| abstract |
The invention relates to non-slow-binding thrombin inhibitors of the formula: A-B-C-Lys-D wherein A is H, 2-hydroxy-3-cyclohexyl-propionyl-, R1, R1-O-CO-, R1-CO-, R1-SO2-, -(CHR2)nCOOR3, or an N-protecting group, wherein R1 is selected from -(1-6C)alkylene-COOH, (1-12C)alkyl, (2-12C)alkenyl, (6-14C)aryl, (7-15C)aralkyl and (8-16C)aralkenyl, the aryl group of which may be substituted with (1-6C)alkyl, (2-12C)alkoxy, hydroxy, or halogen; R2 is H or has the same meaning as R1, R3 is selected from H, (1-12C)alkyl, (2-12C)alkenyl, (6-14C)aryl, (7-15C)aralkyl and (8-16C)aralkenyl, the aryl group of which may be substituted with (1-6C)alkyl, (2-12C)alkoxy, hydroxy or halogen; n is an integer of 1 to 3; B is a bond, L-Asp or an ester derivative thereof, Leu, norLeu, -N(benzyl)-CH2-CO-, -N(2-indane)-CH2-CO-, D-1-Piq, D-3-Piq, D-Tiq, Atc or a D-amino acid having a hydrophobic aromatic side chain; C is Azt, Pro, Pec, norLeu(cyclo)Gly, an amino acid of one of the formulae -N[(3-8C)cycloalkyl]-CH2-CO- or -N(benzyl)-CH2-CO-, D is selected from COOH, tetrazole, oxazole, thiazole and benzothiazole, or A and C have the aforesaid meanings, B is D-(3-8C)cycloalkylalanine, and D is tetrazole, oxazole, thiazole or benzothiazole; or a prodrug thereof; or a pharmaceutically acceptable salt thereof; with the exception of the compound Me-D-Phe-Pro-Lys-COOH. The compounds can be used as antithrombotic agents. |