FIVE-MEMBERED HETEROCYCLIC AMIDINES ELICITING PROPERTIES OF THROMBIN INHIBITORS, COMPOUNDS CONTAINING DERIVATIVES OF FIVE-MEMBERED HETEROCYCLIC AMIDINE AS COMPONENT OF INHIBITORS OF SERINE PROTEASES AND INTERMEDIATE COMPOUNDS

摘要

FIELD: organic chemistry, heterocyclic compounds, biochemistry. SUBSTANCE: invention describes novel five-membered heterocyclic amidines of the formula (I) where A, B, D and E have the following values: A of the formula (II) where m = n = 0, 1 or 2; R¹ means groups: hydroxyl, carboxyl, C_1-6-alkyl-OOC; R² = R³ mean hydrogen atom, alkyl with 1-4 carbon atoms; B of the formula (III) where R⁴ means hydrogen atom, alkyl with 1-4 carbon atoms or R¹ - means (CH)_m - (in this case R¹ and m have the above indicated values); p = 0 or 1; R⁵ - means hydrogen atom or alkyl with 1-4 carbon atoms; R⁶ means hydrogen atom, alkyl with 1-6 carbon atoms, cycloalkyl with 3-8 carbon atoms; R⁴ and R⁶ in common can mean ethylene group; R⁷ means hydrogen atom, alkyl with 1-8 carbon atoms; R⁸ means hydrogen atom, alkyl with 1-4 carbon atoms; E of the formula (IV) where q = 0 or 1; D of the formulas , , where R⁹ means hydrogen atom, alkyl with 1-3 carbon atoms; R¹⁰ = R¹¹ mean hydrogen atom, alkyl with 1-4 carbon atoms; X means oxygen, sulfur atom, NR¹² (R¹² is hydrogen atom, alkyl with 1-6 carbon atoms); Y means nitrogen or -CR¹³ R¹³ is hydrogen atom, alkyl with 1-4 carbon atoms; Z means nitrogen or -CR¹³= where R¹³ has the above indicated value and also their salts with physiologically tolerated acids. Said compounds elicite properties of inhibitors of thrombin. Invention describes also compounds containing derivatives of five-membered heterocyclic amidine as a component of inhibitors of serine proteases and intermediate compounds. EFFECT: valuable medicinal, biochemical and pharmacological properties. 4 cl, 1 tbl, 29 ex