The invention concerns substituted amino isoxazoline derivatives, more in particular
tricyclic dihydrobenzopyranoisoxazoline, dihydroquinolinoisozazoline, dihydronaphthalenoisoxazoline and dihydrobenzothiopyranoisoxazoline derivatives substituted on the phenylpart of the
tricyclic moiety with primary, secondary and / or
tertiary amino groups, according to Formula (I)wherein X=CH2, N—R7, S or O, R1, R2 and R3 are certain specific substituents, with the proviso that at least one of R1 and R2 is an
amino radical of formula N—R10R11 wherein R10 and R11 are each a variety of radicals, Pir is an optionally substituted piperidyl or piperazyl radical and R3 represents an optionally substituted aromatic homocyclic or heterocyclic ring
system including a partially or completely hydrogenated
hydrocarbon chain of maximum 6 atoms long with which the ring
system is attached to the Pir radical and which may contain one or more heteroatoms selected from the group of O, N and S; a process for their preparation, pharmaceutical compositions comprising them and their use as a
medicine, in particular for the treatment of depression and / of
anxiety and disorders of
body weight. The compounds according to the invention have surprisingly been shown to have a
serotonin (5-HT)
reuptake inhibitor activity in combination with additional α2-adrenoceptor
antagonist activity and show a strong anti-
depressant activity without being
sedative. Compounds according to the invention are also suitable for treating depression,
anxiety and
body weight disorders. The invention also relates to novel combination of substituted amino isoxazoline derivatives according to the invention with antidepressants, anxiolytics and / or antipsychotics to improve
efficacy and / or
onset of action.