New substituted styrol stereoisomers are glucocorticoid receptor ligands useful for the treatment of e.g. inflammatory diseases, lung diseases, rheumatic diseases, autoimmune diseases, joint disorders and gastrointestinal disorders

摘要

Substituted styrol stereoisomers of formula (I) are new. Substituted styrol stereoisomers of formula (I) are new. Either R1, R2(1-10C)-alkyl, (1-10C)-alkoxy, (1-10C)-alkylthio, (1-5C)-perfluoroalkyl, (all optionally substituted), H, OH, halo, CN or NO2; or R1R2-O-(CH2)n-O-, -O-(CH2)n-CH2-, -O-CH=CH-, -(CH2)n+2-, -NH-(CH2)n+1, N(1-3C-alkyl)-(CH2)n+1, -NH-N=CH- (where terminal atoms are directly connected with adjacent ring carbon atoms) or NR9R10; or R1R85-8 membered carbocycle- or heterocycle, optionally substituted by 1-2 of keto groups, (1-5C)-alkyl, (1-5C)-alkoxy or 1-4 of halo atoms; R9, R10H, (1-5C)-alkyl or (CO)-(1-5C)-alkyl; R4(1-10C)-alkyl (optionally substituted with OH, halo or (1-5C)-alkoxy), (3-7C)-cycloalkyl, heterocyclyl, aryl or mono- or bicyclic heteroaryl, optionally substituted with (1-5C)-alkyl (optionally substituted with 1-3 of OH or COOR11), (1-5C)-alkoxy, OH, halo or 1-2 of (1-3C)-exoalkylidene, containing 1-4 of N, 1-2 of O or S and/or 1-2 of keto groups, where these groups are connected over any position of the amine of the styrol systems, and optionally hydrated at one or more places; R11(1-5C)-alkyl or benzyl; R5(1-5C)-alkyl (partially or completely fluorinated), (3-7C)-cycloalkyl, (3-7C)-cycloalkyl-(1-8C)-alkyl, (3-7C)-cycloalkyl-(2-8C)-alkenyl, heterocyclyl, heterocyclyl-(1-8C)-alkyl, heterocyclyl-(2-8C)-alkenyl, aryl, aryl-(1-8C)-alkyl, aryl-(2-8C)-alkenyl, aryl-(2-8C)-alkynyl, mono- or bicyclic heteroaryl, optionally substituted with one or more keto groups, (1-5C)-alkyl, (1-5C)-alkoxy, halo or (1-3C)-exoalkylidene, containing 1-4 of N, 1-2 of O or S, where heteroaryl-(1-8C)-alkyl or heteroaryl-(2-8C)-alkenyl are connected over an any position of styrol system and optionally hydrated at one or more places; either R6H, halo or (1-10C)-alkyl, optionally substituted by OR10, SR10, N(R10R9) or 1-3 of halo; or R7H, halo, (1-10C)-alkyl (optionally substituted by OR10, SR10 or N(R10R9) or CN; or R7+C-atom of methyl : (3-6C)-cycloalkyl or (1-5C)-alkylidene; or R6R75-8 membered carbocycle- or heterocycle, optionally substituted with 1-2 of keto groups, (1-5C)-alkyl, (1-5C)-alkoxy or 1-4 of halo); and n : 1 or 2. [Image] ACTIVITY : Antiinflammatory; Respiratory-Gen.; Antiallergic; Antirheumatic; Immunosuppressive; Osteopathic; Antiarthritic; Antipyretic; Dermatological; Muscular-Gen.; Antipsoriatic; Nephrotropic; Hepatotropic; Gastrointestinal-Gen.; Ophthalmological; Neuroprotective; Antibacterial; Gynecological. MECHANISM OF ACTION : Glucocorticoid receptor ligand.