Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones.

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Nieland NP, Moynihan HA, Carrington S, Broadbear J, Woods JH, Traynor JR, Husbands SM, Lewis JW

Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones.

J Med Chem. 2006 Aug 24;49(17):5333-8.

PubMed ID
16913723 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MorphineKappa-type opioid receptorKi (nM)46.9N/AN/ADetails
MorphineKappa-type opioid receptorEC 50 (nM)484N/AN/ADetails
MorphineMu-type opioid receptorKi (nM)1.1N/AN/ADetails
MorphineMu-type opioid receptorEC 50 (nM)15.6N/AN/ADetails