U-50,488 and the κ receptor: A personalized account covering the period 1973 to 1990

Abstract

All clinically significant analgesics for severe pain derive from the morphine model. Morphine has provided a fertile area for medicinal chemistry research and received an additional stimulus in the 1970s with the appearance of the opioid receptors. The background for the birth of U-50,488 is described herein. It occurred before the discovery of the κ receptor and, thus, U-50,488 was classified originally as a non-μ compound, and only later as a κ agonist. U-50,488 provided a succinct template for structural modifications and they are described for the period up to 1990. A description of the structural classes of κ agonists is provided including a summary of κ recognition sites based on known agonists.