Potential Nonequilibrium Analgetic Receptor Inactivators. Synthesis and Biological Activities of N-Acylanileridines

In a effort to prepare nonequilibrium analgetic receptor inactivators, a variety of Ar-acylanileridines having alkylating capacity were synthesized. The analgetic potencies of this series are reported together with experiments designed to detect receptor blockade. Ethyl p-(4-ethoxycarbonyl-4-phenyl-1-piperidinoethyr, fumaranilate (5) caused significant blockade of analgetic activity 2 hr after ip administration. Pretreatment with naloxone, a narcotic antagonist, blocked completely the analgetic activity of 5. Naloxone also protected the analgetic receptors against inactivation. The data suggest that 5 has the capacity to alkylate analgetic receptors selectively.