Synthesis and Antituberculosis Activity of a Novel Series of Optically Active 6-Nitro-2,3-dihydroimidazo[2,1-b]oxazoles
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- 作者：Hirofumi Sasaki ; Yoshikazu Haraguchi ; Motohiro Itotani ; Hideaki Kuroda ; Hiroyuki Hashizume ; Tatsuo Tomishige ; Masanori Kawasaki ; Makoto Matsumoto ; Makoto Komatsu ; Hidetsugu Tsubouchi
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：December 28, 2006
- 年：2006
- 卷：49
- 期：26
- 页码：7854 - 7860
- 全文大小：122K
- 年卷期：v.49,no.26(December 28, 2006)
- ISSN：1520-4804
文摘
In an effort to develop potent new antituberculosis agents that would be effective against both drug-susceptibleand drug-resistant strains of Mycobacterium tuberculosis, we prepared a novel series of optically active6-nitro-2,3-dihydroimidazo[2,1-b]oxazoles substituted at the 2-position with various phenoxymethyl groupsand a methyl group and investigated the in vitro and in vivo activity of these compounds. Several of thesederivatives showed potent in vitro and in vivo activity, and compound 19 (OPC-67683) in particular displayedexcellent in vitro activity against both drug-susceptible and drug-resistant strains of M. tuberculosis H37Rv(MIC = 0.006 
g/mL) and dose-dependent and significant in vivo efficacy at lower oral doses than rifampicinin mouse models infected with M. tuberculosis Kurono. The synthesis and structure-activity relationshipsof these new compounds are presented.
g/mL) and dose-dependent and significant in vivo efficacy at lower oral doses than rifampicinin mouse models infected with M. tuberculosis Kurono. The synthesis and structure-activity relationshipsof these new compounds are presented.