FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel compounds of the formulae (I) and (II) and their pharmaceutically acceptable salts and esters wherein each Z1, Z2 and Z3 is chosen from series of (C1-C6)-alkoxy-group, -CH2OCH3 and -CH2OCH2CH3, or one Z1, Z2 or Z3 means hydrogen atom, and each of two others is chosen independently from series (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CF3, -CH2OCH3, -CH2OCH2CH3, -OCH2CH2R1, -CH2-morpholino, -OR2, -OCH2CF3, -OCH(CH3)CH2OH and -COOQ wherein Q is chosen from series hydrogen atom and (C1-C6)-alkyl, or one of Z1, Z2 or Z3 means hydrogen atom, and two others in common with carbon atoms and in combination with bonds between them and benzene cycle to which they are bound for a cycle chosen from 5- and 6-membered unsaturated cycles and 5- and 6-membered saturated cycles that comprise at least one oxygen atom as heteroatom, and wherein R1 is chosen from series -F, -OCH3, -N(CH3)2 and unsaturated 5-membered cycles comprising at least one nitrogen or oxygen atom as heteroatom, and wherein R2 means 3-6-membered saturated cycle, and each Y1 and Y2 is chosen independently from series -Cl, -Br, -NO2, -C≡N and -C≡CH, and their pharmaceutically acceptable salts and esters and wherein Z4 is chosen from series (C1-C2)-alkyl, (C1-C6)-alkoxy-group, -OH, -SCH3, -CF3, -NO2, -COOQ2, -N(CH3)2, -OCH2-phenyl, -Cl, -Br, -F, -OCH2COQ1, saturated 5- and 6-membered cycles comprising at least one heteroatom wherein heteroatom is chosen from nitrogen (N) and oxygen (O) atom, and wherein Q1 is chosen from series, -OH, -NH2 and -O(C1-C6)-alkyl; Q2 is chosen from series hydrogen atom and (C1-C6)-alkyl; Y1 and Y2 are chosen independently from series -Cl, -Br, -NO2, -C≡N and -C≡CH under condition that if both Y1 and Y2 means -Cl then Z4 doesn't means -Cl, and if both Y1 and Y2 mean -NO2 then Z4 doesn't mean -NO2, and if both Y1 and Y2 mean -CN then Z4 doesn't mean -CN. Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to MDM2. Invention provides synthesis of novel biologically active compounds and preparing pharmaceutical compositions based on thereof possessing inhibitory activity with respect to MDM2.
EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.
14 cl, 50 ex
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Authors
Dates
2007-12-10—Published
2002-12-09—Filed