DeMarinis R M, Boehm J C, Dunn G L, Hoover J R, Uri J V, Guarini J R, Phillips L, Actor P, Weisbach J A
J Med Chem. 1977 Jan;20(1):30-5. doi: 10.1021/jm00211a006.
The synthesis and in vitro and in vivo activities of a series of cephalosporins having side chains derived from 2-[(2,2,2-trifluoroethyl)thio]acetic acid or 2-(cyanomethylthio)acetic acid and with acetoxymethyl or 3-heterocyclic thiomethyl substituents at the 3 position are described. In both series, increasing the oxidation state of the side-chain sulfur atom from sulfide to sulfoxide/sulfone decreased the in vitro gram-positive activity, but the effect on gram-negative activity was variable and less pronounced. The protective effectiveness in mice infected with Escherichia coli increased as the oxidation level of the side-chain sulfur was raised from sulfied to sulfoxide/sulfone. Replacement of the 3-acetoxymethyl by a 3-heterocyclic thiomethyl group resulted in overall improvement of activity both in vitro and in vivo for all oxidation states.
描述了一系列具有源自2-[(2,2,2-三氟乙基)硫基]乙酸或2-(氰基甲基硫基)乙酸的侧链且在3位带有乙酰氧基甲基或3-杂环硫甲基取代基的头孢菌素的合成及其体外和体内活性。在这两个系列中，将侧链硫原子的氧化态从硫化物提高到亚砜/砜会降低体外革兰氏阳性菌活性，但对革兰氏阴性菌活性的影响是可变的且不太明显。在感染大肠杆菌的小鼠中，随着侧链硫的氧化水平从硫化物提高到亚砜/砜，保护效果增强。用3-杂环硫甲基取代3-乙酰氧基甲基导致在所有氧化态下体外和体内活性均得到总体改善。
