Abstract
Lincomycin derivatives that have a 5-(2-nitrophenyl)-1,3,4-thiadiazol-2-yl thio moiety at the 7-position were synthesized. 5-Substituted 2-nitrophenyl derivatives showed potent antibacterial activities against Streptococcus pneumoniae and Streptococcus pyogenes with erm gene. Antibacterial activities of the 4,5-di-substituted 2-nitrophenyl derivatives were generally comparable to those of telithromycin (TEL) against S. pneumoniae with erm gene and clearly superior to those of TEL against S. pyogenes with erm gene. Compounds 6 and 10c that have a methoxy group at the 5-position of the benzene ring exhibited activities comparable to TEL against Haemophilus influenzae. These results suggest that lincomycin derivatives modified at the 7-position would be promising compounds as a clinical candidate. We would like to dedicate this article to the special issue for late Professor Dr. Hamao Umezawa in The Journal of Antibiotics.
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Acknowledgements
We thank Dr E Shitara, Mr A Tamura, Dr T Okutomi for valuable scientific discussion. We are grateful to Professor Emeritus Dr M Konno for supervision through our in-house drug discovery program in LCM field. We are also grateful to Ms T Miyara, Ms S Miki, Ms K Kaneda, Dr T Murata and Mr S Sato for contribution toward analytical chemistry, Ms K Yamada for biological studies, and Ms M Takagi for manuscript. We also thank Ms M Ishii for direction in intellectual properties.
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Kumura, K., Wakiyama, Y., Ueda, K. et al. Synthesis and antibacterial activity of novel lincomycin derivatives. III. Optimization of a phenyl thiadiazole moiety. J Antibiot 71, 104–112 (2018). https://doi.org/10.1038/ja.2017.59
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DOI: https://doi.org/10.1038/ja.2017.59
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