Design and synthesis of biaryloxazolidinone derivatives containing amide or acrylamide moiety as novel antibacterial agents against Gram-positive bacteria

• Published in: Bioorganic & medicinal chemistry letters Vol. 29; no. 23; p. 126747
• Main Authors: Xu, Sicong, Jiang, Jia, Qi, Yinliang, Ding, Xiudong, Wu, Yachuang, Lei, Hong, Zhao, Yanfang
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.12.2019; Elsevier
• Subjects: Antibacterial activity; Biaryloxazolidinone; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Gram-positive bacteria; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Gram-positive bacteria; Antibacterial activity; Biaryloxazolidinone; ANTIBIOTICS; COMMUNITY; OXAZOLIDINONES; RESISTANT ENTEROCOCCI
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2019.126747

A series of novel biaryloxazolidinone derivatives containing amide or acrylamide structure were designed, synthesized and evaluated for their antibacterial activity. [Display omitted] •Biaryloxazolidinone derivatives containing an amide or acrylamide moiety.•Compound 17 exhibited antibacterial activity with MIC values of 0.5 μg/mL against S. aureus, MRSA, MSSA and VRE and 0.25 μg/mL against LREF.•The potency of compound 17 against LREF was 64-fold higher than that of linezolid and 2-fold than that of radezolid.•Compound 17 exhibit higher stability in gastric acid than compound Ⅳ. A series of novel biaryloxazolidinone derivatives containing amide and acrylamide structure were designed, synthesized and evaluated for their antibacterial activity. Most compounds generally exhibited potent antibacterial activity with MIC values of 1 μg/mL against S. aureus, MRSA, MSSA, LREF and VRE pathogens, using linezolid and radezolid as positive controls. Compound 17 exhibited good antibacterial activity with MIC values of 0.5 μg/mL against S. aureus, MRSA, MSSA and VRE and 0.25 μg/mL against LREF. The results indicated that compound 17 might serve as a potential hit-compound for further investigation.