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Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring.

ABSTRACT: The 14-aminodihydromorphinone and codeinone series of opioid ligands have produced a number of ligands of substantial interest. To investigate the importance of the 14-substituent, a series of analogues in which the side chain length is varied and the amide and alkene functions are reduced have been prepared. Binding affinity, particularly at the mu-opioid receptor (MOR), was largely determined by the aromatic group of the side chain. In the [35S]GTPgammaS functional assay, the ligands having a three-carbon side chain were more potent antagonists than their longer chain counterparts, while shorter, two-carbon chain analogues were of higher MOR efficacy, an effect that was confirmed in vivo. Wash-resistant binding was observed within this series and appeared to be unrelated to side-chain length.

SUBMITTER: Rennison D

PROVIDER: S-EPMC2538686 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring.

Rennison David D Moynihan Humphrey H Traynor John R JR Lewis John W JW Husbands Stephen M SM

Journal of medicinal chemistry 20061001 20

The 14-aminodihydromorphinone and codeinone series of opioid ligands have produced a number of ligands of substantial interest. To investigate the importance of the 14-substituent, a series of analogues in which the side chain length is varied and the amide and alkene functions are reduced have been prepared. Binding affinity, particularly at the mu-opioid receptor (MOR), was largely determined by the aromatic group of the side chain. In the [35S]GTPgammaS functional assay, the ligands having a ...[more]

PMID: 17004724

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