Although only a few DHFR inhibitors have progressed as antibiotics to the market there is much renewed interest in the discovery and development of new generation DHFR inhibitors as antibacterial agents. This article describes the success in exploiting DHFR as a drugable target as exemplified by trimethoprim (TMP) and the development of several new diaminopyrimidines. Iclaprim, a recent example of a novel diaminopyrimidine currently in Phase III clinical trials, is also described together with several examples of anti-DHFR antibacterial compounds in pre-clinical development.
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