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Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy.

Abstract：

:Herein we present the outcome of a high throughput screening (HTS) campaign-based strategy for the rapid identification and optimization of selective and general chemotypes for both kappa (κ) opioid receptor (KOR) activation and inhibition. In this program, we have developed potent antagonists (IC(50) < 120 nM) or agonists of high binding affinity (K(i) < 3 nM). In contrast to many important KOR ligands, the compounds presented here are highly modular, readily synthesized and, in most cases, achiral. The four new chemotypes hold promise for further development into chemical tools for studying the KOR or as potential therapeutic lead candidates.

journal_name

ACS Chem Neurosci

journal_title

ACS chemical neuroscience

authors

Frankowski KJ,Hedrick MP,Gosalia P,Li K,Shi S,Whipple D,Ghosh P,Prisinzano TE,Schoenen FJ,Su Y,Vasile S,Sergienko E,Gray W,Hariharan S,Milan L,Heynen-Genel S,Mangravita-Novo A,Vicchiarelli M,Smith LH,Streicher JM,

doi

10.1021/cn200128x

subject

Has Abstract

pub_date

2012-03-21 00:00:00

pages

221-236

issue

3

issn

1948-7193

journal_volume

3

pub_type

杂志文章

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