Patent RU-2311421-C2 (RU)
Inventor: GREKO MAJKL N
IPC: C07F9/6561
Filed: 2002-10-17
Granted: 2007-11-27
Abstract: FIELD: organic chemistry, biochemistry, medicine. 
     SUBSTANCE: invention relates to phosphonic acid compounds used as inhibitors of serine proteinase of the general formula (I):   wherein R 1  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(R 7 R 8 0 wherein this heterocyclic ring is substituted optionally with one or two substitutes chosen independently from group comprising the following compounds: (a) C 1 -C 8 )-alkyl substituted optionally at terminal carbon atom with a substitute chosen from group comprising aryl, heteroaryl; c) phenyl and naphthalenyl; i) benzothiazolyl; R 7  is chosen from group comprising hydrogen atom and (C 1 -C 8 )-alkyl; R 8  is chosen from group comprising: (aa) (C 1 -C 8 )-alkyl; (ab) cycloalkyl; (ac) cycloalkenyl, and (ad) heterocyclyl (wherein R 8  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) (C 1 -C 8 )-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 (C 1 -C 8 )-alkyl); (bb) (C 1 -C 8 )-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 (C 1 -C 8 )-alkyl, aryl, aryl-(C 2 -C 8 )-alkenyl; (bd) aryl; (be) heteroaryl; (bf) amino-group substituted with two substitutes chosen independently from group comprising hydrogen atom and (C 1 -C 8 )-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 ; R 4  is chosen from group comprising aryl and heteroaryl wherein heteroaryl comprises halogen atom as a substitute; R 2  and R 3  are bound with benzene ring and represent hydrogen atom, and R 2  and R 3  form in common optionally at least one ring condensed with benzene ring forming polycyclic system wherein this polycyclic system is chosen from group comprising (C 9 -C 14 )-benzocondensed cycloalkenyl, (C 9 -C 14 )-benzocondensed phenyl; R 5  is chosen from group comprising hydrogen atom and (C 1 -C 8 )-alkyl; R 6  is chosen from group comprising (C 1 -C 8 )-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