2,4- and 2,5-Disubstituted Arylthiazoles: Rapid Synthesis by C-H Coupling and Biological Evaluation

Life‐threatening infections caused by bacteria that have developed resistance to common antibiotics, such as methicillin‐resistant Staphylococcus aureus (MRSA), have become a serious problem in hospitals and other areas all over the world. Thus, the development of an effective class of antibiotics against these bacteria is an urgent subject. Herein, we report a step‐economical and diversity‐oriented synthesis of a series of 2‐arylidenehydrazinyl‐4‐arylthiazole and 2‐arylidenehydrazinyl‐5‐arylthiazole analogues that utilizes C–H coupling methodologies. A library of 54 new congeners were synthesized and tested for their biological potential. Moreover, new knowledge regarding the structure–activity relationships (SARs) of these heterobiaryl compounds was collected. We have established a step‐economical and diversity‐oriented synthesis of 2‐arylidenehydrazinyl‐4‐arylthiazoles and 2‐arylidenehydrazinyl‐5‐arylthiazoles that utilizes C‐4‐ and C‐5‐selective C–H coupling methodologies. A rapidly created library of 54 new 2‐arylidenehydrazinyl‐4‐arylthiazole and 2‐arylidenehydrazinyl‐5‐arylthiazole analogues were tested extensively for their biological activity.