| abstract |
The invention relates to new competitive inhibitors of trypsin-like serine proteases, their synthesis, pharmaceutical compositions containing the compounds as active ingredients, and the use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory inhibitors for prophylaxis and treatment of related diseases, according to the formula 1 A compound of the general formula I, wherein: A1 represents a structural fragment of Formula Iia, Iib or Iic; wherein: k is an integer 0, 1, 2, 3 or 4; q is an integer 1, 2, or 3; R1 represents, H, an alkyl group having 1 to 4 carbon atoms, or R11OOC-alkyl-, where the alkyl group has 1 to 4 carbon atoms and is possibly substituted in the position which is alpha to the carbonyl group, and the alpha substituent is a group R17-(CH2)p-, wherein p is 0, 1 or 2 and R17 is methyl, COOR12, where R12 is H or an alkyl group having 1 to 4 carbon atoms, and R11 is H or an alkyl group having 1 to 6 carbon atoms or a benzyl group, or R1 represents R13-NH-CO-alkyl-, where the alkyl group has 1 to 4 carbon atoms and where R13 is H or -CH2COOR12, where R12 is as defined above, or R1 represents R12-OOC-CH2-alkyl-, where the alkyl group has 1 to 4 carbon atoms and where R12 is as defined above, or R1 represents R14SO2-, Ph(4-COOR12)-SO2-, Ph(3-COOR12)-SO2-, Ph(2-COOR12)-SO2-where R12 is as defined above and R14 is an alkyl group having 1-4 carbon atoms, or R1 represents -CO-R15, wherein R15 is an alkyl group having 1-4 carbon atoms, or R1 represents -CO-R15, where R15 is as defined above, or R1 represents -CO-(CH2)p-COOR12, where R12 is as defined above and p is an integer 0, 1 or 2, or R2 represents H or an alkyl group having 1 to 4 carbon atoms or R21OOC-alkyl-, where the alkyl group has 1 to 4 carbon atoms and where R21 is H or an alkyl group having 1 to 4 carbon atoms or a benzyl group; R3 represents an alkyl group having 1-4 carbon atoms, or R3 represents a cyclopentyl, cyclohexyl- or a phenyl group; R4 represents H or a phenyl group; A2 represents a structural fragment of Formula IIIa, IIIb or IIIc wherein: p is an integer 0, 1 or 2; m is an integer 1, 2, 3 or 4; Y represents a methylene group, or Y represents an ethylene group, or Y represents an n-propylene groups, or Y represent -CH2-CH2-CH2-CH2-; R3 is as defined above; R5 represents H; n is an integer 1, 2, 3 or 4; B represents a structural fragment of Formula Iva or Ivb wherein: r is an integer 0 or 1; X1 represent CH2 or NH or is absent; X2 represents CH2, NH or C=NH; X3 represents NH, C=NH, NH-C(NH)-NH2 or CH-C(NH)-NH2; X4 represents CH2; X5 represents C(NH)-NH2; R6 is H; D is as optional substituent, Z or (Z)2, replacing one or more H atoms to in B as appropriate; and Z is a benzyloxy carbonyl group; either the compound as such or stereo isomers hereof or in the form of a physiologically acceptable salt. |