Scaffold hopping also known as lead hopping is an important strategy used in lead optimization during drug discovery. It includes conversion of an explicit part of a potentially active compound to an alternative structure to discover isofunctional structure. The main goal of scaffold hopping is of creating a structurally different template of chemical structure while safeguarding desired biological activity. It helps in reducing various toxicity issues, obtaining an intellectual property, and addresses issues related to less potency or stability of the drug. Scaffold hopping tools such as isosteric ring replacement include ring opening and closing, functional group isosterism, functional group reversion, chain shortening, chain elongation, and scaffolding. It has truly been a blessing to medicinal chemist since it provides a means to modify the structure and improve physicochemical properties. It also opens the scope for intellectual property if the designed structure is novel.

Dr. Nutan Rao* & Ms. Tanvi Mohan Ramugade

Scaffold hopping, isosteric ring replacement, functional group isosterism, optimization, core structure, lead optimization