Synthetic inhibitors of bovine factor Xa and thrombin comparison of their anticoagulant efficiency.
New derivatives of benzamidine (N alpha-arylsulfonylamino-acylated derivatives of 3-amidinophenylalanine) were found to be potent inhibitors of bovine factor Xa (F Xa). The methyl and ethyl esters of N alpha-Tos-Gly- and N alpha-beta Nas-Gly-substituted 3-amidinophenylalanine, inhibited F Xa more effectively (Ki values near 0.5 mumol/l) than thrombin (Ki about 50 mumol/l). Reinvestigation of inhibition of F Xa by bis-benzamidines showed that compounds containing a cycloheptanone linking bridge are tight-binding inhibitors of F Xa (Ki in the 10 nmol/l range). The use of these inhibitors enabled us to clarify whether inhibition of F Xa or inhibition of thrombin is more efficient in anticoagulation. The thrombin inhibitors and not the potent F Xa inhibitors proved to be particularly effective in anticoagulation in vitro.
Stürzebecher
J
J
Institute of Pharmacology and Toxicology, Medical Academy Erfurt, G.D.R.
Stürzebecher
U
U
Vieweg
H
H
Wagner
G
G
Hauptmann
J
J
Markwardt
F
F
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001550:Benzamidines / Q000494:pharmacology; D002417:Cattle; D015951:Factor Xa; D010314:Partial Thromboplastin Time; D015842:Serine Proteinase Inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D001550:Benzamidines; D015842:Serine Proteinase Inhibitors; D013917:Thrombin; D015951:Factor Xa