THROMBIN INHIBITORS, PHARMACEUTICAL COMPOSITION BASED ON THEREOF, METHOD OF TREATMENT, METHOD OF THEIR SYNTHESIS (VERSIONS) AND PROTECTED DERIVATIVE Russian patent published in 2001 - IPC

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention describes novel compounds of the formula (I) where p and q = 0, 1, 2, 3 or 4 independently; R means H, 2,3-epoxypropyl, C_1-6-alkyl (the latter is possibly substituted or terminated by one or more hydroxy-group), structural fragment of the formula (Ia) where A¹ means C_1-44-alkylene and R^x means H or when p = 0 then in common with R² it means structural fragment of the formula (Ib) where R^y means H; R² means H, naphthyl, indolyl, C_1-4-alkyl (the latter group is possibly substituted or terminated by one or more hydroxy-group), C_3-8-cycloalkyl, phenyl (the two latter groups are possibly substituted with one or more C_1-4-alkyl, C_1-4-alkoxy-group, halogen atom, hydroxy-group, nitro-group, methylenedioxy-group, trifluoromethyl-group, N(H)-R²³ or C(O)O-R²⁴) or when p = 0 then in common with R¹ it means structural fragment of the formula (Ib); R³ means H, naphthyl, indolyl, C_1-6-alkyl (the latter group is possibly substituted or terminated by one or more hydroxy-group), C_3-8-cycloalkyl or phenyl (the two latter groups are possibly substituted with one or more C_1-4-alkyl, C_1-4-alkoxy-group, halogen atom, hydroxy-group, nitro-group, methylenedioxy-group, trifluoromethyl group, N(H)-R²⁷ or C(O)O-R²⁸; R²³ and R²⁷ mean independently H, C_1-4-alkyl or C(O)-R²⁹; R²⁴,R²⁸,R²⁹ mean independently H or C_1-4-alkyl; R⁴ means H or C_1-4-alkyl; Y means C_1-4-alkylene possibly substituted with C_1-4-alkyl, methylene or oxo-group; n = 1 or 2; B means structural fragment of the formula (IVa) , (IVb) or (IVc) where R⁵ means H; X′ and X² mean independently a simple bond or CH₂; under condition that when R¹,R²,R⁴ all mean H, p = 0, Y means (CH₂)₂, n = 1 and: (a) R³ means unsubstituted phenyl and: (1) B is structural fragment of the formula (IVa) and R⁵ means H and then q is not 0 or 1; and (2) B is structural fragment of the formula (IVb) and X′ and X² both mean CH₂ and then q is not 0; and (b) R³ means unsubstituted cyclohexyl group; B means structural fragment of the formula (IVa) and R⁵ means H and then q is not 0; or its pharmaceutically acceptable salt. New compounds are useful as competitive inhibitors of trypsin-like proteases, for example, thrombin and especially in treatment of states where inhibition of thrombin is required (for example, in thrombosis) or as anticoagulating agents. Invention describes also a pharmaceutical composition based on thereof, method of patients treatment, method of their synthesis (variants) and protected derivative. EFFECT: new compounds indicated above, improved method of synthesis and treatment, valuable medicinal properties. 44 cl, 61 ex