Pristinamycin IIB (PIIB) is a potent antibiotic with limited use due to some structural problems, and also to the bacterial resistance exhibited toward the antibiotic. A thorough study led to the design of novel analogs of PIIB, based on the introduction of a difluorostatone moiety. Herein, we describe the initial in silico studies toward these novel analogs using ADMET modeling predictive models in order to compute the physico-chemistry and estimate the pharmacokinetics, drug-likeness and medicinal chemistry friendliness of these newly designed analogs.