Moxazocine (BL-4566) is an

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

analgesic of the benzomorphan family which was never marketed. It acts as a

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

or mixed agonist/ antagonist of the

opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin ...

s and binds preferentially to the

κ-opioid receptor The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind op ...

. Despite its failure to reach the market, clinical studies demonstrated moxazocine to be approximately 10x as potent by weight as

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

as an analgesic.

Synthesis

Reduction of the carbonyl group in oxygenated benzomorphan 1 affords the corresponding alcohol (2). This intermediate is then N-demethylated by means of

BrCN Cyanogen bromide is the inorganic compound with the formula (CN)Br or BrCN. It is a colorless solid that is widely used to modify biopolymers, fragment proteins and peptides (cuts the C-terminus of methionine), and synthesize other compounds ...

. Acylation with cyclopropylcarbonyl chloride gives the amide (3). The alcohol is then converted to the ether by treatment with MeI and base (4). Treatment with LiAlH₄ serves to reduce the amide function. Cleavage of the phenolic ether by one of the standard schemes affords moxazocine (6).

References

{{Opioidergics Analgesics Antitussives Benzomorphans Opioids

Synthesis

See also

References