Therapeutic compositions based on 1,2-dithiole-3-thione derivati

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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549 33, 549 37, C07D33904, A61K 31385

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active

054708710

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BRIEF SUMMARY
This Application is a 371 of PCT/FR92/00392 filed Apr. 30, 1992.
The present invention relates to therapeutic compositions based on 1,2-dithiole-3-thione derivatives.
As prior art, there may be mentioned anethole trithione or 5-(p-methoxyphenyl)-3H-1,2-dithiole-3-thione which is used in therapy as a choleretic (U.S. Pat. No. 2,556,963), and compounds of formula: ##STR5## described by Ebel et al., (Bull. Soc. Chim. Fr. 1963, 161), the compound A being obtained by reaction of sulphur with isophorone and the compound B being obtained from the compound A by reaction with NH.sub.2 OH.
Teicher et al. (Br. J. Cancer, 1990, 62, 17) disclose the use of 1,2-dithiole-3-thiones and in particular 5-(2-thienyl)-1,2-dithiole-3-thione as radioprotectors.
The subject of the present invention is therapeutic compositions containing, as active principle, a compound chosen from compounds of formulae: ##STR6## in which X is-chosen from .dbd.S, .dbd.O, .dbd.N--OH, .dbd.N--R.sub.5, R.sub.5 being a C.sub.1 -C.sub.6 alkyl or an aryl group, .dbd.N--NH--CO--NH.sub.2 and .dbd.N--NH--CS--NH.sub.2, and ##STR7## Z and Z' being electron-attracting groups such as ester or cyano groups, ##STR8## a group of formula ##STR9## (where R.sub.3 is chosen from a C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.6 alkyl group substituted with one more groups chosen from hydroxyl, amino, chloro and C.sub.1 -C.sub.4 alkoxy groups, an aryl (C.sub.1 -C.sub.6 alkyl) group, a (C.sub.1 -C.sub.6 alkyl) carbonyl group and an aryl (C.sub.1 -C.sub.6 alkyl)carbonyl group), ##STR10## R.sub.4 being a C.sub.1 -C.sub.6 alkyl group or an aryl group, and a CHOH group, hydrogen, a halogen, a nitro group, a nitroso group, a thiocyano group, a C.sub.1 -C.sub.6 alkyl group, a C.sub.2 -C.sub.6 alkenyl group, an aryl group, an aryl(C.sub.1 -C.sub.6 alkyl) group, an aryl(C.sub.2 -C.sub.6 alkenyl) group, a carboxyl group, a (C.sub.1 -C.sub.6 alkyl)carbonyl group, an arylcarbonyl group, a (C.sub.1 -C.sub.6 alkoxy)carbonyl group, a (C.sub.1 -C.sub.6 alkoxy)carbonyl(C.sub.1 -C.sub.6 alkyl) group, a C.sub.1 -C.sub.6 alkoxy group, a trifluoromethyl group, an amino group, a di(C.sub.1 -C.sub.6 alkyl)amino(C.sub.1 -C.sub.6 alkyl) group, an acylamino group of formula --NHCOC.sub.n H.sub.2n+1 with n from 0 to 6, a group --NH--CSC.sub.n H.sub.2n+1 with n from 0 to 6, a terpenyl group, a cyano group, a C.sub.2 -C.sub.6 alkynyl group, a C.sub.2 -C.sub.6 alkynyl group substituted with a C.sub.1 -C.sub.6 alkyl or an aryl group, a hydroxy(C.sub.1 -C.sub.6 alkyl) group, a (C.sub.1 -C.sub.6 acyl)-oxy(C.sub.1 -C.sub.6 alkyl) group, a (C.sub.1 -C.sub.6 alkyl)thio group and an arylthio group, C.sub.2 -C.sub.20 alkylene group optionally comprising one or more hetero atoms, with the exception of the 2,2-dimethyltrimethylene group, or a C.sub.3 -C.sub.12 cycloalkylene group,
The present invention relates in particular to a pharmaceutical composition comprising, as active ingredient, a compound chosen from the compounds of formulae: ##STR11## in which: X is chosen from S and O, ##STR12## a group of formula ##STR13## (where R.sub.3 is chosen from a C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.6 alkyl group substituted with one more groups chosen from hydroxyl, amino, chloro and C.sub.1 -C.sub.6 alkoxy groups, an aryl(C.sub.1 -C.sub.6 alkyl) group, a (C.sub.1 -C.sub.6 alkyl)carbonyl group and an aryl (C.sub.1 -C.sub.6 alkyl)carbonyl group), ##STR14## R.sub.4 being a C.sub.1 -C.sub.6 alkyl group or an aryl group, and a CHOH group, hydrogen, a halogen, a C.sub.1 -C.sub.6 alkyl group, an aryl group, an aryl (C.sub.1 -C.sub.6 alkyl) group, a carboxyl group, an alkoxycarbonyl group, a C.sub.1 -C.sub.6 alkoxy group, a trifluoromethyl group, a di(C.sub.1 -C.sub.6 alkyl)amino(C.sub.1 -C.sub.6 alkyl) group and an acylamino group of formula --NHCOC.sub.n H.sub.2n+1 with n from 0 to 6, or alternatively R.sub.1 and R.sub.2 together form a C.sub.2 -C.sub.12 alkylene group, with the exception of the 2,2-dimethyltrimethylene group, or a C.sub.3 -C.sub.12 cycloalkylene group,
In the foregoing definition, aryl group o

REFERENCES:
Chemical Abstracts, No. 114, 1991, Columbus, Ohio, abstract No. 164073, p. 230, col. 2.
Chemical Abstracts, No. 67, 1967, Columbus, Ohio, abstract No. 82141, p. 7745, col. 1.
Chemical Abstracts, No. 66, 1967, Columbus, Ohio, abstract No. 23,919, p. 2269, col. 2.
Chemical Abstracts, No. 113, 1990, Columbus, Ohio, abstract No. 207595, p. 342, col. 1.
C. Trebaul, 1973, Bulletin Des Societes Chimiques de France, vol. 2, No. 2, pp. 721-723, Synthese de quelques derives carbonyles en 5 de la phenyl-4 dithiole-1,2 one-3.
March, Advanced Organic Chemistry pp. 570-571 1985.

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