C-substituted tricyclic isoxazoline derivatives and their...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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Details

C514S293000, C544S360000, C544S374000, C546S083000, C546S089000

Reexamination Certificate

active

07465741

ABSTRACT:
The invention concerns substituted tricyclic isoxazoline derivatives according to Formula (I), the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N-oxide form thereof, more in particular tricyclic dihydrobenzopyranoisoxazoline, dihydroquinolinoisoxazoline, dihydronaphthalenoisoxazoline and dihydrobenzothiopyranoisoxazoline derivatives substituted on the phenylpart of the tricyclic moiety with at least one radical that is attached to the phenyl radical by a carbon-carbon bond as well as processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine, in particular for treating depression, anxiety, movement disorders, psychosis, Parkinson's disease and body weight disorders including anorexia nervosa and bulimia, wherin all variables are defined in claim1. (I) The compounds have surprisingly been shown to have selective serotonine (5-HT) reuptake inhibitor activity in combination with additional α2-adrenocptor antagonist activity and show a strong antidepressant and/or anxiolytic activity and/or antipsychotic and/or a body weight control activity without being sedative. Also, in view of their selective serotonine (5-HT) reuptake inhibitor as well as α2-adrenoceptor antagonist activity, compounds according to the invention are also suitable for treatment and/or prophylaxis in diseases where either one of the activities alone or the combination of said activities may be of therapeutic use.

REFERENCES:
patent: 7169786 (2007-01-01), Andres-Gil et al.
patent: 2005/0222125 (2005-10-01), Andres-Gil et al.
patent: 2006/0122167 (2006-06-01), Andres-Gil et al.
patent: 0885883 (1998-12-01), None
patent: WO 95/07893 (1995-03-01), None
patent: WO 97/25317 (1997-07-01), None
patent: WO 02/066484 (2002-08-01), None
patent: WO 03/082878 (2003-10-01), None
International Search Report for PCT/EP03/50374 dated Nov. 28, 2003.
Andres, J. Ignacio et al., “Synhesis of 3a,4-Dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, Displaying Combined 5-HT Uptake Inhibiting and α2-Adrenoceptor Anagonistic Activities: A Novel Series of Potential Antidepressants,” Bioorganic & Medicinal Chemistry Letter 13 (2003) 2719-2725.
Eichinger, Karl et al., “A Convenient Synthesis of 3-and 3,4-Substituted 4,5-Dihydroisoxazole-5-acetic Acids,” Synthetic Communications, 27(16), 2733-2742 (1997).

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