4''-醚键连接的阿奇霉素-喹诺酮杂合系列的发现：中心连接基对抗菌活性的影响
Discovery of 4''-ether linked azithromycin-quinolone hybrid series: influence of the central linker on the antibacterial activity.
作者信息
Pavlović Dražen, Mutak Stjepan
机构信息
PLIVA Research Institute, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
出版信息
ACS Med Chem Lett. 2011 Mar 15;2(5):331-6. doi: 10.1021/ml100253p. eCollection 2011 May 12.
Abstract
A series of novel C-4''-substituted azithromycins was synthesized and evaluated for in vitro antibacterial activity against a panel of representative erythromycin-susceptible and macrolide-lincosamide-streptogramin (MLS) resistant pathogens. In summary, azithromycin and quinolone substructures merged in a mutually SAR-compatible design gave rise to a new class of antimicrobials with an improved spectrum and potency over azithromycin. Prototypical analogues 7f and 8f display an improved potency versus azithromycin against Gram-positive and fastidious Gram-negative pathogens. In particular, these new leads maintain activity against MLS-resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes. In addition, they represent an improvement over telithromycin (1) and cethromycin (2) against the fastidious Gram-negative pathogen Haemophilus influenzae.
摘要
合成了一系列新型C-4''-取代阿奇霉素，并评估了它们对一组代表性的对红霉素敏感和对大环内酯-林可酰胺-链阳菌素（MLS）耐药病原体的体外抗菌活性。总之，阿奇霉素和喹诺酮亚结构以相互SAR兼容的设计合并，产生了一类新的抗菌剂，其抗菌谱和效力优于阿奇霉素。原型类似物7f和8f对革兰氏阳性和苛求革兰氏阴性病原体显示出比阿奇霉素更高的效力。特别是，这些新先导化合物对肺炎链球菌和化脓性链球菌的MLS耐药菌株保持活性。此外，它们在针对苛求革兰氏阴性病原体流感嗜血杆菌方面比泰利霉素（1）和西罗莫霉素（2）有所改进。
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