Journal of Medicinal Chemistry p. 8503 - 8512 (2015)
Update date:2022-08-17
Topics:
Zhang, Jing
Yang, Qingyi
Cross, Jason B.
Romero, Jan Antoinette C.
Poutsiaka, Katherine M.
Epie, Felix
Bevan, Douglas
Wang, Bin
Zhang, Yanzhi
Chavan, Ajit
Zhang, Xin
Moy, Terence
Daniel, Anu
Nguyen, Kien
Chamberlain, Brian
Carter, Nicole
Shotwell, Joseph
Silverman, Jared
Metcalf, Chester A.
Ryan, Dominic
Lippa, Blaise
Dolle, Roland E.
The emergence and spread of multidrug resistant bacteria are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the discovery of azaindole ureas as a novel class of bacterial gyrase B inhibitors and detail the story of their evolution from a de novo design hit based on structure-based drug design. These inhibitors show potent minimum inhibitory concentrations against fluoroquinolone resistant MRSA and other Gram-positive bacteria.
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