biostudies-literatureJansen PAMNederlandse Brandwonden Stichting682-692https://www.ebi.ac.uk/biostudies/studies/S-EPMC6760626biostudies-literatureUnknown72(9)The emergence of multidrug resistant bacteria has prioritized the development of new antibiotics. N-substituted pantothenamides, analogs of the natural compound pantetheine, were reported to target bacterial coenzyme A biosynthesis, but these compounds have never reached the clinic due to their instability in biological fluids. Plasma-stable pantothenamide analogs could overcome these issues. We first synthesized a number of bioisosteres of the prototypic pantothenamide N7-Pan. A compound with an inverted amide bond (CXP18.6-012) was found to provide plasma-stability with minimal loss of activity compared to the parent compound N7-Pan. Next, we synthesized inverted pantothenamides with a large variety of side chains. Among these we identified a number of novel stable inverted pantothenamidThe Journal of antibioticsStable pantothenamide bioisosteres: novel antibiotics for Gram-positive bacteria.PMC6760626WO/16.101Pennings LJBlaauw RHRutjes FPJTJansen PAMBotman PNMCavina LSandrock JHermkens PHHSchalkwijk Jde Heuvel EZeeuwen PLJMvan der Krieken DARaaijmakers EMfalseStable pantothenamide bioisosteres: novel antibiotics for Gram-positive bacteria.The emergence of multidrug resistant bacteria has prioritized the development of new antibiotics. N-substituted pantothenamides, analogs of the natural compound pantetheine, were reported to target bacterial coenzyme A biosynthesis, but these compounds have never reached the clinic due to their instability in biological fluids. Plasma-stable pantothenamide analogs could overcome these issues. We first synthesized a number of bioisosteres of the prototypic pantothenamide N7-Pan. A compound with an inverted amide bond (CXP18.6-012) was found to provide plasma-stability with minimal loss of activity compared to the parent compound N7-Pan. Next, we synthesized inverted pantothenamides with a large variety of side chains. Among these we identified a number of novel stable inverted pantothenamid2019-01-01T00:00:00Z2019 Sep2026-05-06T21:29:45.134Z2019-10-11T07:11:00ZS-EPMC67606263117184810.1038/s41429-019-0196-6