2,3-Dideoxy hex-2-enopyranosid-4-uloses as promising new anti-tubercular agents: Design, synthesis, biological evaluation and SAR studies
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- 作者：Mohammad Saquib ; Irfan Husain ; Smriti Sharma ; Garima Yadav ; Vipul K. Singh ; S ; eep K. Sharma ; Priyanka Shah ; Mohammad Imran Siddiqi ; Brijesh Kumar ; Jawahar Lal ; Girish K. Jain ; Brahm S. Srivastava ; Ranjana Srivastava ; Arun K. Shaw
- 关键词：Anti-tubercular agents ; 2 ; 3-Dideoxy hex-2-enopyranosid-4-uloses ; Modified deoxy sugars ; Small molecules ; Non-natural sugars ; α ; β ; -Unsaturated keto system
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：June 2011
- 年：2011
- 卷：46
- 期：6
- 页码：2217-2223
- 全文大小：675 K
文摘
The alarming resurgence of tuberculosis (TB) underlines the urgent need for development of new and potent anti-TB drugs. Towards this goal we herein report the design and synthesis of 2,3-dideoxy hex-2-enopyranosid-4-uloses as promising new anti-tubercular agents. These easily accessible, small molecules were found to exhibit in vitro activity against Mycobacterium tuberculosis H37Rv in a MIC range of 0.78 μg/mL to 25 μg/mL. A detailed SAR study on these hex-2-enopyranosid-4-uloses led to the identification of compound 5g (S007–724) which on the basis of low MIC (0.78 μg/mL-M. tuberculosis H37Rv; 1.56 μg/mL-MDR, SDR strains of M. tuberculosis; 0.78 μg/mL-inhibition of intracellular replication of M. tuberculosis) and SI value of 13.5 has been identified as a promising lead molecule.