| abstract |
The invention concerns substituted isoxazolines derivatives according to formula wherein X = CH2, N-R7, S or O, R1, R2 and R3 have substituents defined in the description. 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/or anxiety and disorder of the 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 alpha2-adrenoceptor antagonist activity and show a strong anti-depressant activity without being sedative. The invention also relates to novel combination of substituted isoxazolines derivatives having anti-depressant activity and/or anxiolytic activity and/or body weight control activity with antidepressants, anxiolytic activity and/or body weight control activity with antidepressants, anxiolytics and/or antipsychotics to improve efficacy and/or onset of action. 18 claims |