Kukolja S, Draheim S E, Pfeil J L, Cooper R D, Graves B J, Holmes R E, Neel D A, Huffman G W, Webber J A, Kinnick M D
J Med Chem. 1985 Dec;28(12):1886-96. doi: 10.1021/jm00150a022.
A structure-activity relationship study of a number of orally absorbed cephalosporins together with their syntheses is described. These new cephalosporins are benzothienyl- and naphthylglycine derivatives of 7-aminodeacetoxycephalosporanic acid. Several different synthetic methods for the glycine side chains, their protection, and the final acylations are reported. Several of these analogues were more active than cephalexin both in vitro and in vivo against commonly encountered Gram-positive bacteria. (R)-7-(3-Benzothienylglycylamido)-3-methyl-3-cephem-4-carboxylic acid (1R) has emerged as a potent antibacterial agent and is currently undergoing preclinical evaluation.
描述了一系列口服吸收的头孢菌素的构效关系研究及其合成方法。这些新型头孢菌素是7-氨基去乙酰氧基头孢烷酸的苯并噻吩基和萘基甘氨酸衍生物。报道了几种不同的甘氨酸侧链合成方法、它们的保护以及最终的酰化反应。其中几种类似物在体外和体内对常见的革兰氏阳性菌的活性均高于头孢氨苄。(R)-7-(3-苯并噻吩基甘氨酰胺基)-3-甲基-3-头孢烯-4-羧酸(1R)已成为一种有效的抗菌剂，目前正在进行临床前评估。
