From Virtual to Real Screening for D 3 Dopamine Receptor Ligands

Even in the absence of receptor‐structure information, iterative virtual screening cycles with support vector machines (SVM) offer a rapid way to identify novel leads with minimal experimental effort. First, an SVM is trained for prediction of D 3 receptor‐selective ligands. Based on the prediction of this virtual filter, compounds are tested for binding affinity at D 2 and D 3 receptors. Second, a similarity search is performed with the most promising candidate from round one. Four out of five compounds from the final hit list exhibited nanomolar affinity at the D 3 receptor including a novel scaffold structure. The K i value of the best molecule ( 1 ) was 40±6 n M .