Prodrugs of thrombin inhibitors, process for their preparation, pharmaceutical composition containing its and their use

A compound of formula R1O(O)C-CH2-(R)Cgl-Aze-Pab-R2, wherein R1 represents R3 or A1C(O)N(R4)R5 or A1C(O)OR4, A1 represents C1-5 alkylene, R2 (which replaces one of the hydrogen atoms in the amidino unit of Pab-H) represents OH, OC(O)R6, C(O)OR7 or C(O)OCH(R8)OC(O)R9, R3 represents H, C1-10 alkyl or C1-3 alkylphenyl, which is optionally substituted by C1-6 alkoxy, nitro or halogen, R4 and R5 independently represent H, C1-6 alkyl, phenyl, 2-naphthyl or, when R1 represents A1C(O)N(R4)R5, together with the nitrogen atom to which they are attached represent pyrrolidinyl or piperidinyl, R6 represents C1-17 alkyl, phenyl or 2-naphthyl, all of which are optionally substituted by C1-6 alkyl or halogen, R7 represents 2-naphthyl, phenyl, C1-3 alkylphenyl, all of which are optionally substituted by C1-6 alkyl, C1-6 alkoxy, nitro, or halogen, or C1-12 alkyl, which is optionally substituted by C1-6 alkoxy, C1-6 acyloxy or halogen, R8 represents H, C1-4 alkyl, R9 represents 2-naphthyl, phenyl, C1-6 alkoxy or C1-8 alkyl, which is optionally substituted by halogen, C1-6 alkoxy or C1-6 acyloxy, provided that when R1 represents R3, R3 represents benzyl, methyl, ethyl, n-butyl or n-hexyl and R2 represents C(O)OR7, then R7 does not represent benzyl, and a pharmaceutically acceptable salt thereof, process for their preparation, pharmaceutical composition containing its, and its use for the treatment of a condition where inhibition of thrombin is required, e.g. thrombosis or as an anticoagulant. Zlúčenina vzorca R1O(O)C-CH2-(R)Cgl-Aze-Pab-R2, kde R1 znamená R3 alebo A1C(O)N(R4)R5, alebo A1C(O)OR4, A1 znamená C1-5 alkylén, R2 (ktorý nahrádza jeden z H amidínovej jednotky Pab-H) predstavuje OH, OC(O)R6, C(O)OR7 alebo C(O)OCH(R8)OC(O)R9, R3 znamená H, C1-10 alkyl, C1-3 alkylfenyl, voliteľne substituovaný C1-6 alkyloxy, NO2 alebo halogén, R4 a R5 znamenajú od seba nezávisle H, C1-6 alkyl, fenyl, 2-naftyl, alebo v prípade, keď R1 predstavujeA1C(O)N(R4)R5, spolu s N, na ktorý sú viazané pyrolidinyl alebo piperidinyl, R6 znamená C1-17 alkyl, fenyl alebo 2-naftyl, ktoré sú všetky voliteľne substituované C1-6 alkylovou skupinou alebo halogénom, R7 znamená 2-naftyl, fenyl, C1-3 alkylfenyl, ktoré sú všetky voliteľne substituované C1-6 alkylovou skupinou, C1-6 alkoxy, NO2 alebo halogénom, alebo prestavuje C1-12 alkyl voliteľne substituovaný C1-6 alkoxy, C1-6 acyloxy alebo halogénom, R8 znamená H, C1-4 alkyl, R9 znamená 2-naftyl, fenyl, C1-6 alkoxy, C1-8 alkyl voliteľne substituovaný halogén