Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones.
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.
Nieland
Nick P R
NP
School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.
Moynihan
Humphrey A
HA
Carrington
Simon
S
Broadbear
Jillian
J
Woods
James H
JH
Traynor
John R
JR
Husbands
Stephen M
SM
Lewis
John W
JW
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
D002934:Cinnamates; D008024:Ligands; D009022:Morphine Derivatives; D017450:Receptors, Opioid, mu; C076806:clocinnamox; D003061:Codeine