HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS Russian patent published in 2010 - IPC C07D233/88 C07D239/22 C07D401/04 C07D401/10 C07D401/12 C07D401/14 C07D403/06 C07D403/10 C07D403/14 C07D405/06 C07D405/14 C07D407/14 A61K31/4168 A61K31/4178 A61P9/00 A61P25/28 A61P31/18 

FIELD: chemistry.

SUBSTANCE: present invention relates to heterocyclic compounds of formula I or their stereo isomer, tautomer or pharmaceutically acceptable salt or solvate, where W denotes -C(=S)- or -C(=O); X denotes -N(R⁵)-; U denotes a bond or -(C(R⁶)(R⁷))_b- where b equals 1; R¹, R² and R⁵ are independently selected from a group comprising H, alkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms, cycloalkyl with 3-7 carbon atoms and other radicals given in claim 1 of the formula of invention; R³, R⁴, R⁶ and R⁷ are independently selected from a group comprising H, alkyl with 1-6 carbon atoms, cycloalkyl with 3-7 carbon atoms, cycloalkylalkyl with 3-7 carbon atoms in the cycloalkyl part and 1-6 carbon atoms in the alkyl part and other radicals given in claim 1 of the formula of invention; R¹⁵, R¹⁶ and R¹⁷ indicated below are independently selected from a group comprising H, alkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms, alkynyl with 2-4 carbon atoms, cycloalkyl with 3-7 carbon atoms, cycloalkylalkyl with 3-7 carbon atoms in the cycloalkyl part and 1-6 carbon atoms in the alkyl part and other radicals given in claim 1 of the formula of invention; or R¹⁵, R¹⁶ and R¹⁷ denote ; , where R²³ denotes 0-2 substitutes, m equals 0 and n equals 1 or 2, and where all alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroaryl alkyl, alkenyl and alkynyl groups in R¹, R², R³, R⁴, R⁵, R⁶, R⁷ can be independently substituted with 1-3 R²¹ groups independently selected from alkyl with 1-6 carbon atoms, cycloalkyl with 3-7 carbon atoms, halogen, aryl with 6-10 carbon atoms; -CN, -OR¹⁵, -C(O)R¹⁵, -C(O)OR¹⁵, - C(O)N(R¹⁵)(R¹⁶), -S(O)₂N(R¹⁵)(R¹⁶), -N(R¹⁵)(R¹⁶), -N(R¹⁵)C(O)R¹⁶, -CH₂-N(R¹⁵)C(O)R¹⁶, - CH₂-R¹⁵; -N(R¹⁵)S(O)R¹⁶, -N(R¹⁵)S(O)₂R¹⁶, -N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), -CH₂-N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), -N(R¹⁵)C(O)OR¹⁶, -CH₂-N(R¹⁵)C(O)OR¹⁶, -N₃, -NO₂ and -S(O)₂R¹⁵; and where alkyl with 1-6 carbon atoms and cycloalkyl with 3-7 carbon atoms are independently substituted or contain substitutes in form of 1-5 R²² groups, independently selected from a group comprising halogen, -CN or -OR¹⁵; R²³ denotes alkyl with 1-6 carbon atoms; provided that if W denotes -C(O)- and U denotes a bond, then R¹ does not denote, if needed, a substituted phenyl, provided that neither R¹ nor R⁵ denotes alkyl disubstituted with -CO(O)R¹⁵ or -C(O)N(R¹⁵)(R¹⁶)) and (-N(R¹⁵)(R¹⁶), -N(R¹⁵)C(O)R¹⁶, -N(R¹⁵)S(O)R¹⁶, -N(R¹⁵)S(O)₂R¹⁶, -N(R¹⁵)C(O)N(R¹⁶)(R¹⁷) or -N(R¹⁵)C(O)OR¹⁶) groups; provided that if R¹ denotes methyl, R² denotes H, W denotes C(O)- and U denotes a bond, then (R³, R⁴) does not denote (H, H), (phenyl, phenyl), (H, phenyl), (benzl, H), (benzyl, phenyl), (isobutyl, H), (isobutyl, phenyl), (OH-phenyl, phenyl), (halogenphenyl, phenyl) or (CH₃O-phenyl, NO₂-phenyl);provided that if R¹ and R⁵ both denote H, W denotes -C(O)- and U denotes a bond, then (R³, R⁴) does not denote (substituted phenyl if needed, substituted benzyl if needed), (substituted phenyl if needed, heteroarylalkyl) or (heteroaryl, heteroarylalkyl); provided that if R¹ denotes R²¹-aryl or R²¹ arylalkyl, where R²¹ denotes -OCF₃, -S(O)₂CF₃, -S(O)₂alkyl, -S(O)₂CHF₂, -S(O)₂CF₂CF₃, -OCF₂CHF₂, -OCHF₂, -OCH₂CF₃ or -S(O)₂NR¹⁵R¹⁶; where R¹⁵ and R¹⁶ are independently selected from a group comprising H, said alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R¹⁸-alkyl, R¹⁸-cycloalkyl, R¹⁸-heterocycloalkyl and R¹⁸ -aryl, and U denotes a bond; then R⁵ denotes H, where R¹⁸ is as defined in claim 1 of the formula of invention. The present invention also relates to a pharmaceutical composition based on the compound of formula , use of the formula I compound in preparing a medicinal agent.

EFFECT: novel heterocyclic derivatives of formula I, having aspartyl protease inhibiting properties, are obtained.

16 cl, 1 tbl