Original Article

Synthesis and antibacterial activity of novel lincomycin derivatives. IV. Optimization of an N-6 substituent

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The design and synthesis of lincomycin derivatives modified at the C-6 and C-7 positions are described. A substituent at the C-7 position is a 5-aryl-1,3,4-thiadiazol-2-yl-thio group that generates antibacterial activities against macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes carrying an erm gene. An additional modification at the C-6 position was explored in application of information regarding pirlimycin and other related compounds. These dual modifications were accomplished by using methyl α-thiolincosaminide as a starting material. As a result of these dual modifications, the antibacterial activities were improved compared with those of compounds with a single modification at the C-7 position. The antibacterial activities of selected compounds in this report against macrolide-resistant S. pneumoniae and S. pyogenes with an erm gene were superior to those of telithromycin.

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We thank Dr E Shitara, Mr. A Tamura and 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 lincomycin 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; Mr. Y Takayama for biological studies; and Ms. M Takagi for manuscript. We also thank Ms. M Ishii for direction in intellectual properties.

Author information


  1. Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Yokohama, Japan

    • Ko Kumura
    • , Yoshinari Wakiyama
    • , Kazutaka Ueda
    • , Eijiro Umemura
    • , Yoko Hirai
    • , Keiko Yamada
    •  & Keiichi Ajito


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The authors declare no conflict of interest.

Corresponding author

Correspondence to Keiichi Ajito.