STRUCTURE-ACTIVITY-RELATIONSHIPS IN A SERIES OF MONOCYCLIC ENDOTHELINANALOGS

Monocyclic fragment analogues of endothelin-1 (ET-1) were prepared to explore the importance of the bicyclic structure of ET-1 to its bindin g affinity and functional activity. Most of the monocyclic analogues p repared showed low micro to high nanomolar binding affinities and were functional antagonists of ET-1 induced accumulation of inositol phosp hates. However, one analogue possessed mixed antagonist/agonist activi ty at the two endothelin receptor subtypes.