Endothelin antagonists: discovery of EMD 122946, a highly potent and orally active ETA selective antagonist.

@article{Mederski1998EndothelinAD,
  title={Endothelin antagonists: discovery of EMD 122946, a highly potent and orally active ETA selective antagonist.},
  author={Werner W K R Mederski and Dieter Dorsch and Monika Osswald and Soheila Anzali and Maike Christadler and C J Schmitges and Pierre Schelling and Claudia Wilm and Markus Fluck},
  journal={Bioorganic & medicinal chemistry letters},
  year={1998},
  volume={8 13},
  pages={1771-6}
}
The discovery, in vitro and in vivo studies of the highly potent ETA antagonist EMD 122946 are presented. This compound displayed high binding affinity and functional antagonism [IC50 = 3.2 x 10(-11) M, pA2 = 9.5 (ETA)] and inhibited the ET-1 induced pressor response in pithed rats with an ED50 of 0.3 mg/kg. In conscious spontaneously hypertensive rats and in DOCA-salt hypertensive rats the compound lowered mean blood pressure with an ED50 of 0.06 mg/kg. EMD 122946 exhibited high… CONTINUE READING