SYNTHESIS AND USAGE OF ORTHO-SULFONEAMIDO-BICYCLIC HETEROARYL HYDROXAMIC ACIDS AS INHIBITORS OF MATRIX METALLOPROTEINASES AND TACE (TNF-α-CONVERTING ENZYME) Russian patent published in 2003 - IPC

FIELD: organic chemistry, biochemistry, pharmacy. SUBSTANCE: invention relates to novel orthosulfoneamidobicyclic heteroaryl hydroxamic acids of the formula: where W and X both are carbon atom; T is nitrogen atom; U represents CR¹ where R¹ represents hydrogen atom or alkyl containing 1-8 carbon atoms; P represents -N(CH₂R⁵)-SO₂-Z; Q represents -(C=O)-NHOH being is benzene ring or heteroaryl ring with 5-6 atoms in cycle that can contain 0-2 heteroatoms taken among nitrogen, oxygen and sulfur atoms in addition to nitrogen heteroatom designated as W; where benzene or heteroaryl ring can include optionally one or two substituents R¹ if it is admissible; Z is phenyl that is optionally substituted with phenyl. Alkyl with 1-8 carbon atoms or group OR²; R¹ represents halogen atom, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl with 1-4 carbon atoms, phenyl optionally substituted with 1-2 groups of -OR², -NO₂-group, -(CH₂)_n--group where Z is phenyl and n = 1-6; thienyl and -OR²-group where R² represents alkyl with 1-8 carbon atoms; R² represents alkyl with 1-8 carbon atoms, phenyl optionally substituted with halogen atom or heteroaryl radical including 5-6 atoms in cycle, among them, 1-2 heteroatoms taken among nitrogen, oxygen and sulfur atoms; R⁵ represents hydrogen atom, alkyl with 1-8 carbon atoms, phenyl or heteroaryl containing 5-6 atoms in cycle, among them 1-2 heteroatoms taken among nitrogen, oxygen and sulfur atoms; or their pharmaceutically acceptable salts. Indicated compounds are inhibitors of matrix metalloproteinases and TACE-enzyme converts tumor necrosis α-factor. Invention proposes also methods of inhibition of pathological alternations mediated by matrix metalloproteinases and TNF-α-converting enzyme (TACE) and pharmaceutical composition comprising indicated compounds. EFFECT: improved method of synthesis and application, valuable biochemical and medicinal properties. 11 cl, 1 tbl, 99 ex