US 9,809,599 B2
Aryl-quinoline derivatives
Simona M. Ceccarelli, Basel (CH); Aurelia Conte, Shanghai (CN); Holger Kuehne, Loerrach (DE); Bernd Kuhn, Reinach (CH); Werner Neidhart, Hagenthal-le-Bas (FR); Ulrike Obst Sander, Reinach (CH); and Markus Rudolph, Basel (CH)
Assigned to Hoffmann-La Roche Inc., Nutley, NJ (US)
Filed by Hoffmann-La Roche Inc., Nutley, NJ (US)
Filed on Nov. 11, 2015, as Appl. No. 14/938,005.
Application 14/938,005 is a continuation of application No. 13/666,202, filed on Nov. 1, 2012, granted, now 9,199,938.
Claims priority of application No. 11187967 (EP), filed on Nov. 4, 2011.
Prior Publication US 2016/0060270 A1, Mar. 3, 2016
Int. Cl. C07D 215/00 (2006.01); C07D 215/02 (2006.01); C07D 215/54 (2006.01); C07D 401/04 (2006.01); C07D 413/04 (2006.01); C07D 491/048 (2006.01); C07D 401/14 (2006.01); C07D 215/227 (2006.01); C07D 413/14 (2006.01)
CPC C07D 491/048 (2013.01) [C07D 215/00 (2013.01); C07D 215/02 (2013.01); C07D 215/227 (2013.01); C07D 215/54 (2013.01); C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 413/04 (2013.01); C07D 413/14 (2013.01)] 26 Claims
 
1. A compound according to formula (I),

OG Complex Work Unit Drawing
wherein
R1 is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, haloalkoxy, cycloalkoxy, halocycloalkoxy, hydroxyalkyl, heterocycloalkyl, substituted heterocycloalkyl, substituted amino, aminocarbonyl or substituted aminocarbonyl, wherein substituted heterocycloalkyl is substituted with one to three substituents independently selected from the group consisting of oxo, halogen, alkyl, cycloalkyl and haloalkyl, and wherein substituted amino and substituted aminocarbonyl are substituted on the nitrogen atom with one to two substituents independently selected from the group consisting of alkyl, cycloalkyl, haloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcycloalkylalkyl, hydroxyalkyl and alkoxyalkyl, with the proviso that R1 is not methyl or ethyl;
R2 is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, nitro, cyano, amino, aminoalkyl, substituted amino and substituted aminoalkyl, wherein substituted amino and substituted aminoalkyl are substituted on the nitrogen atom with one to two substituents independently selected from the group consisting of alkyl, cycloalkyl, haloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcycloalkylalkyl, hydroxyalkyl and alkoxyalkyl;
R3 is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, nitro, cyano, amino, aminoalkyl, substituted amino and substituted aminoalkyl, wherein substituted amino and substituted aminoalkyl are substituted on the nitrogen atom with one to two substituents independently selected from the group consisting of alkyl, cycloalkyl, haloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcycloalkylalkyl, hydroxyalkyl and alkoxyalkyl;
R4 is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, nitro, cyano, amino, aminoalkyl, substituted amino and substituted aminoalkyl, wherein substituted amino and substituted aminoalkyl are substituted on the nitrogen atom with one to two substituents independently selected from the group consisting of alkyl, cycloalkyl, haloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcycloalkylalkyl, hydroxyalkyl and alkoxyalkyl;
R5 is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, nitro, cyano, amino, aminoalkyl, substituted amino and substituted aminoalkyl, wherein substituted amino and substituted aminoalkyl are substituted on the nitrogen atom with one to two substituents independently selected from the group consisting of alkyl, cycloalkyl, haloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcycloalkylalkyl, hydroxyalkyl and alkoxyalkyl;
R6 is selected from the group consisting of phenyl, substituted phenyl, pyridinyl and substituted pyridinyl, wherein substituted phenyl and substituted pyridinyl are substituted with one to three substituent independently selected from the group consisting of alkyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylalkoxyalkyl, cycloalkoxy, cycloalkoxyalkyl, alkylcycloalkylalkyl, halocycloalkyl, halocycloalkylalkyl, halogen, cyano, haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, haloalkoxy, hydroxyalkoxy, alkoxyalkoxy, alkoxyalkoxyalkyl, hydroxyhaloalkyl, amino and substituted amino, wherein substituted amino is substituted with one to two substituents independently selected from the group consisting of alkyl, cycloalkyl, haloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylcycloalkylalkyl, hydroxyalkyl and alkoxyalkyl;
R7 is selected from the group consisting of —COOH, 3H-[1,3,4]oxadiazol-2-on-5-yl, 3H-[1,3,4]oxadiazole-2-thion-5-yl, 4H-[1,2,4]oxadiazol-5-on-3-yl, 4H-[1,2,4]oxadiazole-5-thion-3-yl, 3H-[1,2,3,5]oxathiadiazole-2-oxide-4-yl, 4H-[1,2,4]thiadiazol-5-on-3-yl, isoxazol-3-ol-5-yl, 5-alkylisoxazol-3-ol-4-yl, 5-cycloalkylisoxazol-3-ol-4-yl, furazan-3-ol-4-yl, 5-alkylsulfonylamino-[1,3,4]oxadiazol-2-yl, 5-cycloalkylsulfonylamino-[1,3,4]oxadiazol-2-yl, 5-alkylsulfonylamino-2H-[1,2,4]triazol-3-yl, 5-cycloalkylsulfonylamino-2H-[1,2,4]triazol-3-yl, 5-alkylisothiazol-3-ol-4-yl, 5-cycloalkylisothiazol-3-ol-4-yl, [1,2,5]thiadiazol-3-ol-4-yl, 1,4-dihydro-tetrazol-5-on-1-yl, 2H-tetrazol-5-ylcarbamoyl, 2H-tetrazole-5-carbonyl, [1,2,4]oxadiazolidine-3,5-dion-2-y, 4H-[1,2,4]oxadiazol-5-on-3-yl, 2,4-dihydro-[1,2,4]triazol-3-on-5-sulfanyl, 4H-[1,2,4]triazole-3-sulfanyl, 4H-[1,2,4]triazole-3-sulfinyl, 4H-[1,2,4]triazole-3-sulfonyl, 4-alkyl-pyrazol-1-ol-5-yl, 4-cycloalkyl-pyrazol-1-ol-5-yl, 4-alkyl-[1,2,3]triazol-1-ol-5-yl, 4-cycloalkyl-[1,2,3]triazol-1-ol-5-yl, 5-alkyl-imidazol-1-ol-2-yl, 5-cycloalkyl-imidazol-1-ol-2-yl, 4-alkyl-imidazol-1-ol-5-yl, 4-cycloalkyl-imidazol-1-ol-5-yl, 4-alkyl-1,1-dioxo-1%-[1,2,5]thiadiazolidin-3-on-5-yl, 4,4-dialkyl-1,1-dioxo-1λ6-[1,2,5]thiadiazolidin-3-on-5-yl, 4-cycloalkyl-1,1-dioxo-1λ6-[1,2,5]thiadiazolidin-3-on-5-yl, 4,4-dicycloalkyl-1,1-dioxo-1λ61,2,5]thiadiazolidin-3-on-5-yl, thiazolidine-2,4-dion-5-yl, oxazolidine-2,4-dion-5-yl, 3-[1-Hydroxy-meth-(E)-ylidene]-pyrrolidine-2,4-dion-1-yl, 3-[1-Hydroxy-meth-(Z)-ylidene]-pyrrolidine-2,4-dion-1-yl, 5-methyl-4-hydroxy-5H-furan-2-on-3-yl, 5,5-dialkyl-4-hydroxy-5H-furan-2-on-3-yl, 5-cycloalkyl-4-hydroxy-5H-furan-2-on-3-yl, 5,5-dicycloalkyl-4-hydroxy-5H-furan-2-on-3-yl, 3-hydroxy-cyclobut-3-ene-1,2-dion-4-yl and 3-hydroxy-cyclobut-3-ene-1,2-dion-4-amino; and
n is zero or 1;
with the proviso that at least one of R2, R3, R4 and R5 is different from hydrogen and that said compound is not 6-methoxy-4-phenyl-2-trifluoromethyl-quinoline-3-carboxylic acid or 4-(3,4-dimethoxy-phenyl)-2-hydroxymethyl-6,7-dimethoxy-quinoline-3-carboxylic acid; or a pharmaceutically acceptable salt thereof.