title: Synthesis of new heparinoids with high anticoagulant activity.
abstract: New heparinoids were synthesized by the chemical method starting from ring-opening polymerization of anhydro sugar derivatives. Sulfation of synthetic (1----6)-alpha-linked 3-amino-3-deoxy-D-glucopyranan and its copolymers gave dextran-type heparinoids having a sulfamide group on the C-3 carbon of the sugar unit. Heparinoids with different sulfamide contents indicated that the anticoagulant activity (35.3-41.3 units/mg) is independent of the sulfamide content, while an increase in sulfamide content lowered the toxicity. Sulfation of (1----5)-alpha-D-xylofuranan and -ribofuranan provided furanan-type heparinoids the anticoagulant activities of which were higher than those of the corresponding sulfated pyranan-type polysaccharides (1----4)-beta-D-xylopyranan and -ribopyranan. The highest activity (69.1 units/mg) was shown by sulfated (1----5)-alpha-D-xylofuranan. The dextran-type heparinoid having a sulfamide group showed a high anticoagulant activity also in vivo and high lipemia-clearing activity.
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology; D006496:Heparinoids / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D011817:Rabbits; D013431:Sulfates
chemical_list: D003911:Dextrans; D006496:Heparinoids; D008055:Lipids; D013431:Sulfates; D000990:Antithrombin III; D016264:Dextran Sulfate