Preclinical discovery and development of oliceridine (Olinvyk®) for the treatment of post-operative pain

Morphine‐induced mechanical hypersensitivity in mice requires δ receptors, β‐arrestin2, and c‐Src activity

“…There has been a concerted effort to develop μ agonists biased against β-arrestin2 recruitment in favour of G protein stimulation leading to the recent approval of oliceridine by the US Food and Drug Administration (Colvin et al, 2019;Azzam & Lambert, 2022). Our findings suggest that the development of such drugs may be beneficial to minimise opioid-induced hyperalgesia caused by diminished opioid signalling.…”

β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

“…Following the successful completion of a series of clinical studies, oliceridine was approved by the FDA in 2020 for intravenous use in moderate to severe pain in adults (Azzam and Lambert, 2022). As reviewed recently (Azzam and Lambert, 2022), oliceridine possesses potent analgesic activity but appears to have less abuse potential and an improved side effect profile, as compared to traditional opioid drugs.…”

A free-radical design featuring an intramolecular migration for a synthetically versatile alkyl–(hetero)arylation of simple olefins

“…We then sought to demonstrate the utility of this alkyl-(hetero)arylation in a new synthesis of oliceridine, a novel painkiller approved by the FDA in 2020 (Scheme 1). [100][101][102][103] To this end, olen 57 (prepared in 3 steps from 3-buten-1-ol and cyclopentanone) underwent alkyl-(hetero)arylation with sulfone 12 (prepared in 2 steps from 2-mercaptopyridine and methyl bromoacetate). Using ideal 1 : 1 stoichiometry, alkyl-arylation product 58 was isolated in 95% yield.…”