title: Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones.
abstract: In recent years there has been substantial interest in the 14-aminodihydromorphinone derivatives methoclocinnamox (MC-CAM) and clocinnamox (C-CAM). To investigate the importance of the cinnamoyl ring substituent, a series of analogues have been prepared with chloro, methyl, and nitro substituents in the 2' and 4' positions. Despite some discrepancies between the in vitro and in vivo data, a clear SAR could be observed where the 2'-chloro and 2'-methyl ligands consistently displayed higher efficacy than their 4'-substituted analogues. The new series also followed the well-established SAR that 17-methyl ligands have greater efficacy at the mu opioid receptor than their 17-cyclopropylmethyl counterparts.
authors.affiliation: School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.
authors.forename: Nick P R
authors.initials: NP
authors.lastname: Nieland
authors.forename: Humphrey A
authors.initials: HA
authors.lastname: Moynihan
authors.forename: Simon
authors.initials: S
authors.lastname: Carrington
authors.forename: Jillian
authors.initials: J
authors.lastname: Broadbear
authors.forename: James H
authors.initials: JH
authors.lastname: Woods
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Husbands
authors.forename: John W
authors.initials: JW
authors.lastname: Lewis
mesh_terms: D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003061:Codeine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D009022:Morphine Derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D002934:Cinnamates; D008024:Ligands; D009022:Morphine Derivatives; D017450:Receptors, Opioid, mu; C076806:clocinnamox; D003061:Codeine