Fragment library design, synthesis and expansion: nurturing a synthesis and training platform. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Ray, Peter C.; Kiczun, Michael; Huggett, Margaret; Lim, Andrew; Prati, Federica; Gilbert, Ian H.; Wyatt, Paul G.
• Is Part Of: Drug discovery today. Volume 22:Issue 1(2017)
• Page Start: 43
• Page End: 56
• Publication Date: 2017-01
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2016.10.005
• Languages: English
• ISSNs: 1359-6446

Abstract

Graphical abstract: Highlights: A platform for the production of novel, high-quality fragment and lead-like libraries. Parameters for the design of monomer sets, fragments and lead-like libraries. Synthesis of multiple diverse scaffolds from common intermediates. Quality analysis of the fragments. Abstract : The availability of suitable diverse fragment- and lead-oriented screening compounds is key for the identification of suitable chemical starting points for drug discovery programs. The physicochemical properties of molecules are crucial in determining the success of small molecules in clinical development, yet reports suggest that pharmaceutical and academic sectors often produce molecules with poor drug-like properties. We present a platform to design novel, high quality and diverse fragment- and lead-oriented libraries with appropriate physicochemical properties in a cost-efficient manner. This approach has the potential to assist the way libraries are constructed by significantly addressing the historical uneven exploration of chemical space for drug discovery. Additionally, this platform can teach undergraduates and graduates about compound library design. Abstract : We describe an approach to develop diverse and novel fragment libraries, which can also be used as a training platform for medicinal chemists at the undergraduate and graduate levels.