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Discovery of Small Molecule Antagonists of TRPV1

Harshad K Rami, Mervyn Thompson, Paul Wyman, Jeffrey C Jerman, Julie Egerton, Stephen Brough, Alexander J Stevens, Andrew D Randall, Darren Smart, Martin J Gunthorpe, John B Davis

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3631-4.

PMID: 15203132

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 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 series cause inhibition via an extracellularly accessible binding site on the TRPV1 receptor.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP459429391 SB 452533 SB 452533 459429-39-1 Price
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