Irreversible enzyme inhibitors LXXXVII. Hydrophobic bonding to dihydrofolic reductase IX. Mode of binding of m-aryloxyalkyl groups on 4, 6-diamino-1,2-dihydro-2, 2-dimethyl-1-phenyl-s-triazine

Abstract

The relative binding to dihydrofolic reductase by 16 m -substituted 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-phenyl- s -triazines—nine of which are newly synthesized— has been measured. Strong evidence is presented to indicate that the increased binding by terminal phenyl groups on a m -substituent is due to complexing to a relatively hydrophilic area since terminal benzyl and terminal phenoxy groups give nearly the same increments in binding. The possible conversion of such compounds to candidate active-site-directed irreversible inhibitors of dihydrofolic reductase is discussed.