ORBi: Liégeois Jean-François - Pyridobenzoxazepine and Pyridobenzothiazepine Derivatives as Potential Central Nervous System Agents: Synthesis and Neurochemical Study

Reference : Pyridobenzoxazepine and Pyridobenzothiazepine Derivatives as Potential Central Nervous S...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Psychiatry Social & behavioral sciences, psychology : Neurosciences & behavior Human health sciences : Pharmacy, pharmacology & toxicology
	To cite this reference:	http://hdl.handle.net/2268/35307

Title :	Pyridobenzoxazepine and Pyridobenzothiazepine Derivatives as Potential Central Nervous System Agents: Synthesis and Neurochemical Study
Language :	English
Author, co-author :	Liégeois, Jean-François [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
	Rogister, F. A. [> > > >]
	Bruhwyler, J. [> > > >]
	Damas, Jacques [Université de Liège - ULg > 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. [> > > >]
Publication date :	10-Feb-1994
Journal title :	Journal of Medicinal Chemistry
Volume :	37
Issue/season :	4
Pages :	519-25
Audience :	International
ISSN :	0022-2623
Abstract :	[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.
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/2268/35307

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