Synthetic aci-reductones: 3,4-dihydroxy-2H-1-benzopyran-2-ones and their cis- and trans-4a,5,6,7,8,8a-hexahydro diastereomers. Antiaggregatory, antilipidemic, and redox properties compared to those of the 4-substituted 2-hydroxytetronic acids.
Synthetic procedures for the elaboration of aci-reductones belonging to the 6- or 7-mono- or bis-substituted-3,4-dihydroxy-2H-1-benzopyran-2-ones (6-10) and their cis- and trans-4a,5,6,7,8,8a-hexahydro diastereomers (11, 12) are described. hexahydrobenzopyranone aci-reductones were conveniently prepared by using Meldrum's synthon (2,2-dimethyl-1,3-dioxane-4,6-dione, 49). Certain of these substances were evaluated for antilipidemic activity in the cholesterol-fed rat model, and all analogues were studied for their ability to inhibit aggregation of human platelets. Results are compared to aci-reductones belonging to the 4-aryl- and 4-spiroalkyl-2-hydroxytetronic acid systems (4,5a,b). Redox potentials for all aci-reductones were determined with cyclic voltammetry. It would appear that the 4-aryl-2-hydroxytetronic acids represent leads for further study as antiatherosclerotic drugs owing to their favorable antilipidemic and antiaggregatory properties whereas the benzopyranones are of most interest as probes for platelet antiaggregatory mechanism studies.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001205:Ascorbic Acid; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000097:blood; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000960:Hypolipidemic Agents; D008297:Male; D010084:Oxidation-Reduction; D010975:Platelet Aggregation Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000097:blood; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood
D001095:Arachidonic Acids; D003374:Coumarins; D000960:Hypolipidemic Agents; D010975:Platelet Aggregation Inhibitors; D014280:Triglycerides; D016718:Arachidonic Acid; D012701:Serotonin; D000244:Adenosine Diphosphate; D002784:Cholesterol; D001205:Ascorbic Acid