2,4-diamino-5-benzylpyrimidines

Hopfinger, A. J. (1981) Inhibition of dihydrofolate reductase structure-activity correlations of 2,4-diamino-5-benzylpyrimidines based upon molecular shape analysis. J. Med. Chem. 24, 818-822. 

Tab. 4.31 Code, structure, /50-values against various E. coli mutants, and physicochemical properties of the tested 2,4-diamino-5-benzylpyrimidines. (Reprinted from Tab. 2 of ref. 106)... 

Diamino-5-benzylpyrimidines and analogues antibacterial agents. II. C-AIkylation of pyrimidines with Mannich bases and application to the synthesis of trimetoprim and analogues, J. Med. Chem.. 23,379. 1980 see also J. Med. Chem.. 23, 384 and 5.35. 1980. 

Hopfinger, A.J. (1981). Inhibition of Dihydrofolate Reductase Structure-Activity Correlations of 2,4-Diamino-5-benzylpyrimidines Based upon Molecular Shape Analysis. J.Med.Chem., 24, 818-822. 

Hopfinger, A.J. (1983) Theory and application of molecular potential energy fields in molecular shape analysis a quantitative structure-activity relationship study of 2,4-diamino-5-benzylpyrimidines as dihydrofolate reductase inhibitors. J. Med. Chem., 26,... 

Hopfinger s method is illustrated by his treatment of a series of 2,4-diamino-5-benzylpyrimidines 16.1), of which the most outstanding member is the antibacterial drug, trimethoprim (9.32), discussed on p. 352. The test, inhibition of bovine liver DHFR (dihydrofolate reductase), furnished the following equation ... 

A. J. Hopfinger, /. Med. Chem., 26, 990 (1983). Theory and Application of Molecular Potential Energy Fields in Molecular Shape Analysis A Quantitative Structure—Activity Relationship Study of 2,4-Diamino-5-benzylpyrimidines as Dihydrofolate Reductase Inhibitors. 

Benzylpyrimidine sulfonamides are based on the combination of a sulfonamide with trimethoprim or tetroxoprim. Chemically, trimethoprim is a 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine and has the following structural formula. 

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