High-affinity inhibitors of dihydrofolate reductase: antimicrobial and anticancer activities of 7, 8-dialkyl-1, 3-diaminopyrrolo [3, 2-f] quinazolines with small molecular …

LF Kuyper, DP Baccanari, ML Jones…

Index: Kuyper, Lee F.; Baccanari, David P.; Jones, Michael L.; Hunter, Robert N.; Tansik, Robert L.; Joyner, Suzanne S.; Boytos, Christine M.; Rudolph, Sharon K.; Knick, Vince; Wilson, H. Robert; Caddell, J. Marc; Friedman, Henry S.; Comley, John C. W.; Stables, Jeremy N. Journal of Medicinal Chemistry, 1996 , vol. 39, # 4 p. 892 - 903

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Citation Number: 86

Abstract

A series of 7, 8-dialkylpyrrolo [3, 2-f] quinazolines were prepared as inhibitors of dihydrofolate reductase (DHFR). On the basis of an apparent inverse relationship between compound size and antifungal activity, the compounds were designed to be relatively small and compact. Inhibitor design was aided by a GRID analysis of the three-dimensional structure of Candida albicans DHFR, which suggested that relatively small, branched alkyl ...