Perhydroisoindole derivatives as antagonists of substance P

Details Perhydroisoindole derivatives as antagonists of substance P Perhydroisoindole derivatives as antagonists of substance P

1994-10-11

1996-01-16

Haley, Jacqueline

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514307, 514314, 514339, 514363, 514365, 514372, 514374, 514378, 514383, 514397, 514416, 546148, 546174, 548181, 548214, 548236, 548247, 5482678, 5483121, 548455, 548470, A61K 3140, C07D40106

Patent

active

054848040

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to new perhydroisoindole derivatives of the general formula: ##STR2## and to their salts, where these exist, which antagonize he effects of substance P and as a result are of particular interest in therapeutic fields where this substance is known to be involved.


BACKGROUND OF THE INVENTION

European Patent Application EP 429 366 has described antagonists of substance P having the 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 been found to be active mainly in binding tests using rat brain homogenates, and display less activity in binding tests using cultures of human lymphoblast cells.
U.S. Pat. No. 4,042,707 had described products derived from isoindole, of the general formula: ##STR4## having an opiate activity. These products do not have any activity against substance P.
To date, in spite of research carried out and in spite of the abovementioned interest [M. R. Hanley, TINS, (5) 139 (1982)], no product which acts specifically on substance P and has a nonpeptide structure had been discovered in practice, and for this reason the isoindole derivatives of the general formula (I) are of considerable interest.


DESCRIPTION OF THE INVENTION

In the general formula (I): optionally substituted by a halogen atom or by a methyl radical in position 2 or 3, substituted by one or more halogen atoms or hydroxyl radicals, alkyl radicals which may be optionally substituted (by halogen atoms or amino, alkylamino or dialkylamino radicals), alkyloxy radicals or alkylthio radicals which may be optionally substituted [by hydroxyl radicals, amino radicals, alkylamino radicals or dialkylamino radicals which are optionally substituted (by phenyl, hydroxyl or amino radicals), or dialkylamino radicals, the alkyl parts of which, with the nitrogen atom to which they are attached, form a heterocycle having 5 to 6 chain members which may contain another heteroatom chosen from oxygen, sulphur or nitragen and optionally substituted by an alkyl, hydroxyl or hydroxyalkyl radical)], or is substituted by amino radicals, alkylamino radicals or dialkylamino radicals, the alkyl parts of which, with the nitrogen atom to which they are attached, may form a heterocycle as defined above, or represents a cyclohexadienyl radical, naphthyl radical, indenyl radical or mono- or polycyclic, saturated or unsaturated, heterocyclyl radical containing 5 to 9 carbon atoms and one or more heteroatoms chosen from oxygen; nitrogen or sulphur, which is optionally substituted by a halogen atom or by an alkyl or alkyloxy radical, alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkyloxy, alkylthio, acyloxy, carboxyl, alkyloxycarbonyl, dialkylaminoalkyloxycarbonyl, benzyloxycarbonyl, amino or acylamino radical, substituted in position 2 by an alkyl or alkyloxy radical containing 1 or 2 carbon atoms and symbol R.sub.5 represents a hydrogen atom, or
It is understood that the alkyl or acyl radicals mentioned above contain (unless mentioned specifically) 1 to 4 carbon atoms in a straight or branched chain.
If R carries a halogen substituent, this may be chosen from chlorine or fluorine.
If R.sub.1 contains a halogen atom, this may be chosen from chlorine, bromine, fluorine or iodine.
If R.sub.1 represents a mono- or polycyclic, saturated or unsaturated, heterocyclyl radical, it may be chosen from, by way of example, thienyl, furyl, pyridyl, dithiinyl, indolyl, isoindolyl, benzothienyl, thiazolyl, isothiazolyl, oxazolyl, imidazolyl, pyrrolyl, triazolyl, thiadiazolyl, quinolyl, isoquinolyl and naphthyridinyl.
If R.sub.1 represents phenyl which is substituted by a chain carrying a heterocycle, this can be chosen from pyrrolidinyl, morpholino, piperidinyl, tetrahydropyridinyl, piperazinyl or thiomorpholino.
Furthermore, the products of the general formula (I) have various stereoisomer forms, and it i

REFERENCES:
patent: 4042707 (1977-08-01), Ripka
McMurry, J. Organic Chemistry, Monterey, Calif., Brooks/Cole Publishing Co., 1984, pp. 642-644, QD251.2M43.

Affiliated with

Also associated with

Rating

Perhydroisoindole derivatives as antagonists of substance P does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Perhydroisoindole derivatives as antagonists of substance P, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Perhydroisoindole derivatives as antagonists of substance P will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-309648