SERINE PROTEASE INHIBITOR

摘要

The invention relates to a serine protease inhibitor having formula (I), in which J is H, R1, R1-O-C(O)-, R1-C(O)-, R1-SO2-, R3OOC-(CHR2)p-, (R2a, R2b)N-CO-(CHR2)p- or Het-CO-(CHR2)p-; D is an amino-acid of the formula -NH-CHR1-C(O)-, -NR4-CH[(CH¿2?)qC(O)OR?1¿]-C(O)-, -NR4-CH[(CH¿2?)qC(O)N(R?2a,R2b¿)]-C(O)-, -NR4-CH[(CH¿2?)qC(O)Het]-C(O)-, D-1-Tiq, D-3-Tiq, D-Atc, Aic, D-1-Piq or D 3-Piq; E is -NR?2-CH¿2 or the fragment (a), optionally substituted with (1-6C)alkyl, (1-6C)alkoxy or benzyloxy; R1 is selected from (1-12C)alkyl, (2-12C)alkenyl, (2-12C)alkynyl, (3-12C)cycloalkyl and (3-12C)cycloalkyl(1-6C)alkylene, which groups may optionally be substituted with (3-12C)cycloalkyl, (1-6C)alkoxy, oxo, OH, CF¿3? or halogen, and from (6-14C)aryl, (7-15C)aralkyl, (8-16C)aralkenyl and (14-20C)(bisaryl)alkyl, whereby the aryl groups may optionally be substituted with (1-6C)alkyl, (3-12C)cycloalkyl, (1-6C)alkoxy, OH, CF3 or halogen; R?2, R2a and R2b¿ are each independently selected from H, (1-8C)alkyl, (3-8C)alkenyl, (3-8C)alkynyl, (3-8C)cycloalkyl and (3-6C)cycloalkyl(1-4C)alkylene, which can each be optionally substituted with (3-6C)cycloalkyl, (1-6C)alkoxy, CF¿3? or halogen, and from (6-14C)aryl and (7-15C)aralkyl whereby the aryl groups may optionally be substituted with (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, CF3 or halogen; R?3¿ is defined for R2 or Het-(1-6C)alkyl; R4 is H or (1-3C)alkyl; X and Y are CH or N with the proviso that they are not both N; Het is a 4-, 5- or 6-membered heterocycle containing one or more heteroatoms selected from O, N and S; m is 1 or 2; p is 1, 2 or 3; q is 1, 2 or 3; t is 2, 3 or 4; or a prodrug; or a pharmaceutically acceptable addition salt and/or solvate thereof and its use in therapy and manufacture of a medicament for treating or preventing thrombin-mediated and thrombin-associated diseases.