Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-01-29
1997-04-29
Haley, Jacqueline
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514300, 514307, 514314, 514361, 514397, 514383, 514372, 514373, 546122, 546139, 546174, 5462771, 548127, 548128, 548181, 548214, 548215, 5482676, 5483121, 5483647, 548455, 548454, 548465, C07D20944, A61K 3140
Patent
active
056249500
DESCRIPTION:
BRIEF SUMMARY
This application is a National Stage of PCT/FR94/00952 filed Jul. 28, 1994 and published as WO 95/04040 on Feb. 9, 1995.
The present invention relates to novel perhydroisoindole derivatives of general formula: ##STR2## and to their salts when they exist, which antagonize the effects of substance P and are, as a result, particularly advantageous in the therapeutic fields in which this substance is known to be involved.
European Patent Application EP 429,366 has described substance P antagonists 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 have proved to be mainly active in binding tests using rat brain homogenates, and display less activity in binding tests using human lymphoblast cells in culture.
U.S. Pat. No. 4,042,707 has described products derived from isoindole, of general formula: ##STR4## having an opiate activity. These products have no activity towards substance P.
In the general formula (I): substituted with one or more halogen atoms or hydroxyl radicals, alkyl radicals which may be optionally substituted (with halogen atoms or amino, alkylamino or dialkylamino radicals), alkyloxy or alkylthio radicals which may be optionally substituted [with hydroxyl, amino, alkylamino or dialkylamino radicals which are optionally substituted (with phenyl, hydroxyl or amino radicals), or dialkylamino radicals in which the alkyl parts 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, optionally substituted with an alkyl, hydroxyl or hydroxyalkyl radical)], or substituted with amino, alkylamino or dialkylamino radicals in which the alkyl parts may form, 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 or alkyloxy radical, alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkyloxy, alkylthio, acyloxy, carboxyl, alkyloxycarbonyl, dialkylaminoalkyloxycarbonyl, benzyloxycarbonyl, amino or acylamino radical, substituted in the 2-position with an alkyl or alkyloxy radical containing 1 or 2 carbon atoms or with a fluorine atom, or disubstituted with trifluoromethyl radicals, and represents a hydrogen atom or a hydroxyl or alkyl radical and the other represents a hydrogen atom or an alkyl radical, and R'.sub.5 represent a hydrogen atom or an alkyl radical, or alternatively hydroxyalkyl radical, and hydroxyl or hydroxyalkyl radical and the other represents a hydrogen atom or an alkyl, phenyl or hydroxyalkyl radical.
It is understood that the abovementioned alkyl or acyl radicals contain (except where especially mentioned) 1 to 4 carbon atoms in a straight or branched chain.
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, benzothienyl, thiazolyl, isothiazolyl, oxazolyl, imidazolyl, pyrrolyl, triazolyl, thiadiazolyl, quinolyl, isoquinolyl or naphthyridinyl.
When R.sub.1 represents phenyl which is substituted with a chain hearing a heterocycle, the latter may he chosen from pyrrolidyl, morpholino, piperidyl, tetrahydropyridyl, piperazinyl or thiomorpholino.
Moreover, the products of general formula (I) have different stereoisomeric forms, and it is understood that the racemic forms and the stereoisomeric forms of structure: ##STR5## and their mixtures enter into the context of the present invention, In addition, when the symbo
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.
patent: 5508433 (1996-04-01), Achard et al.
Derwent Abstract of EP-514273. (1992).
Derwent Abstract of EP-514274. (1992).
Achard Daniel
Grisoni Serge
James-Surcouf Evelyne
Malleron Jean-luc
Morgat Anne
Haley Jacqueline
Rhone-Poulenc Rorer S.A.
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