Derivatives of 2-oxothiadiazoline-4-carboxylic acid and its use as active photoprotective agent

摘要

Fused-ring derivatives (I) of 2-oxo-thiazolidine-4-carboxylic acid, their optical and/or geometric isomers, singly or in any proportion, and their salts are new. Fused-ring derivatives of formula (I) of 2-oxo-thiazolidine-4-carboxylic acid, their optical and/or geometric isomers, singly or in any proportion, and their salts are new. [Image] X : O or NR''; R'' : 1-12C linear, cyclic or branched alkyl, optionally substituted; Y1(CH2)n; Z1>CRR'; or Y1> + Z1, each containing a carbon atom, may together : aromatic (hetero)cycle, optionally substituted, of 4-6 C; n : 0-3; R, R' : H, -SiMe2-Q, -Si(isopropyl)2-OEt, halo, (cyclo)alkyl (as above), or, both optionally substituted, aryl or aralkyl; and Q : Me, hydroxy, ethoxy or benzyloxy. Provided that when X = NR'', R'' and R may together form, with the two atoms that carry them, a heterocycle containing 4-6 C. An independent claim is also included for preparation of (I) by reacting 2-oxothiaxolidine-4-carboxylic acid with an amino-, hydroxy- or halo-acid, protected on carboxy; deprotection and intramolecular cyclization to form a peptide bond. ACTIVITY : Dermatological. Protection of keratinocytes against UV-induced oxidative stress was measured by the fluorescent method of J. Photochem. Photobiol., B, 57 (2000) 102. In presence of 5 mM tetrahydro[1,3]thiazolo[3,4-a]pyrazine-3,5,8-trione, the mean degree of fluorescence was 63.5% of that in an unprotected control. MECHANISM OF ACTION : Inducing intracellular synthesis of glutathione, which prevents oxidative damage caused by free radicals.