Novel vanilloid receptor-1 antagonists: 3. The identification of a second-generation clinical candidate with improved physicochemical and pharmacokinetic properties.

@article{Wang2007NovelVR,
  title={Novel vanilloid receptor-1 antagonists: 3. The identification of a second-generation clinical candidate with improved physicochemical and pharmacokinetic properties.},
  author={H. Wang and J. Katon and C. Balan and A. Bannon and C. Bernard and E. Doherty and C. Dom{\'i}nguez and N. Gavva and V. Gore and V. Ma and N. Nishimura and S. Surapaneni and P. Tang and Rami Tamir and O. Thiel and J. Treanor and M. Norman},
  journal={Journal of medicinal chemistry},
  year={2007},
  volume={50 15},
  pages={
          3528-39
        }
}
  • H. Wang, J. Katon, +14 authors M. Norman
  • Published 2007
  • Chemistry, Medicine
  • Journal of medicinal chemistry
  • Based on the previously reported clinical candidate, AMG 517 (compound 1), a series of related piperazinylpyrimidine analogues were synthesized and evaluated as antagonists of the vanilloid 1 receptor (VR1 or TRPV1). Optimization of in vitro potency and physicochemical and pharmacokinetic properties led to the discovery of (R)-N-(4-(6-(4-(1-(4-fluorophenyl)ethyl)piperazin-1-yl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide (16p), a potent TRPV1 antagonist [rTRPV1(CAP) IC50 = 3.7 nM] with… CONTINUE READING
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