Crystal and molecular structure of an (S)-()-enantiomer of modafinil, a novel wake-promoting agent

Abstract

The (+)-enantiomer of modafinil [(RS)-2-(diphenylmethylsulfinyl)acetamide], a novel wake-promoting agent, was clarified to be S-configuration by X-ray crystal structure analysis. The crystal consists of two crystallographically independent conformers that are different at the torsion angles around the sulfinylacetamide moiety, and this results from the molecular packing requirement to form a two-dimensional hydrogen-bonding network via neighboring amide groups in the crystal. The crystal structure is characterized by the formation of alternative hydrophobic and hydrophilic layers, which are formed among the symmetry-translated assemblies of diphenylmethyl and sulfinylacetamide moieties, respectively. The spatial orientation between the diphenyl and amide groups is believed to be important for the activity of modafinil. © 2004 Pharmaceutical Society of Japan.