Synthesis and platelet aggregation inhibiting activity of 1′-carboxyl modified hydantoin prostaglandin analogues

Abstract

A series of hydantoin prostaglandin analogues, in which the 1′-carboxy group was replaced by tetrazole, amine, alcohol, amide, cyanamide, or sulphonamide functionalities, was prepared and evaluated for platelet aggregation inhibiting activity. The 2′-decarboxy-2′-(tetrazol-5-yl) analogue (30) proved to have interesting activity, being approximately equipotent (ca. 17 × PGE₁) to BW245C (1). Activity was often lost when the carboxy group was replaced by neutral or basic moieties. Substitution of the carboxy terminus by other groups of similar acidity gave rise to reduced activity. These results suggest that the platelet receptor which mediates these effects possesses a cationic site requiring binding of an anionic group at the agonist 1′-position. However, additional factors are clearly involved in determining agonist potency.