Sprague P W, Heikes J E, Gougoutas J Z, Malley M F, Harris D N, Greenberg R
J Med Chem. 1985 Nov;28(11):1580-90. doi: 10.1021/jm00149a007.
A series of chemically stable TXA2/PGH2 analogues modeled after the structure of the natural products was prepared in search of useful inhibitors of TXA2/PGH2-mediated pathophysiology. Each of the 16 isomers implied in structure 1 was prepared in chiral form and evaluated for activity in vitro in platelets and smooth muscle. Depending on relative side chain and carbinol stereochemistry, TXA2/PGH2 agonist and antagonist and, surprisingly, PGD2/PGI2 agonist activities were observed. The enantiomers possessing the alpha heterocycle shown in 1 were generally more potent than their mirror-image isomers.
