fenoolid

Fenoolid is a synthetic organic compound belonging to the class of amino ketones with a phenoxy side chain. It was first synthesized in the early 1990s by a research group at the University of Geneva as part of a screening program for novel analgesic agents. The IUPAC name of fenoolid is (R)-2-(3‑phenoxypropyl)‑4-methyl‑1‑piperidyl‑2‑oxo‑methanol, and its molecular formula is C18H22NO3. The compound is obtained by reductive amination of 4‑methyl‑2‑oxo‑piperidine with 3‑phenoxypropanol using sodium cyanoborohydride, followed by regioselective Boc protection of the amine.

Preclinical studies indicate that fenoolid exhibits potent antagonism at the N-methyl-D-aspartate (NMDA) receptor and modest affinity for the dopamine D2 receptor. In rodent models of inflammatory pain, a single oral dose of 10 mg/kg reduced nociceptive thresholds by more than 60 % over a 4‑hour period, and the effect was significantly attenuated by co‑administration of a selective NMDA antagonist. In vitro binding assays confirmed a Ki of 5.3 µM at the NMDA GluN1/GluN2B subtype. Pharmacokinetic profiling shows rapid absorption (Tmax ≈ 1 h) and a half‑life of approximately 6 h, with hepatic metabolism primarily via CYP3A4‑mediated hydroxylation.

Because of its dual action on glutamatergic and dopaminergic signaling, fenoolid has been investigated for potential use in chronic pain and movement disorders such as Parkinson’s disease. However, several studies report a propensity for mild, reversible hepatotoxicity at high doses, and the compound’s safety margin is considered narrow. As a result, fenoolid has not progressed beyond Phase I clinical trials, and its current status remains that of a lead compound for future analog development.