B. R. Baker, D. Santi
Mar 1, 1967
Citations
0
Influential Citations
3
Citations
Journal
Journal of Pharmaceutical Sciences
Abstract
5-( p -Aminophenoxypropyl)-2,4,6-triaminopyrimidine (XIVd) was synthesized by alkylation of malononitrile by 3-bromopropyl p -nitrophenyl ether (Xb), followed by ring closure with guanidine and catalytic reduction of the nitro group. Selective haloacylation of the aromatic amino group of XIVb was accomplished by protonation of the triaminopyrimidine moiety of XIVd with acetic acid. Treatment with the anhydrides of bromoacetic acid, p -bromoacetamidophenylbutyric acid, and N-bromoacetyl- β -alanine gave the pure bromoacyl derivatives, XIVe, i , and j . These three compounds were good reversible inhibitors of dihydrofolic reductase, but failed to show irreversible inhibition; these failures are attributed to the phenoxypropyl group of the inhibitors (XIV) being complexed with a hydrophobic region on the enzyme—a region not apt to have groups that could form a covalent bond.