ANTHRANILIC ACID AMIDES AND THEIR USING IN PHARMACEUTICALS Russian patent published in 2008 - IPC C07D213/38 C07D213/89 C07C237/40 A61K31/44 A61K31/166 A61K31/167 

FIELD: organic chemistry, medicine, biochemistry.

SUBSTANCE: invention relates to anthranilic acid amides of the formula (I): wherein Ar means subformula (I_a): wherein R_a means hydrogen atom (H) or (lower)-alkyl; R₁ means H or perfluoro-(lower)-alkyl; R₂ means H; or Ar means subformula (I_b): ; R₁ means perfluoro-(lower)-alkyl; R₂ means bromine, atom, fluorine atom, chlorine atom, (C₂-C₇)-alkyl, (C₂-C₇)-alkenyl or (lower)-alkynyl; or R₁ means H; R₂ means bromine atom or (lower)-alkynyl, or its N-oxide or tautomer, or anthranilic acid amide salt, or its tautomer. Also, invention relates to a pharmaceutical composition possessing inhibitory effect on activity of tyrosine kinase receptors VEGF and comprising anthranilic acid amide of the formula (I) or its N-oxide, or its tautomer, either pharmaceutically acceptable salt of such compound, and at least one pharmaceutically acceptable carrier. Also, invention relates to a method for synthesis of anthranilic acid amide of the formula (I) wherein R₂ means hydrogen atom or halogen atom, and other symbols R₁ and Ar have values given in claim 1. Method involves interaction of compound of the formula (II): wherein R₁ and R₂ have values given above for compound of the formula (I) with carbonyl derivative of the formula (III): wherein Ar has values given above for compound of the formula (I) in the presence of a reducing agent. In the parent compounds of formula (II) and (III) functional groups, if necessary, can be in a protected form and/or as salts under condition of presence of salt-forming group and reaction with participation of compounds as salt is possible. Then any protecting groups in a protected derivative of compound of the formula (I) are removed. If necessary, synthesized compound of the formula (I) is converted to other compound of the formula (I) or its N-oxide, or free compound of the formula (I) is converted to salt and prepared salt of compound of the formula (I) is converted to free compound or another salt. Invention provides synthesis of anthranilic acid amide of the formula (I) or its N-oxide or tautomer, or pharmaceutically acceptable salt of such compound designated for treatment of diseases showing sensitivity to inhibition of activity of tyrosine kinase receptors VEGF.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds.

16 cl, 12 ex