Synthesis, biological in vitro evaluation and stereoselectivity of ondansetron analogues: novel 5-HT2A receptor antagonists

The tetrahydrocarbazolone moiety of the 5-HT3 receptor antagonist ondansetron has been combined with molecular fragments of typical 5-HT2A receptor ligands. Several of the resulting compounds are potent 5-HT2A antagonists. The antipodes of the most potent compound, a N-substituted 4-(4-fluorobenzoyl)piperidine, are analogues of ketanserin which display a high degree of stereoselectivity at 5-HT2A receptors (148:1).