2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 9. Lipophilic trimethoprim analogues as antigonococcal agents.

@article{Roth198824Diamino5benzylpyrimidinesAA,
  title={2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 9. Lipophilic trimethoprim analogues as antigonococcal agents.},
  author={Bruce L Roth and David P. Baccanari and C W Sigel and James Hubbell and J A Eaddy and James C Kao and Marie E. Grace and B S Rauckman},
  journal={Journal of medicinal chemistry},
  year={1988},
  volume={31 1},
  pages={122-9}
}
Lipophilic analogues of trimethoprim (1) bearing 3,5-dialkyl-4-hydroxy substituents in the benzene ring are much more active in vitro against Neisseria gonorrhoeae than is 1. The 3,5-diisopropyl-4-hydroxy derivative (2) was selected as a candidate for clinical evaluation as an antigonococcal agent, and as part of the preliminary evaluation it was submitted to extended pharmacokinetic and metabolism studies in dogs. Although the compound was not extensively conjugated by metabolic enzymes, one… CONTINUE READING