Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-06-07
1997-05-20
Haley, Jacqueline
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514298, 514307, 514314, 514339, 514365, 514372, 514374, 514383, 514397, 514416, 546102, 546146, 546175, 5462771, 548181, 548214, 548236, 5482676, 5483121, 548455, 548465, 548470, C07D20944, A61K 3140
Patent
active
056312792
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION OF THE INVENTION
The present invention relates to perhydroisoindole derivatives of general formula: ##STR2## and to their salts when they exist, which antagonize the effects of neurokinin A and are, as a result, particularly advantageous in the therapeutic fields in which this substance is known to be involved.
Neurokinin A is involved in many pathologies, such as pain transmission, arthritis, asthma, inflammatory phenomena, psychosis, vascular tension disorders, vesical disorders, cystisis, etc., which is why the isoindole derivatives of general formula (I) are of considerable value.
The effects of neurokinin A are mainly mediated by the NK2 receptors.
European Patent Application EP 429,366 has described antagonists of substance P of structure: ##STR3## in which the symbols R are hydrogen or together form a bond, the symbols R' are optionally substituted phenyl radicals and the symbols R.sub.1 and R.sub.2 represent various substitutions. However, these perhydroisoindolone derivatives do not display any antagonistic activity to NK2 receptors.
American Patent No. 4,042,707 has described products derived from the isoindole of general formula: ##STR4## having an opiate activity. These products have no activity towards neurokinin A.
In the general formula (I): optionally substituted with a halogen atom or with a methyl radical in the 2- or 3-position, substituted with one or more halogen atoms or hydroxyl, benzyloxy or alkyl radicals which may optionally be substituted (with halogen atoms or with amino, alkylamino or dialkylamino radicals) or with alkyloxy or alkylthio radicals which may optionally be substituted [with hydroxyl, amino, alkylamino or dialkylamino radicals which are optionally substituted (with phenyl, hydroxyl or amino radicals), or dialkylamino radicals whose alkyl portions form, with the nitrogen atom to which they are attached, a 5- to 6-membered heterocycle which may contain another hetero atom chosen from oxygen, sulphur or nitrogen, and optionally substituted with an alkyl, hydroxyl or hydroxyalkyl radical], or substituted with amino, alkylamino or dialkylamino radicals whose alkyl portions may form, together with the nitrogen atom to which they are attached, a heterocycle as defined above, or represents a cyclohexadienyl, naphthyl or indenyl radical, or a saturated or unsaturated mono- or polycyclic heterocyclic radical containing 5 to 9 carbon atoms and one or more hetero atoms chosen from oxygen, nitrogen or sulphur, and optionally substituted with a halogen atom or with an alkyl, alkyloxy, aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl radical, alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkyloxy, alkylthio, acyloxy, carboxyl, alkyloxycarbonyl, dialkylaminoalkyloxycarbonyl, benzyloxycarbonyl, amino or acylamino radical, and substituted in the 2-position with an alkyl or alkyloxy radical containing 1 or 2 carbon atoms.
It is understood that the alkyl or acyl radicals cited above contain (except where especially mentioned) 1 to 4 carbon atoms in a straight or branched chain.
When R carries a halogen substituent, the latter may be chosen from chlorine or fluorine.
When R.sub.1 contains a halogen atom, the latter may be chosen from chlorine, bromine, fluorine or iodine.
When R.sub.1 represents a saturated or unsaturated mono- or polycyclic heterocyclic radical, it may, by way of example, be chosen from thienyl, furyl, pyridyl, dithiinyl, indolyl, isoindolyl, thiazolyl, isothiazolyl, oxazolyl, imidazolyl, pyrrolyl, triazolyl, thiadiazolyl, quinolyl, isoquinolyl or naphthyridinyl.
When R.sub.1 represents phenyl substituted with a chain carrying a heterocycle, the latter may be chosen from pyrrolidinyl, morpholino, piperidyl, tetrahydropyridyl, piperazinyl or thiomorpholino.
When the symbol R.sub.2 is other than a hydrogen atom, the substituted chain on the isoindole has a chiral center, and it is understood that the (R) or (S) stereoisomeric forms and their mixtures form part of the present invention.
Moreover, the (3aRS,4RS,5RS,7aRS) racemic forms of the perhydroi
REFERENCES:
patent: 5102667 (1992-04-01), Dubroeucq et al.
patent: 5112988 (1992-05-01), Dubroeucq et al.
patent: 5451601 (1995-09-01), Achard et al.
patent: 5484804 (1996-01-01), Achard et al.
Crespo Andre
Fardin Veronique
Guillaume Jean-Marc
Malleron Jean-luc
Peyronel Jean-Francois
Haley Jacqueline
Rhone-Poulenc Rorer S.A.
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