新型6-氟-1-[(1R,2S)-2-氟环丙基]-4-氧代喹啉-3-羧酸的合成及其抗菌活性，该化合物在C-7位带有环丙烷稠合的2-氨基-8-氮杂双环[4.3.0]壬-8-基取代基

Synthesis and antibacterial activity of novel 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-4-oxoquinoline-3-carboxylic acids bearing cyclopropane-fused 2-amino-8-azabicyclo[4.3.0]nonan-8-yl substituents at the C-7 position.

作者信息

Inagaki Hiroaki, Takahashi Hisashi, Takemura Makoto

机构信息

Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan.

出版信息

Bioorg Med Chem Lett. 2004 Oct 18;14(20):5193-8. doi: 10.1016/j.bmcl.2004.07.064.

DOI:10.1016/j.bmcl.2004.07.064

PMID:15380226

Abstract

A series of novel 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-4-oxoquinoline-3-carboxylic acids bearing cyclopropane-fused 2-amino-8-azabicyclo[4.3.0]nonan-8-yl substituents at the C-7 position were synthesized to obtain potent drugs for the treatment of Gram-positive infections. Some compounds exhibited excellent antibacterial activity, and potent inhibitory activity against bacterial DNA topoisomerase IV. In addition, some of the potent compounds showed reduced inhibitory activity against human DNA topoisomerase II compared with the corresponding noncyclopropane-fused compounds.

摘要

合成了一系列新型的6-氟-1-[(1R,2S)-2-氟环丙基]-4-氧代喹啉-3-羧酸，这些化合物在C-7位带有与环丙烷稠合的2-氨基-8-氮杂双环[4.3.0]壬-8-基取代基，以获得用于治疗革兰氏阳性感染的强效药物。一些化合物表现出优异的抗菌活性以及对细菌DNA拓扑异构酶IV的强效抑制活性。此外，与相应的非环丙烷稠合化合物相比，一些强效化合物对人DNA拓扑异构酶II的抑制活性降低。