Zhongli Gao
Sanofi, USA
Title: Drug design via a scaffold hopping strategy: Case studies on discovery of clinical candidates H3 receptor antagonist and β-tryptase inhibitor
Biography
Biography: Zhongli Gao
Abstract
Scaffold hopping is a technique that generates compounds containing a topologically different scaffold from the parent compound, but with similar or improved activity and other properties. This can be done intellectually by medicinal chemists or by computational algorithm. The technique is based on topological pharmacophore models developed from SAR of the current lead. In scaffold hopping, medicinal chemist’s insights into pharmacophore and SAR are crucial in this iterative process. Scaffold hopping can be used to generate new chemical entity; overcome patent or other limitations for the current leads; generate differentiated series of chemical matters. Common approaches include heterocyclic replacements, bonds formation and cleavage, and topology-based hopping. This presentation will describe medicinal chemistry of H3 receptor antagonist and tryptase inhibitor programs via using scaffold hopping strategy to generate multi-genesis of chemical leads. Through optimization of the leads, clinical candidates were identified. The profile of the candidates and in vivo effects in disease animal models will also be briefly discussed.
