Synthesis and evaluation of novel peripherally restricted κ-opioid receptor agonists

…, RN DeHaven, DL DeHaven-Hudkins…

Index: Kumar, Virendra; Guo, Deqi; Cassel, Joel A.; Daubert, Jeffrey D.; DeHaven, Robert N.; DeHaven-Hudkins, Diane L.; Gauntner, Erin K.; Gottshall, Susan L.; Greiner, Susan L.; Koblish, Michael; Little, Patrick J.; Mansson, Erik; Maycock, Alan L. Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 4 p. 1091 - 1095

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Citation Number: 19

Abstract

A series of 3-substituted analogs (3) of the parent κ agonist, 1, were prepared to limit access to the central nervous system. With the exception of compound 3j, all other compounds bound to the human κ opioid receptor with high affinity (Ki= 0.31–9.5 nM) and were selective for κ over μ and δ opioid receptors. Compounds 3c, d, and 3g–i produced potent antinociceptive activity in the rat formalin assay (i. paw) and the mouse acetic acid- ...