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

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Progress in Drug Research

Part of the book series: Progress in Drug Research ((PDR,volume 52))

Summary

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 K receptor and, thus, U-50,488 was classified originally as a non-μ compound, and only later as a K 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 K agonists is provided including a summary of K recognition sites based on known agonists.

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Abbreviations

SAR:

structure activity relationship

KDa:

kilo daltons

nor-BNI:

nor-bisnaltorphimine

EKC:

ethylketocyclazocine

PD:

Parke-Davis

Dyn:

dyrnophin

LY:

Lilly

U:

Upjohn

ICI:

Imperial Chemical Industries

RP:

Rhône-Poulenc

ZT:

Zambeletti

GABA:

gamma amino butyric acid

CCK:

cholecystokinin

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  1. Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556-5670, USA

    Jacob Szmuszkovicz

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  1. Steinweg 28, CH-4107, Ettingen, Switzerland

    Ernst Jucker

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Szmuszkovicz, J. (1999). U-50,488 and the к receptor: A personalized account covering the period 1973 to 1990. In: Jucker, E. (eds) Progress in Drug Research. Progress in Drug Research, vol 52. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8730-4_4

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  • DOI: https://doi.org/10.1007/978-3-0348-8730-4_4

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9746-4

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