4,5-DIHYDRO-ISOXAZOLE DERIVATIVES AND THEIR PHARMACEUTICAL USE

摘要

The present invention is concerned with the compounds of formula (I), wherein m, n and p are each independently 0 or 1 and q is 0, 1, 2, 3, 4 or 5; -A<1>=A<2>-A<3>=A<4>- is pyridinylidene, pyridazinylidene, pyrimidinylidene, pyrazinylidene or phenylidene; B represents an amide, ketone or oxadiazole; D represents Ar or Het; Q represents a covalent direct bond or a ketone, -N-, -O-, -CR<5>R<6>-, amide, ethenyl, imine, sulfonyl, sulfinyl, 3-oxobutenyl, pyrazole isoxazole or thiazole; L represents Ar or Het; R<1> represents hydrogen, halo, hydroxy C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, cyano, guanidine, nitro NR<17>R<18>, an optionally substituted C(1-6)alkyl or C(1-6)alkyloxy; R<2> and R<3> each independently represent hydrogen, halo, C(1-6)alkyloxy or an optionally substituted C(1-6)alkyl; R<5> and R<6> each independently represent hydrogen, hydroxy, halo, an optionally substituted C(1-6)alkyl, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloaklyl, C(3-6)cycloalkenyl, C(1-6)alkyloxy, cyano, (C=O)R<25>, (C=O)OR<16>, (SO2)R<16>, aminocarbonyloxy, amino C(1-6)alkyl, NR<17>R<18>, N3, Ar or Het; or R<5> and R<6> together with the carbon atom to which they are attached, form an Ar or Het; Ar represents an optionally substituted C(6-14)aryl; Het represents an optionally substituted C(1-14)heterocycle; or a N-oxide, pharmaceutically acceptable addition salt, quaternary amine or stereochemically isomeric form thereof; the process for their preparation and compositions comprising them. It further relates to their use as a medicine.