ANDRES-GIL, JOSE IGNACIO,ALCAZAR-VACA, MANUEL JESUS,MATESANZ-BALLESTEROS, MARIA ENCARNACION,BAKKER, MARGARETHA HENRICA MARIA,MEGENS, ANTONIUS ADRIANUS HENDRIKUS PETRUS
申请号：
CA2495058
公开号：
CA2495058C
申请日:
2003.08.19
申请国别(地区):
CA
年份:
2012
代理人:
摘要：
The invention concerns substituted tricyclic isoxazoline derivatives, more inparticular tricyclicdihydrobenzopyranoisoxazoline, dihydroquinolinoisoxazoline,dihydronaphthalenoisoxazolineand dihydrobenzothiopyranoisoxazoline derivatives substituted on at least oneof the C6- andC9-positions of the phenylpart of the tricyclic moiety with a selectedradical, according toFormula (I) wherein X = CH2, N-R7, S or O, R1, R2, R14 and R15 are certainspecific substituents,with the proviso that at least one of R14 and R15 is not hydrogen, Pir ispreferably anoptionally substituted piperidinyl or piperazinyl radical and R3 represents anoptionallysubstituted aromatic homocyclic or heterocyclic ring system including apartially or completelyhydrogenated hydrocarbon chain of maximum 6 atoms long with which the ringsystem isattached to the Pir radical and which may contain one or more heteroatomsselected from thegroup of O, N and S； a process for their preparation, pharmaceuticalcompositions comprisingthem and their use as a medicine, in particular for the treatment ofdepression, anxiety,movement disorders, psychosis, Parkinson's disease and body weight disorders.The compoundsaccording to the invention have surprisingly been shown to have a serotonine(5-HT) reuptakeinhibitor activity in combination with additional .alpha.2-adrenoceptorantagonist activity and show astrong anti-depressant activity without being sedative. The invention alsorelates to novelcombination of isoxazoline derivatives according to the invention with one ormore othercompounds selected from the group of antidepressants, anxiolytics, anti-psychotics andanti-Parkinson's disease drugs to improve efficacy and/or onset of action.(see formula I)
