Structure-based design of lipophilic quinazoline inhibitors of thymidylate synthase

…, GP Marzoni, CL Palmer, V Kathardekar…

Index: Jones, Terence R.; Varney, Michael D.; Webber, Stephen E.; Lewis, Kathleen K.; Marzoni, Gifford P.; Palmer, Cindy L.; Kathardekar, Vinit; Welsh, Katharine M.; Webber, Stephanie; Matthews, David A.; Appelt, Krzysztof; Smith, Ward W.; Janson, Cheryl A.; Villafranca; Bacquet, Russell J.; Howland, Eleanor F.; Booth, Carol L. J.; Herrmann, Steven M.; Ward, Robert W.; White, Jennifer; Moomaw, Ellen W.; Bartlett, Charlotte A.; Morse, Cathy A. Journal of Medicinal Chemistry, 1996 , vol. 39, # 4 p. 904 - 917

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Citation Number: 36

Abstract

To develop novel lipophilic thymidylate synthase (TS) inhibitors, the X-ray structure of Escherichia coli TS in ternary complex with FdUMP and the inhibitor 10-propargyl-5, 8- dideazafolic acid (CB3717) was used as a basis for structure-based design. A total of 31 novel lipophilic TS inhibitors, lacking a glutamate residue, were synthesized; 26 of them had in common a N-((3, 4-dihydro-2-methyl-6-quinazolinyl) methyl)-N-prop-2-ynylaniline ...