N10-substituted 5,8-dideazafolate inhibitors of glycinamide ribonucleotide transformylase.
A series of 5,8-dideazafolates bearing ethyl, isopropyl, cyclopropylmethyl, propargyl, 3-cyanopropyl, carboxymethyl, 2-carboxyethyl, phenacyl, 3-fluorobenzyl, and 5-uracilylmethyl substituents at N10 were tested as inhibitors of purified L5178Y glycinamide ribonucleotide transformylase (GAR TFase), which requires 10-formyltetrahydrofolate as cofactor. All of these cofactor analogues exhibited competitive inhibition against N10-formyl-5,8-dideazafolate, with Ki's ranging from 2 to 32 microM.
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D005492:Folic Acid / Q000031:analogs & derivatives*; D019877:Hydroxymethyl and Formyl Transferases; D051026:Phosphoribosylglycinamide Formyltransferase; D013329:Structure-Activity Relationship
D005492:Folic Acid; D019877:Hydroxymethyl and Formyl Transferases; D051026:Phosphoribosylglycinamide Formyltransferase; D000217:Acyltransferases