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

Abstract A series of C1, C2, C3 and N 6 analogs of nantenine ( 2 ) was synthesized and evaluated in 5-HT 2A and α 1A receptor functional assays. Alkyl substitution of the C1 and N 6 methyl groups of nantenine provided selective 5-HT 2A and α 1A antagonists, respectively. The C2 alkyloxy analogs studied were generally selective for α 1A versus 5-HT 2A . The C3 bromo analog 15 is one of the most potent aporphinoid 5-HT 2A antagonists known presently.