Kumura Ko, Wakiyama Yoshinari, Ueda Kazutaka, Umemura Eijiro, Watanabe Takashi, Yamamoto Mikio, Yoshida Takuji, Ajito Keiichi
Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd, Yokohama, Japan.
J Antibiot (Tokyo). 2017 Jul 5. doi: 10.1038/ja.2017.59.
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.The Journal of Antibiotics advance online publication, 5 July 2017; doi:10.1038/ja.2017.59.
合成了在7位具有5-(2-硝基苯基)-1,3,4-噻二唑-2-基硫部分的林可霉素衍生物。5-取代的2-硝基苯基衍生物对携带erm基因的肺炎链球菌和化脓性链球菌显示出强效抗菌活性。4,5-二取代的2-硝基苯基衍生物对携带erm基因的肺炎链球菌的抗菌活性通常与泰利霉素（TEL）相当，并且明显优于泰利霉素对携带erm基因的化脓性链球菌的抗菌活性。在苯环5位具有甲氧基的化合物6和10c对流感嗜血杆菌表现出与泰利霉素相当的活性。这些结果表明，在7位修饰的林可霉素衍生物有望成为临床候选化合物。我们谨将本文献给《抗生素杂志》纪念已故的羽泽浜男教授的特刊。《抗生素杂志》网络预发表，2017年7月5日；doi:10.1038/ja.2017.59 。
