Novel non-covalent azaphenylalanine thrombin inhibitors with an aminomethyl or amino group at the P1 position.
Design, synthesis and biological evaluation of a series of novel non-covalent azaphenylalanine thrombin inhibitors are presented. Replacement of the basic benzamidine moiety in azaphenylalanine derivatives by benzylamine (P1 part of a molecule) and the introduction of a N-cyclopentyl-N-methylamine moiety in the P2 part of a molecule resulted in the thrombin inhibitor LK-733 with greatly increased selectivity against trypsin and an in vitro Ki of 31 nM.
Obreza
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A
Faculty of Pharmacy, University of Ljubljana, University Medical Centre, Ljubljana, Slovenia.
Stegnar
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M
Urleb
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U
D001665:Binding Sites; D065427:Factor Xa Inhibitors; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology
D065427:Factor Xa Inhibitors; D006834:Hydrazines; D007202:Indicators and Reagents; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D010649:Phenylalanine; D013917:Thrombin