Importance of phenolic address groups in opioid kappa receptor selective antagonists

In vitro characterization and comparison of JDTic, its dehydroxy analogue and nor-BNI, and its dehydroxy analogue demonstrates that the N-substituted 3,4-dimethyl-(3-hydroxyphenyl)-piperidine-derived antagonist, JDTic, relies more heavily on its phenol address group for affinity and antagonist activity relative to the corresponding naltrexone derived antagonists, nor-BNI. The structural flexibility of the former class of compound relative to the latter is postulated to underlie the difference

Thomas, J., Fix, S., Rothman, R. B., Mascarella, S., Dersch, C. M., Cantrell, B. E., ... Carroll, F. (2004). Importance of phenolic address groups in opioid kappa receptor selective antagonists. Journal of Medicinal Chemistry, 47(4), 1070-1073. DOI: 10.1021/jm030467v