Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1992-01-31
1994-04-05
Higel, Floyd D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514266, 514269, 514274, 514397, 514427, 544280, 544301, 544316, 5483147, 548557, 548562, A61K 3140, A61K 700, C07D207327, C07D40304, C07D47334
Patent
active
053005082
DESCRIPTION:
BRIEF SUMMARY
The invention relates to interceptors of activated species of dioxygen, their preparation process and the pharmaceutical and cosmetic compounds containing them.
Activated species of dioxygen, plus especially singlet oxygen(.sup.1 O.sub.2), the superoxide radical ion (O.sup.2:), the hydroxyl radical (OH.sup.1), alkoperoxyl radicals (AOO.sup.1) and alkoxyl radicals (AO.sup..), in which A represents an alcoyl (alkyl) grouping, are pathogenic entities relative to the cell.
These activated species play a fundamental role in the development or aggravation of numerous illnesses such as cancer, infarction, emphysema, arteriosclerosis, and rheumatoid arthritis.
Further, these activated species are involved in the aging processes of organs, in particular of the skin, whether these processes are natural or whether they result from luminous radiation.
Up to now, several types of interceptors of activated species of dioxygen have been used in medical practice or in cosmetology. Those most commonly used are vitamins or their derivates, in particular ascorbic acid and vitamin E, oxidants derived from phenol (tert-butyl hydroxytoluene and tert-butyl hydroxyanisole), thiol derivates such as cysteine and its derivates, dismutase superoxide and the carotenoids.
However, these substances are not totally satisfactory as interceptors against activated species of dioxygen. Indeed, some of them react only with a single activated species, or are unstable or even prove inappropriate because of their hydrophilic or hydrophobic or photosensitizing nature.
The inventors have searched for products able to react more efficiently against the activated species of oxygen involved in the aging processes of organs and of cells and in diverse pathologies associated with the involvement of these activated species of dioxygen.
They have thus confirmed that the substitution of the nitrogen atom of pyrrol derivates by groups involved in cellular metabolism gives them, in particular, advantageous properties as interceptors relative to activated species of dioxygen.
The object of the invention is new pyrrol derivates having properties of interceptors of activated species of dioxygen. The object also is compounds containing these pyrrol derivates. The object of the invention is also their preparation process and pharmaceutical compounds containing them.
The invention thus relates to new pyrrol derivates that fulfill the following characteristics: oxygen, OH radicals, free radicals of the inorganic radical type. Toward these radicals, they have an activity distinguished by a bimolecular reaction rate constant on the order of 10.sup.9 M.sup.-1. Some of them react also with the superoxide ion formed during cellular photooxidation or autooxidation reactions, buffered, neutral solution and in darkness, they are stable practically indefinitely at 4.degree. C. (more than a month), and at room temperature, some of them exhibit an equivalent stability. hydrophilic phase that varies between 2 and 50 for the conventional water-octanol mixture, particular at room temperature,
they are not sensitive to the action of cellular hydrolases and esterases.
Derivates particularly adapted to achieving the invention are N-substituted pyrrol derivates corresponding to following formula (I): ##STR2## in which: R is a physiologically acceptable constituent, able to penetrate into cells, insensitive to the action of cellular hydrolases and esterases, this grouping being in particular a derivate of amino acids, of biologically desirable nonproteinic peptides, of osamines having a free primary amine grouping, of purine bases, if necessary substituted in position 9 by groupings other than phenyl, for example by alkyl groupings, or of pyrimidic bases having a free primary amine grouping, pyrimidic bases being substituted by at least one SH group, among a hydrogen or an alcoyl radical comprising 1 to 6 carbon atoms, a primary, secondary --NHB, or tertiary --N(B,B') amine radical, with B and B' identical or different and representing an alcoyl group of 1 to 6 carbon atoms, an SH o
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Bazin Marc
Giraud Michel
Santus Rene
Valla Alain
Centre National de la Recherche Scientifique
Higel Floyd D.
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