Opioid ligands with mixed properties from substituted enantiomeric N-phenethyl-5-phenylmorphans. Synthesis of a µ-agonist δ-antagonist and δ-inverse agonists

Content Provider	Semantic Scholar
Author	Cheng, Kejun Lee, §. Mei-Jing Adah, Steven A. Raymond, Tyler J. Bilsky, Edward J. Aceto, Mario D. G. May, Everette L. Harris, Louis S. Coop, Andrew Dersch, Christina M. Rothman, Richard B. Jacobson, Arthur E. Rice, Kenner C.
Copyright Year	2007
Abstract	Enantiomeric N-phenethyl-m-hydroxyphenylmorphans with various substituents in the ortho, meta or para positions of the aromatic ring in the phenethylamine side-chain (chloro, hydroxy, methoxy, nitro, methyl), as well as a pyridylethyl and a indolylethyl moiety on the nitrogen atom, were synthesized and their binding affinity to the µ-, δ-, and κ-opioid receptors was examined. The higher affinity ligands were further examined in the [35S]GTPγS assay to study their function and efficacy. 3-((1R,5S)-(−)-2-(4-Nitrophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((−)-10m) was found to be a µ-agonist and δ-antagonist in that functional assay and was about 50 fold more potent than morphine in vivo. 3-((1R,5S)-(−)-2-(4-Chlorophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((−)-10i) and several other ligands displayed inverse agonist activity at the δ-opioid receptor. The absolute configuration of all of the reported compounds was established by chemical conversion of (−)-6 to 1R,5S-(−)-8b·HBr.
Starting Page	1177
Ending Page	1190
Page Count	14
File Format	PDF HTM / HTML
DOI	10.1039/B618875C
Volume Number	5
Alternate Webpage(s)	http://www.rsc.org/suppdata/ob/b6/b618875c/b618875c.pdf
Alternate Webpage(s)	http://gsbse.siteturbine.com/facultystorm/profile/research/publication.php?publicationId=237
Alternate Webpage(s)	https://doi.org/10.1039/B618875C
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article