Yoshimura Y, Tomimatsu K, Nishimura T, Miyake A, Hashimoto N
Chemistry Research Laboratory, Takeda Chemical Industries, Ltd., Osaka, Japan.
J Antibiot (Tokyo). 1992 May;45(5):721-34. doi: 10.7164/antibiotics.45.721.
As a part of our studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)2(Z)-methoxyiminoacetamido] cephalosporins (1-16, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido] cephalosporins (17,18) and 7 beta-[2-(5-amino- 1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido) cephalosporins (19-23) containing a variety of condensed-heterocyclic triazolium methyl groups at the 3 position in the cephalosporin nucleus. These cephalosporins exhibited potent antibacterial activity, and it appears that condensed-heterocyclic triazolium as well as condensed-heterocyclic imidazolium rings are effective moieties for improving antibacterial activity and the spectrum of activity. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(5- methyl[1,2,3]triazolo-[1,5-alpha]pyridinium-1-yl)methyl-3-cephem-4- carboxylate (9) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(6- methoxy[1,2,4]triazolo[1,5-alpha]pyridinium-1-yl)methyl-3-cephem-4- carboxylate (11) showed good antibacterial activity.
作为我们对头孢菌素核3位带有稠合杂环唑鎓甲基的头孢菌素研究的一部分，我们在此描述7β-[2-(2-氨基噻唑-4-基)-2(Z)-甲氧基亚氨基乙酰胺基]头孢菌素（1-16）、7β-[2-(2-氨基-5-氯噻唑-4-基)-2(Z)-甲氧基亚氨基乙酰胺基]头孢菌素（17,18）和7β-[2-(5-氨基-1,2,4-噻二唑-3-基)-2(Z)-甲氧基亚氨基乙酰胺基]头孢菌素（19-23）的合成及抗菌活性，这些头孢菌素在头孢菌素核的3位含有多种稠合杂环三唑鎓甲基。这些头孢菌素表现出强效抗菌活性，并且似乎稠合杂环三唑鎓以及稠合杂环咪唑鎓环是提高抗菌活性和活性谱的有效部分。在所测试的头孢菌素中，7β-[2-(2-氨基噻唑-4-基)-2(Z)-甲氧基亚氨基乙酰胺基]-3-(5-甲基[1,2,3]三唑并-[1,5-α]吡啶鎓-1-基)甲基-3-头孢烯-4-羧酸酯（9）和7β-[2-(2-氨基噻唑-4-基)-2(Z)-甲氧基亚氨基乙酰胺基]-3-(6-甲氧基[1,2,4]三唑并[1,5-α]吡啶鎓-1-基)甲基-3-头孢烯-4-羧酸酯（11）显示出良好的抗菌活性。
