Potent Oxazolidinone Antibacterials with Heteroaromatic C-Ring Substructure

被引：24

作者：

Suzuki, Hideyuki ^{[1
]}

Utsunomiya, Iwao ^{[1
]}

Shudo, Koichi ^{[1
]}

Fujimura, Takaji ^{[2
]}

Tsuji, Masakatsu ^{[2
]}

Kato, Issei ^{[2
]}

Aoki, Toshiaki ^{[2
]}

Ino, Akira ^{[2
]}

Iwaki, Tsutomu ^{[2
]}

机构：

[1] Res Fdn Itsuu Lab, Setagaya Ku, Tokyo 1580094, Japan

[2] Shionogi & Co Ltd, Med Res Labs, Toyonaka, Osaka 5610825, Japan

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2013年 / 4卷 / 11期

关键词：

Antibacterial; oxazolidinone; methicillin-resistant Staphylococcus aureus; condensed heteroaromatic ring; STAPHYLOCOCCUS-AUREUS; RESISTANT; AGENTS; DERIVATIVES; SAR;

D O I：

10.1021/ml400280z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel oxazolidinone analogues bearing a condensed heteroaromatic ring as the C-ring substructure were synthesized as candidate antibacterial agents. Analogues 16 and 21 bearing imidazo[1,2-a]pyridine and 18 and 23 bearing [1,2,4]triazolo[1,5-a]pyridine as the C-ring had excellent in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). They also showed promising therapeutic effects in a mouse model of lethal infection. Preliminary safety data (inhibitory effects on cytochrome P450 isoforms and monoamine oxidases) were satisfactory. Further evaluation of 18 and 23 is ongoing.

引用

页码：1074 / 1078

页数：5

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