Flashback Forward: Reaction-Driven De Novo Design of Bioactive Compounds

Abstract

Over the past 20 years, the computer-assisted de novo design of chemical entities has matured as an innovative methodology for identifying hits and leads in early drug discovery. In particular, its recent prominence is entwined in a mixture of extraordinary success stories and the urge for the discovery of innovative chemotypes. Here, we describe and comment on our own experiences in developing and applying software tools to unravel new chemical space, as well as the experimental challenges entailed in the de novo design of G-protein coupled receptor ligands and kinase inhibitors. 1 Introduction 2 Approaches to De Novo Design and Selected Success Stories 3 Ligand-Based De Novo Design of G-Protein Coupled Receptor Ligands 4 Reaction-Based De Novo Design of Kinase Inhibitors 5 Concluding Remarks