The Structural Basis of the Activity Cliff in Modafinil-Based Dopamine Transporter Inhibitors
Modafinil analogs with either a sulfoxide or sulfide moiety have improved binding affinities at the human dopamine transporter (hDAT) compared to modafinil, with lead sulfoxide-substituted analogs showing characteristics of atypical inhibition (e.g., JJC8-091).Interestingly, the only distinction between sulfoxide and sulfide substitution is the pre