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

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

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.