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Probes for narcotic receptor mediated phenomena. 39. Enantiomeric N-substituted benzofuro[2,3-c]pyridin-6-ols: synthesis and topological relationship to oxide-bridged phenylmorphans

Zhang, Y.; Lee, Y.S.; Rothman, R.B.; Dersch, C.M.; Deschamps, J.R.; Jacobson, A.E.; Rice, K.C.

Journal of Medicinal Chemistry 52(23): 7570-7579

2009

ISSN/ISBN: 1520-4804
PMID: 19627147
DOI: 10.1021/jm9004225
Accession: 055189652
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Enantiomers of N-substituted benzofuro[2,3-c]pyridin-6-ols have been synthesized, and the subnanomolar affinity and potent agonist activity of the known racemic N-phenethyl substituted benzofuro[2,3-c]pyridin-6-ol can now be ascribed to the 4aS,9aR enantiomer. The energy-minimized structures suggest that the active enantiomer bears a greater three-dimensional resemblance to morphine than to an ostensibly structurally similar oxide-bridged phenylmorphan. Structural features of the conformers of N-substituted benzofuro[2,3-c]pyridin-6-ols were compared to provide the rationale for their binding affinity.

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Related References

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