A new series of phenylthiazoles with t-butyl lipophilic component was synthesized and their antibacterial activity against a panel of multidrug-resistant bacterial pathogens was evaluated. Five compounds demonstrated promising antibacterial activity against methicillin-resistant staphylococcal strains and several vancomycin-resistant staphylococcal and enterococcal species. Additionally, three derivatives 19, 23 and 26 exhibited rapid bactericidal activity, and remarkable ability to disrupt mature biofilm produced by MRSA USA300. More importantly, a resistant mutant to 19 couldn't be isolated after subjecting MRSA to sub-lethal doses for 14 days. Lastly, this new series of phenylthiazoles possesses an advantageous attribute over the first-generation compounds in their stability to hepatic metabolism, with a biological half-life of more than 9 h.

合成了一系列新的具有叔丁基亲脂性成分的苯基噻唑，并评估了它们对一组多药耐药细菌病原体的抗菌活性。五种化合物显示出对甲氧西林耐药葡萄球菌菌株以及几种耐万古霉素葡萄球菌和肠球菌的抗菌活性。此外，三衍生物19，23和26显示出快速杀菌活性，并且破坏由MRSA USA300产生的成熟生物膜非凡的能力。更重要的是，抗性突变株19对MRSA施加亚致死剂量14天后无法分离。最后，该新系列的苯基噻唑对肝脏代谢的稳定性优于第一代化合物，其生物半衰期超过9小时。