脱水内酯大环内酯类化合物。2. 2,3-脱水-6-O-甲基-11,12-肼基甲酸酯红霉素A类似物的合成及抗菌活性

Anhydrolide macrolides. 2. Synthesis and antibacterial activity of 2,3-anhydro-6-O-methyl 11,12-carbazate erythromycin A analogues.

作者信息

Griesgraber G, Kramer M J, Elliott R L, Nilius A M, Ewing P J, Raney P M, Bui M H, Flamm R K, Chu D T, Plattner J J, Or Y S

机构信息

Anti-Infective Discovery Research, Pharmaceutical Products Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-3500, USA.

出版信息

J Med Chem. 1998 May 7;41(10):1660-70. doi: 10.1021/jm970548p.

DOI:10.1021/jm970548p

PMID:9572891

Abstract

A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-cyclic carbazate analogues was prepared and evaluated for antibacterial activity. These 2,3-anhydro macrolides were found to be potent antibacterial agents in vitro against macrolide-susceptible organisms including Staphylococcus aureus 6538P, Streptococcus pyogenes EES61, and Streptococcuspneumoniae ATCC6303. These compounds were also very active against some organisms that show macrolide resistance (S. aureus A5177, S. pyogenes PIU2584, and S. pneumoniae 5649). The compounds generally showed poor activity against organisms with constitutive MLS resistance. Selected compounds were evaluated in vivo in mouse protection studies. Although most of the compounds tested in vivo showed poor efficacy, two compounds, 38 and 57, were more active than clarithromycin against S. pneumoniae ATCC6303.

摘要

制备了一系列3-去克拉定糖基-2,3-脱水-6-O-甲基红霉素A 11,12-环氨基甲酸酯类似物，并对其抗菌活性进行了评估。发现这些2,3-脱水大环内酯类化合物在体外对包括金黄色葡萄球菌6538P、化脓性链球菌EES61和肺炎链球菌ATCC6303在内的大环内酯敏感菌具有强效抗菌活性。这些化合物对一些表现出大环内酯耐药性的菌株（金黄色葡萄球菌A5177、化脓性链球菌PIU2584和肺炎链球菌5649）也非常有效。这些化合物对组成型MLS耐药菌通常表现出较差的活性。在小鼠保护实验中对选定的化合物进行了体内评估。尽管大多数在体内测试的化合物疗效不佳，但两种化合物38和57对肺炎链球菌ATCC6303的活性比克拉霉素更高。