DERIVATIVES OF ANTHRANILIC ACID, METHODS OF THEIR SYNTHESIS AND PHARMACEUTICAL COMPOSITION BASED ON THEREOF

摘要

FIELD: organic chemistry, biochemistry, pharmacy. SUBSTANCE: invention relates to novel derivatives of anthranilic acid of the formula (I) where R¹, R² mean H, alkyl, OH, alkoxy-group, halogen atom, nitro-group, N(R¹⁰R¹¹); R³ means H, alkyl; R⁴ means alkyl or R⁴ means -CH₂- or -CH₂CH₂- that is bound either at position 2 of cycle b completing saturated 5- or 6-membered nitrogen-containing cycle or at position 2 of cycle a with which X is bound by a single bond completing saturated 5- or 6-membered nitrogen-containing cycle; R⁵ means H, OH, alkyl; X means a single bond, O, S, -O--(CH₂)_p- where p is a number from 1 to 6; R⁶ means H, alkyl, alkoxy-group; q is a number from 0 to 1; Ar means phenyl, naphthyl or heterocyclic group containing S or N; each among R⁷ and R⁸ means H, alkyl, alkoxy-group, hydroxy-group, phenyl, -NHOH, nitro-group, N(R¹⁰R¹¹), SR¹²; or each among R⁷ and R⁸ in common with carbon atoms forms benzene or methylenedioxy- -substitute; R⁹ means phenyl or heterocyclic group containing 1 or 2 atoms among O, S or N; n = 0 or 1; m = 0-3. Compounds of the formula (I) show activity as inhibitor of P-glycoprotein and can be used in pharmaceutical composition and for enhancement of cytotoxic effect of chemotherapeutic agent. Also, invention relates to methods of synthesis of compounds of the formula (I) and formula (Ia) that involve treatment of compound of the formula (VI) with carboxylic acid, compound of the formula (XII) with compound of the formula (XX) , compound of the formula (VIII') with carboxylic acid, compound of the formula (XII') with compound of the formula (IX') and compound of the formula (XIII') with compound of the formula (IX') . EFFECT: improved methods of synthesis, valuable medicinal properties of compounds. 17 cl, 19 tbl, 7 sch, 23 ex