Bicyclic azetidines kill the diarrheal pathogen <i>Cryptosporidium</i> in mice by inhibiting parasite phenylalanyl-tRNA synthetase
Sumiti Vinayak, Rajiv S. Jumani, Peter G. Miller, Muhammad M. Hasan, Briana McLeod, Jayesh Tandel, Erin E. Stebbins, José E. Teixeira, Julien Borrel, Arthur Gonse, Mingliang Zhang, Xianshui Yu, Amy K. Wernimont, Chris Walpole, Sean Eckley, Melissa S. Love, Case W. McNamara, Manmohan Sharma, Amit Sharma, Christina Scherer, Nobutaka Kato, Stuart L. Schreiber, Bruno Melillo, Boris Striepen, Christopher D. Huston, Eamon Comer
Abstract
PheRS. Medicinal chemistry optimization led to the identification of an optimal pharmacokinetic/pharmacodynamic profile for this series. Collectively, these data demonstrate that bicyclic azetidines are a promising series for anticryptosporidial drug development and establish a broad framework to enable target-based drug discovery for this infectious disease.