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- ...
