Synthesis and Biological Evaluation of Polar Functionalities Containing Nitrodihydroimidazooxazoles as Anti-TB Agents

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• 作者：Kushalava Reddy Yempalla ; Gurunadham Munagala ; Samsher Singh ; Gurleen Kour ; Shweta Sharma ; Reena Chib ; Sunil Kumar ; Priya Wazir ; G. D. Singh ; Sushil Raina ; Sonali S. Bharate ; Inshad Ali Khan ; Ram A. Vishwakarma ; Parvinder Pal Singh
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：October 8, 2015
• 年：2015
• 卷：6
• 期：10
• 页码：1059-1064
• 全文大小：410K
• ISSN：1948-5875

文摘

Novel polar functionalities containing 6-nitro-2,3-dihydroimidazooxazole (NHIO) analogues were synthesized to produce a compound with enhanced solubility. Polar functionalities including sulfonyl, uridyl, and thiouridyl-bearing NHIO analogues were synthesized and evaluated against Mycobacterium tuberculosis (MTB) H₃₇Rv. The aqueous solubility of compounds with MIC values 鈮?.5 渭g/mL were tested, and six compounds showed enhanced aqueous solubility. The best six compounds were further tested against resistant (Rif^R and MDR) and dormant strains of MTB and tested for cytotoxicity in HepG2 cell line. Based on its overall in vitro characteristics and solubility profile, compound 6d was further shown to possess high microsomal stability, solubility under all tested biological conditions (PBS, SGF and SIF), and favorable oral in vivo pharmacokinetics and in vivo efficacy.