Design, synthesis and molecular modelling of 1-amidinopiperidine thrombin inhibitors.
Design, synthesis and biochemical evaluation of a series of novel non-covalent thrombin inhibitors with a 1-amidinopiperidine moiety are presented. Replacement of the planar benzamidine group in azaphenylalanine derivatives with 1-amidinopiperidine resulted in lower activity but higher selectivity for this type of compounds. The binding conformation of inhibitors in the active site of thrombin was revealed by molecular modelling studies.
Smolnikar
I
I
Faculty of Pharmacy, University of Ljubljana, University Medical Centre, Slovenia.
Perdih
A
A
Stegnar
M
M
Prezelj
A
A
Solmajer
T
T
Urleb
U
U
Obreza
A
A
D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D015195:Drug Design; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D010314:Partial Thromboplastin Time; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011517:Prothrombin Time; D013055:Spectrophotometry, Infrared; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013918:Thrombin Time; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C519958:1-amidinopiperidine; D007202:Indicators and Reagents; D010880:Piperidines; D014361:Trypsin Inhibitors; D013917:Thrombin