New azaphenylalanine derivatives are thrombine inhibitors useful to treat or inhibit thrombin, fibrin or thrombus formation in the blood

摘要

Azaphenylalanine derivatives (I) and their salts are new. Azaphenylalanine derivatives of formula (I) and their salts are new. [Image] R1>, Z : H, -C(=NR4>)NH2 or CH2-NH3+>Cl->; R4>H, 1-3C alkyl, OH, O-(1-3C alkyl) or NH2; R2>heterocyclic derivative of formula (1-3), azepine o r N(R8>)R9>; R5>-R7>H, 1-3C alkyl or COOR1>0>; R1>0>H or 1-3C alkyl; R8>, R9>H, 1-3C alkyl or 3-6C cycloalkyl; R1>1>H, 1-3C alkyl or benzyl; X : CH, O or S; Y : NR1>2>, O or S; R1>2>H, COCH3 or 1-3C alkyl; and R3>group of formula (4-6) or napthylsufonyl, benzylderivative of formula (9) (where R1> = -CH2-NH3+>Cl->). Provided that: (1) one of R1> and Z is H; and (2) R3>can only be napthylsulfonyl when R1> is -CH2>-NH3+>Cl-> An independent claim is also included for preparation of (I). ACTIVITY : Anticoagulant. MECHANISM OF ACTION : Thrombine inhibitor; Factor Xa inhibitor. (I) were tested for their thrombin inhibitory activity using enzyme assay. The negative logarithm of inhibitory constant for (4-{[1-{[Cyclopentyl(methyl)amino]carbonyl}-2-(2-naphthylsulfonyl)hydrazino]methyl}phenyl)methanaminium chloride was 0.031.