2, 4-Diamino-5-benzylpyrimidines as antibacterial agents. 7. Analysis of the effect of 3, 5-dialkyl substituent size and shape on binding to four different dihydrofolate …

…, R Ferone, DP Baccanari, JN Champness…

Index: Roth; Rauckman; Ferone; Baccanari; Champness; Hyde Journal of Medicinal Chemistry, 1987 , vol. 30, # 2 p. 348 - 356

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Citation Number: 33

Abstract

A group of trimethoprim (TMP) analogues containing 3, 5-dialkyl (or halo)-4-alkoxy,-hydroxy, or-amino substitution were analyzed in terms of their inhibitory activities against four dihydrofolate reductase (DHFR) isozymes. Although selectivities were lower than with TMP, the activities against vertebrate DHFR were usually at least 2 orders of magnitude less than against enzymes from microbial sources. However, the profiles of activity were remarkably ...