Fragment library design, synthesis and expansion: nurturing a synthesis and training platform.

Ray PC, Kiczun M, Huggett M, Lim A, Prati F, Gilbert IH, et al.

Drug Discovery Today. 2017;22(1):43–56.

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.