Nefazodone (NFZ)

Nefazodone is a potent inhibitor of CYP3A4, an isozyme of the cytochrome P450 system, and may therefore interact adversely with many commonly used medications that are metabolized by CYP3A4. Nefazadone is a piperazine compound incorporating a 1,2,4-triazol-3-one ring. Rxn of the starting propionamide with phosgene leads to the corresponding imino chloride. This intermediate is condensed with hydrazine methylurethane to afford the corresponding guanidine from the displacement of chlorine by basic hydrazine nitrogen. Rxn with sodium methoxide leads first to the ionization of the amine on the side chain; this then cyclizes to a triazolone by displacing the carbamate methoxyl. Alkylation of the anion from rxn of the triazolone with a strong base with chloride affords nefazodone. Nefazodone acts primarily as a potent antagonist at the 5-HT2A receptors.