B. R. Baker, D. Santi
Sep 1, 1965
Citations
0
Influential Citations
51
Citations
Journal
Journal of pharmaceutical sciences
Abstract
2-Amino-6-methyl-5-(3-phenylpropylamino)-4-pyrimidinol (VI) was found to be as effective as 2-amino-5-(3-anilinopropyl)-6-methyl-4-pyrimidinol and 2-amino-6-methyl-5-(4-phenylbutyl)-4-pyrimidinol (IV) as an inhibitor of thymidylate synthetase. The effectiveness of IV was reduced when the 6-methyl group was replaced by 6-amino (VIII). In contrast, VIII was about a fourfold better inhibitor of dihydrofolic reductase than IV. Similarly, 5-(4-phenylbutyl)-2,4,6-triaminopyrimidine (IX) was about a ninefold better inhibitor of dihydrofolic reductase than IV; however, IX was only about one-eightieth as effective as 2,4-diamino-6-methyl-5-(4-phenylbutyl)pyrimidine (XVII). With dihydrofolic reductase, 5-(3-phenylpropyl)-2,4,6-triaminopyrimidine (XV) was nearly as effective as IX. Compounds VIII, IX, and XV bind to dihydrofolic reductase about as well as the substrate, dihydrofolate, and are easily synthesized in two steps from commercially available materials.