• Journal Article

N-substituted 9 beta-methyl-5-(3-hydroxyphenyl)morphans are opioid receptor pure antagonists

Citation

Thomas, J., Zheng, X. L., Mascarella, S., Rothman, R. B., Dersch, C. M., Partilla, J. S., ... Carroll, F. (1998). N-substituted 9 beta-methyl-5-(3-hydroxyphenyl)morphans are opioid receptor pure antagonists. Journal of Medicinal Chemistry, 41(21), 4143-4149.

Abstract

The inhibition of radioligand binding and [S-35]GTP gamma S functional assay data for N-methyl- and N-phenethyl-9 beta-methyl-5-(3-hydroxyphenyl (5b and 5c) show that these compounds are pure antagonists at the mu, delta, and kappa opioid receptors. Since 5b and 5c have the 5-(3-hydroxyphenyl) group locked in a conformation comparable to an equatorial group of a piperidine chair conformation, this information provides very strong evidence that opioid antagonists can interact with opioid receptors in this conformation. In addition, it suggests that the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of antagonist operates via a phenyl equatorial piperidine chair conformation. Importantly, the close relationship between the 4-(3-hydroxyphenyl)piperidines and 5-(3-hydroxyphenyl)morph an antagonists shows that the latter class of compound provides a rigid platform on which to build a novel series of opioid antagonists.