S-nitrosothiols as agents for the treatment of circulatory...

C - Chemistry – Metallurgy – 07 – K

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C07K 5/037 (2006.01) A61K 31/198 (2006.01) A61K 31/351 (2006.01) A61K 31/445 (2006.01) A61K 38/06 (2006.01) A61P 9/08 (2006.01) C07C 323/07 (2006.01) C07C 381/00 (2006.01) C07D 211/54 (2006.01) C07D 309/08 (2006.01) C07K 5/02 (2006.01)

Patent

CA 2359027

Novel S-nitrosothiols derivatives of penicillamine or glutathione, which correspond to following general formula(I) (see formula I) in which: A and B are phenyl groups or together form the rest -CH2-Q-CH2- constituting a ring of six units in which Q represents an atom of oxygen, of sulfur, or a group N-R3, in which R3 is hydrogen or an alkyl group C1-C4; R1 is an acyl rest, which may be an aliphatic acyl group C1-C5 or a rest of glutamic acid bound via its non amino acid carboxyl; R2 is a hydroxyl group or a glycine rest bound via a peptide bond; with the proviso that if R1 is an aliphatic acyl rest then R2 is a hydroxyl group, and if R1 is a rest of glu-tamic acid then R2 is a glycine rest. The novel compounds have vasodilating activity arid inhibit the aggregation of the platelets, which make them useful for the treatment of dysfunctions of the cir-culatory system, specially at cardiovascular level.

L'invention concerne de nouveaux S-nitrosothiols dérivés de la pénicillamine ou du gluthation de formule générale (I), dans laquelle A et B représentent des groupes phényle ou représentent, pris ensemble, le reste CH2-Q-CH2- formant un noyau à six chaînons dans lequel Q représente un atome d'oxygène ou de soufre ou un reste N-R<3>, où R<3> représente un hydrogène ou un groupe alkyle C1-C4; R<1> représente un reste acyle, qui peut désigner un acyle aliphatique C1-C5 ou un reste acide glutamique lié par son carboxyle non aminoacide; R<2> représente un groupe hydroxyle ou un reste glycine uni par une liaison peptidique; de sorte que lorsque R<1> représente un reste acyle aliphatique R<2> représente un groupe hydroxyle, et lorsque R<1> représente un reste acide glutamique R<2> représente un reste glycine. Les nouveaux composés présentent une activité vasodilatatrice et inhibitrice de l'agrégation des plaquettes, ce qui les rend utiles pour les traitements de troubles du système circulatoire, surtout au niveau cardio-vasculaire.

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