US2021094940A1PendingUtilityA1
Modulators of ror-gamma
Est. expiryJan 29, 2036(~9.5 yrs left)· nominal 20-yr term from priority
Inventors:David A. ClaremonLawrence Wayne DillardYi FanStephen D. LotestaSuresh B. SinghColin M. TiceWei ZhaoLinghang Zhuang
C07D 403/14C07D 403/06C07D 401/06C07D 235/10A61P 37/06A61P 25/08A61P 21/04A61P 19/00A61P 11/02A61P 5/00A61P 1/18C07D 401/14A61P 37/02A61P 27/02A61P 19/02A61P 9/10A61P 1/04A61P 35/00A61P 25/28A61P 25/24A61P 25/00A61P 17/10A61P 17/06A61P 17/00A61P 11/06A61P 11/00A61P 3/10A61P 3/04A61P 1/16A61P 1/00A61P 15/00C07D 401/12C07D 413/06A61K 31/424A61K 31/445A61K 31/4245A61P 29/00A61K 31/4439C07D 405/06A61K 31/4709A61K 31/4184C07D 471/04A61K 31/4192C07D 487/04C07D 405/14C07D 235/08C07D 233/90A61P 21/00A61K 31/4433A61P 17/04C07D 233/88A61P 25/18A61P 9/12A61P 17/02A61P 9/02C07D 405/10A61P 5/14A61P 25/14A61P 19/08
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Claims
Abstract
Provided are novel compounds of Formula I pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions comprising the novel compounds of Formula I and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.
Claims
exact text as granted — not AI-modified1 - 54 . (canceled)
55 . A method of treating a disease or disorder selected from asthma, chronic obstructive pulmonary disease (COPD), bronchitis, allergic rhinitis, atopic dermatitis, contact dermatitis, acne, cystic fibrosis, allograft rejection, multiple sclerosis, scleroderma, arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), Hashimoto's disease, pancreatitis, autoimmune diabetes, type I diabetes, autoimmune ocular disease, ulcerative colitis, Crohn's disease, regional enteritis, inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), Sjögren's syndrome, optic neuritis, obesity, hepatosteatosis, adipose tissue-associated inflammation, insulin resistance, type II diabetes, neuromyelitis optica, myasthenia gravis, age related macular degeneration, dry eye, uveitis, Guillain-Barré syndrome, psoriasis, psoriatic arthritis (PsA), steroid resistant asthma, Graves' disease, scleritis, major depression, seasonal affective disorder, PTSD, bipolar disorder, autism, epilepsy, Alzheimer's, CNS disorders associated with altered sleep and/or circadian rhythms, endometriosis, obstructive sleep apnea syndrome (OSAS), Behçet's disease, dermatomyositis, polymyocitis, graft versus host disease, primary biliary cirrhosis, liver fibrosis, non-alcoholic fatty liver disease (NAFLD), sarcoidosis, primary sclerosing cholangitis, autoimmune thyroid disease, autoimmune polyendocrine syndrome type I, autoimmune polyendocrine syndrome type II, celiac disease, neuromyelitis, juvenile idiopathic arthritis, systemic sclerosis, myocardial infarction, pulmonary hypertension, osteoarthritis, cutaneous leishmaniasis, sinonasal polyposis, and cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the Formula VI:
or a pharmaceutically acceptable salt thereof, wherein
A is N or CH;
R 1 is (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, or cycloalkyl optionally substituted with 1 to 3 halo;
L 2 is CH 2 or CHMe;
Cy 2 is bi-cyclic heterocyclyl or bi-cyclic heteroaryl, each of which are optionally substituted with 1 to 3 groups independently selected from halo, (C 1 -C 4 )alkyl, and (C 1 -C 4 )alkoxy, wherein said (C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy are optionally substituted with 1 to 3 halo;
R 7 is hydrogen or —CH 2 OH; and
R 9 is —NH(C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl, or (C 1 -C 4 )alkyl substituted with OH.
56 . The method of claim 55 , wherein the compound is of the Formula VIII:
or a pharmaceutically acceptable salt thereof, wherein Z is a 5- or 6-membered heterocyclyl ring having one or more heteroatoms selected from oxygen or nitrogen; and wherein Z is optionally substituted with (C 1 -C 4 )alkyl or 1 to 3 halo.
57 . The method of claim 56 , wherein the compound is of the Formula XI:
or a pharmaceutically acceptable salt thereof, wherein R 10 and R 11 are each independently hydrogen or halo.
58 . The method of claim 57 , wherein R 1 is halo(C 1 -C 4 )alkyl, cyclopropyl, or cyclobutyl, wherein said cyclopropyl and cyclobutyl are each optionally substituted with 1 to 3 halo.
59 . The method of claim 57 , wherein L 2 is CH 2 .
60 . The method of claim 57 , wherein R 7 is —CH 2 OH; and A is N.
61 . The method of claim 57 , wherein R 10 and R 11 are each fluoro.
62 . A method of treating a disease or disorder selected from asthma, chronic obstructive pulmonary disease (COPD), bronchitis, allergic rhinitis, atopic dermatitis, contact dermatitis, acne, cystic fibrosis, allograft rejection, multiple sclerosis, scleroderma, arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), Hashimoto's disease, pancreatitis, autoimmune diabetes, type I diabetes, autoimmune ocular disease, ulcerative colitis, Crohn's disease, regional enteritis, inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), Sjögren's syndrome, optic neuritis, obesity, hepatosteatosis, adipose tissue-associated inflammation, insulin resistance, type II diabetes, neuromyelitis optica, myasthenia gravis, age related macular degeneration, dry eye, uveitis, Guillain-Barré syndrome, psoriasis, psoriatic arthritis (PsA), steroid resistant asthma, Graves' disease, scleritis, major depression, seasonal affective disorder, PTSD, bipolar disorder, autism, epilepsy, Alzheimer's, CNS disorders associated with altered sleep and/or circadian rhythms, endometriosis, obstructive sleep apnea syndrome (OSAS), Behçet's disease, dermatomyositis, polymyocitis, graft versus host disease, primary biliary cirrhosis, liver fibrosis, non-alcoholic fatty liver disease (NAFLD), sarcoidosis, primary sclerosing cholangitis, autoimmune thyroid disease, autoimmune polyendocrine syndrome type I, autoimmune polyendocrine syndrome type II, celiac disease, neuromyelitis, juvenile idiopathic arthritis, systemic sclerosis, myocardial infarction, pulmonary hypertension, osteoarthritis, cutaneous leishmaniasis, sinonasal polyposis, and cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt of any of the foregoing formulae.
63 . The method of claim 62 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
64 . The method of claim 62 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
65 . The method of claim 62 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
66 . The method of claim 62 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
67 . The method of claim 62 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
68 . The method of claim 62 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
69 . A method of treating a disease or disorder selected from asthma, chronic obstructive pulmonary disease (COPD), bronchitis, allergic rhinitis, atopic dermatitis, contact dermatitis, acne, cystic fibrosis, allograft rejection, multiple sclerosis, scleroderma, arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), Hashimoto's disease, pancreatitis, autoimmune diabetes, type I diabetes, autoimmune ocular disease, ulcerative colitis, Crohn's disease, regional enteritis, inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), Sjögren's syndrome, optic neuritis, obesity, hepatosteatosis, adipose tissue-associated inflammation, insulin resistance, type II diabetes, neuromyelitis optica, myasthenia gravis, age related macular degeneration, dry eye, uveitis, Guillain-Barré syndrome, psoriasis, psoriatic arthritis (PsA), steroid resistant asthma, Graves' disease, scleritis, major depression, seasonal affective disorder, PTSD, bipolar disorder, autism, epilepsy, Alzheimer's, CNS disorders associated with altered sleep and/or circadian rhythms, endometriosis, obstructive sleep apnea syndrome (OSAS), Behçet's disease, dermatomyositis, polymyocitis, graft versus host disease, primary biliary cirrhosis, liver fibrosis, non-alcoholic fatty liver disease (NAFLD), sarcoidosis, primary sclerosing cholangitis, autoimmune thyroid disease, autoimmune polyendocrine syndrome type I, autoimmune polyendocrine syndrome type II, celiac disease, neuromyelitis, juvenile idiopathic arthritis, systemic sclerosis, myocardial infarction, pulmonary hypertension, osteoarthritis, cutaneous leishmaniasis, sinonasal polyposis, and cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound selected from:
N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;
N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-((2-hydroxyethyl)sulfonyl)phenyl)acetamide;
N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-((2-methoxyethyl)sulfonyl)phenyl)acetamide;
N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(N-methylsulfamoyl)phenyl)acetamide;
2-(4-cyanophenyl)-N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)acetamide;
ethyl 2-(4-(2-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)amino)-2-oxoethyl)phenyl)acetate;
2-(4-(2-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)amino)-2-oxoethyl)phenyl)acetic acid;
N-(2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;
N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(1-(methylsulfonyl)piperidin-4-yl)acetamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1,1-difluoroethyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((R)-tetrahydrofuran-2-yl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(1-fluorocyclobutyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(methoxymethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-ethyl-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
2-(tert-butyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-isopropyl-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-methyl-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-isobutyl-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(methylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(N-methylsulfamoyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1,1-difluoroethyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-(4-(methylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-(4-((2-hydroxyethyl)sulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-(4-(N-methylsulfamoyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(1-fluorocyclobutyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(4-((2-hydroxyethyl)sulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-((2-hydroxyethyl)sulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(N-methylsulfamoyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-((2-hydroxyethyl)sulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(methylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(1-methoxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(1-methoxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(4-(methylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-sulfamoylbenzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(propylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
methyl 2-((4-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)phenyl)sulfonyl)acetate;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(2-methoxypropan-2-yl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-methoxy-1H-benzo[d]imidazole-5-carboxamide;
2-((1S,2R)-2-cyanocyclopropyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
2-((1R c ,2R)-2-cyanocyclopropyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
methyl (1R c ,2R)-2-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-5-((4-(ethylsulfonyl)benzyl)carbamoyl)-1H-benzo[d]imidazol-2-yl)cyclopropane-1-carboxylate;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-methoxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-methoxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-methoxyethyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-methoxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1,1-difluoroethyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-((5-(methylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(1-fluorocyclobutyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(methylsulfonyl)pyridin-2-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-(methylsulfonyl)piperidin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-(methylsulfonyl)piperidin-4-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-((1-(methylsulfonyl)piperidin-4-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;
methyl 2-((4-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)piperidin-1-yl)sulfonyl)acetate;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-((2-(methylamino)-2-oxoethyl)sulfonyl)piperidin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
methyl 2-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)-2-(1-(methylsulfonyl)piperidin-4-yl)acetate;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-(N-methylsulfamoyl)piperidin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
N-((1-((2-amino-2-oxoethyl)sulfonyl)piperidin-4-yl)methyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-((2-(methylamino)-2-oxoethyl)sulfonyl)piperidin-4-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,3-dihydrobenzofuran-7-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-(benzo[d][1,3]dioxol-4-ylmethyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
N-(4-(ethylsulfonyl)benzyl)-1-((2-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
N-(4-(ethylsulfonyl)benzyl)-1-((2-oxo-1,2-dihydroquinolin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-(benzofuran-4-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,3-dihydrobenzofuran-7-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((1H-indazol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-(benzo[d][1,3]dioxol-4-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((1H-pyrrolo[2,3-c]pyridin-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclopropyl-1-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclopropyl-1-((2,3-dihydrobenzofuran-7-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-2-cyclopropyl-1-(1-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)ethyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
2-(4-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)cyclohexyl)acetic acid;
N-((1H-benzo[d][1,2,3]triazol-6-yl)methyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)—N-(1-(4-cyanophenyl)-2-hydroxyethyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)-2-fluorophenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-(1-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)ethyl)-2-ethyl-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-(1-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)ethyl)-2-ethyl-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)-2-hydroxybenzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
methyl 2-((4-((1-((1H-indazol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)piperidin-1-yl)sulfonyl)acetate;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((4-oxo-1,4-dihydroquinolin-7-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(5-(methylsulfonyl)pyridin-2-yl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
N-(4-(ethylsulfonyl)benzyl)-1-((1-methyl-1H-indazol-7-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
N-(4-(ethylsulfonyl)benzyl)-1-((2-methyl-2H-indazol-7-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((1,2-dimethyl-1H-benzo[d]imidazol-7-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
N-(4-(ethylsulfonyl)benzyl)-1-((1-methyl-1H-indazol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((1H-indazol-7-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
N-(4-(ethylsulfonyl)benzyl)-1-((2-methyl-2H-indazol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-(benzo[d]oxazol-4-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
2-cyclopropyl-1-((2,3-dihydrobenzo[b][1,4]dioxin-5-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-2-cyclopropyl-1-(1-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)ethyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-(benzo[c][1,2,5]oxadiazol-4-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-(benzo[d]oxazol-7-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
2-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)-5-(ethylsulfonyl)pyridine 1-oxide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(dimethylamino)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-((2-hydroxyethyl)sulfonyl)piperidin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(1-(methylsulfonyl)piperidin-4-yl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(1-(methylsulfonyl)piperidin-4-yl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)-3-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)-3-(4-(ethylsulfonyl)phenyl)propanoic acid;
(R)-2-(2-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)-2-(4-(ethylsulfonyl)phenyl)ethoxy)acetic acid;
(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-3-(methylamino)-3-oxopropyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
(S)—N-(3-amino-1-(4-(ethylsulfonyl)phenyl)-3-oxopropyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-((2-(methylamino)-2-oxoethyl)sulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(ethylsulfonyl)phenyl)-2-hydroxyacetamide;
(R)—N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(ethylsulfonyl)phenyl)-2-hydroxyacetamide;
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((4-methyl-1-(methylsulfonyl)-1,4-diazepan-5-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
1-((2,3-dihydrobenzofuran-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;
methyl 1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-5-((4-(ethylsulfonyl)benzyl)carbamoyl)-1H-benzo[d]imidazole-2-carboxylate; and
1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-(4-(ethylsulfonyl)phenyl)-1,3-dihydroxypropan-2-yl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide, or a pharmaceutically acceptable salt of any of the foregoing.
70 . The method of claim 55 , wherein the disease or disorder is selected from asthma, atopic dermatitis, acne, Crohn's disease, regional enteritis, ulcerative colitis, Sjögren's syndrome, uveitis, Behçet's disease, dermatomyositis, multiple sclerosis, ankylosing spondylitis, systemic lupus erythematosus (SLE), scleroderma, psoriasis, psoriatic arthritis (PsA), steroid resistant asthma, and rheumatoid arthritis.
71 . The method of claim 62 , wherein the disease or disorder is selected from asthma, atopic dermatitis, acne, Crohn's disease, regional enteritis, ulcerative colitis, Sjögren's syndrome, uveitis, Behçet's disease, dermatomyositis, multiple sclerosis, ankylosing spondylitis, systemic lupus erythematosus (SLE), scleroderma, psoriasis, psoriatic arthritis (PsA), steroid resistant asthma, and rheumatoid arthritis.
72 . The method of claim 69 , wherein the disease or disorder is selected from asthma, atopic dermatitis, acne, Crohn's disease, regional enteritis, ulcerative colitis, Sjögren's syndrome, uveitis, Behçet's disease, dermatomyositis, multiple sclerosis, ankylosing spondylitis, systemic lupus erythematosus (SLE), scleroderma, psoriasis, psoriatic arthritis (PsA), steroid resistant asthma, and rheumatoid arthritis.
73 . The method of claim 70 , wherein the disease or disorder is selected from atopic dermatitis, acne, dermatomyositis, scleroderma, psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis.
74 . The method of claim 71 , wherein the disease or disorder is selected from atopic dermatitis, acne, dermatomyositis, scleroderma, psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis.
75 . The method of claim 72 , wherein the disease or disorder is selected from atopic dermatitis, acne, dermatomyositis, scleroderma, psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis.Cited by (0)
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