Diversity-Oriented Synthesis for Novel, Selective and Drug-like Inhibitors for a Phosphatase from Mycobacterium Tuberculosis

Medchemcomm. 2014 Oct;5(10):1496-1499. doi: 10.1039/C4MD00099D.


Mycobacterium protein tyrosine phosphatase B (mPTPB) is a potential drug target of Tuberculosis (TB). Small molecule inhibitors of mPTPB could be a treatment to overcome emerging TB drug resistance. Using a Diversity-Oriented Synthesis (DOS) strategy, we successfully developed a salicylic acid based and drug-like mPTPB inhibitor with an IC50 of 2 μM and >20-fold specificity over many human PTPs, making it an excellent lead molecule for anti-TB drug discovery. In addition, DOS generated bicyclic salicylic acids are also promising starting points for acquiring inhibitors targeting other PTPs.