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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.

SUBMITTER: Nieland NP

PROVIDER: S-EPMC2443285 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

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

Nieland Nick P R NP 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

Journal of medicinal chemistry 20060801 17

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 effica ...[more]

PMID: 16913723

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