DERIVATIVES OF N,S-SUBSTITUTED N'-1-[(HETERO)ARYL]-N'-[(HETERO)ARYL]- METHYLISOTHIOUREAS OR THEIR SALTS AND BASES, PHARMACEUTICAL COMPOSITION, METHOD FOR TREATMENT AND METHOD FOR STUDY OF GLUTAMATERGIC SYSTEM Russian patent published in 2004 - IPC

FIELD: organic chemistry, chemical technology, medicine, pharmacy. SUBSTANCE: invention relates to new derivatives of N,S-substituted N'-1-[(hetero)aryl] -N'-[(hetero)-aryl] methylisothioureas of the general formula (I) or their salts with pharmacologically acceptable acids HX as racemic mixture or mixture of stereoisomers that can be used for treatment and prophylaxis of diseases associated with dysfunction of glutamatergic neurotransmission. Invention relates also to methods for preparing their salts and bases, pharmaceutical composition, method for treatment and method for study of glutamatergic system. In compounds of the general formula (I) wherein sign (#) means possibility for the presence of chiral carbon atom Y and Z can be similar or different and mean independently aryl or possibly substituted heteroaryl; R¹ means hydrogen atom, lower alkyl, aryl; R²-R³ represent lower alkyl, alkenyl, cycloalkyl, cycloalkenyl and other values indicated in the invention claim. Compounds show ability to inhibit intake of calcium ions stimulated by exciting amino acids taken among glutamic, aspartic acids and their agonist, in particular, that inhibit glutamate-induced uptake of calcium ions by brain cells and therefore eliciting properties of specific neuroprotecting agents. Method for preparing salts of compounds of the formula (I) involves interaction of thiourea with equivalent or excessive amount of corresponding alkylating agent R³-G, possibly, in polar inert solvent medium and in the case if alkylating agent is R³-OH taken in excess, possibly, in the presence of acid excess, possibly, by effect of microwave-radiation or as homogenized mixture of parent compounds without solvent to yield corresponding salt of (II) (see scheme). For preparing stable bases neutralization of isothiourea salts in two-phase is carried out. EFFECT: improved preparing method, valuable medicinal properties of compounds. 28 cl, 2 tbl, 21 ex