Heterocyclic prostaglandin analogues. Part 2. Hydantoins and other imidazole analogues

Abstract
The stable hydantoin prostaglandin analogues (2b) and (3b) have been synthesised as racemic compounds. The less polar diastereoisomer of (2b) is a potent inhibitor of platelet aggregation in human platelet-rich plasma and its cyclohexyl analogue (22, R = C6H11) has ca. 14 times the potency of prostaglandin E1 in this test coupled with selectivity of biological action. Other structural modifications such as introduction of a 15-methyl group and insertion of the m-phenylene or m-oxaphenylene moieties into the acid side-chain of (2b) led to a reduction in anti-aggregatory potency. Synthesis of the imidazole (41) is described.