title: 4'-Arylpyrrolomorphinans: effect of a pyrrolo-N-benzyl substituent in enhancing delta-opioid antagonist activity.
abstract: A new method for the preparation of N-benzylpyrrolomorphinans has been developed. Thus Michael reaction of the benzylimines of oxycodones and oxymorphones with nitrostyrenes gave a series of 4'-aryl-N-benzylpyrrolomorphinans. These were selective delta antagonists of much higher in vitro potency (with 5a having K(e) delta = <1 nM) than their binding affinities predicted. In mice in vivo assays 5a showed good delta antagonist activity in the anti-writhing analgesic assay and also inhibited delta agonist-induced convulsant activity.
authors.affiliation: School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Husbands
authors.forename: Mario D
authors.initials: MD
authors.lastname: Aceto
authors.forename: Carl N
authors.initials: CN
authors.lastname: Miller
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
authors.forename: John W
authors.initials: JW
authors.lastname: Lewis
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced; D013329:Structure-Activity Relationship; D014162:Transfection; D014649:Vas Deferens / Q000378:metabolism
chemical_list: D008024:Ligands; D009019:Morphinans; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta