Structure-based design of substituted diphenyl sulfones and sulfoxides as lipophilic inhibitors of thymidylate synthase

…, KK Lewis, V Kathardekar, H Mazdiyasni…

文献索引：Jones, Terence R.; Webber, Stephen E.; Varney, Michael D.; Reddy, M. Rami; Lewis, Kathleen K.; Kathardekar, Vinit; Mazdiyasni, Hormoz; Deal, Judith; Nguyen, Dzuy; Welsh, Katharine M.; Webber, Stephanie; Johnston, Amanda; Matthews, David A.; Smith, Ward W.; Janson, Cheryl A.; Bacquet, Russell J.; Howland, Eleanor F.; Booth, Carol L. J.; Herrmann, Steven M.; Ward, Robert W.; White, Jennifer; Bartlett, Charlotte A.; Morse, Cathy A. Journal of Medicinal Chemistry, 1997 , vol. 40, # 5 p. 677 - 683

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被引用次数: 38

摘要

Six new diphenyl sulfoxide and five new diphenyl sulfones were designed, synthesized, and tested for their inhibition of human and Escherichia coli thymidylate synthase (TS) and of the growth of cells in tissue culture. The best sulfoxide inhibitor of human TS was 3-chloro-N-((3, 4-dihydro-2-methyl-4-oxo-6-quinazolinyl) methyl)-4-(phenylsulfinyl)-N-(prop-2-ynyl) aniline (7c) that had a K i of 27 nM. No sulfone improved on TS inhibition by the previously ...