[Synthesis and antiaggregation activity of prostacyclin analogs. 1. Bicyclo [3.2.0] heptane analogs].
Bicyclo[3.2.0]heptane analogues of prostacyclin were synthesized starting from 2,3-epoxy-bicyclo[3.2.0]heptane-6-one ethylene ketale by means of alkynydlithium-BF3-reagents and Wittig reaction. The regioselectivity of the oxirane ring opening reaction is 3:2 and stereoselectivity of Wittig olefinization is 1:1. The synthesised compounds were identified by 13C NMR spectra. The antiaggregative activity of the prostacyclin analogues on rabbit blood platelets was 10(-3)-10(-4) of the activity of PGE1, the isomers with (E)-double bond in alpha-chain being by an order more active that the (Z)-isomers. Elongation of the alpha- and omega-side chain by one carbon atom gives 2-4 fold increase of the activity. Bicyclo[3.2.0]heptane analogues of prostacyclin represent-simple and readily obtainable models for elucidation of structure-activity relationship among prostacyclin analogues.
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D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D011464:Epoprostenol / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D011817:Rabbits
D010975:Platelet Aggregation Inhibitors; D011465:Prostaglandins, Synthetic; D011464:Epoprostenol
Sintez i antiaggregatsionnaia aktivnost' analogov prostatsiklina. 1. Bitsiklo [3.2.0] geptanovye analogi.