Opioids, agonist activity 14-hydroxy

The introduction of a hydroxy group at C-14 afforded cis and trans isomers (P and a in optically active compounds). Studies carried out mostly with racemic mixtures are incomplete (Belleau 1982). A great number of 14-j3-OH substituted ketomor-phinans were evaluated (Rahman and Brossi 1977, Seki et al. 1964, Schmidhammer et al. 1981) and it was found that ]8-hydroxylation at C-14 did not drastically alter the opioid agonist activity. Conversion of a 14-j3-OH into a 14-]3-OMe group, on the other hand, afforded compounds with very high antinociceptive potency accompanied by considerable opioidtype side-effects (Schmidhammer et al. in press). 

Alfaro-Lopez J, Okayama T, Hosohata K et al (1999) Exploring the structure-activity relationships of [l-(4-tert-butyl-3 -hydroxy)benzhydryl-4-benzylpiperazine] (SL-3111), a high-affinity and selective 8-opioid receptor nonpeptide agonist ligand. J Med Chem... 

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