Discovery of an orally bioavailable NK1 receptor antagonist, (2S,3S)-(2-methoxy-5-tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine (GR203040), with potent antiemetic activity.

@article{Ward1995DiscoveryOA,
  title={Discovery of an orally bioavailable NK1 receptor antagonist, (2S,3S)-(2-methoxy-5-tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine (GR203040), with potent antiemetic activity.},
  author={Peter Ward and Danielle Armour and D E Bays and Bob Evans and Gerard M P Giblin and Nicola M. Heron and Tim Hubbard and Kun Liang and David Middlemiss and Julie Mordaunt},
  journal={Journal of medicinal chemistry},
  year={1995},
  volume={38 26},
  pages={4985-92}
}
The antiemetic, pharmacokinetic, and metabolic profile of CP-99,994, a potent NK1 receptor antagonist, has been carefully evaluated. As a result we began a medicinal chemistry program which initially identified a 3-furanyl analogue (6) with improved antiemetic potency and a methyl sulfone (5) with enhanced metabolic stability and oral bioavailability. The improved pharmacokinetic profile of methyl sulfone (5) was associated with its low lipophilicity, and a therefore a number of heterocyclic… CONTINUE READING