Though clinicians once possessed a robust arsenal of antibiotics, many of these valuable therapeutic agents have fallen prey to the expanded resistance of pathogenic bacteria. Phenylthiazoles were reported previously as a new scaffold that possesses antibacterial activity against an array of clinically-relevant strains of multidrug-resistant staphylococci. Close inspection of the structure-activity-relationships (SAR) of phenylthiazoles revealed important structural features necessary for their antibacterial activity: a nitrogenous head and a lipophilic tail. Incorporating the nitrogenous part within an oxadiazole ring resulted in analogues with a prolonged half-life, while the biphenyl tail revealed the most potent analogue. In the present work, advantageous moieties have been combined together to generate new hybrid scaffolds of phenylpyridine with the objective of promoting new moieties enhancing both antimicrobial resistance activity and drug-like properties. Among the tested oxadiazolylbiphenylpyridines, derivatives 14 and 23 were identified as the most potent analogues with MIC values as low as 8 mg/mL on MRSA-US300 and other studied species.