Author/Authors :
Harshad K Rami، نويسنده , , Mervyn Thompson، نويسنده , , Paul Wyman، نويسنده , , Jeffrey C. Jerman، نويسنده , , Julie Egerton، نويسنده , , Stephen Brough، نويسنده , , Alexander J Stevens، نويسنده , , Andrew D Randall، نويسنده , , Darren Smart، نويسنده , , Martin J Gunthorpe، نويسنده , , John B Davis، نويسنده ,
Abstract :
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 Ca2+ 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 series cause inhibition via an extracellularly accessible binding site on the TRPV1 receptor.
Keywords :
e-mail: harshad.rami@gsk.com , SB-366791.* Corresponding author. Tel.: +44-(0)-1279-627818 , trpv1 , Vanilloid antagonist , VR1 , SB-452533 , fax: +44-(0)-1279-622122
