Bioisosteres in De Novo Design
Nicholas C. Firth, Julian Blagg, Nathan Brown · 2013
This chapter provides a brief history and overview of isosterism and bioisosterism in medicinal chemistry. Popular approaches for the identification of bioisosteres from literature databases–Bioster, CSD (Cambridge Structural Database), and ChEMBL–are introduced. A discussion on molecular descriptors is presented–including physicochemical properties, molecular topology, and shape–as an approach to identifying potential bioisosteric pairings that have not necessarily been exemplified. This chapter concludes with three case studies from the literature where bioisosterism has been considered in de novo design: IADE (Intelligent Automatic Design), Drug Guru, and SkelGen.