Oirish Drug Discovery

[4DQSAR]

N-Phenethyl Noroxymorphone — NPS Discovery new drug monograph. - Drugs and Alcohol

Irish drugs and alcohol research, data, policy and sources of evidence on prevention, treatment, rehabilitation, crime and consequences.

www.drugsandalcohol.ie

The joke?

In 1989 Professor Helmut Schmidhammer published an huge tranche of articles on the QSAR of the 14 hydroxy and 14 alkoxy derivatives of oxymorphone including N-phenylethyl noroxymorphone.

So the Irish researcher could just have looked up the result.

I think I know why. There is a refence book by Lenz et al which tries to use a diagram of the scaffold and asserted how altering one specific moiety increased activity. BUT the 14-hydroxy (or indeed the 14-alkoxy) derivatives turned out to be only around twice as active as N-phenylethylnormorphine i.e. you can have an oxygen at the 14, but it's presence means that the pendent phenyl doesn't fit the lipophilic pocket in a minimum or near-minimum conformation.

So while yes, N-phenylethylnoroxymorphone is around twice as potent as N-phenylethylnormorphine, it has no clinical advantage and the synthesis is more complex and crucially, costly.

Still, Ah, the amadán of those resarrchers, god love them.

BTW MAYBE the (slight) increase in activity is mediated by the DOR receptors so may be less abusable but equally is known to reduce seizure thresholds.