Cyanopeptide analogues: new lead structures for the design and synthesis of new thrombin inhibitors.
This contribution deals with the structure-based design and syntheses of the new serine protease inhibitors RA-1001 and RA-1002, which are analogues of the blue-green algae derived cyanopeptide aeruginosin 98-B. Both compounds inhibit thrombin with Ki values of 5.6 microM and 8.7 microM, respectively.
Radau
G
G
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, The Ernst-Moritz-Arndt-University, Greifswald, Friedrich-Ludwig-Jahn-Str. 17, D-17487 Greifswald. radau@pharmazie.uni-greifswald.de
Stürzebecher
J
J
D000458:Cyanobacteria / Q000737:chemistry; D015195:Drug Design; D005341:Fibrinolysin / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology
D007202:Indicators and Reagents; D009842:Oligopeptides; C472545:RA1001; C472546:RA1002; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; C472547:aeruginosin 98-B; D013917:Thrombin; D005341:Fibrinolysin