2,4-diamino-5-benzylpyrimidines and analogues as antibacterial agents. 6. A one-step synthesis of new trimethoprim derivatives and activity analysis by molecular modeling.
A Stuart, T Paterson, B Roth, E Aig
Index: J. Med. Chem. 26(5) , 667-73, (1983)
Full Text: HTML
Abstract
A new route to 2,4-diamino-5-(4-hydroxybenzyl)pyrimidines has been developed that involves the condensation of 2,4-diamino-5-(hydroxymethyl)pyrimidine with phenols in acidic medium. The use of phenol and its 2,6-dialkyl derivatives produces 5-(4-hydroxybenzyl)pyrimidines exclusively. However, 2,6-dimethoxyphenol produces a mixture of 5-(3-hydroxy-2,4-dimethoxybenzyl)- and 5-(4-hydroxy-3,5-dimethoxybenzyl)pyrimidines. The phenolic condensation has been used to prepare a series of alkyl-substituted 5-(4-hydroxybenzyl)- and 5-(4-alkoxybenzyl)pyrimidines. The use of 1,2,3-trimethoxybenzene in place of a phenol produces 2,4-diamino-5-(2,3,4-trimethoxybenzyl)pyrimidine, a trimethoprim isomer with low antibacterial activity. The use of molecular models of several of the new ortho-substituted derivatives in the active site of dihydrofolate reductase has provided a rational explanation for their activities relative to trimethoprim.
Related Compounds
Related Articles:
2007-01-01
[Magn. Reson. Chem. 45(1) , 37-45, (2007)]
1994-08-01
[Solid State Nucl. Magn. Reson. 3(4) , 181-97, (1994)]
2004-05-19
[J. Am. Chem. Soc. 126(19) , 5964-5, (2004)]
2002-07-21
[Chem. Commun. (Camb.) (14) , 1550-1, (2002)]
1992-11-01
[Solid State Nucl. Magn. Reson. 1(4) , 185-95, (1992)]