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