1H),6.11(q,1H),4.62(q,1 H),4.20-4.37(m,1H),4.16-4.19(m,2H),3.75(s,3H)3.40(s,3H),3.07(s,3H),2.26(s,3H),1.17(t,3H).

[0680] ESI MS m / z: 497.18 [M+1] +

[0681] Example 81, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-ethylphenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0682]

[0683] Synthesized according to the method in Example 2.

[0684] 1 HNMR(400MHz,DMSO-D6)δ11.28(s,1H),7.82(d,1H),7.38-7.18(m,7H),6.90(d,1H),6.07(q,1H),4.61( t,1H),4.35-4.22(m,1H),4.20-4.13(m,2H),3.76(t,3H),3.08(q,3H),1.21-1.16(m,4H),1.05(t,3H).

[0685] ESI MS m / z: 497.18 [M+1] +

[0686] Example 82, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-ethylphenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0687]

[0688] Synthesized according to the method in Example 19.

[0689] 1 HNMR(400MHz,DMSO-D6)δ7.87(d,1H),7.57(d,1H),7.36(m,2H),7.29-7.27(m,2H),7.23(q,1H),6.94(d,1H),6.11(q,1H),4.6 3(q,1H),4.34(q,1H),4.17-4.11(m,2H),3.75(s,3H),3.39(s,3H),3.07(s,3H),2.60-2.50(m,2H),1.17(t,3H),1.05(t,3H).

[0690] ESI MS m / z: 511.19 [M+1] +

[0691] Example 83, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-methoxyphenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0692]

[0693] Synthesized according to the method in Example 2.

[0694] 1 H NMR (400MHz, DMSO-D6) δ11.26(s,1H),7.95(d,1H),7.41(d,1H),7.30-7.38(m,2H),7.24(d,1H),7.13(d,1H),7.03( t,1H),6.83(d,1H),6.06(q,1H),4.35-4.63(m,1H),4.19-4.34(m,3H),3.75(d,6H),3.06(s,3H),1.15-1.22(m,3H)

[0695] ESI MS m / z: 499.16 [M+1] +

[0696] Example 84, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-methoxyphenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0697]

[0698] Synthesized according to the method in Example 19.

[0699] 1 H NMR(400MHz, DMSO-D6)δ8.01(d,1H),7.65(d,1H),7.04-7.07(m,1H),7.14-7.16(d,1H),7.33--7.40(m,2H),6.10(dd,1H), 4.60-4.65(m,1H),4.32-4.36(m,1H),4.17-4.24(m,2H),3.79(s,3H),3.75(s,3H)3.40(s,3H),3.,07(s,3H),1.21(t,3H)..

[0700] ESI MS m / z: 513.17 [M+1] +

[0701] Example 85, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-(trifluoromethyl)phenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0702]

[0703] Synthesized according to the method in Example 2.

[0704] 1 HNMR(400MHz,DMSO-D6)δ11.33(s,1H),7.84(q,2H),7.74(t,1H),7.64(t,1H),7.47(d,1H),7.27(t,2H),6. 93(d,1H),6.07(q,1H),4.61(q,1H),4.32(q,1H),4.17-4.08(m,2H),3.75(s,3H),3.07(s,3H),1.17(t,3H)

[0705] ESI MS m / z: 537.13 [M+1] +

[0706] Example 86, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-(trifluoromethyl)phenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0707]

[0708] Synthesized according to the method in Example 19.

[0709] 1 HNMR(400MHz,DMSO-D6)δ7.88(d,2H),7.76(t,1H),7.66(t,1H),7.59(s,1H),7.49(d,1H),7.27(d,1H),6.96(d,1 H),6.12(q,1H),4.63(q,1H),4.35(q,1H),4.12-4.06(m,2H),3.75(s,3H),3.30(s,3H),3.07(s,3H),1.15(t,3H).

[0710] ESI MS m / z: 551.15 [M+1] +

[0711] Example 87, (S)-6-(2-cyclopropylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0712]

[0713] Synthesized according to the method in Example 2.

[0714] ESI MS m / z: 509.18 [M+1] +

[0715] Example 88: (S)-6-(2,6-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0716]

[0717] Synthesized according to the method in Example 2.

[0718] ESI MS m / z: 505.13 [M+1] +

[0719] Example 89: (S)-6-(2,6-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0720]

[0721] Synthesized according to the method in Example 19.

[0722] ESI MS m / z: 519.14 [M+1] +

[0723] Example 90: (S)-6-(2,3-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0724]

[0725] Synthesized according to the method in Example 2.

[0726] 1HNMR(400MHz,DMSO-D6)δ11.45(s,1H),8.09(s,1H),7.52-7.38(m,3H),7.32(t,1H),7.25(d,1H),6.87( d,1H),6.08(q,1H),4.59(q,1H),4.34(q,1H),4.20(q,2H),3.75(s,3H),3.08(s,3H),1.24-1.18(m,3H).

[0727] ESI MS m / z: 505.13 [M+1] +

[0728] Example 91, (S)-6-(2,3-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0729]

[0730] Synthesized according to the method in Example 19.

[0731] 1 HNMR(400MHz,DMSO-D6)δ8.15(s,1H),7.82(s,1H),7.52-7.41(m,2H),7.35(t,1H),7.24(d,1H),6.90(d,1H), 6.12(q,1H),4.59(q,1H),4.35(q,1H),4.21-4.15(m,2H),3.74(s,3H),3.43(s,3H),3.07(s,3H),1.19(t,3H).

[0732] ESI MS m / z: 519.14 [M+1] +

[0733] Example 92, (S)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0734]

[0735] Synthesized according to the method in Example 2.

[0736] 1HNMR(400MHz,DMSO-D6)δ11.44(s,1H),8.10(s,1H),7.52-7.47(m,2H),7.43-7.37(m,1H),7.29-7.23(m,2H),6.8 6(d,1H),6.07(q,1H),4.58(t,1H),4.36-4.23(m,1H),4.21-4.18(m,2H),3.75(s,3H),3.07(s,3H),1.21(t,3H).

[0737] ESI MS m / z: 505.13 [M+1] +

[0738] Example 93, (S)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0739]

[0740] Synthesized according to the method in Example 19.

[0741] 1 HNMR(400MHz,DMSO-D6)δ8.15(s,1H),7.81(s,1H),7.54-7.50(m,1H),7.49-7.39(m,1H),7.32-7.23(m,2H),6.89(d ,1H),6.11(q,1H),4.58(t,1H),4.35(q,1H),4.22-4.15(m,2H),3.74(s,3H),3.42(s,3H),3.07(s,3H),1.19(t,3H).

[0742] ESI MS m / z: 519.14 [M+1] +

[0743] Example 94, (S)-6-(2,4-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0744]

[0745] Synthesized according to the method in Example 2.

[0746] ESI MS m / z: 505.13 [M+1] +

[0747] Example 95: (S)-6-(2,4-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0748]

[0749] Synthesized according to the method in Example 19.

[0750] ESI MS m / z: 519.14 [M+1] +

[0751] Example 96, (S)-6-(2,4,5-trifluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0752]

[0753] Synthesized according to the method in Example 2.

[0754] 1 H NMR (400MHz, DMSO-D6) δ11.45(s,1H),8.07(s,1H),7.82-7.67(m,2H),7.49(s,1H),7.24(d,1H),6.86(d,1 H),6.07(q,1H),4.57(t,1H),4.35-4.31(m,1H),4.25-4.17(m,2H),3.75(s,3H),3.07(s,3H),1.20(q,3H).

[0755] ESI MS m / z: 523.12 [M+1] +

[0756] Example 97: (S)-6-(2,4,5-trifluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0757]

[0758] Synthesized according to the method in Example 19.

[0759] 1H NMR (400MHz, DMSO-D6) δ11.55(s,1H),7.67-7.77(m,2H),7.60(q,1H),7.24(d,1H),6.83(d,1H),6.06(q ,1H),4.58(q,1H),4.31(q,1H),4.23(q,2H),3.74(s,3H),3.34(s,3H),3.05(d,3H),1.15-1.22(m,3H).

[0760] ESI MS m / z: 537.13 [M+1] +

[0761] Example 98, (R)-6-(2,5-difluorophenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0762]

[0763] Synthesized according to the method in Example 2.

[0764] ESI MS m / z: 505.13 [M+1] +

[0765] Example 99: (S)-6-(2,4-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0766]

[0767] Synthesized according to the method in Example 2.

[0768] 1 HNMR(400MHz,DMSO-D6)δ11.27(s,1H),7.82(d,1H),7.28(t,3H),7.09(m,3H),6.88(d,1H),6.07(q,1H) ,4.62(q,1H),4.35(q,1H),4.21(q,1H),3.75(s,3H),3.06(s,3H),2.31(s,3H),2.20(s,3H),1.19(t,3H)

[0769] ESI MS m / z: 497.18 [M+1] +

[0770] Example 100: (S)-6-(2,4-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0771]

[0772] Synthesized according to the method in Example 19.

[0773] 1 HNMR(400MHz,DMSO-D6)δ7.87(d,1H),7.57(d,1H),7.25(d,1H),7.10(q,3H),6.91(d,1H),6.10(q,1H),4.62(q,1 H),4.33(q,1H),4.19-4.13(m,2H),3.74(s,3H),3.40(s,3H),3.06(s,3H),2.32(s,3H),2.20(d,3H),1.18(t,3H).

[0774] ESI MS m / z: 511.19 [M+1] +

[0775] Example 101, (S)-6-(2,5-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0776]

[0777] Synthesized according to the method in Example 2.

[0778] 1 HNMR(400MHz,DMSO-D6)δ11.29(s,1H),7.84(d,1H),7.26(t,2H),7.19(d,1H),7.10(d,1H),7.05(s,1H),6.88(d,1H),6. 07(q,1H),4.62(q,1H),4.32(q,1H),4.23-4.16(m,2H),3.75(s,3H),3.07(s,3H),2.29(s,3H),2.18(s,3H),1.20(t,3H).

[0779] ESI MS m / z: 497.18 [M+1] +

[0780] Example 102, (S)-6-(2,5-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0781]

[0782] Synthesized according to the method in Example 19.

[0783] 1 HNMR(400MHz,DMSO-D6)δ7.88(d,1H),7.59(d,1H),7.23(q,2H),7.10(t,2H),6.91(d,1H),6.10(q,1H),4.62(q,1 H),4.32(q,1H),4.19-4.13(m,2H),3.75(s,3H),3.40(s,3H),3.06(s,3H),2.31(s,3H),2.20(s,3H),1.18(t,3H).

[0784] ESI MS m / z: 511.19 [M+1]

[0785] Example 103, (S)-6-(2,3-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0786]

[0787] Synthesized according to the method in Example 2.

[0788] 1 HNMR(400MHz,DMSO-D6)δ11.29(s,1H),7.81(d,1H),7.27-7.13(m,4H),7.05(d,1H),6.89(d,1H),6.07(q,1H), 4.62(q,1H),4.32(q,1H),4.22-4.16(m,2H),3.75(s,3H),3.07(s,3H),2.30(s,3H),2.11(s,3H),1.20(t,3H).

[0789] ESI MS m / z: 497.18 [M+1] +

[0790] Example 104, (S)-6-(2,3-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0791]

[0792] Synthesized according to the method in Example 19.

[0793] 1 HNMR(400MHz,DMSO-D6)δ7.85(d,1H),7.55(d,1H),7.26-7.14(m,3H),7.08(d,1H),6.92(d,1H),6.11(q,1H),4.63(q ,1H),4.34(q,1H),4.19-4.12(m,2H),3.75(s,3H),3.39(s,3H),3.07(s,3H),2.31(s,3H),2.12(s,3H),1.18(t,3H).

[0794] ESI MS m / z: 511.19 [M+1] +

[0795] Example 105, (S)-6-(2,6-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0796]

[0797] Synthesized according to the method in Example 2.

[0798] ESI MS m / z: 497.18 [M+1] +

[0799] Example 106, (S)-6-(2,6-dimethylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0800]

[0801] Synthesized according to the method in Example 19.

[0802] ESI MS m / z: 511.19 [M+1] +

[0803] Example 107, (S)-6-(4-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0804]

[0805] Synthesized according to the method in Example 2.

[0806] 1 H NMR (400MHz, DMSO-D6) δ11.32(s,1H),7.84(d,1H),7.28-7.21(m,3H),7.18(t,1H),7.12-7.07(m,1H),6.89(d,1H), 6.07(q,1H),4.61(q,1H),4.35-4.22(m,1H),4.21-4.16(m,2H),3.75(s,3H),3.07(s,3H),2.24(s,3H),1.19(t,3H).

[0807] ESI MS m / z: 501.15 [M+1] +

[0808] Example 108, (S)-6-(4-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0809]

[0810] Synthesized according to the method in Example 19.

[0811] 1 H NMR(400MHz,DMSO-D6)δ7.89(d,1H),7.60(d,1H),7.31-7.19(m,3H),7.13(q,1H),6.92(d,1H),6.11(q,1H),4 .61(q,1H),4.34(q,1H),4.17-4.13(m,2H),3.74(s,3H),3.40(s,3H),3.07(s,3H),2.26(s,3H),1.17(t,3H).

[0812] ESI MS m / z: 515.17 [M+1] +

[0813] Example 109, (S)-6-(5-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0814]

[0815] Synthesized according to the method in Example 2.

[0816] ESI MS m / z: 501.15 [M+1] +

[0817] Example 110, (S)-6-(5-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0818]

[0819] Synthesized according to the method in Example 19.

[0820] ESI MS m / z: 515.17 [M+1] +

[0821] Example 111, (S)-6-(3-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0822]

[0823] Synthesized according to the method in Example 2.

[0824] ESI MS m / z: 501.15 [M+1] +

[0825] Example 112, (S)-6-(3-fluoro-2-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0826]

[0827] Synthesized according to the method in Example 19.

[0828] ESI MS m / z: 515.17 [M+1] +

[0829] Example 113, (S)-6-(2-fluoro-5-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0830]

[0831] Synthesized according to the method in Example 2.

[0832] ESI MS m / z: 501.15 [M+1] +

[0833] Example 114, (S)-6-(2-fluoro-5-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0834]

[0835] Synthesized according to the method in Example 19.

[0836] ESI MS m / z: 515.17 [M+1] +

[0837] Example 115, (S)-6-(2-fluoro-4-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0838]

[0839] Synthesized according to the method in Example 2.

[0840] ESI MS m / z: 501.15 [M+1] +

[0841] Example 116, (S)-6-(2-fluoro-4-methylphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0842]

[0843] Synthesized according to the method in Example 19.

[0844] ESI MS m / z: 515.17 [M+1] +

[0845] Example 117, (S)-6-(5-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0846]

[0847] Synthesized according to the method in Example 2.

[0848] ESI MS m / z: 517.15 [M+1] +

[0849] Example 118, (S)-6-(5-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0850]

[0851] Synthesized according to the method in Example 19.

[0852] ESI MS m / z: 531.16 [M+1] +

[0853] Example 119, (S)-6-(4-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0854]

[0855] Synthesized according to the method in Example 2.

[0856] ESI MS m / z: 517.15 [M+1] +

[0857] Example 120, (S)-6-(4-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0858]

[0859] Synthesized according to the method in Example 19.

[0860] ESI MS m / z: 531.16 [M+1]+

[0861] Example 121, (S)-6-(6-fluoro-2-methoxyphenyl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0862]

[0863] Synthesized according to the method in Example 2.

[0864] ESI MS m / z: 517.15 [M+1] +

[0865] Example 122, (S)-6-(pyridin-2-yl)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0866]

[0867] Synthesized according to the method in Example 2.

[0868] ESI MS m / z: 470.14 [M+1] +

[0869] Example 123, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0870]

[0871] Synthesized according to the method in Example 19.

[0872] ESI MS m / z: 484.16 [M+1] +

[0873] Example 124, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-ethyl-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0874]

[0875] Synthesized according to the method in Example 19.

[0876] ESI MS m / z: 498.17 [M+1]+

[0877] Example 125, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-(2-methoxyethyl)-6-(pyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0878]

[0879] Synthesized according to the method in Example 19.

[0880] ESI MS m / z: 528.18 [M+1] +

[0881] Example 126, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(2-fluorophenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0882]

[0883] Synthesized according to the method in Example 19.

[0884] 1 H NMR (400MHz, DMSO-D6) δ8.11(m,1H),7.77(t,1H),7.58-7.62(m,1H),7.43-7.47(m,1H),7.32--7.38(m,2H),6.12( dd,1H),4.58-4.64(m,1H),4.16-4.22(m,2H),4.32-437(m,1H),3.74(s,3H),3.43(s,3H),2.96(s,3H),1.21(t,3H)

[0885] ESI MS m / z: 501.15 [M+1] +

[0886] Example 127, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0887]

[0888] Synthesized according to the method in Example 19.

[0889] ESI MS m / z: 496.18 [M+1] +

[0890] Example 128, (S)-3-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-6-(4-fluorophenyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

[0891]

[0892] Synthesized according to the method in Example 19.

[0893] ESI MS m / z: 501.16 [M+1] +

[0894] Example 129, (S)-5-bromo-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[0895]

[0896] Synthesized according to the method in Example 2.

[0897] ESI MS m / z: 470.03 [M+1] +

[0898] Example 130, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-phenyl-1H-benzo[d]imidazol-2(3H)-one

[0899]

[0900] Synthesized according to the method in Example 2.

[0901] 1 H NMR (400MHz, DMSO-D6) δ11.11(s,1H),7.45-7.41(t,2H),7.33-7.31(d,2H),7.27-7.20(q,5H),6.84-6.82(d ,1H),6.06-6.03(q,1H),4.40-4.35(m,3H),4.28-4.24(t,1H),3.75(s,6H),3.04(s,3H),1.33-1.30(q,3H).

[0902] ESI MS m / z: 468.15 [M+1] +

[0903] Example 131, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-phenyl-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[0904]

[0905] Synthesized according to the method in Example 19.

[0906] 1 HNMR(400MHz,DMSO-D6)δ7.68-7.66(d,2H),7.48-7.43(q,3H),7.34-7.24(m,4H),6.86-6.84(d,1H),6.09-6 .06(q,1H),4.40-4.30(q,3H),4.28-4.24(t,1H),3.74(s,3H),3.41(s,3H),3.04(s,3H),1.32-1.29(t,3H).

[0907] ESI MS m / z: 482.17 [M+1] +

[0908] Example 132, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one

[0909]

[0910] Synthesized according to the method in Example 2.

[0911] 1 H NMR (400MHz, DMSO-D6) δ11.12(s,1H),7.47-7.51(m,1H),7.28-7.38(m,1H),7.24-7.27(m,4H),7.13(t,2 H),6.85(d,1H),6.05(q,1H),4.33-4.41(m,3H),4.22-4.28(m,1H),3.74(s,3H),3.03(d,3H),1.29(t,3H)

[0912] ESI MS m / z: 486.14 [M+1] +

[0913] Example 133, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[0914]

[0915] Synthesized according to the method in Example 19.

[0916] 1 H NMR(400MHz,DMSO-D6)δ7.40-7.54(m,1H),7.34-7.39(m,1H),7.26-7.32(m,5H),7.25(d,1H),6 .85(d,1H),6.08(q,1H),4.25-4.43(m,4H),3.74(s,3H),3.38(s,3H),3.05(s,3H),1.27(q,3H).

[0917] ESI MS m / z: 486.14 [M+1] +

[0918] Example 134, (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one

[0919]

[0920] Synthesized according to the method in Example 2.

[0921] ESI MS m / z: 486.14 [M+1] +

[0922] Example 135, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(4-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one

[0923]

[0924] Synthesized according to the method in Example 2.

[0925] ESI MS m / z: 486.14 [M+1] +

[0926] Example 136, (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(4-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one

[0927]

[0928] Synthesized according to the method in Example 2.

[0929] ESI MS m / z: 486.14 [M+1] +

[0930] Example 137, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-5-(4-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one

[0931]

[0932] Synthesized according to the method in Example 19.

[0933] ESI MS m / z: 500.16 [M+1] +

[0934] Example 138, (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-5-(4-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one

[0935]

[0936] Synthesized according to the method in Example 19.

[0937] ESI MS m / z: 500.16 [M+1] +

[0938] Example 139, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(o-tolyl)-1H-benzo[d]imidazol-2(3H)-one

[0939]

[0940] Synthesized according to the method in Example 2.

[0941] 1H NMR(400MHz,DMSO-D6)δ11.04(s,1H),7.15-7.19(m,6H),6.86-6.90(m,3H), 6.04(q,1H),4.35(q,4H),4.00(q,3H),3.05(s,3H),2.21(s,3H),1.29(t,3H)

[0942] ESI MS m / z: 482.17 [M+1] +

[0943] Example 140, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(o-tolyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[0944]

[0945] Synthesized according to the method in Example 19.

[0946] 1 H NMR(400MHz,DMSO-D6)δ7.15-7.30(m,6H),7.88-6.97(m.,1H),7.16(t.,1H),6.90(d.,1H),6.0 7(q.,1H),4.28-4.44(m.,4H),3.75(s,3H),3.36(s,3H),3.34(s,3H),2.50(t,3H),2.45(t,3H).

[0947] ESI MS m / z: 496.18 [M+1] +

[0948] Example 141, (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(o-tolyl)-1H-benzo[d]imidazol-2(3H)-one

[0949]

[0950] Synthesized according to the method in Example 2.

[0951] ESI MS m / z: 482.17 [M+1] +

[0952] Example 142, (S)-5-(2-chlorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[0953]

[0954] Synthesized according to the method in Example 2.

[0955] ESI MS m / z: 502.11 [M+1] +

[0956] Example 143, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-methoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one

[0957]

[0958] Synthesized according to the method in Example 2.

[0959] 1 H NMR(400MHz,DMSO-D6)δ11.00(s,1H),7.23-7.32(m,3H),7.14(d,1H),7.08(t,2H),6.97-7.02(m,2H), 6.83(d,1H),6.03(q,1H),4.35-4.42(m,3H),4.21-4.27(m,1H),3.74(d,6H),3.05(s,3H),1.32(t,3H).

[0960] ESI MS m / z: 498.16 [M+1] +

[0961] Example 144, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-methoxyphenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[0962]

[0963] Synthesized according to the method in Example 19.

[0964] 1 H NMR (400MHz, DMSO-D6) δ7.21-7.34(m,5H),7.07-7.10(m,2H),7.02(t,1H),6.84(d,1H) ),6.07(q,1H),4.24-4.43(m,4H),3.74(d,6H),3.33(t,3H),3.05(s,3H),1.29(q,3H)

[0965] ESI MS m / z: 512.18 [M+1]+

[0966] Example 145, (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-methoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one

[0967]

[0968] Synthesized according to the method in Example 2.

[0969] ESI MS m / z: 498.16 [M+1] +

[0970] Example 146, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazol-2(3H)-one

[0971]

[0972] Synthesized according to the method in Example 2.

[0973] 1 H NMR (400MHz, DMSO-D6) δ11.08(s,1H),7.82-7.80(d,1H),7.69-7.67(d,1H),7.60-7.58(d,1H),7.41-7.39(d,1H),7.29- 7.24(q.2H),6.91-6.87(q,2H),6.05-6.02(q,1H),4.38-4.27(m,5H),3.77-3.74(t,3H),3.05(s,3H),1.28-1.25(t,3H).

[0974] ESI MS m / z: 536.14 [M+1] +

[0975] Example 147, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-(trifluoromethyl)phenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[0976]

[0977] Synthesized according to the method in Example 19.

[0978] 1HNM(400MHz,DMSO-D6)7.84-7.82(d,1H),7.73-7.59(m,2H),7.44-7.42(d,1H),7.33-7.27(q,2H),7.15(s,1H),6.96-6.91(t, 2H),6.09-6.06(q,1H),4.45-4.37(m,1H),4.34-4.24(m,3H),3.78-3.74(t,3H),3.35(s,3H),3.05(s,3H),1.27-1.23(t,3H).

[0979] ESI MS m / z: 550.15 [M+1] +

[0980] Example 148, (S)-5-(2-cyclopropylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[0981]

[0982] Synthesized according to the method in Example 2.

[0983] ESI MS m / z: 508.18 [M+1] +

[0984] Example 149, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-isopropylphenyl)-4-methyl-1H-benzo[d]imidazol-2(3H)-one

[0985]

[0986] Synthesized according to the method in Example 2.

[0987] ESI MS m / z: 524.21 [M+1] +

[0988] Example 150, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-ethylphenyl)-1H-benzo[d]imidazol-2(3H)-one

[0989]

[0990] Synthesized according to the method in Example 2.

[0991] 1H NMR(400MHz,DMSO-D6)δ11.03(s,1H),7.28(q,3H),7.21(d,2H),7.13(d,2H),6.86(t,3 H),4.33-4.42(m,4H),3.75(s,3H),3.05(s,3H),2.53(q,2H),1.27(q,3H),1.03(t,3H).

[0992] ESI MS m / z: 496.18 [M+1] +

[0993] Example 151, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-ethylphenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[0994]

[0995] Synthesized according to the method in Example 19.

[0996] 1 H NMR(400MHz,DMSO-D6)δ7.11-7.34(m,7H),6.91(t,2H),6.07(q,1H),4.29-4.44(m,4H ),3.75(s,3H),3.34(d,3H),3.05(s,3H),2.50-2.58(m,2H),1.25(q,3H),1.03(t,3H).

[0997] ESI MS m / z: 510.20 [M+1] +

[0998] Example 152, (S)-5-(2,3-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[0999]

[1000] Synthesized according to the method in Example 2.

[1001] 1H NMR (400MHz, DMSO-D6) δ11.18(s,1H),7.43-7.34(m,1H),7.32-7.24(m,4H),7.16-7.13(q,2H),6.86-6.84(t ,1H),6.07-6.03(q,1H),4.38-4.33(m,3H),4.29-4.23(q,1H),3.75(s,3H),3.06(s,3H),1.32-1.29(t,3H).

[1002] ESI MS m / z: 504.13 [M+1] +

[1003] Example 153, (S)-5-(2,3-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1004]

[1005] Synthesized according to the method in Example 19.

[1006] 1 HNMR(400MHz,DMSO-D6)δ7.43-7.20(m,7H),6.88-6.86(d,1H),6.11-6.07(q,1H ),4.42-4.26(m,4H),3.75(s,3H),3.40(s,3H),3.06(s,3H),1.31-1.28(t,3H).

[1007] ESI MS m / z: 518.15 [M+1] +

[1008] Example 154, (S)-5-(2,6-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1009]

[1010] Synthesized according to the method in Example 2.

[1011] 1H NMR (400MHz, DMSO-D6) δ11.14-11.00(d,1H),7.28-7.20(m,2H),7.13-7.03(t,1H),6.99-6.90(m,3H),6.81-6.79(d,1H), 6.03-5.99(q,1H),4.42-4.28(m,4H),4.26-4.13(m,1H),3.74(s,3H),3.12-3.07(d,1H),3.02(s,3H),1.31-1.28(t,3H).

[1012] ESI MS m / z: 504.13 [M+1] +

[1013] Example 155, (S)-5-(2,6-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1014]

[1015] Synthesized according to the method in Example 19.

[1016] 1 HNMR(400MHz,DMSO-D6)δ7.27-7.15(m,4H),7.08-7.06(t,1H),7.04-7.00(t,1H),6.83-6.81(d,1 H),6.07-6.03(q,1H),4.39-4.22(m,5H),3.74(s,3H),3.35(s,3H),3.02(s,3H)1.30-1.27(t,3H).

[1017] ESI MS m / z: 518.15 [M+1] +

[1018] Example 156, (S)-5-(2,4-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1019]

[1020] Synthesized according to the method in Example 2.

[1021] 1H NMR (400MHz, DMSO-D6) δ11.14(s,1H),7.57-7.51(m,1H),7.37-7.31(m,1H),7.27-7.24(q,2H),7.22-7.17(m,1H),7.16-7.07(m ,2H),6.85-6.83(t,1H),6.06-6.03(q,1H),4.38-4.34(m,3H),4.33-4.22(m,1H),3.75(s,3H),3.05(s,3H),1.32-1.29(t,3H).

[1022] ESI MS m / z: 504.13 [M+1] +

[1023] Example 157, (S)-5-(2,4-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1024]

[1025] Synthesized according to the method in Example 19.

[1026] 1 HNMR(400MHz,DMSO-D6)δ7.38-7.31(m,1H),7.29-7.13(m,6H),6.87-6.85(d,1H),6.10-6 .06(q,1H),4.42-4.28(m,4H),3.75(s,3H),3.38(s,3H),3.05(s,3H),1.31-1.24(q,3H).

[1027] ESI MS m / z: 518.15 [M+1] +

[1028] Example 158, (S)-5-(2,4,5-trifluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1029]

[1030] Synthesized according to the method in Example 2.

[1031] 1H NMR (400MHz, DMSO-D6) δ11.17(s,1H),7.68-7.62(m,2H),7.27-7.23(t,2H)7.14-7.11(m,2H),6.85-6.83(d ,1H),6.06-6.03(q,1H),4.40-4.34(m,3H),4.28-4.25(t,1H),3.75(s,3H),3.05(s,3H),1.32-1.29(t,3H).

[1032] ESI MS m / z: 522.12 [M+1] +

[1033] Example 159, (S)-5-(2,4,5-trifluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1034]

[1035] Synthesized according to the method in Example 19.

[1036] 1 HNMR(400MHz,DMSO-D6)δ7.75-7.63(m,2H),7.38(s,1H),7.33-7.31(d,1H),7.27-7.25(d,1H),7.20-7.18(d,1H), 6.87-6.85(d,1H),6.10-6.07(q,1H),4.41-4.25(m,4H),3.75(s,3H),3.39(s,3H),3.05(s,3H),1.31-1.28(t,3H).

[1037] ESI MS m / z: 536.14 [M+1] +

[1038] Example 160, (S)-5-(2,5-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1039]

[1040] Synthesized according to the method in Example 2.

[1041] 1H NMR (400MHz, DMSO-D6) δ11.17(s,1H),7.39-7.25(m,2H),7.24-7.1(m,3H),7.16-7.14(q,2H),6.85-6.83(t ,1H),6.07-6.03(q,1H),4.40-4.35(m,3H),4.33-4.22(m,1H),3.75(s,3H),3.05(s,3H),1.32-1.29(t,3H).

[1042] ESI MS m / z: 504.13 [M+1] +

[1043] Example 161, (S)-5-(2,5-difluorophenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1044]

[1045] Synthesized according to the method in Example 19.

[1046] 1 HNMR(400MHz,DMSO-D6)δ7.46-7.31(m,4H),7.26-7.21(m,3H),6.87-6.85(d,1H),6.10-6 .07(q,1H),4.37-4.25(m,4H),3.74(s,3H),3.39(s,3H),3.05(s,3H),1.31-1.27(q,3H).

[1047] ESI MS m / z: 518.15 [M+1] +

[1048] Example 162, (S)-5-(2,4-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1049]

[1050] Synthesized according to the method in Example 2.

[1051] 1H NMR (400MHz, DMSO-D6) δ11.00(s,1H),7.36-7.26(m,1H),7.19-7.17(t,2H),7.11-7.01(m,1H),6.99-6.94(t,3H),6.87-6.85(q,1H),6.05-6.0 1(q,1H),4.51-4.26(m,3H),4.41-4.22(q,1H),3.77-3.74(q,3H),3.07 -3.02(t,3H),2.30-2.29(d,3H),2.20-2.28(d,3H),1.31-1.25(q,3H).

[1052] ESI MS m / z: 496.18 [M+1] +

[1053] Example 163, (S)-5-(2,4-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1054]

[1055] Synthesized according to the method in Example 19.

[1056] 1 HNMR(400MHz,DMSO-D6)δ7.27-7.24(q,2H),7.11-7.05(q,5H),6.93-6.87(q,1H),6.08-6.05(q,1H), 4.42-4.31(m,4H),3.77-3.75(d,3H),3.35(s,3H),3.07-3.05(s,3H),2.30(s,3H),1.29-1.23(q,3H).

[1057] ESI MS m / z: 510.20 [M+1]+

[1058] Example 164, (S)-5-(2,5-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1059]

[1060] Synthesized according to the method in Example 2.

[1061] 1H NMR(400MHz,DMSO-D6)δ11.02(s,1H),7.28-7.26(d,1H),7.20-7.13(q,2H),7.05-7.03(d,1H),6.98(s,1H),6.88-6.86(q,3H),6.05-6.0 2(q,1H),4.42-4.33(m,3H),4.28-4.26(d,1H),3.78-3.75(d,3H),3.08-3.05(d,3H),2.27(s,3H),2.19-2.16(d,3H),1.31-1.26(q,3H).

[1062] ESI MS m / z: 496.18 [M+1] +

[1063] Example 165, (S)-5-(2,5-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1064]

[1065] Synthesized according to the method in Example 19.

[1066] 1 HNMR(400MHz,DMSO-D6)δ7.27-7.25(q,2H),7.17-7.13(t,2H),7.06-7.02(t,2H),6.94-6.92(d,1H),6.89-6.87(d,1H),6 .09-6.05(q,1H),4.44-4.27(m,4H),3.75(s,3H),3.36(s,3H),3.05(s,3H),2.28(s,3H),2.18(s,3H),1.30-1.26(t,3H).

[1067] ESI MS m / z: 510.20 [M+1] +

[1068] Example 166: (S)-5-(2,3-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1069]

[1070] Synthesized according to the method in Example 2.

[1071] 1 H NMR (400MHz, DMSO-D6) δ11.02(s,1H),7.28-7.26(d,1H),7.18-7.08(m,3H),7.00-6.99(d,1H),6.88-6.83(m.3H),6.05-6 .02(q,1H),4.42-4.33(m,3H),4.29-4.27(d,1H),3.75(s,3H),3.05(s,3H),2.08(s,3H),2.09(s,3H),1.31-1.24(q,3H).

[1072] ESI MS m / z: 496.18 [M+1] +

[1073] Example 167, (S)-5-(2,3-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1074]

[1075] Synthesized according to the method in Example 19.

[1076] 1 H NMR(400MHz, DMSO-D6)7.28-7.26(d,2H),7.17-7.10(m,3H),7.04-7.03(d,1H),6.91-6.88(m,2H),6.10-6.06( q,1H),4.44-4.30(m,4H),3.75(s,3H),3.36(s,3H),3.05(s,3H),2.29(s,3H),2.11(s,3H),1.30-1.26(t,3H).

[1077] ESI MS m / z: 510.20 [M+1] +

[1078] Example 168, (S)-5-(2,6-dimethylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1079]

[1080] Synthesized according to the method in Example 2.

[1081] ESI MS m / z: 496.18 [M+1] +

[1082] Example 169, (S)-5-(4-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1083]

[1084] Synthesized according to the method in Example 2.

[1085] 1 H NMR(400MHz,DMSO-D6)δ11.01(s,1H),7.25-7.20(t,1H),7.12-7.10(d,2H),7.09-7.07(d,2H),6.84-6.82(d,1H),6.0 5-6.02(q,1H),4.40-4.33(m,3H),4.28-4.22(q,1H),3.75(s,3H),3.05-3.01(d,3H),2.34(s,3H),1.33-1.29(q,3H).

[1086] ESI MS m / z: 500.16 [M+1] +

[1087] Example 170, (S)-5-(4-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1088]

[1089] Synthesized according to the method in Example 19.

[1090] ESI MS m / z: 514.17 [M+1] +

[1091] Example 171, (S)-5-(5-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1092]

[1093] Synthesized according to the method in Example 2.

[1094] ESI MS m / z: 500.16 [M+1] +

[1095] Example 172, (S)-5-(5-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1096]

[1097] Synthesized according to the method in Example 19.

[1098] 1 HNMR(400MHz,DMSO-D6)δ7.34-7.26(m,3H),7.20(s,1H),7.12-7.03(m,2H),7.00-6.98(q,1H),6.90-6.88(d,1H ),6.10-6.06(q,1H),4.44-4.26(m,4H),3.75(s,3H),3.37(s,3H),3.06(s,3H),2.21(s,3H),1.30-1.26(t,3H).

[1099] ESI MS m / z: 514.17 [M+1] +

[1100] Example 173, (S)-5-(3-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1101]

[1102] Synthesized according to the method in Example 2.

[1103] 1 H NMR(400MHz,DMSO-D6)δ11.08(s,1H),7.16-7.11(t,3H),7.06-7.04(d,1H),6.91-6.90(t,1H),6.88-6.8 6(d,3H),6.05-6.02(q,1H),4.42-4.23(m,4H),3.75(s,3H),3.05(s,3H),2.12(s,1H),1.31-1.27(t,3H).

[1104] ESI MS m / z: 500.16 [M+1] +

[1105] Example 174, (S)-5-(3-fluoro-2-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1106]

[1107] Synthesized according to the method in Example 19.

[1108] 1 HNMR(400MHz,DMSO-D6)δ7.30-7.25(q,3H),7.18-7.13(t,2H),7.10-7.08(d,1H),6.98-6.96(q,1H),6.90-6.88(d ,1H),6.09-6.06(q,1H),4.44-4.26(m,4H),3.75(s,3H),3.37(s,3H),3.05(s,3H),2.14(s,3H),1.29-1.26(t,3H).

[1109] ESI MS m / z: 514.17 [M+1] +

[1110] Example 175, (S)-5-(2-fluoro-5-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1111]

[1112] Synthesized according to the method in Example 2.

[1113] 1 H NMR(400MHz,DMSO-D6)δ11.11(s,1H),7.30-7.21(m,3H),7.16-7.09(q,4H),6.85-6.83(d,1H),6.06-6.0 3(q,1H),4.40-4.33(m,3H),4.28-4.22(q,1H),3.75(s,3H),3.05(s,3H),2.32(s,3H),1.34-1.24(q,3H)

[1114] ESI MS m / z: 500.16 [M+1] +

[1115] Example 176, (S)-5-(2-fluoro-5-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1116]

[1117] Synthesized according to the method in Example 19.

[1118] 1 HNMR(400MHz,DMSO-D6)δ7.35-7.24(m,4H),7.18-7.15(q,3H),6.86-6.84(d,1H),6.10-6.06(q ,1H),4.42-4.25(m,4H),3.74(s,3H),3.39(s,3H),3.05(s,3H),2.33(s,3H),1.33-1.29(t,3H).

[1119] ESI MS m / z: 514.17 [M+1] +

[1120] Example 177, (S)-5-(2-fluoro-3-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1121]

[1122] Synthesized according to the method in Example 2.

[1123] 1 H NMR (400MHz, DMSO-D6) δ11.11(s,1H),7.29-7.22(m,4H),7.16-7.08(m,3H),6.85-6.83(d,1H),6.06-6.02(q ,1H),4.41-4.33(m,3H),4.28-4.26(d,1H),3.75(s,3H),3.05(s,3H),2.29-2.28(d,3H),1.32-1.29(q,3H).

[1124] ESI MS m / z: 500.16 [M+1]+

[1125] Example 178, (S)-5-(2-fluoro-3-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1126]

[1127] Synthesized according to the method in Example 19.

[1128] 1 HNMR(400MHz,DMSO-D6)δ7.31-7.22(m,5H),7.18-7.11(q,2H),6.87-6.83(t,1H),6.10-6.06(q ,1H),4.42-4.29(m,4H),3.75(s,3H),3.38(s,3H),3.05(s,3H),2.29(s,3H),1.31-1.27(t,3H).

[1129] ESI MS m / z: 514.17 [M+1]+

[1130] Example 179, (S)-5-(2-fluoro-4-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1131]

[1132] Synthesized according to the method in Example 2.

[1133] 1 H NMR(400MHz,DMSO-D6)δ11.01(s,1H),7.25-7.20(t,1H),7.12-7.10(d,2H),7.09-7.07(d,2H),6.84-6.82(d,1H),6.0 5-6.02(q,1H),4.40-4.33(m,3H),4.28-4.22(q,1H),3.75(s,3H),3.05-3.01(d,3H),2.34(s,3H),1.33-1.29(q,3H).

[1134] ESI MS m / z: 500.16 [M+1] +

[1135] Example 180, (S)-5-(2-fluoro-4-methylphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1136]

[1137] Synthesized according to the method in Example 19.

[1138] 1 HNMR(400MHz,DMSO-D6)δ7.44-7.40(t,1H),7.31-7.24(m,3H),7.15-7.09(q,3H),6.86-6.84(d,1H),6.0 9-6.06(q,1H),4.38-4.24(m,4H),3.74(s,3H),3.38(s,3H),3.04(s,3H),2.35(s,3H),1.31-1.28(q,3H).

[1139] ESI MS m / z: 514.17 [M+1] +

[1140] Example 181, (S)-5-(2-fluoro-5-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1141]

[1142] Synthesized according to the method in Example 2.

[1143] 1 H NMR(400MHz,DMSO-D6)δ11.11(s,1H),7.27-7.18(m,3H),7.13-7.11(d,2H),6.99-6.97(q,1H),6.06- 6.03(q,1H),4.40-4.35(m,3H),4.28-4.22(q,1H),3.78-3.75(d,6H),3.05(s,3H),1.33-1.29(t,3H).

[1144] ESI MS m / z: 516.15 [M+1] +

[1145] Example 182, (S)-5-(2-fluoro-5-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1146]

[1147] Synthesized according to the method in Example 19.

[1148] 1HNMR(400MHz,DMSO-D6)δ7.29-7.08(m,7H),6.86-6.84(d,1H),6.10-6.06(q,1H), 4.43-4.24(m,4H),3.75-3.74(d,6H),3.37(s,3H),3.06(s,3H),1.33-1.29(t,3H).

[1149] ESI MS m / z: 530.17 [M+1] +

[1150] Example 183, (S)-5-(2-fluoro-3-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1151]

[1152] Synthesized according to the method in Example 2.

[1153] ESI MS m / z: 516.15 [M+1] +

[1154] Example 184, (S)-5-(2-fluoro-4-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1155]

[1156] Synthesized according to the method in Example 2.

[1157] 1 H NMR (400MHz, DMSO-D6) δ11.07(s,1H),7.25-7.20(d,1H),7.18(s,1H),7.07-7.04(t,1H),6.93-6.90(t,2H),6.89-6.8 2(m,3H),6.05-6.02(q,1H),4.40-4.35(m,3H),4.27-4.21(q,1H),3.80-3.75(t,3H),3.05(s,3H),1.33-1.29(t,3H).

[1158] ESI MS m / z: 516.15 [M+1] +

[1159] Example 185, (S)-5-(2-fluoro-4-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1160]

[1161] Synthesized according to the method in Example 19.

[1162] 1 H NMR(400MHz, DMSO-D6)7.48-7.43(t,1H),7.28-7.24(q,3H),7.13-7.11(d,1H),6.95-6.84(m,3H),6.10-6.06( q,1H),4.42-4.33(m,3H),4.30-4.24(q,1H),3.81-3.75(t,6H),3.38(s,3H),3.05(s,3H),1.32-1.28(t,3H)..

[1163] ESI MS m / z: 530.17 [M+1] +

[1164] Example 186, (S)-5-(5-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1165]

[1166] Synthesized according to the method in Example 2.

[1167] 1 H NMR(400MHz,DMSO-D6)δ11.04(s,1H),7.27-7.10(m,1H),7.09-7.03(m,6H),6.84-6.82(d,1H),6.05-6 .02(q,1H),4.41-4.34(m,3H),4.27-4.21(q,1H),3.75-3.73(d,6H),3.05(s,3H),1.34-1.24(q,3H)..

[1168] ESI MS m / z: 516.15 [M+1] +

[1169] Example 187, (S)-5-(5-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1170]

[1171] Synthesized according to the method in Example 19.

[1172] 1 HNMR(400MHz,DMSO-D6)δ7.36(s,1H),7.30-7.18(m,4H),7.06-7.03(q,1H),6.95-6.91(m,1H),6.87-6.85(d,1H), 6.11-6.07(q,1H),4.39-4.25(m,4H),3.79(s,3H),3.75(s,3H),3.40-3.37(d,3H),3.05(s,3H)1.32-1.18(t,3H)..

[1173] ESI MS m / z: 530.17 [M+1] +

[1174] Example 188, (S)-5-(4-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1175]

[1176] Synthesized according to the method in Example 2.

[1177] 1 H NMR (400MHz, DMSO-D6) δ11.11(s,1H),7.29-7.22(m,4H),7.16-7.08(m,3H),6.85-6.83(d,1H),6.06-6.02(q ,1H),4.41-4.33(m,3H),4.28-4.26(d,1H),3.75(s,3H),3.05(s,3H),2.29-2.28(d,3H),1.32-1.29(q,3H)..

[1178] ESI MS m / z: 516.15 [M+1] +

[1179] Example 189, (S)-5-(4-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1180]

[1181] Synthesized according to the method in Example 19.

[1182] 1 HNMR(400MHz,DMSO-D6)δ7.20(s,4H),7.06-7.01(m,2H),6.99-6.81(m,2H),6.09-6.05(q,1 H),4.42-4.24(m,4H),3.77-3.75(d,6H),3.36(s,3H),3.07-3.05(d,3H),1.32-1.29(t,3H).

[1183] ESI MS m / z: 530.17 [M+1] +

[1184] Example 190, (S)-5-(6-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1185]

[1186] Synthesized according to the method in Example 2.

[1187] 1 H NMR(400MHz,DMSO-D6)δ11.01(s,1H),7.28-7.26(d,1H),7.18-7.16(d,1H),6.89-6.85(t,5H),6.06-6.0 2(q,1H),4.42-4.34(m,3H),4.28-4.22(q,1H),3.76-3.72(q,6H),3.10-3.06(d,3H),1.32-1.27(q,3H).

[1188] ESI MS m / z: 516.15 [M+1] +

[1189] Example 191, (S)-5-(6-fluoro-2-methoxyphenyl)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1190]

[1191] Synthesized according to the method in Example 19.

[1192] 1 HNMR(400MHz,DMSO-D6)δ7.39-7.34(q,1H),7.27-7.24(q,2H),7.12(s,1H),6.97-6.87(m,4H),6. 10-6.07(q,1H),4.39-4.28(m,4H),3.77-3.73(q,6H),3.34(s,3H),3.07(s,3H)1.31-1.28(t,3H).

[1193] ESI MS m / z: 530.17 [M+1] +

[1194] Example 192, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-ethoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one

[1195]

[1196] Synthesized according to the method in Example 2.

[1197] ESI MS m / z: 512.18 [M+1] +

[1198] Example 193, (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-ethoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one

[1199]

[1200] Synthesized according to the method in Example 2.

[1201] ESI MS m / z: 512.18 [M+1] +

[1202] Example 194, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one

[1203]

[1204] Synthesized according to the method in Example 2.

[1205] ESI MS m / z: 469.15 [M+1] +

[1206] Example 195, (R)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one

[1207]

[1208] Synthesized according to the method in Example 2.

[1209] ESI MS m / z: 469.15 [M+1] +

[1210] Example 196, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-methyl-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one

[1211]

[1212] Synthesized according to the method in Example 19.

[1213] ESI MS m / z: 483.16 [M+1] +

[1214] Example 197, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-ethyl-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one

[1215]

[1216] Synthesized according to the method in Example 19.

[1217] ESI MS m / z: 497.18 [M+1] +

[1218] Example 198, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-(2-methoxyethyl)-5-(pyridin-2-yl)-1H-benzo[d]imidazol-2(3H)-one

[1219]

[1220] Synthesized according to the method in Example 19.

[1221] ESI MS m / z: 527.19 [M+1] +

[1222] Example 199, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(4-fluoro-2-methylphenyl)-1H-benzo[d]imidazol-2(3H)-one

[1223]

[1224] Synthesized according to the method in Example 2.

[1225] 1 H NMR(400MHz,DMSO-D6)δ11.05(s,1H),7.18-7.28(m,1H),7.12(t,3H),7.04(d,1H),6.86(t,3H), 6.04(q,1H),4.28-4.38(m,3H),4.27(d,1H),3.75(s,3H),3.05(s,3H),2.21(s,3H),1.27(q,3H)

[1226] ESI MS m / z: 500.16 [M+1] +

[1227] Example 200, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(4-fluoro-2-methylphenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1228]

[1229] Synthesized according to the method in Example 19.

[1230] 1 H NMR(400MHz,DMSO-D6)δ7.23-7.28(m,3H),7.17(t,2H),7.04-7.09(m,1H),6.91(q,2H),6.06 (q,1H),4.25-4.44(m,4H),3.74(s,3H),3.34(t,3H),3.05(s,3H),2.23(s,3H),1.26(q,3H).

[1231] ESI MS m / z: 500.16 [M+1] +

[1232] Example 201, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluoro-5-methylphenyl)-1H-benzo[d]imidazol-2(3H)-one

[1233]

[1234] Synthesized according to the method in Example 2.

[1235] ESI MS m / z: 500.16 [M+1] +

[1236] Example 202, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluoro-5-methylphenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one

[1237]

[1238] Synthesized according to the method in Example 19.

[1239] ESI MS m / z: 514.17 [M+1] +

[1240] Example 203, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-(2-methoxyphenyl)-1H-benzo[d]imidazol-2(3H)-one

[1241]

[1242] Synthesized according to the method in Example 2.

[1243] ESI MS m / z: 498.16 [M+1] +

[1244] Example 204, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-(o-tolyl)-1H-benzo[d]imidazol-2(3H)-one

[1245]

[1246] Synthesized according to the method in Example 2.

[1247] ESI MS m / z: 482.17 [M+1] +

[1248] Example 205, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-(2-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one

[1249]

[1250] Synthesized according to the method in Example 2.

[1251] ESI MS m / z: 486.14 [M+1] +

[1252] Example 206, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-phenyl-1H-benzo[d]imidazol-2(3H)-one

[1253]

[1254] Synthesized according to the method in Example 2.

[1255] ESI MS m / z: 468.15 [M+1] +

[1256] Example 207, (S)-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4-(2-fluorobenzyl)-1H-benzo[d]imidazol-2(3H)-one

[1257]

[1258] Synthesized according to the method in Example 2.

[1259] ESI MS m / z: 500.16 [M+1] +

[1260] Example 208: (S)-3-cyclopropyl-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(2-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one

[1261]

[1262] Synthesized according to the method in Example 19.

[1263] ESI MS m / z: 526.17 [M+1] +

[1264] Example 209, (S)-3-cyclopropyl-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-methyl-1H-benzo[d]imidazol-2(3H)-one

[1265]

[1266] Synthesized according to the method in Example 19.

[1267] ESI MS m / z: 446.17 [M+1] +

[1268] Example 210, (S)-5-bromo-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-(2-(methanesulfonyl)ethyl)-1H-benzo[d]imidazol-2(3H)-one

[1269]

[1270] Synthesized according to the method in Example 19.

[1271] ESI MS m / z: 576.04 [M+1] +

[1272] Example 211, (S)-3-cyclopropyl-1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-2(3H)-one

[1273]

[1274] Synthesized according to the method in Example 19.

[1275] ESI MS m / z: 500.14 [M+1] +

[1276] Example 212, (S)-Ethyl 1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazolium-5-carboxylic acid ester

[1277]

[1278] Synthesized according to the method in Example 2.

[1279] ESI MS m / z: 464.14 [M+1] +

[1280] Example 213, (S)-Isopropyl 1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazolium-5-carboxylic acid ester

[1281]

[1282] Synthesized according to the method in Example 2.

[1283] ESI MS m / z: 478.16 [M+1] +

[1284] Example 214: (S)-2,2,2-trifluoroethyl 1-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazolium-5-carboxylic acid ester

[1285]

[1286] Synthesized according to the method in Example 2.

[1287] ESI MS m / z: 518.11 [M+1] +

[1288] Example 215, (S)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindole-4-yl)acetamide

[1289]

[1290] Step 1. Methyl (S)-2-((((1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)amino)methyl)-6-nitrobenzoate

[1291]

[1292] Methyl 2-(bromomethyl)-6-nitrobenzoate (200 mg, 0.73 mmol) was dissolved in 2.0 mL of acetonitrile. (S)-1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethylamine (215 mg, 0.78 mg) and potassium carbonate (201 mg, 1.45 mmol) were added. The mixture was heated to 80 °C and refluxed for 2 hours. The system was concentrated and extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The solution was filtered and concentrated to obtain an oily substance. This oil was dissolved in a small amount of ethyl acetate, and a large amount of petroleum ether was added to precipitate a solid. The solid was filtered and washed twice with methanol to obtain 210 mg of a yellow solid.

[1293] Step 2, (S)-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-7-nitroisoindol-1-one).

[1294]

[1295] The product from step 1 (200 mg, 0.43 mmol) was dissolved in 4.0 mL of solvent (acetonitrile:ethanol = 1:1), and 0.2 mL of glacial acetic acid was added. The mixture was heated to 90 °C and refluxed. The system was concentrated, and the extract was obtained with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The solution was filtered and concentrated to obtain 150 mg of the target compound.

[1296] Step 3, (S)-7-amino-2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)isoindol-1-one

[1297]

[1298] Reduced iron powder was added to 125 mL of ethanol / water (4:1) solvent, and 4 drops of glacial acetic acid were added. The mixture was heated to 70-80 °C and refluxed for 30 minutes. The product from step 2 (150 mg, 0.345 mmol) was added, and the mixture was refluxed for 2 hours. The diatomaceous earth was filtered, and the filtrate was concentrated and extracted with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 100 mg of the target substance. Step 4: (S)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)acetamide

[1299] The product from step 3 (100 mg, 0.25 mmol) was dissolved in 4.0 mL of tetrahydrofuran, and 0.1 mL of acetyl chloride was added. The mixture was heated under reflux for 2 hours. The system was concentrated and extracted with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 80 mg of the target product.

[1300] 1H NMR (400MHz, DMSO-D6) δ10.23(s,1H),8.28-8.26(d,1H),7.55-7.51(t,1H),7.29-7.22(q,2H),6.94-6.92(d,1H),5.88-5.8 5(q,1H),4.73-4.68(d,1H),4.41-4.31(m,3H),4.14-4.00(m,2H)3.76(s,3H),3.03(s,3H),2.17(s,3H),1.32-1.29(t,3H).

[1301] ESI MS m / z: 448.15 [M+1] +

[1302] Example 216, (R)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindole-4-yl)acetamide

[1303]

[1304] Synthesized according to the method in Example 215.

[1305] ESI MS m / z: 448.15 [M+1] +

[1306] Example 217, (S)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methylsulfonyl)ethyl)-3-oxoisoindol-4-yl)cyclopropaneformamide

[1307]

[1308] Synthesized according to the method in Example 215.

[1309] ESI MS m / z: 474.16 [M+1] +

[1310] Example 218, (R)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)cyclopropaneformamide

[1311]

[1312] Synthesized according to the method in Example 215.

[1313] ESI MS m / z: 474.16 [M+1] +

[1314] Example 219, (S)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)propionamide

[1315]

[1316] Synthesized according to the method in Example 215.

[1317] ESI MS m / z: 462.16 [M+1] +

[1318] Example 220, (R)-N-(2-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-3-oxoisoindol-4-yl)propionamide

[1319]

[1320] Synthesized according to the method in Example 215.

[1321] ESI MS m / z: 462.16 [M+1] +

[1322] Example 221, 5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-nitro-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione

[1323]

[1324] Step 1: 2-Nitrothiophene-3,4-dicarboxylic acid

[1325] 20 mL of fuming nitric acid (95% purity) was added to a 250 mL round-bottom flask equipped with an electromagnetic stirrer and a drying tube. The flask was cooled to 0-5 °C in an ice bath. 5 g of thiophene[3,4-c]furan-1,3-dione was added in portions. After the addition was complete, the mixture was reacted at this temperature for 30 minutes. The reaction mixture was poured into a 40 mL ice-water mixture and extracted with ethyl acetate. All ethyl acetate layers were combined and washed successively with 50 mL × 2 water and saturated brine. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain 3.5 g of solid.

[1326] Step 2: 4-Nitrothiophene[3,4-c]furan-1,3-dione

[1327] Add 2g of the compound from step 1 and 2mL of acetic anhydride to a 50mL round-bottom flask equipped with an electromagnetic stirrer, a reflux condenser and a drying tube. Reflux for 3 hours, evaporate the solvent to dryness, and obtain 1.2g of the target compound.

[1328] Step 3: 5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-nitro-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione

[1329] In a 250 mL round-bottom flask equipped with an electromagnetic stirrer and a drying tube, add 1.0 g of the compound from step 2, 1.36 g of 1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethylamine (synthesized according to the method disclosed in WO2018157779), and 10 mL of THF. Stir overnight at room temperature. Add 1.2 g of CDI and reflux in an oil bath for 2 hours. Allow to cool to room temperature, add 30 mL of ethyl acetate and 150 mL of water, extract, separate, wash the organic layer with 100 mL of 0.5 N hydrochloric acid and 100 mL of saturated brine, dry to anhydrous magnesium sulfate, filter, evaporate the solvent, and column chromatography to obtain 0.52 g of the target compound. ESI MS m / z: 456.05 [M+1] +

[1330] Example 222, (S)-5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-1-nitro-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione

[1331]

[1332] Synthesized according to the method in Example 221.

[1333] ESI MS m / z: 456.05 [M+1] +

[1334] Example 223, (S)-1-amino-5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione

[1335]

[1336] In a 250 mL round-bottom flask equipped with an electromagnetic stirrer, reflux condenser, and drying tube, 2.0 g of the product from Example 134 and 100 mL of ethanol / water (2:1) were added. The mixture was heated to reflux, and 1.8 g of reduced iron powder was added. The mixture was refluxed for 2 hours. The mixture was filtered, and the filtrate was evaporated to dryness. 200 mL of ethyl acetate and 150 mL of water were added, and the mixture was extracted. The layers were separated, and the organic layer was washed with 100 mL of water and 100 mL of saturated brine. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to dryness. After purification by column chromatography, 1.1 g of a yellowish-brown solid was obtained.

[1337] ESI MS m / z: 426.07 [M+1]+

[1338] Example 224, N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)acetamide

[1339]

[1340] Example 223: The product was acetylated to obtain the target compound.

[1341] ESI MS m / z: 468.08 [M+1] +

[1342] Example 225, (R)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrole-1-yl)acetamide

[1343]

[1344] Synthesized according to the method in Example 224.

[1345] ESI MS m / z: 468.08 [M+1] +

[1346] Example 226, (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)propionamide

[1347]

[1348] Synthesized according to the method in Example 224.

[1349] ESI MS m / z: 482.10 [M+1] +

[1350] Example 227, (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrole-1-yl)cyclopropaneformamide

[1351]

[1352] Synthesized according to the method in Example 224.

[1353] ESI MS m / z: 494.10 [M+1] +

[1354] Example 228: (S)-2-(dimethylamino)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)acetamide

[1355]

[1356] Synthesized according to the method in Example 224.

[1357] ESI MS m / z: 511.12 [M+1] +

[1358] Example 229: (S)-2-(diethylamino)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)acetamide

[1359]

[1360] Synthesized according to the method in Example 224.

[1361] ESI MS m / z: 539.16 [M+1] +

[1362] Example 230: (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)-2-(piperidin-1-yl)acetamide

[1363]

[1364] Synthesized according to the method in Example 224.

[1365] ESI MS m / z: 551.16 [M+1] +

[1366] Example 231, (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)-2-(pyrrolidine-1-yl)acetamide

[1367]

[1368] Synthesized according to the method in Example 224.

[1369] ESI MS m / z: 537.14 [M+1] +

[1370] Example 232, (S)-N-(5-(1-(6-ethoxy-5-methoxypyridin-2-yl)-2-(methanesulfonyl)ethyl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrolo-1-yl)-2-morpholinoacetamide

[1371]

[1372] Synthesized according to the method in Example 224.

[1373] ESI MS m / z: 553.13 [M+1] +

[1374] Example 233: PDE4 inhibitory activity assay

[1375] The IC50 values ​​of the compounds of this invention against the inhibitory activity of PDE4A1A, PDE4B1, and PDE4D2 were tested.

[1376] Experimental materials:

[1377] Enzymes: PDE4A1A (BPS, Cat No. 60040); PDE4B1 (BPS, Cat No. 60041), PDE4D2.

[1378] Positive compound: Trequinsin (Sigma, Cat No. T20S7).

[1379] Reaction plate: 384-well plate (Perkin EImer, Cat No. 60077).

[1380] Experimental apparatus: Wallac Victor Multi-Label counter (Pekin Elmer)

[1381] Experimental steps:

[1382] I. Prepare 1× reaction solution and final reaction solution;

[1383] II. PDE enzymatic reaction;

[1384] 1) Dissolve PDE in 1× reaction solution to prepare 2× enzyme solution;

[1385] 2) Dissolve FAM-cAMP in 1× reaction solution to prepare 2× substrate solution;

[1386] 3) Use an Echo 550 to transfer the appropriate volume of the DMSO compound solution to the reaction plate;

[1387] 4) Add 2× enzyme solution to the corresponding well of the reaction plate and incubate with the compound solution at room temperature for 15 minutes;

[1388] 5) Add 2× substrate solution to the corresponding well of the reaction plate to initiate the reaction;

[1389] 6) After incubating the reaction plate at room temperature for 30 minutes, add the reaction termination solution to stop the reaction. Continue incubation at room temperature for another 60 minutes;

[1390] III. Read the values ​​on Victor;

[1391] IV. Curve fitting;

[1392] Calculate the inhibition rate using Excel; calculate the IC using Graphpad Prism. 50 .

[1393]

[1394]

[1395]

[1396]

[1397]

[1398] *WX011: This is Example 11 of WO2018036470, synthesized according to the method disclosed herein;

[1399] *WX063: This is Example 63 of WO2018036469, synthesized according to the method disclosed therein;

[1400] +: 20 nM has a significant inhibitory effect;

[1401] - No significant inhibitory effect was observed at 20 nM;

[1402] Example*: refers to the implementation plan*

[1403] Conclusion: Compared with Apremilast and Example 11 (WX011) of WO2018036470, Examples 2, 8, 10, 12, and 30 of the present invention showed significantly enhanced inhibitory activities against PDE4A1A, PDE4B1, and PDE4D2. Compared with Example 63 (WX063) of WO2018036469, the compounds of the present invention showed lower inhibitory activity against PDE4D2, suggesting that they have fewer vomiting side effects (Osamu Suzuki et al. J. Pharmacol. Sci. 2013, 123: 219-226).

Claims

1. A compound, or a pharmaceutically acceptable salt, said compound being selected from: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

2. A compound, or a pharmaceutically acceptable salt, said compound being selected from: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , and .

3. The use of the compound according to any one of claims 1-2, or a pharmaceutically acceptable salt, in the manufacture of a medicament for treating PDE4-related conditions.

4. The application according to claim 3, characterized in that, The PDE4-related diseases refer to immune inflammatory and autoimmune diseases or conditions, including systemic lupus erythematosus (SLE), lupus nephritis, psoriasis, cutaneous lupus, Crohn's disease, ulcerative colitis, type 1 diabetes, rheumatoid arthritis, systemic paroxysmal juvenile idiopathic arthritis, atopic dermatitis, ankylosing spondylitis, and multiple sclerosis.

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