METHOD FOR INHIBITION OF CASPASE ACTIVITY Russian patent published in 2004 - IPC

FIELD: organic chemistry, biochemistry, biotechnology.

SUBSTANCE: invention relates to inhibition of activity of aspartate-specific cysteine protease (caspase) and can be used cellular biology, physiology and pharmacology for study and directed regulation of processes associated with induction, development and/or prophylaxis of the scheduled cellular death (apoptosis). Method for inhibition of activity of caspases is carried out by administration to medium nitrogen-containing compound, namely, derivative of 1,2-isothiazole-3-one of the general formula [1] indicated in the description wherein if R¹ means unsubstituted phenyl or phenyl comprising as a substituent chlorine atom, methyl, trifluoromethyl, ethoxycarbonyl or methoxy-group then R² means hydrogen atom, phenyl, ethoxycarbonyl, methoxy- or cyano-group, and R³ means unsubstituted phenyl or phenyl comprising as a substituent chlorine atom, methyl, trifluoromethyl or methoxy-group; or R² and R³ in common with adjacent carbon atoms form annelated benzene or pyridine cycle that can be substituted with halogen atom, nitro-, amino- or methoxy-group; or if R¹ means (C₁-C₄)-alkyl, benzyl, thiazolyl, pyridyl, benzothiazolyl or phenyl comprising as a substituent 4-F, 4-Br, 4-J, two (C₁-C₄)-alkyl groups, 4-aminocarbonyl, 4-[(dimethyl)amino]carbonyl, nitro-, amino-, 4-cyano-group, 2-3 methoxy-groups or methoxycarbonyl and methoxy-group simultaneously then R²-R³ means -CH=CH-CH=N-; or if R¹ - R⁴ means -NR⁵R wherein R means (C₁-C₁₂)-alkylene; R and R mean (C₁-C₄)-alkyl groups or NR⁵, and R⁶ forms unsaturated nitrogen-containing heterocycle, such as pyrrolidine, piperidine, azepine then R² and R³ in common with adjacent carbon atoms form annelated benzene cycle that can comprise 1-2 substituents taken among the group: halogen atom, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxyl, nitro-, amino- or acylamino-group, or its biochemically acceptable salt. Invention provides effective reducing activity of caspases in the presence of other proteins (for the known isatin derivative the value IC₅₀ = 7.5 ± 3.5 mcM; in the presence of 10 mcM compounds used in the describing method, in particular, 2-phenyl- and 2-benzyl-6-nitro-1,2-benzoisothiazole-3-one activity of caspases is determined to be 4.84 ± 0.80 and 4.30 ± 0.64% of the parent value, respectively).

EFFECT: enhanced inhibition method, valuable biochemical properties of compounds.

1 ex