Discovery of small molecule antagonists of TRPV1.

  title={Discovery of small molecule antagonists of TRPV1.},
  author={Harshad K Rami and Mervyn Thompson and Paul Wyman and Jeffrey C. Jerman and Julie Egerton and Stephen Brough and Alexander J. Stevens and Andrew D Randall and Darren Smart and Martin J. Gunthorpe and John B. Davis},
  journal={Bioorganic & medicinal chemistry letters},
  volume={14 14},
Small molecule antagonists of the vanilloid receptor 1 (TRPV1, also known as VR1) are disclosed. Ureas such as 5 (SB-452533) were used to explore the structure activity relationship with several potent analogues identified. Pharmacological studies using electrophysiological and FLIPR Ca(2+) based assays showed compound 5 was an antagonist versus capsaicin, noxious heat and acid mediated activation of TRPV1. Study of a quaternary salt of 5 supports a mode of action in which compounds from this… CONTINUE READING