Antibiotics are a cornerstone of medical treatment for various bacterial infections and are prescribed at a rate that exceeds the limit of prescribing. Phenylthiazoles were reported previously as a new scaffold that possesses antibacterial activity against an array of clinically-relevant strains of multidrug-resistant staphylococci.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 acetylene part in analogues with a prolonged half-life, while the cyclic nitrogenous extention revealed the most potent analogue. In the current work, advantageous moieties have been tethered together to produce a new scaffold of phenylthiazole with the objective of promoting new scaffold enhancing both antimicrobial resistance activity and drug-like properties. Among the tested phenylthiazoles, compounds 14 and 16 were found to exert a bactericidal activity against MRSA. The pharmacokinetic profile of compound 15 was significantly enhanced against biofilm of the bacteria.