ARGINASE INHIBITORS AND THERAPEUTIC USE THEREOF Russian patent published in 2016 - IPC C07F5/02 A61K31/69 

FIELD: chemistry.

SUBSTANCE: invention relates to compound of formula I (I), wherein R¹ is selected from group consisting of-OH and OR^a; R^a is selected from group consisting of hydrogen, linear or branched (C₁-C₆)alkyl, (C₃-C₁₄)aryl, (C₃-C₁₄)heterocycloalkyl-(C₁-C₆)alkylene-, containing 1-4 heteroatoms selected from O, S and N, (C₃-C₁₄)heteroaryl-(C₁-C₆)alkylene-, containing 1-4 heteroatoms selected from O, S and N, and (C₃-C₁₄)aryl(C₁-C₆)alkylene-; and where (A) R² is selected from group consisting of (C₃-C₁₄)heterocycloalkyl-(C₁-C₆)alkylene-, containing 1-4 heteroatoms selected from O, S and N, and -(CH₂)_m-(X)_u-(CH₂)_n-(Y)_v-R^f where u is 1; v represents 0; each m and n independently equal to 0, 1, 2, 3, 4, 5 or 6, where m + n≥1, each X and Y is -NH-; R^f is (C₃-C₁₄)aryl; and R⁵ represents linear or branched (C₁-C₆)alkyl; or where (B) R² is (C₃-C₁₄)heterocycloalkyl-(C₁-C₂)alkylene, containing 1-4 heteroatoms selected from O, S and N, and R⁵ is selected from group consisting of n and linear or branched (C₁-C₆)alkyl; and where each R³ and R⁴ is hydrogen; D is -CH₂CH₂CH₂CH₂-; and where any alkyl or alkylene optionally contains one or more substitutes selected from group consisting of halogen,-OH and (C₁-C₆)alkoxy; and where any aryl, heteroaryl or heterocycloalkyl, possibly containing one or more substitutes selected from a group consisting of halogen,-OH, oxo,-COOH, (C₃-C₁₄)aryl(C₁-C₆)alkylene-, (C₃-C₁₄)aryl, (C₃-C₁₄)heteroaryl containing 1-4 heteroatoms selected from O, S and N, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)halogen alkyl and (C₁-C₆)hydroxy alkyl; or its pharmaceutically acceptable salt, stereoisomer, tautomer or prodrug is revealed. Invention also discloses compound of formula II, pharmaceutical composition, method of inhibiting arginase I, arginase II or their combination in cell, method of treating or preventing disease or condition associated with expression or activity of arginase I, arginase II or their combination, and compound specified in table.

EFFECT: compound of formula I and formula II represent high-activity arginase I and II inhibitors.

30 cl, 6 tbl, 255 ex