A series of fourteen 5,8-dideaza analogues of folic and pteroic acids was evaluated for inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (AICAR TFase) from chicken liver. Of the 5,8-dideaza folate derivatives studied, 10-oxa-5,8-dideazafolic acid was the most potent inhibitor. The addition of one l-glutamate moiety to the γ-carboxyl group caused a 6- to 7-fold reduction in Ki in three instances. Two compounds devoid of an l-glutamate were 4- to 6-fold less inhibitory than their parent counterparts possessing one l-glutamate residue.
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