PHOSPHONIC ACID COMPOUNDS AS SERINE PROTEINASE INHIBITORS Russian patent published in 2007 - IPC C07F9/38 C07F9/40 C07F9/42 A61K31/662 A61P29/00 

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention relates to phosphonic acid compounds used as inhibitors of serine proteinase of the general formula (I): wherein R₁ is chosen from group comprising piperidinyl, pyrrolidinyl and 1,3,8-triazaspiro[4,5]dec-8-yl (wherein heterocyclic ring as added to nitrogen atom in ring) and -N(R₇R₈0 wherein this heterocyclic ring is substituted optionally with one or two substitutes chosen independently from group comprising the following compounds: (a) C₁-C₈)-alkyl substituted optionally at terminal carbon atom with a substitute chosen from group comprising aryl, heteroaryl; c) phenyl and naphthalenyl; i) benzothiazolyl; R₇ is chosen from group comprising hydrogen atom and (C₁-C₈)-alkyl; R₈ is chosen from group comprising: (aa) (C₁-C₈)-alkyl; (ab) cycloalkyl; (ac) cycloalkenyl, and (ad) heterocyclyl (wherein R₈ is added to carbon atom in ring) wherein (ab) cycloalkyl; (ac) cycloalkenyl, and (ad) heterocyclyl (wherein heterocyclyl (ad) comprises at least one cyclic nitrogen atom) substitutes and cycloalkyl moiety (aa) of a substitute is substituted optionally with substitutes chosen independently from group comprising: (ba) (C₁-C₈)-alkyl substituted at terminal carbon atom with a substitute chosen from group comprising amino-group (with two substitutes chosen independently from group comprising hydrogen atom and (C₁-C₈)-alkyl); (bb) (C₁-C₈)-alkoxy-group substituted at terminal carbon atom with a substitute chosen from group comprising carboxyl; (bc) carbonyl substituted with a substitute chosen from group comprising (C₁-C₈)-alkyl, aryl, aryl-(C₂-C₈)-alkenyl; (bd) aryl; (be) heteroaryl; (bf) amino-group substituted with two substitutes chosen independently from group comprising hydrogen atom and (C₁-C₈)-alkyl; (bh) halogen atom; (bi) hydroxy-group; (bk) heterocyclyl wherein (bd) is aryl substitute, and heteroaryl moiety (bc) comprise a substitute (halogen atom)_1-3; R₄ is chosen from group comprising aryl and heteroaryl wherein heteroaryl comprises halogen atom as a substitute; R₂ and R₃ are bound with benzene ring and represent hydrogen atom, and R₂ and R₃ form in common optionally at least one ring condensed with benzene ring forming polycyclic system wherein this polycyclic system is chosen from group comprising (C₉-C₁₄)-benzocondensed cycloalkenyl, (C₉-C₁₄)-benzocondensed phenyl; R₅ is chosen from group comprising hydrogen atom and (C₁-C₈)-alkyl; R₆ is chosen from group comprising (C₁-C₈)-alkyl and hydroxy-group; Y is absent, and X represents a single substitute that is added by a double bond and represents oxygen atom (O), and Z is chosen from group comprising a bond, hydrogen atom, and its salts. Also, invention relates to a method for synthesis of these compounds, to their composition inhibiting serine proteinase and to a method for its preparing. Proposed invention describes a method for treatment of inflammatory or serine proteinase-mediated disorder.

EFFECT: valuable biochemical and medicinal properties of compounds.

64 cl, 5 tbl, 38 ex