Reversal of subtype-selectivity and function by the introduction of a para-benzamidyl substituent to N-cyclopropylmethyl nornepenthone.

The discovery and development of novel μ-opioid receptor (MOR) antagonists is a significant area to combat Opioid Use Disorder (OUD). In this work, a series of para-substituted N-cyclopropylmethyl-nornepenthone derivatives were designed and synthesized and pharmacologically assayed. Compound 6a was identified as a selective MOR antagonist both in vitro and in vivo.