SERINE PROTEASE INHIBITORS Russian patent published in 2001 - IPC

FIELD: pharmaceutical chemistry. SUBSTANCE: invention provides serine protease inhibitors having piperidine side chain of general formula I: (I), wherein A is hydrogen atom, optionally substituted D, L-alpha-hydroxyacetyl, R¹,R¹-O-C(O)-,R¹-SO₂- and R²OOC-(CHR²)_m-, in which R¹ is selected from C1-C12-alkyl and C3-C8- cycloalkyl, indicated groups being optionally substituted by OH group, and C7-C15-arylalkyl; each group R² independently denotes hydrogen atom or has the same denotations as indicated for R¹; m=1,2 or 3; B denotes chemical bond, amino acid of formula -NH-CH[(CH₂)_pC(O)OH]-C(O)- with p=0,1,2, or 3, -N((1-12C)alkyl)-CH₂-CO-, or D-1-Piq; or B represents D-amino acid having hydrophobic side chain; or A and B, taken together, represent group R³R⁴N-CHR⁵-C(O), in which R³ and R⁴ independently denote R¹,R¹-O-C(O)-,R¹-C(O)-,R¹-SO²- and R⁵ denotes hydrophobic or basic side chain; X represents L-amino acid with hydrophobic side chain; Y is CO-NH-C1-C6- alkylene-C₆H₅, -COOR⁶, in which R⁶ denotes hydrogen atom or C1-C6-alkyl, CONR⁷R⁸, in which R⁷ and R⁸, independent from each other, denote hydrogen atom or C1-C6- alkyl, or R⁷ and R⁸, taken together, represent C3-C6- alkylene; or Y denotes residue of heterocycle, selected from 2-thiazole, 2-benzothiazole, 20oxazole, or 2- benzoxazole; r = 0,1,2, or 3; or their pharmaceutically acceptable salts. Proposed compounds show anticoagulation activity and can be used for treating or preventing thrombin-caused diseases. Invention also provides pharmaceutical composition containing such inhibitor. EFFECT: increased assortment of anticoagulants. 15 cl, 2 tbl, 64 ex