New isosteric peptides.

摘要

The invention relates to new competitive inhibitors of thrombin, their synthesis, pharmaceutical compositions containing the compounds as active ingredients, and the use of the compounds as anticoagulants for prophylaxis and treatment of thromboembolic diseases, according to the formula wherein: A represents -CH2-, -CH=CH-, -CH2-CH2- or -CH2-CH2-CH2- ; R<1> and R<2> are the same or different and each represents H or X-B-, where B is a straight or branched alkylene group having 1-3 carbon atoms and X is H, methyl, ethyl, a cycloalkyl group having 3-6 carbon atoms or R min CO-, where R min is OH, a straight or branched alkoxy group having 1-4 carbon atoms, NH2 or NHR sec , where R sec is a straight or branched alkyl group having 1-4 carbon atoms, or X is a carboxylic acid mimic, known per se, selected from -PO(OR sec min )2, -SO3H and 5-(1H)-tetrazolyl, and R sec min is H, methyl or ethyl, or B is -SO2- and X is methyl or ethyl; m is 0, 1 or 2, R<3> represents a cyclohexyl group and R<3A> represents H: or m is 1 and R<3> represents a cyclohexyl or phenyl group and R<3A> forms an ethylene bridge together with R<1> ; Y represents O or S(O)p, where p is 0, 1 or 2; R<4> represents H; a straight or branched alkyl or a cycloalkyl having 1 to 6 carbon atoms unsubstituted or substituted with one or more fluoro atoms and/or substituted with a phenyl group: a substituted or unsubstituted aromatic ring selected from phenyl, 4-methoxy-phenyl, 4-tertiary-butyl-phenyl, 4-methyl-phenyl, 2-, 3- or 4-trifluoro-methyl-phenyl, phenyl substituted with 1-5 fluoro atoms: or -CH(CF3)-phenyl, either as such or in the form of a physiologically acceptable salt and including stereoisomers.