Helvetica chimica acta

5??(N??Arylnortropan??3??yl)??and 5??(N??Arylpiperidin??4??yl)??2, 4??diaminopyrimidines. Novel Inhibitors of Dihydrofolate Reductase

H Maag, R Locher, JJ Daly, I Kompis

Index: Maag, Hans; Locher, Rita; Daly, John J.; Kompis, Ivan Helvetica Chimica Acta, 1986 , vol. 69, p. 887 - 897

Full Text: HTML

Citation Number: 18

Abstract

Abstract Based on a computer-assisted analysis of the three-dimensional structure of the binary complex of E. coli dihydrofolate reductase (DHFR) with methotrexate, 5-(N- arylnortropan-3-yl)-and 5-(N-arylpiperidin-4-yl)-2, 4-diaminopyrimidines 2 and 4 were designed as inhibitors of DHFR. Syntheses of the designed compounds have been carried out. The most potent compound 2a inhibited E. coli DHFR with K i= 0.49. 10− 9 M. The ...