Use of quinoline derivatives as antagonists of alpha - 2; compounds quinoline derivatives and compositions

摘要

The use of compounds quinoline Derivatives of formula (1) wherein: R1 is H, or C1 - 6 each alkyl; R2 is independently Oh, halogen, alkyl of C1 - C2 - alquenilo 6, 6, 6 - alkoxy haloalquilo C1, C1 - 6, NO2, NH2, mono - or di - alquilamino C1 C1 - alkyl - 6, 6 - S - or hidroxialquilo C1 - 6 is a Ring; Benzene or cycloalkyl C5 - 7; when a is a benzene Ring each R3 is independently oHalogen, alkyl of C1 - C2 - alquenilo 6, 6, 6 - alkoxy haloalquilo C1, C1 - 6, NO2, NH2, mono - or di - alquilamino C1 C1 - alkyl - 6, 6 - CO -, mono -, di - or alquilcarbamoilo C1 C1 - alkyl - 6, 6 - S -, hidroxialquilo C1 - 6 or - NH2 co; when is cycloalkyl C5 7, each independently R3 is Oh, halogen, alkyl of C1 - 6 6 - alkoxy C1, mono - or di - alquilamino C1 - 6 or hidroxialquilo C1 - 6; R4 and R5 are,Along with the nitrogen Atom in where they are United, a rest of formula (2), in which X is o or NR6 R6 =; h, Oh, NH2, alkyl - 6 alquenilo C1, C2, CN - 6 - alkoxy alkyl C1, C1 - 6 - CO alkyl C1 - 6 C1 alkyl -, CO -, NH2 -, co -, mono -, di - or alquilcarbamoilo C1 - 6 - 6 hidroxialquilo cycloalkyl, C1, C3 - 6 benzyl, phenyl, naphthyl, where the phenylNaphthyl benzyl or is optionally substituted with 1 to 3 substituents each selected irrespective of o, NO2, NH2, halogen, alkoxy alkyl C1 C1 - 6, 6 - or mono -, di - alquilamino haloalquilo C1 and C1 - 6 - 6; R4 and R5 or Form, along with the nitrogen Atom in where you are UnitedA rest of formula (3), where n is 1 or 2; R6 are as defined above; and R is 0 to 3; R4 and R5 or Form, along with the nitrogen Atom in where are United, imidazolilo - 1, 1 - or 1 - imidazolinilo triazolilo, each of which can be replaced optionally substituted with 1 to 3 R7, authorities,Each selected regardless of C1 - and NH2 6 alkyl; R4 and R5 is one of so2r8 - and the other is H or alkyl R4 and R5 C1 - 6; R8 is selected independently from alkyl of C1 - 6, phenyl, naphthyl benzyl, where the phenyl, naphthyl benzyl or is optionally substituted with 1 to 3 substituents R9, each independently selected from Halogen, NO2, Oh, NH2,Alkyl alkoxy C1 C1 - 6, 6 - or mono -, di - alquilamino C1 - 6; ra and RB are independently h, Oh, halogen, alkyl of C1 - C2 - alquenilo 6, 6, 6 - alkoxy alquinilo C2, C1 - 6, 6 haloalquilo C1 -, NO2, NH2, mono - or Di - alquilamino C1 C1 - alkyl - 6, 6 - s or - ns; or ra and RB form, along with the Atoms of the Ring ca Where are rbono UnitedA benzene Ring condensate optionally substituted with 1 to 3 '3 substituents R each independently selected from o, halogen, alkyl - 6 alquenilo C1, C2 C1 - alkoxy - 6, 6, 6 haloalquilo C1 -, NO2, NH2, mono - or di - alqulamino C1 C1 - 6 - 6, alkyl - CO -, Mono -, di - or alquilcarbamoilo C1 - 6, 6 - S and C1 - alkyl -, hidroxialquilo C1 - 6 or - NH2 or co; ra and RB form,Along with the Ring carbon Atoms are linked in a Ring where carboxylic acid, 5 to 7 members, condensate optionally substituted with 1 to 4 substituents R10 each independently selected from alkyl Oh, halogen, alkoxy C1 C1 - 6, 6 - or mono -, di - alquilamino C1 - 6, and Hidroxialquilo C1 - 6; or ra and RB form, along with the Atoms of the carbon Ring where they are UnitedA Ring of Bicyclo [2.2.1] - heptane condensate optionally substituted with 1 to 4 substituents each independently selected from alkyl Oh, halogen, alkoxy C1 and C1 - 6 - 6; or ra and RB form, along with the carbon Atoms of the Ring where they are United, a Heterocyclic Ring of 5 to 6 members, C Ondensado Atom with a Ring = nr11,Heterocyclic Ring that is optionally substituted with 1 to 3 substituents as defined above R10, R11 is C1 - 6 h or alkyl or phenyl, R11 is optionally substituted with 1 to 3 substituents R12 each independently selected from o, NO2, NH2, halogen, alkyl C1 - 66 - alkoxy C1 and mono - or di - alquilamino C1 - 6; M is 0 to 3; and t is 0 to 3; or pharmaceutically acceptable Salts and Esters thereof, in the manufacture of a Medicament for the treatment of diseases or conditions in which indicates that the alpha-2 antagonists are effective. Preferably in the treatment of disorders of the central nervous system.Compounds quinoline derivatives and Pharmaceutical compositions containing same.