Recent progress in the medicinal chemistry of 2,4-diaminopyrimidines.

@article{Roth1982RecentPI,
  title={Recent progress in the medicinal chemistry of 2,4-diaminopyrimidines.},
  author={Barbara Roth and C. C. Cheng},
  journal={Progress in medicinal chemistry},
  year={1982},
  volume={19},
  pages={
          269-331
        }
}
  • B. Roth, C. Cheng
  • Published 1982
  • Biology, Chemistry
  • Progress in medicinal chemistry
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References

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: Thirteen new analogs of 2,4-diamino-5(p-chlorophenyl)-6-ethylpyrimidine (Daraprim, pyrimethamine) in which the alph position of the 6-ethyl substituent was modified were prepared. The respective…

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It appears that the adamantyl group in position 5 greatly facilitates the passage of pyrimidines through the plasma membrane of the cells, thereby increasing the inhibitory potency of these compounds in cellular systems over and above that expected from enzyme inhibition analysis.

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A new route to 5-(p-hydroxybenzyl)pyrimidine has been developed which utilizes phenolic Mannich bases plus pyrimidines containing at least two activating groups, and has been used to prepare trimethoprim, a broad-spectrum antibacterial agent.

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A series of 19 quinazoline analogs of pteroic and isopteroic acid was prepared with particular emphasis being placed upon carboxylic acid esters, with several of the more potent inhibitors found to be inactive against L1210 leukemia in mice at low dose levels and were lethal to mice at 100 mg/kg.
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