| 摘要 |
FIELD: organic chemistry of heterocyclic compounds, pharmacy. SUBSTANCE: invention relates to pharmaceutical composition used for inhibition of activity of integrase and comprising as an active component a compound of the formula (I): wherein X means hydroxy-group; Y means group -COOR4 wherein RA represents hydrogen atom or ester residue, or it means group -CON-RBRC wherein each RB and RC means independently of one another hydrogen atom or amide residue, optionally substituted aryl or optionally substituted heteroatyl; A1 means optionally substituted heteroaryl with exception for a compound wherein Y and/or A1 mean optionally substituted indole-3-yl, or it comprises its tautomer, prodrug, pharmaceutically acceptable salt or hydrate. Invention relates also to compound of the formula (II): wherein X and Y are given above; A1 means optionally substituted heteroaryl; Z1,Z2 mean a bond; Z2 means a bond, (lower)-alkylene, -CH(OH)-, -S-, -SO2-, -O- or -CO; Z4 means a bond, (lower)- alkylene, (lower)-alkenylene or -CO-; R1 means optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycle; R2 means optionally substituted (lower)-alkyl, optionally substituted (lower)-alkyloxy-group, optionally substituted (lower)- alkoxycarbonyl, optionally substituted aryl, optionally substituted aryloxy-group, carboxy-group or halogen atom; p = 0 or 1 with exception for compounds wherein: (1) Y and/or A1 means optionally substituted indole-3-yl and (2) X means hydroxy-group; Y means 2-thienyl; A1 means 1H-1,2,4- triazole-3-yl; each Z1,Z3 means a bond; Z2 means NH-; R1 means phenyl or para-tolyl; p = 0; (3) X means hydroxy-group; Y means 4-methoxyphenyl or 4-chlorophenyl; A1 means thiazole-5-yl; each Z1,Z2,Z3,Z4 means a bond; R1 means phenyl, 4-methoxyphenyl or 4-chlorophenyl; R2 means methyl; p = 1; (4) X means hydroxyl group; Y means phenyl, 4-methylphenyl, 4-bromophenyl or 4-chlorophenyl; A1 means imidazole-2-yl; each Z1,Z3 means a bond; Z2 means methylene group; R1 means phenyl; Z4 means a bond; means 4-dimethylaminophenyl or 4-methoxyphenyl; p = 1; (5) X means hydroxyl group; Y means phenyl, 4-methylphenyl or 4-methoxyphenyl; A1 means 1,2,3-triazole-4-yl; each Z1,Z2,Z3 means a bond; R1 means phenyl; p = 0; (6) X means hydroxyl group; Y means -COORA wherein RA means hydrogen atom or ethyl group; A1 means 3-indolyl, imidazo[1,2-a]pyridine-3-yl or imidazo[2,1-b] thiazole-5-yl; each Z1,Z2,Z3 means a bond; R1 means optionally substituted phenyl and also tautomer, prodrug, pharmaceutically acceptable salt or hydrate; and to different pharmaceutical compositions comprising as an active component the compound of the formula (II), to medicinal mixture eliciting with an anti-HIV- activity. Invention relates also to method for preparing compounds of the formula (III) and also to intermediate compounds of the formula: wherein Z2 means a bond, -CO-, -O-, -CH2- or -(CH2)2-; R1 means phenyl substituted with fluorine atom, and to formula: wherein A means C-W wherein W means hydrogen atom, (lower)-alkyl, (lower)-haloalkyl or halogen atom or N; Q means trityl; L means ethoxy-group. EFFECT: valuable medicinal properties of compounds. 27 cl, 4 tbl, 162 ex |
