Heterocyclic thrombin inhibitors. Part 1: design and synthesis of amidino-phenoxy quinoline derivatives.
Amidino-phenoxy quinoline derivatives represent a new class of potent thrombin inhibitors with good selectivity and remarkably low molecular weight (M(W): 335-391). X-ray analyses of thrombin-bound inhibitors revealed that enzyme inhibition is mainly based on hydrophobic interactions.
Ries
Uwe J
UJ
Department of Chemical Research, Boehringer Ingelheim Pharma KG, Birkendorfer Strasse 65, D-88397, Biberach/Riss, Germany. uwe.ries@bc.boehringer-ingelheim.com
Priepke
Henning W M
HW
Hauel
Norbert H
NH
Haaksma
Eric E J
EE
Stassen
Jean M
JM
Wienen
Wolfgang
W
Nar
Herbert
H
D000578:Amidines / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D015195:Drug Design; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008958:Models, Molecular; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology
D000578:Amidines; D005343:Fibrinolytic Agents; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D011804:Quinolines; D014361:Trypsin Inhibitors; C481394:amidino-phenoxy quinoline; D013917:Thrombin; D005341:Fibrinolysin