4,6,7,13-SUBSTITUTED DERIVATIVES OF 1-BENZYLISOQUINOLINE AND PHARMACEUTICAL COMPOSITION POSSESSING INHIBITORY ACTIVITY WITH RESPECT TO GFAT Russian patent published in 2008 - IPC C07D217/18 C07D217/22 C07D217/26 C07D401/12 C07D405/10 C07D409/10 C07D413/06 C07D417/06 C07D401/06 C07D401/04 A61K31/472 A61K31/4725 A61K31/5377 A61K31/541 A61K31/497 

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to compounds of the formula (I): wherein R¹ means -lower alkyl, -CH₂-aryl, -cycloalkyl, -(CH₂)₃, -OC(=O)CH₃, -lower alcohol, -lower alkyl-R¹⁰, -CH₂COOH or -CH₂CH₂OCH₂CH₃; R² means -lower alkyl, -CH₂-aryl, -lower alcohol, -CH₂C(=O)-NH₂ or lower alkyl-R₁₀ wherein at least one radical among R¹ or R² means -CH₃; R³ means -COOH, -lower alkyl-COOH, -lower alcohol, -CH₂OCH₂, -CH₂NH₂, -CHNHSO₂R¹¹, -C(=O)-R¹², -(CH₂)_nNHC(=O)-R¹³, -(CH₂)_mC(=O)N-(R¹⁵)(R¹⁶), -C(=NH)-R¹⁷ or -(CH₂)_n-R¹⁸; R⁴ means hydrogen atom (-H), -lower alkoxy group, -O-C(R⁷R⁸)C(=O)-R¹⁹, -halogen atom, -SCH₃, -C=CHC(=O)-R¹⁰, -CH₂CH₂C(=O)-R¹⁰, -O-lower alcohol, -OCH₂CH(OH)CH₂N=N^±N^-, -OCH₂CH₂OCH₂CH₂Cl, -NHC9=O)-CH₂-lower alkyl, -O(CH₂)_n-cycloalkyl, -O-lower alkene or 5-membered unsaturated heterocyclic ring comprising one heteroatom representing sulfur (S) or oxygen (O) atom; R⁵ and R⁶ mean independently -H, -halogen atom or -lower alkoxy group; R⁷ and R⁸ mean independently -H or -CH₃; R¹⁰ means 5-6-membered saturated heterocyclyl comprising 1 or 2 heteroatoms, such as N and O, and this group is bound with other moiety of molecule by a ring N atom; R¹¹ means -CF₃, -lower alkyl, -CH₂Cl, -CH₂CF₃ or -R¹²; R¹² means 5-6-membered saturated substituted or unsubstituted heterocyclic ring comprising 1 heteroatom, such as N, O and S wherein substituted ring represents heterocyclic ring substituted with -OH or -phenyl; R¹³ means -lower alkyl, -lower alkoxy group or -(CH₂)_nR¹⁴; R¹⁴ means 5-6-membered saturated or unsaturated heterocyclic ring comprising 1 and 2 heteroatoms, that are chosen from group comprising N and O; R¹⁵ means -H, -lower alkyl, -OH, -lower alkoxy group or -CH₂COOCH₂CH₃; R¹⁷ means -lower alkoxy group, -NH₂ or -N-lower alkyl; R¹⁸ means saturated or unsaturated 5-membered substituted or unsubstituted heterocyclic ring comprising from 1 to 4 heteroatoms, such as N, O and S wherein substituted ring represents heterocyclic ring that is substituted by one or two cyclic carbon atoms by =O, or it is substituted by cyclic N atom by -lower alcohol or -lower alkyl; R¹⁹ means -OH, -NHCH(CH₃)₂, -N(CH₃)CH₂-aryl, -N(CH₃)-lower alkyl, 1-(aryl-(CH₂)_n-)-[1,4]-diazin-4-yl or 5-6-membered saturated heterocyclyl and optionally substituted with lower alkyl comprising 1 or 2 heteroatoms, such as N and O; m = 0, 1 or 2; n = 0 or 1, and their pharmaceutically acceptable salts and esters. Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to GFAT and containing the effective amount of compound of the formula (I). Invention provides expanding assortment of agents possessing inhibitory activity with respect to GFAT. Proposed compounds can be used as inhibitors of GFAT, and pharmaceutical composition possessing inhibitory activity with respect to GFAT containing above said compound of the formula (I) also.

EFFECT: valuable biochemical properties of compounds and pharmaceutical composition.

25 cl, 134 ex