Functionalization of the 6,14-bridge of the orvinols. Part 3: preparation and pharmacological evaluation of 18- and 19-hydroxyl substituted orvinols.
The orvinols are a class of potent opioids which have been extensively studied, yet little is known about the effects of introducing substituents into the 18- and 19-positions. The etheno bridge of thevinone was hydroxylated to give both the 18- and 19-hydroxyl substituted thevinols. After 3-O-demethylation to the corresponding orvinols, binding and GTPgammaS functional assays indicated that hydroxyl substitution at the 18- and 19-positions differentially affects the mu opioid efficacy of orvinols.
Wu
Huifang
H
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Smith
Trudy A
TA
Huang
Hongyan
H
Wang
Jia Bei
JB
Deschamps
Jeffrey R
JR
Coop
Andrew
A
D000438:Alcohols / Q000737:chemistry; D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002047:Buprenorphine / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008956:Models, Chemical; D011485:Protein Binding; D017450:Receptors, Opioid, mu / Q000737:chemistry
D000438:Alcohols; D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002047:Buprenorphine