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Recent advances in design, synthesis and biological activity of aminoalkylsulfonates and sulfonamidopeptides
Obreza, Aleš ; Gobec, Stanislav, 1970-
The search for an ideal anticoagulant has spanned decades and has resulted in several approaches and the identification of novel target molecules for preventing and treating thrombosis. The first ...group of new anticoagulant agents acting through direct inhibition of coagulation factors were inhibitorsof thrombin, but factor Xa inhibitors and, most recently, factor VIIa inhibitors have become attractive candidates. The structures of thrombin,factor Xa and factor VIIa show similarities in their active sites and, for this reason, attempts have been made to develop synthetic agents containing in a single molecule inhibitory activity against two of the enzymesof the blood coagulation cascade. Such dual inhibitors are now in preclinical studies and are, potentially, new anticoagulant drugs with improved properties. The emphasis of this review will be placed on dual inhibitors of thrombinžfactor Xa and factor Xažfactor VIIa. Comparison of the active sites of these enzymes is included for better understanding of the structural demands to be met in designing effective dual inhibitors.
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