[From heparin to synthetic antithrombotic oligosaccharides].
In the early eighties, following breakthroughs in oligosaccharide chemistry, we achieved the total chemical synthesis of pentasaccharides related to the antithrombin-binding domain in heparin. Selective inhibitors of coagulation factor Xa, thus obtained, represent a new class of efficient antithrombotic drugs. In a further step, we have designed and synthesised oligosaccharides (pentadeca--to eicosasaccharides), comprising an antithrombin binding domain prolonged by a thrombin binding domain. These compounds inhibit both factor Xa and thrombin, in the presence of antithrombin, while they are devoid of undesirable non-specific interactions, particularly with platelet factor 4 (PF4). The efficacy of these new synthetic antithrombotics, with a unique biological profile, will be evaluated in clinical trials.
Petitou
Maurice
M
Sanofi-Synthélabo, Département Cardiovasculaire/Thrombose, 195 Route d'Espagne, F-31036 Toulouse.
D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D000990:Antithrombin III / Q000187:drug effects; D000991:Antithrombins / Q000187:drug effects; D015951:Factor Xa / Q000187:drug effects; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010978:Platelet Factor 4 / Q000187:drug effects; D013917:Thrombin / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D009844:Oligosaccharides; D010978:Platelet Factor 4; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin; D015951:Factor Xa