Activity‐Directed Synthesis: A Flexible Approach for Lead Generation. (4th September 2020)

• Record Type: Journal Article
• Authors: Karageorgis, George; Liver, Samuel; Nelson, Adam
• Is Part Of: ChemMedChem. Volume 15:Number 19(2020)
• Page Start: 1776
• Page End: 1782
• Publication Date: 2020-09-04
• Subjects: lead generation -- molecular diversity -- reaction toolkit; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000524
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Activity‐directed synthesis (ADS) is a structure‐blind, functional‐driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed. Abstract : Parallel discovery of diverse bioactive small molecules for a range of targets: Activity‐directed synthesis has enabled a range of medicinal chemistry strategies to be realised, including scaffold constraint; fragment‐based discovery; expansion of a series of ligands; and scaffold hopping. Future scientific challenges, and the prospects of activity‐directed synthesis becoming a mainstream lead generation approach, are discussed.