摘要:
Further structure activity relationship studies on a previously reported 8-azabicyclo[3.2.1]octan-3-yloxy-benzamide series of potent and selective kappa opioid receptor antagonists is discussed. Modification of the pendant N-substitution to include a cyclohexylurea moiety produced analogs with greater in vitro opioid and hERG selectivity such as 12 (kappa IC50 = 172 nM, mu:kappa ratio = 93, delta:kappa ratio = >174, hERG IC50 = >33 mu M). Changes to the linker conformation and identity as well as to the benzamide ring moiety were also investigated. (c) 2010 Published by Elsevier Ltd.