Non-peptide kappa opioid

The primary purpose of this chapter is to review the structure-activity relationships (SAR) of non-peptide kappa opioid agonists and antagonists from the viewpoint of a medicinal chemist. It is intended to present an account of work in this area published in journals and in patents from 1985 up to the end of 1990. During the late 1980 s there was a significant increase in the literature on kappa opioids and this has resulted in several publications which, at the time of writing, have not been previously reviewed. Three pharmaceutical companies, Upjohn, Parke-Davis and Zambeletti (SB-Italy), have progressed kappa agonists into clinical trials, so it seems an appropriate and opportune time to review the preclinical data. 

Barber, A.,Gottschlich, R. Novel developments with selective, non-peptidic kappa-opioid receptor agonists, Exp. Opin. Invest. Drugs 1997, 6, 1354-1368. 

Structure-Activity-Relationships of Non-Peptide Kappa-Opioid Analgesics A Perspective of the Last 10 Years... 

Structure-activity relationships of non-peptide kappa-opioid analgesics a perspective of the last 10 years... 

As discussed above, the discovery by the Upjohn Company in 1982 of U-50488 (5) was a milestone achievement in opioid research. This compound has significantly greater selectivity for the kappa opioid receptor than the previously used ketazocine (2) or EKC (3) and its widespread use in opioid research to study the properties of the kappa receptor has led to its being generally regarded as the prototype non-peptide kappa selective agonist. 

Chemical Structures and Biological Activities of Non-Peptide Selective Kappa Opioid Ligands... 

A comprehensive review of receptor selective opioid peptide analogues by Schiller [7] appeared in the previous volume of this Series and for this reason the present chapter describes only non-peptide structures. A leading review which introduces kappa opioid analgesics was written by Horwell in 1988 [8] and a subsequent article focusing on kappa receptors and analgesia by Millan appeared in 1990 [9]. 

The aim of this project was to synthesise non-peptide selective kappa opioid agonists for evaluation as new analgesic drugs. 

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