Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1986-05-15
1988-07-26
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514425, 548453, 548544, C07D49504, C07D207273, A61K 3140, A61K 31385
Patent
active
047600772
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns the use of pyrrothine compounds for the inhibition of allergen-induced degranulation of peripheral leukocytes.
It is known that the derivatives of pyrrothine (4-methyl-6-amino-1,2-dithiolo[4,3-b]pyrrol-5(4H)-one, such as e.g. the N-acetyl derivative (thiolutin) or the N-propionyl derivative (aureothricin), obtained from Streptomyces culture filtrates, represent antibiotics with action against gram-positive and gram-negative bacteria, pathogenic fungi and protozoa (cf. W. D. Celmer and I. A. Solomons, J. Am. Chem. Soc. 77 (1955) 2861); the total synthesis of these antibiotics is described by U. Schmidt and F. Geiger (cf. Angew. Chemie 74 (1962) 328; Liebigs Ann. Chem. 664 (1963) 168).
Surprisingly, it has now been found that such pyrrothine derivatives also possess an outstanding anti-allergic action; they inhibit e.g. the human allergen-induced degranulation of peripheral leukocytes. The corresponding dimercapto compounds obtained by the reductive fission of the S--S bond of the pyrrothine derivatives also show a similar action.
Therefore, the subject of the present invention is the use of pyrrothine derivatives of the general formula I ##STR2## wherein R.sub.1 and R.sub.3 signify hydrogen or methyl, R.sub.2 hydrogen, methyl or an acyl group with 1 to 5, especially 2 to 4 carbon atoms and X and Y hydrogen, an equivalent of a physiologically acceptable cation or together a single bond, for the inhibition of allergeninduced degranulation of peripheral leukocytes.
In preferred compounds of the formula I, R.sub.1 and R.sub.2 are different and especially R.sub.1 hydrogen and R.sub.2 methyl or acyl with 1 to 5, especially 2 to 4 carbon atoms. R.sub.3 is preferably a methyl group.
For the use according to the invention for the combating of allergies, compounds of the formula Ia are preferred, i.e. thus the compounds of the formula I, in which X and Y together form a single bond, ##STR3## wherein R.sub.1, R.sub.2 and R.sub.3 possess the above-given meaning.
The compounds of the formula I, in which X and Y together do not form a single bond but rather signify a hydrogen atom or an equivalent of a physiologically acceptable cation, are represented by the formula Ib: ##STR4## wherein R.sub.1, R.sub.2 and R.sub.3 possess the above-given meanings. They are preferably present in the form of their salts (X,Y=equivalent of a physiologically acceptable cation).
The compounds of the formula I, wherein R.sub.1, R.sub.2 and R.sub.3 signify methyl and X and Y hydrogen, an equivalent of a physiologically acceptable cation or together a single bond, are new compounds.
The compounds of the general formula Ib, for which hitherto a use as medicament is not known, show, in the case of the use according to the invention, the same anti-allergic effectiveness as the compounds of the formula Ia. Therefore, the subject of the present invention is also a pharmaceutical composition which contains a compound of the formula Ib, wherein X, Y, R.sub.1, R.sub.2 and R.sub.3 possess the above-given meaning, or a new compound of the formula I, wherein R.sub.1, R.sub.2 and R.sub.3 signify methyl and X and Y hydrogen, an equivalent of a physiologically acceptable cation or together a single bond. The pharmaceutical compositions can also contain two or more of the compounds of the formula I employed according to the invention.
An acyl group with 1 to 5 carbon atoms can be straight-chained or branched and is e.g. valeryl, isovaleryl and trimethylacetyl and especially butyryl, isobutyryl, propionyl, acetyl and formyl.
A physiologically acceptable cation X and Y can be mono- or polyvalent and is especially a mono- or divalent physiologically acceptable cation, such as e.g. Ca.sup.2+, Na.sup.+ or K.sup.+ ; however, it can also signify ammonium or an organic ammonium cation, such as e.g. mono-, di- or trialkylammonium, whereby the alkyl group then especially signifies methyl.
The compounds of the formula Ia are known or can be prepared in per se known manner by synthetic ways or from Actinomycetales (cf. The Chemistry of Het
REFERENCES:
patent: 2689854 (1954-09-01), Tanner et al.
patent: 2752359 (1956-06-01), Celmer
Ninomiya et al., Chem. and Pharm. Bull., vol. 28, pp. 3157-3162, (1980).
Roesch Androniki
Seidel Hans
Stahl Peter
von der Eltz Herbert
Wilhelms Otto-Henning
Boehringer Mannheim GmbH
Raymond Richard L.
Springer D. B.
LandOfFree
Pyrrothine derivatives and pharmaceutical use thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pyrrothine derivatives and pharmaceutical use thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyrrothine derivatives and pharmaceutical use thereof will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-258163