Scaffold hopping: Application to the discovery of novel GABA_A receptor ligands

Scaffold Hopping has been applied to the discovery of novel GABA _A receptor ligands. Thus, bioisosteric replacement of the bicyclic imidazo[1,2-a]pyridine central core of Zolpidem by different heterocycles has been studied. The study has been divided into four different parts: 1) Scaffold Hopping calculations by using Shop software, 2) synthesis in the laboratory of all different chemical series, following an unique synthetic strategy, 3) screening of the molecules and 4) comparison of the activities found to the Shop predictions. Using this approach different tricycles have been discovered, showing interesting biological profile.