New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine

A series of C1, C2, C3 and N6 analogs of nantenine (2) was synthesized and evaluated in 5-HT2A and α1A receptor functional assays. Alkyl substitution of the C1 and N6 methyl groups of nantenine provided selective 5-HT2A and α1A antagonists, respectively. The C2 alkyloxy analogs studied were generally selective for α1A versus 5-HT2A. The C3 bromo analog 15 is one of the most potent aporphinoid 5-HT2A antagonists known presently.

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