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Published on: August 5, 2022
Novel non-nucleobase inhibitors of Staphylococcus aureus DNA polymerase IIIC
Yannick Rose1, Stéphane Ciblat, Ranga Reddy
1Targanta Therapeutics Inc., 7170 Frederick-Banting, 2nd Floor, Montréal, Québec, Canada H4S 2A1. yrose@targanta.com
Abstract:
The preparation and biological evaluation of 5-substituted-6-hydroxy-2-(anilino)pyrimidinones as a new class of DNA polymerase IIIC inhibitors, required for the replication of chromosomal DNA in Gram-positive bacteria, are described. These new dGTP competitive inhibitors displayed good levels of in vitro inhibition and antibacterial activity against Staphylococcus aureus. A new class of dATP competitive inhibitors, 6-substituted-2-amino-5-alkyl-pyrimidin-4-ones, whose antibacterial activity was unaffected by serum, were identified.
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