article with SARs for all classes of opioids (link)

[wungchow]

very good article, even shows you visually how the molecules conform to the receptor

 

[wungchow]

http://www.aapsj.org/view.asp?art=aapsj080115

 

[fastandbulbous]

Not quita all classes, but comprehensive enough - very interesting read

 

[mad_scientist]

Ok so repacing the N-methyl group of morphine / oxymorphone etc with a phenethyl group markedly boosts potency right...

Now it looks from this article that this phenethyl group in phenethylmorphine is equivalent to the phenethyl group in fentanyl, which is what i had assumed anyway.

So...this makes me wonder

(i) would the beta-hydroxyphenethyl and (thiophen-2-yl)ethyl derivatives of normorphine / noroxymorphone be similarly more potent than the simple phenethyl, a la beta-hydroxyfentanyl and sufentanil? How about 6-methylene-N-(4-fluorophenyl)-beta-hydroxyethyl-oxymorphone?

(ii) also what about substitutions on the aniline ring of fentanyl? Would a meta-hydroxy group boost activity or is the conformation wrong? I guess it would be a bitch to make but you could use meta-methoxyaniline and then strip off the CH3 later maybe?

(iii) and what about ketobemidone? It looks pretty similar to fentanyl just without the nitrogen spacer and the phenethyl group...would replacing the N-methyl group of ketobemidone with phenethyl similarly boost activity?

 

[vecktor]

(ii) also what about substitutions on the aniline ring of fentanyl? Would a meta-hydroxy group boost activity or is the conformation wrong? I guess it would be a bitch to make but you could use meta-methoxyaniline and then strip off the CH3 later maybe?

I'm not sure about the potency of aniline ring substituted fentanyls I have seen a jannsen paper/patent somewhere that had fluoros on the aniline ring but I can't remember whether it was good or bad. I'm really not interested in opioids.
from a chemistry POV would be better to use a labile ether to do this benzyloxy and remove with hydrogen. easy chemistry for someone interested in opioids, I believe however the substance would be illegal in the UK as it is covered by the fentanyl catch all.
V