Reference : Pyridobenzoxazepine and Pyridobenzothiazepine Derivatives as Potential Central Nervou...
Scientific journals : Article
Human health sciences : Psychiatry
Social & behavioral sciences, psychology : Neurosciences & behavior
Human health sciences : Pharmacy, pharmacology & toxicology
Pyridobenzoxazepine and Pyridobenzothiazepine Derivatives as Potential Central Nervous System Agents: Synthesis and Neurochemical Study
Liégeois, Jean-François mailto [Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique >]
Rogister, F. A. [> > > >]
Bruhwyler, J. [> > > >]
Damas, Jacques mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Nguyen, T. P. [> > > >]
Inarejos, M. O. [> > > >]
Chleide, E. M. [> > > >]
Mercier, M. G. [> > > >]
Delarge, J. E. [> > > >]
Journal of Medicinal Chemistry
Yes (verified by ORBi)
[en] In order to characterize the pharmacological profile of the different chemical classes of pyridobenzazepine derivatives, a series of N-methylpiperazinopyrido[1,4]- and -[1,5]- benzoxa- and benzothiazepine derivatives were prepared. The affinities for D2, D1, 5-HT2, and cholinergic (M) receptors were measured. In comparison to dibenzazepine reference compounds, a strong decrease of the affinities was observed, less pronounced, however, for the substituted analogues. Oxazepine and thiazepine analogues like clozapine (except 8-chloro-6-(4-methylpiperazin-1-yl)-pyrido[2,3-b][1,4]benzoxazepin e (9) and 8-chloro-6-(4-methylpiperazin-1-yl)pyrido[2,3-b][1,4]- benzothiazepine (11)) were found to be inactive against apomorphine stereotypies. In the open-field test in rats, different molecules showed a high disinhibitory activity as observed with anxiolytic drugs. Moreover, 8-chloro-5-(4-methylpiperazin-1-yl)pyrido[2,3-b][1,5]benzoxazepine (14) presented a clozapine-like profile that was confirmed in the behavioral model in dogs and showed most of the behavioral characteristics described for antipsychotic drugs. Its neurochemical profile, in particular the 5-HT2/D2 ratio, was also compatible with atypical antipsychotic activity.
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