Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors

…, S Surade, D Leys, AW Munro, C Abell

文献索引：Hudson, Sean A.; McLean, Kirsty J.; Surade, Sachin; Yang, Yong-Qing; Leys, David; Ciulli, Alessio; Munro, Andrew W.; Abell, Chris Angewandte Chemie - International Edition, 2012 , vol. 51, # 37 p. 9311 - 9316 Angew. Chem., 2012 , vol. 124, # 37 p. 9445 - 9450,6

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被引用次数: 6

摘要

The essential enzyme CYP121 is a target for drug development against antibiotic resistant strains of Mycobacterium tuberculosis. A triazol-1-yl phenol fragment 1 was identified to bind to CYP121 using a cascade of biophysical assays. Synthetic merging and optimization of 1 produced a 100-fold improvement in binding affinity, yielding lead compound 2 (KD= 15 μM). Deconstruction of 2 into its component retrofragments allowed the group efficiency of ...