1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase. (1st January 2019)

• Record Type: Journal Article
• Authors: Jian, Yanlin; Risseeuw, Martijn D. P.; Froeyen, Mathy; Song, Lijun; Cappoen, Davie; Cos, Paul; Munier-Lehmann, Hélène; van Calenbergh, Serge
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 34:Number 1(2019)
• Page Start: 1730
• Page End: 1739
• Publication Date: 2019-01-01
• Subjects: Thymidylate kinase -- inhibitors -- Mycobacterium tuberculosis -- modelling; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2019.1662790
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A series of readily accessible 1-(piperidin-3-yl)thymine amides was designed, synthesised and evaluated as Mycobacterium tuberculosis TMPK ( Mtb TMPK) inhibitors. In line with the modelling results, most inhibitors showed reasonable Mtb TMPK inhibitory activity. Compounds 4b and 4i were slightly more potent than the parent compound 3 . Moreover, contrary to the latter, amide analogue 4g was active against the avirulent M. tuberculosis H37Ra strain (MIC50 =35 µM). This finding opens avenues for future modifications.