Discovery of an opioid kappa receptor selective pure antagonist from a library of N-substituted 4 beta-methyl-5-(3-hydroxyphenyl)morphans

Thomas, J., Atkinson, R., Namdev, N., Rothman, R. B., Gigstad, K., Fix, S., ... Carroll, F. (2002). Discovery of an opioid kappa receptor selective pure antagonist from a library of N-substituted 4 beta-methyl-5-(3-hydroxyphenyl)morphans. Journal of Medicinal Chemistry, 45(16), 3524-3530.

A library of compounds biased toward opioid receptor antagonist activity was prepared by incorporating N-phenylpropyl-4p-methyl-5-(3-hydroxyphenyl)morphans as the core scaffold using simultaneous solution phase synthetic methodology. From this library, N-phenylpropyl-4beta-methyl-5-(3-hydroxyphenyl)-7alpha-[3-(1-piperidinyl )propanamido]morphan [(-)-3b] was identified as the first potent and selective k opioid receptor antagonist from the 5-phenylmorphan class of opioids