Amide and l-amino derivatives of F prostaglandins as prostaglandin antagonists

Abstract

THE formation in tissues and organs of the different prostaglandins (PGs) is now known to be associated with various pathophysiological situations. There is an urgent need for specific PG antagonists to facilitate experimental differentiation and analysis of the roles of these endogenous PGs. Compounds which have been introduced as PG antagonists include 7-oxaprostaglandin analogues (for example, 7-oxa-13-prostynoic acid)¹, dibenzoxazepine derivatives (SC-19220)², and phos-phorylated polymers of phloretin (PPP)³. More recently, sodium-4-(1-oxo-2-(4-chlorobenzyl)-3-phenylpropyl)phenylbenzyl phos-phonate (N-0164)⁴ and 8-ethoxycarbonyl-10,ll-dihydro A prostaglandins⁵ have been studied. Unfortunately, although these compounds inhibit in vitro, their usefulness is limited in terms of potency, specificity and competitiveness, especially in the intact animal. We describe here a simple and novel approach to the design of PG antagonists which are active both in vitro and in vivo⁶.