C4 phenyl aporphines with selective h5-HT2B receptor affinity

A group of aporphine alkaloids related to (±)-nantenine (1) and bearing a C4 phenyl and various C1 or N-substituents, was synthesized and evaluated for affinity to h5-HT receptors. In general, unlike nantenine, the analogs lack affinity for the h5-HT2A receptor and other 5-HT receptors but bind selectively to the h5-HT2B receptor. With regards to 5-HT2B affinity, there appears to be a low tolerance for bulky C1 or N-substituents when the C4 phenyl moiety is present. Compound 5a had the highest 5-HT2B affinity of the compounds tested, was found to be an antagonist and is selective vs other CNS receptors.

Figure optionsDownload as PowerPoint slide