Absorption, distribution, metabolism, and excretion considerations in selection of orally active indole-containing endothelin antagonist.

@article{Walker2001AbsorptionDM,
  title={Absorption, distribution, metabolism, and excretion considerations in selection of orally active indole-containing endothelin antagonist.},
  author={Don K Walker and Kevin N. Dack and Roger P. Dickinson and Katherine S Fenner and Kim Turnbull James and David J. Rawson and Dennis A. Smith},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2001},
  volume={29 11},
  pages={1424-31}
}
A series of potent indole-containing endothelin antagonists were evaluated in rat pharmacokinetic studies as part of a rational drug design program. Early compounds in this series were found to show poor gastrointestinal absorption, limiting their utility as oral agents. Structural modifications and pharmacokinetic studies indicated that reducing the overall H-bonding potential, through a reduction in the number of H-bond donors and acceptors, could increase absorption of the molecules. There… CONTINUE READING

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Showing 1-10 of 27 references

Hydrogen bond strength estimation by means of the HYBOT program package, in Computer-Assisted Lead Finding and Optimization

  • OA Raevsky
  • (van de Waterbeemd H, Testa B, and Folkers G eds…
  • 1997
Highly Influential
4 Excerpts

Estimation of Caco-2 permeability using calculated molecular descriptors

  • H van de Waterbeemd, G Camenisch, G Folkers, OA Raevsky
  • Quant Struct Act Relat 15:480–490
  • 1996
Highly Influential
3 Excerpts

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