Ror gamma (rory) modulators
Abstract
Treatment methods including administering a compound according to Formula (I) Meta or para or a pharmaceutically acceptable salt thereof wherein: A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 are simultaneously N; A 6 , A 7 , A 8 , A 9 , A 10 are N or CR 6 , CR 7 , CR 8 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the five positions A in A 6 , A 7 , A 8 , A 9 , A 10 is N; R 1 is C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(2-5) heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl; —SO 2 R 1 is represented by one of R 7 , R 8 or R 9 ; R 15 is H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl; R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl.
Claims
exact text as granted — not AI-modified1 . A method of therapeutically treating at least one condition selected from the group consisting of ROR-γ mediated autoimmune diseases, ROR-γ mediated inflammatory diseases and ROR-γ mediated infectious diseases, the method comprising administering an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof to a person in need of a therapeutic treatment, wherein Formula I is:
wherein
A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 can be simultaneously N;
A 6 , A 7 , A 8 , A 9 , A 10 are N or CR 6 , CR 7 , CR 8 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the five positions A in A 6 , A 7 , A 8 , A 9 , A 10 is N;
R 1 is C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino, with all carbon atoms of alkyl groups optionally substituted with one or more F and all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl;
R 2 and R 3 are independently H, F, methyl, ethyl, hydroxy, methoxy or R 2 and R 3 together is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F;
R 4 is H or C(1-6)alkyl;
R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano;
the sulfonyl group with R 1 is represented by one of R 7 , R 8 or R 9 ;
the remaining R 6 -R 14 are independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl, all of the alkyl groups optionally being substituted with one or more F; and
R 15 is H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; and,
R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkyl, C(1-2)alkoxy or cyano.
2 . The method according to claim 1 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 can be simultaneously N; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl or (di)C(3-6)cycloalkylamino with all carbon atoms of alkyl groups optionally substituted with one or more F and all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H, halogen, C(1-3)alkoxy or C(1-6)alkyl, all of the alkyl groups optionally being substituted with one or more F or hydroxy; and R 15 is C(1-6)alkyl or C(3-6)cycloalkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; and, R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkyl, C(1-2)alkoxy or cyano.
3 . The method according to claim 1 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 -A 14 are respectively CR 11 , CR 12 , CR 13 , CR 14 ; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl, all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl or C(2-5)heterocycloalkylC(1-3)alkyl; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H, halogen, C(1-3)alkoxy or C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one hydroxy; R 15 is C(1-6)alkyl or C(3-6)cycloalkyl, all carbon atoms of the alkyl groups optionally substituted with one or more F; and, R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl or C(6-10)aryl, all carbon atoms of the alkyl groups optionally substituted with one or more F.
4 . The method according to claim 1 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 or A 14 is N, the remaining position A being CR 11 or CR 14 ; A 12 and A 13 are respectively CR 12 and CR 13 ; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H; R 15 is C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one or more F; and, R 16 is C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one or more F.
5 . The method according to claim 1 , wherein the administered compound is selected from the group consisting of:
2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; N-[3-chloro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-methoxy-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-methoxy-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-2-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-1-(trifluoromethyl)butyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-3-methyl-1-(trifluoromethyl)butyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-4-methyl-1-(trifluoromethyl)pentyl]phenyl]acetamide; N-[4-(1-cyclopentyl-2,2,2-trifluoro-1-hydroxy-ethyl)phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; N-[4-[1-(cyclopentylmethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; N-[4-[1-(cyclohexylmethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[5-(2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl)-2-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[dicyclopropyl(hydroxy)methyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-1-(trifluoromethyl)propyl]phenyl]acetamide (racemate); (−)-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (levogyre enantiomer); (+)-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (dextrogyre enantiomer); 2-[6-[(2-methylcyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (racemate); (+)-2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (dextrogyre enantiomer); (−)-2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (levogyre enantiomer); 2-[6-(cyclopropylmethylsulfonyl)-4-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-2-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-5-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(oxetan-3-ylmethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(2-methoxyethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(2-hydroxyethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-isopropoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[3-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[3-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[dicyclopropyl(hydroxy)methyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)pyrimidin-2-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)pyrazin-2-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)pyridazin-3-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; and, 2-[2-(cyclopropylmethylsulfonyl)pyrimidin-5-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide.
6 . The method according to claim 1 , wherein the at least one condition is selected from the group consisting of rheumatoid arthritis, psoriasis, inflammatory bowel disease, Crohn's disease and multiple sclerosis.
7 . The method according to claim 1 , wherein the at least one condition is selected from osteoarthritis and asthma.
8 . The method according to claim 1 , wherein the at least one condition is mucosal leishmaniasis.
9 . A method of prophylactically treating at least one condition selected from the group consisting of ROR-γ mediated autoimmune diseases, ROR-γ mediated inflammatory diseases and ROR-γ mediated infectious diseases, the method comprising administering an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof to a patient, wherein Formula I is.
wherein
A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 can be simultaneously N;
A 6 , A 7 , A 8 , A 9 , A 10 are N or CR 6 , CR 7 , CR 8 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the five positions A in A 6 , A 7 , A 8 , A 9 , A 10 is N;
R 1 is C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino, with all carbon atoms of alkyl groups optionally substituted with one or more F and all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl;
R 2 and R 3 are independently H, F, methyl, ethyl, hydroxy, methoxy or R 2 and R 3 together is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F;
R 4 is H or C(1-6)alkyl;
R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano;
the sulfonyl group with R 1 is represented by one of R 7 , R 8 or R 9 ;
the remaining R 6 -R 14 are independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl, all of the alkyl groups optionally being substituted with one or more F; and
R 15 is H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; and,
R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkyl, C(1-2)alkoxy or cyano.
10 . The method according to claim 9 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 can be simultaneously N; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl or (di)C(3-6)cycloalkylamino with all carbon atoms of alkyl groups optionally substituted with one or more F and all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H, halogen, C(1-3)alkoxy or C(1-6)alkyl, all of the alkyl groups optionally being substituted with one or more F or hydroxy; and R 15 is C(1-6)alkyl or C(3-6)cycloalkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; and, R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkyl, C(1-2)alkoxy or cyano.
11 . The method according to claim 9 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 -A 14 are respectively CR 11 , CR 12 , CR 13 , CR 14 ; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl, all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl or C(2-5)heterocycloalkylC(1-3)alkyl; the sulfonyl group with R 1 is represented by Re; the remaining R 6 -R 14 are independently H, halogen, C(1-3)alkoxy or C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one hydroxy; R 15 is C(1-6)alkyl or C(3-6)cycloalkyl, all carbon atoms of the alkyl groups optionally substituted with one or more F; and, R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl or C(6-10)aryl, all carbon atoms of the alkyl groups optionally substituted with one or more F.
12 . The method according to claim 9 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 or A 14 is N, the remaining position A being CR 11 or CR 14 ; A 12 and A 13 are respectively CR 12 and CR 13 ; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H; R 15 is C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one or more F; and, R 16 is C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one or more F.
13 . The method according to claim 9 , wherein the administered compound is selected from the group consisting of:
2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; N-[3-chloro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-methoxy-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-methoxy-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-2-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-1-(trifluoromethyl)butyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-3-methyl-1-(trifluoromethyl)butyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-4-methyl-1-(trifluoromethyl)pentyl]phenyl]acetamide; N-[4-(1-cyclopentyl-2,2,2-trifluoro-1-hydroxy-ethyl)phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; N-[4-[1-(cyclopentylmethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; N-[4-[1-(cyclohexylmethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[5-(2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl)-2-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[dicyclopropyl(hydroxy)methyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-1-(trifluoromethyl)propyl]phenyl]acetamide (racemate); (−)-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (levogyre enantiomer); (+)-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (dextrogyre enantiomer); 2-[6-[(2-methylcyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (racemate); (+)-2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (dextrogyre enantiomer); (−)-2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (levogyre enantiomer); 2-[6-(cyclopropylmethylsulfonyl)-4-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-2-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-5-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(oxetan-3-ylmethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(2-methoxyethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(2-hydroxyethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-isopropoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[3-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[3-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[dicyclopropyl(hydroxy)methyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)pyrimidin-2-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)pyrazin-2-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)pyridazin-3-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; and, 2-[2-(cyclopropylmethylsulfonyl)pyrimidin-5-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide.
14 . The method according to claim 9 , wherein the at least one condition is selected from the group consisting of rheumatoid arthritis, psoriasis, inflammatory bowel disease, Crohn's disease and multiple sclerosis.
15 . The method according to claim 9 , wherein the at least one condition is selected from osteoarthritis and asthma.
16 . The method according to claim 9 , wherein the at least one condition is mucosal leishmaniasis.
17 . A method of therapeutically treating at least one condition selected from the group consisting of Kawaski disease and Hashimoto's thyroiditis, the method comprising administering an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof to a person in need of a therapeutic treatment, wherein Formula I is:
wherein
A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 can be simultaneously N;
A 6 , A 7 , A 8 , A 9 , A 10 are N or CR 6 , CR 7 , CR 8 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the five positions A in A 6 , A 7 , A 8 , A 9 , A 10 is N;
R 1 is C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino, with all carbon atoms of alkyl groups optionally substituted with one or more F and all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl;
R 2 and R 3 are independently H, F, methyl, ethyl, hydroxy, methoxy or R 2 and R 3 together is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F;
R 4 is H or C(1-6)alkyl;
R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano;
the sulfonyl group with R 1 is represented by one of R 7 , R 8 or R 9 ;
the remaining R 6 -R 14 are independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl, all of the alkyl groups optionally being substituted with one or more F; and
R 15 is H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; and,
R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkyl, C(1-2)alkoxy or cyano.
18 . The method according to claim 17 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 can be simultaneously N; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl or (di)C(3-6)cycloalkylamino with all carbon atoms of alkyl groups optionally substituted with one or more F and all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H, halogen, C(1-3)alkoxy or C(1-6)alkyl, all of the alkyl groups optionally being substituted with one or more F or hydroxy; and R 15 is C(1-6)alkyl or C(3-6)cycloalkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; and, R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkyl, C(1-2)alkoxy or cyano.
19 . The method according to claim 17 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 -A 14 are respectively CR 11 , CR 12 , CR 13 , CR 14 ; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl, all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl or C(2-5)heterocycloalkylC(1-3)alkyl; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H, halogen, C(1-3)alkoxy or C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one hydroxy; R 15 is C(1-6)alkyl or C(3-6)cycloalkyl, all carbon atoms of the alkyl groups optionally substituted with one or more F; and, R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl or C(6-10)aryl, all carbon atoms of the alkyl groups optionally substituted with one or more F.
20 . The method according to claim 17 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 or A 14 is N, the remaining position A being CR 11 or CR 14 ; A 12 and A 13 are respectively CR 12 and CR 13 ; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H; R 15 is C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one or more F; and, R 16 is C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one or more F.
21 . The method according to claim 17 , wherein the administered compound is selected to from the group consisting of:
2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; N-[3-chloro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-methoxy-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-methoxy-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-2-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-1-(trifluoromethyl)butyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-3-methyl-1-(trifluoromethyl)butyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-4-methyl-1-(trifluoromethyl)pentyl]phenyl]acetamide; N-[4-(1-cyclopentyl-2,2,2-trifluoro-1-hydroxy-ethyl)phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; N-[4-[1-(cyclopentylmethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; N-[4-[1-(cyclohexylmethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[5-(2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl)-2-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[dicyclopropyl(hydroxy)methyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-1-(trifluoromethyl)propyl]phenyl]acetamide (racemate); (−)-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (levogyre enantiomer); (+)-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (dextrogyre enantiomer); 2-[6-[(2-methylcyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (racemate); (+)-2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (dextrogyre enantiomer); (−)-2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (levogyre enantiomer); 2-[6-(cyclopropylmethylsulfonyl)-4-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-2-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-5-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(oxetan-3-ylmethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(2-methoxyethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(2-hydroxyethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-isopropoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[3-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[3-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[dicyclopropyl(hydroxy)methyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)pyrimidin-2-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)pyrazin-2-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)pyridazin-3-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; and, 2-[2-(cyclopropylmethylsulfonyl)pyrimidin-5-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide.
22 . A method of prophylactically treating at least one condition selected from the group consisting of Kawaski disease and Hashimoto's thyroiditis, the method comprising administering an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof to a patient, wherein Formula I is:
wherein
A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 can be simultaneously N;
A 6 , A 7 , A 8 , A 9 , A 10 are N or CR 6 , CR 7 , CR 8 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the five positions A in A 6 , A 7 , A 8 , A 9 , A 10 is N;
R 1 is C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino, with all carbon atoms of alkyl groups optionally substituted with one or more F and all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl;
R 2 and R 3 are independently H, F, methyl, ethyl, hydroxy, methoxy or R 2 and R 3 together is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F;
R 4 is H or C(1-6)alkyl;
R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano;
the sulfonyl group with R 1 is represented by one of R 7 , R 8 or R 9 ;
the remaining R 6 -R 14 are independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl, all of the alkyl groups optionally being substituted with one or more F; and
R 15 is H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; and,
R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkyl, C(1-2)alkoxy or cyano.
23 . The method according to claim 22 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 -A 14 are N or CR 11 , CR 12 , CR 13 , CR 14 , respectively, with the proviso that no more than two of the four positions A in A 11 -A 14 can be simultaneously N; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl or (di)C(3-6)cycloalkylamino with all carbon atoms of alkyl groups optionally substituted with one or more F and all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H, halogen, C(1-3)alkoxy or C(1-6)alkyl, all of the alkyl groups optionally being substituted with one or more F or hydroxy; and R 15 is C(1-6)alkyl or C(3-6)cycloalkyl, all groups optionally substituted with one or more F, C(1-2)alkoxy or cyano; and, R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl, all groups optionally substituted with one or more F, C(1-2)alkyl, C(1-2)alkoxy or cyano.
24 . The method according to claim 22 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 -A 14 are respectively CR 11 , CR 12 , CR 13 , CR 14 ; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl, all carbon atoms of cycloalkyl groups optionally substituted with one or more F or methyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl or C(2-5)heterocycloalkylC(1-3)alkyl; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H, halogen, C(1-3)alkoxy or C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one hydroxy; R 15 is C(1-6)alkyl or C(3-6)cycloalkyl, all carbon atoms of the alkyl groups optionally substituted with one or more F; and, R 16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl or C(6-10)aryl, all carbon atoms of the alkyl groups optionally substituted with one or more F.
25 . The method according to claim 22 , wherein in the administered compound according to Formula I or the pharmaceutically acceptable salt thereof:
A 11 or A 14 is N, the remaining position A being CR 11 or CR 14 ; A 12 and A 13 are respectively CR 12 and CR 13 ; A 6 , A 7 , A 9 , A 10 are N or CR 6 , CR 7 , CR 9 , CR 10 , respectively, with the proviso that at least one but no more than two of the four positions A in A 6 , A 7 , A 9 , A 10 is N; A 8 is CR 8 ; R 1 is C(3-6)cycloalkylC(1-3)alkyl; R 2 and R 3 are independently H; R 4 is H; R 5 is H; the sulfonyl group with R 1 is represented by R 8 ; the remaining R 6 -R 14 are independently H; R 15 is C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one or more F; and, R 16 is C(1-6)alkyl, all carbon atoms of alkyl groups optionally substituted with one or more F.
26 . The method according to claim 22 , wherein the administered compound is selected from the group consisting of:
2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; N-[3-chloro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[3-methoxy-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[2-methoxy-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-2-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-1-(trifluoromethyl)butyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-3-methyl-1-(trifluoromethyl)butyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-4-methyl-1-(trifluoromethyl)pentyl]phenyl]acetamide; N-[4-(1-cyclopentyl-2,2,2-trifluoro-1-hydroxy-ethyl)phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; N-[4-[1-(cyclopentylmethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; N-[4-[1-(cyclohexylmethyl)-2,2,2-trifluoro-1-hydroxy-ethyl]phenyl]-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[5-(2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl)-2-pyridyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[dicyclopropyl(hydroxy)methyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[1-hydroxy-1-(trifluoromethyl)propyl]phenyl]acetamide (racemate); (−)-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (levogyre enantiomer); (+)-2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (dextrogyre enantiomer); 2-[6-[(2-methylcyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (racemate); (+)-2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (dextrogyre enantiomer); (−)-2-[6-[(2,2-difluorocyclopropyl)methylsulfonyl]-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide (levogyre enantiomer); 2-[6-(cyclopropylmethylsulfonyl)-4-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-2-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropyl methylsulfonyl)-5-methyl-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(oxetan-3-ylmethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(2-methoxyethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropyl methylsulfonyl)-3-pyridyl]-N-[4-[2,2,2-trifluoro-1-(2-hydroxyethoxy)-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-isopropoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[3-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[3-fluoro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[dicyclopropyl(hydroxy)methyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)-2-pyridyl]-N-[4-[2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)pyrimidin-2-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[5-(cyclopropylmethylsulfonyl)pyrazin-2-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; 2-[6-(cyclopropylmethylsulfonyl)pyridazin-3-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide; and, 2-[2-(cyclopropylmethylsulfonyl)pyrimidin-5-yl]-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]acetamide.Join the waitlist — get patent alerts
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