Synthesis and anti-aggregative activity of novel ω-achiral carba-analogues of prostacyclin

Article abstract of DOI:10.1016/0223-5234(92)90104-9

Novel stable bicyclo[3.3.0]octanic and bicyclo[4.2.0]octanic 13,14-didehydrocarbacyclins 1a-c, 2a bearing an achiral cyclohexanoic group at C-14 were synthesized. These analogues have been characterized by ¹³C NMR spectroscopy. Compounds 1a-c and 2a were tested on rabbit and human platelet-rich blood plasma and 1a-c on rat stomach and guinea pig trachea smooth muscles. E-isomers of 1a-b were found to be less active but more selective than PGE₁. The anti-aggregative potency of E-isomer of compounds 1a-b and Z-isomer of 2a on human platelets was 10^-1-10^-2 of the activity of PGE₁. The contractive activity of bicyclo[3.3.0]octane analogues 1a-c was 10^-3-10^-4 of that for PGE₁. On platelets and guinea-pig trachea 5E-isomers of the corresponding analogues were more potent, whereas on rat stomach muscle 5Z-isomers were.