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14-O-Heterocyclic-substituted naltrexone derivatives as non-peptide mu opioid receptor selective antagonists: design, synthesis, and biological studies.

ABSTRACT: Mu opioid receptor antagonists have clinical utility and are important research tools. To develop non-peptide and highly selective mu opioid receptor antagonist, a series of 14-O-heterocyclic-substituted naltrexone derivatives were designed, synthesized, and evaluated. These compounds showed subnanomolar-to-nanomolar binding affinity for the mu opioid receptor. Among them, compound 1 exhibited the highest selectivity for the mu opioid receptor over the delta and kappa receptors. These results implicated an alternative 'address' domain in the extracellular loops of the mu opioid receptor.

SUBMITTER: Li G

PROVIDER: S-EPMC2802822 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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14-O-Heterocyclic-substituted naltrexone derivatives as non-peptide mu opioid receptor selective antagonists: design, synthesis, and biological studies.

Li Guo G Aschenbach Lindsey C K LC He Hengjun H Selley Dana E DE Zhang Yan Y

Bioorganic & medicinal chemistry letters 20081229 6

Mu opioid receptor antagonists have clinical utility and are important research tools. To develop non-peptide and highly selective mu opioid receptor antagonist, a series of 14-O-heterocyclic-substituted naltrexone derivatives were designed, synthesized, and evaluated. These compounds showed subnanomolar-to-nanomolar binding affinity for the mu opioid receptor. Among them, compound 1 exhibited the highest selectivity for the mu opioid receptor over the delta and kappa receptors. These results im ...[more]

PMID: 19217280

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