Crystal-structure-based design and synthesis of benz [cd] indole-containing inhibitors of thymidylate synthase

MD Varney, GP Marzoni, CL Palmer…

Index: Varney, Michael D.; Marzoni, Gifford P.; Palmer, Cindy L.; Deal, Judith G.; Webber, Stephanie; et al. Journal of Medicinal Chemistry, 1992 , vol. 35, # 4 p. 663 - 676

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Citation Number: 110

Abstract

The X-ray crystal-structurebased design, synthesis, and biological activity of a novel family of benz [cd] indole-containing inhibitors of thymidylate synthase (TS) are described. The structure-activity of the lead compound was studied by conceptually dividing the molecule into four regions and independently optimizing the substituents for each region. Combination of favored substituents for each region led to inhibitors with K: s against the ...