Thrombin inhibitors

Compounds of general formula (I)

• D—CO—B—A-Het (I)
• wherein
• Het represents a group selected from the group consisting of formulae:
• 97
• R1 and R2 independently represent H or NH2;
• A represents
• group —CONH— or —CH2NH— attached to Het by the NH fragment,
• group —CONHCH2— or —CH2NHCH2 attached to Het by the CH2 fragment,
• group —CH2NHCONH—, —CH2NHCH2CONH— or —CH2NHCOCH2NH-attached to Het by the NH fragment,
• group —CH2NHCONHCH2—, —CH2NHCH2CONHCH2— or —CH2NHCOCH2NHCH2— attached to Het by the CH2 fragment;
• B is selected from the group consisting of groups of formulae:
• 98
• wherein:
• Z is CH2, S or CH—OH
• R3 is H, straight or branched C1-C4 alkyl, C3-C7 cycloalkyl
• R4 is H, straight or branched C1-C4 alkyl, C3-C7 cycloalkyl;
• D represents a group
• 99
• wherein Rd is H, CH2OH, CH2SH or a group
• 100
• wherein
• Ra and Rb are independently selected from the following groups:
• H,
• C1-C4 straight or branched alkyl which can be substituted with C3-C7 cycloalkyl or with 1 to 9 atoms of halogen selected from F, Cl, Br, I,
• C3-C7 cycloalkyl,
• C9-C10 bicycloalkyl,
• a stable saturated or unsaturated 5- to 7-membrered monocyclic heterocyclic system, or a 8- to 10-membrered bicyclic heterocyclic system which, in addition to carbon atoms, contains 1 to 3 heteroatoms selected from N, O and S, in which N or S can be oxidized or N quaternized,
• aryl (e.g., phenyl, naphthyl) which can be optionally unsubstituted or substituted at any position with one or two substituents selected from C1-4 alkyl, C1-4 alkoxy, halogen or hydroxy,
• Rc is selected from groups:
• NH2
• NH(CH2)nCH3, where n is 0, 1, 2 or 3,
• NH(CH2)mOH, where m is 2, 3 or 4,
• NH(CH2)kCOOH, where k is 1, 2 or 3,
• NH(CH2)nCOOR5, where n is 0, 1, 2 or 3 and R5 represents C1-4 straight or branched alkyl,
• NH(CH2)kCONR6R7, where k is 1, 2 or 3 and R6 in R7 are independently H or straight or branched C1-4 alkyl, or R6 and R7 together are —(CH2)4-5—, —(CH2)2O(CH2)2— or —(CH2)2NH(CH2)2—,
• NHO2S(CH2)n—W where n is 0, 1, 2 or 3, W represents phenyl, naphthyl, a saturated or unsaturated monocyclic 5- or 6-membered or saturated or unsaturated bicyclic 8- to 10-membered heterocyclic ring which contains from 1 to 3 heteroatoms selected from N, O or S in which N or S can be oxidized or N quaternized;
• each ring may be optionally substituted by one or more substituents selected from C1-4 alkyl, C1-4 alkoxy, amino, cyano, halogen or hydroxy,
• N[O2S(CH2)n—W][(CH2)kCOOH]where n is 0, 1, 2 or 3 and where k is 1, 2 or 3,
• NH(CH2)kNH2, where k is 1, 2 or 3,
• NHC(Ph)3,
• in the form of pure diastereomers or a mixture of diastereomers or pharmaceutically acceptable salts thereof with anticoagulant activity.