Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate

Molecules

Tingting Zhang³  Jinwei Wu¹  Shihong Chen¹  Kaixiang Liu²  Yabin Lin⁴  Huiyuan Guo³ 

[1] Zhejiang Starry Pharmaceutical Co. Ltd., Xianju 317300, China;China Resources Double-Crane Pharmaceutical Co. Ltd., Beijing 100102, China;Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;Harbin Stomatological Hospital, Harbin 150010, China

关键词: IMB-070593;    prodrugs;    synthesis;    water solubility;    antibacterial activity;   

DOI  :  10.3390/molecules19056822

来源: mdpi

【 摘 要 】

A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate discovered in our lab, were synthesized and evaluated for their water solubility and then antibacterial activity. Our results reveal that four amino acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have much greater solubility (>85 mg/mL) than IMB-070593 mesylate (22.5 mg/mL). Compounds 4a and 4k show good in vivo efficacy against MSSA 12-1 (p.o./i.v., 5.32–7.68 mg/kg) and S. pneumoniae12-10 (p.o., 18.39–23.13 mg/kg) which is 1.19–1.50 fold more active than the parent drug.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.