Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-06-29
2004-08-31
Bernhardt, Emily (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S254110, C514S254080, C514S255030, C514S310000, C514S321000, C514S331000, C514S398000, C514S399000, C514S401000, C544S372000, C544S373000, C544S377000, C544S393000, C546S143000, C546S197000, C546S231000, C548S333100, C548S343500, C548S354100
Reexamination Certificate
active
06784183
ABSTRACT:
The present invention relates to new diphenylurea compounds.
The invention relates also to their use as mixed &agr;
2
/5-HT
2c
ligands.
DESCRIPTION OF THE PRIOR ART
Compounds having a diphenylurea structure have been described in the Application JP 11130750 for their serotonergic antagonistic properties, and in the Application WO 99 32436 for their use as raf kinase inhibitors.
BACKGROUND OF THE INVENTION
The frontal cortex plays an essential role in the processes that control the functions affected in psychiatric disorders. In particular, it is now accepted that the disturbance of monoaminergic transmission is strongly implicated in the etiology of those various disorders. For example, in the case of depression, monoaminergic activity is reduced in the corticolimbic regions.
Among the various monoamine auto- and hetero-receptors implicated in regulatory mechanisms, &agr;
2
-A.R. (autoreceptors) and 5-HT
2c
receptors have proved to be of major importance. Those two receptor sub-types act in the same way by inhibiting dopaminergic and adrenergic transmission. On the one hand a retrocontrol is exerted by &agr;
2
-A.R. receptors on noradrenergic neurons (J. Pharmacol. Exp. Ther., 1994, 270, 958), and on the other hand 5-HT
2c
receptors exert an inhibiting control on dopaminergic and noradrenergic transmission (Neuropharmacology, 1997, 36, 609).
In the past, compounds binding one or the other of those receptor sub-types have demonstrated their potential in the treatment of a plurality of pathologies.
For example, the beneficial role of &agr;
2
antagonist compounds has been studied in the treatment of cognitive disorders (J. Pharmacol., 1992, 6, 376), Parkinson's disease (CNS Drugs, 1998, 10, 189), libido disorders and sexual dysfunction (J. Pharmacol., 1997, 11, 72). Similarly, 5HT
2c
receptor antagonist compounds have demonstrated their usefulness in the treatment of sexual dysfunction (ref. J. Pharmacol., ibid.), Parkinson's disease (Drug News Perspect., 1999, 12, 477), and also anxiety (Br. J. Pharmacol., 1996, 117, 427) and schizophrenia (Neurosci. Lett., 1996, 181, 65).
Compounds having a dual &agr;
2
-A.R. and 5-HT
2c
antagonist character may be of significant use for clinicians for achieving, with the administration of a single compound, an appreciably enhanced action in the restoration of neurotransmission by means of a synergistic effect. That kind of compound furthermore presents a considerable advantage in comparison with the administration of two different products.
The compounds of the invention have a novel structure that confers on them such a dual &agr;
2
/5-HT
2c
antagonist character, and they are accordingly useful in the treatment of depression, anxiety, schizophrenia, Parkinson's disease, cognitive disorders, libido disorders and sexual dysfunction, sleep disorders, drug abuse, and impulsive behaviour disorders.
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Brocco Mauricette
Dekeyne Anne
Lavielle Gilbert
Millan Mark
Muller Olivier
Bernhardt Emily
Les Laboratoires Servier
The Firm of Hueschen and Sage
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