U-50,488 and the kappa receptor: a personalized account covering the period 1973 to 1990.
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 kappa receptor and, thus, U-50,488 was classified originally as a non-mu compound, and only later as a kappa 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 kappa agonists is provided including a summary of kappa recognition sites based on known agonists.
Szmuszkovicz
J
J
Department of Chemistry and Biochemistry, University of Notre Dame, IN 46556-5670, USA.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000266:history / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000266:history / Q000494:pharmacology*; D000818:Animals; D049673:History, 20th Century; D006801:Humans; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000266:history
D018712:Analgesics, Non-Narcotic; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer