Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA.

Prati F, Zuccotto F, Fletcher D, Convery MA, Fernandez-Menendez R, Bates R, et al.

ChemMedChem. 2018;13(7):672–7.

Our findings reported herein provide support for the benefits of including functional group complexity (FGC) within fragments when screening against protein targets such as Mycobacterium tuberculosis InhA. We show that InhA fragment actives with FGC maintained their binding pose during elaboration. Furthermore, weak fragment hits with functional group handles also allowed for facile fragment elaboration to afford novel and potent InhA inhibitors with good ligand efficiency metrics for optimization.