| Autor: |
Gallardo-Macias, Ricardo, Russo, Riccardo, Sherwood, Matthew, Jaskowski, Mark, Nasser, Wissam, Sharma, Pankaj, Tuckman, Margareta, Singleton, Eric, Ho, Hsin Pin, Park, Steven, Patel, Jimmy S., George, Amir, Perlin, David, Zimmerman, Matthew D., Connell, Nancy, Freundlich, Joel S. |
| Zdroj: |
Journal of Medicinal Chemistry; January 2024, Vol. 67 Issue: 2 p1384-1392, 9p |
| Abstrakt: |
Hospital-acquired infections, caused by ESKAPE bacteria, are a challenging global public health concern, in part due to the emergence of drug-resistant strains. While profiling a diverse set of compounds for in vitroactivity versusthis class of bacteria, we noted that the benzothiophene JSF-2827 exhibited promising antibacterial activity against Enterococcus faecium. A hit evolution campaign ensued, involving the design, synthesis, and biological assay of analogues designed to address early issues such as a short mouse liver microsome half-life and a modest mouse pharmacokinetic profile. Among these derivatives, JSF-3269 was found to exhibit an enhanced profile and in vivoefficacy in an immunocompetent mouse model of acute, drug-resistant E. faeciuminfection. The findings suggest a rationale for the further evolution of this promising series to afford a novel therapeutic strategy to treat drug-resistant E. faeciuminfection. |
| Databáze: |
Supplemental Index |
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