Is nevirapine atropisomeric? Experimental and computational evidence for rapid conformational inversion

The non-nucleoside reverse transcriptase inhibitor nevirapine displays in its room temperature (1)H-NMR spectrum signals characteristic of a chiral compound. Following suggestions in the recent literature that nevirapine may display atropisomerism-and therefore be a chiral compound, due to slow interconversion between two enantiomeric conformers-we report the results of an NMR and computational study which reveal that while nevirapine does indeed possess two stable enantiomeric conformations, they interconvert with a barrier of about 76 kJ mol(-1) at room temperature. Nevirapine has a half life for enantiomerisation at room temperature of the order of seconds, is not atropisomeric, and cannot exist as separable enantiomers.