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

• Published in: European journal of organic chemistry Vol. 2014; no. 16; pp. 3387 - 3394
• Main Authors: Lohrey, Lilia, Uehara, Takahiro N., Tani, Satoshi, Yamaguchi, Junichiro, Humpf, Hans-Ulrich, Itami, Kenichiro
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.06.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Antibiotics; C-H arylation; Chemistry; Chemistry, Organic; Cross-coupling; Physical Sciences; Science & Technology; Staphylococcus infections; Structure-activity relationships; Thiazoles; AZOLES; CATALYSIS; DIRECT ARYLATION; C-H arylation; Structure-activity relationships; ARYLBORONIC ACIDS; (HETERO)ARENES; FUNCTIONALIZATION; Cross-coupling; Antibiotics; BOND ARYLATION; Thiazoles; THIOPHENES
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201402129

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.