Design and Validation of FRESH, a Drug Discovery Paradigm Resting on Robust Chemical Synthesis.

ABSTRACT: A method capable of identifying novel synthetic targets for small molecule lead optimization has been developed. The FRESH (FRagment-based Exploitation of modular Synthesis by vHTS) approach relies on a multistep synthetic route to a target series of compounds devised by a close collaboration between synthetic and computational chemists. It combines compound library generation, quantitative structure-acitvity relationship construction, fragment processing, virtual high throughput screening and display of results within the Pipeline Pilot framework. Outcomes enumerate tailored selection of novel synthetic targets with improved potency and optimized physical properties for an emerging compound series. To validate the application of FRESH, three retrospective case studies have been performed to pinpoint reported potent analogues. One prospective case study was performed to demonstrate that FRESH is able to capture additional potent analogues.

SUBMITTER: Shi Q 

PROVIDER: S-EPMC4434458 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature