Jung F, Delvare C, Boucherot D, Hamon A, Ackerley N, Betts M J
I.C.I. Pharma, Centre de Recherches, Zone Industrielle La Pompelle, Reims, France.
J Med Chem. 1991 Mar;34(3):1110-6. doi: 10.1021/jm00107a035.
Cephalosporins with new aminobenzimidazole and aminoimidazoline heterocycles at C-7 have been synthesized starting with versatile C-7 isocyanide dihalide synthons. The aminobenzimidazoles have a broad spectrum of antibacterial activity, including Gram-positive and Gram-negative organisms, but possess limited beta-lactamase stability. In contrast, the aminoimidazolines have a narrow spectrum of antibacterial activity, limited to Gram-negative strains only, but possess outstanding beta-lactamase stability. Structure-activity relationships are discussed in terms of their dependence on the pKa of the C-7 amino heterocycle, basic C-7 residues giving cephalosporins with exceptional beta-lactamase stability.
以多功能的C-7异氰二卤化物合成子为起始原料，合成了在C-7位带有新型氨基苯并咪唑和氨基咪唑啉杂环的头孢菌素。氨基苯并咪唑具有广谱抗菌活性，包括革兰氏阳性菌和革兰氏阴性菌，但β-内酰胺酶稳定性有限。相比之下，氨基咪唑啉的抗菌活性谱较窄，仅局限于革兰氏阴性菌株，但具有出色的β-内酰胺酶稳定性。根据它们对C-7氨基杂环pKa的依赖性讨论了构效关系，碱性C-7残基赋予头孢菌素优异的β-内酰胺酶稳定性。
