Title of article
Discovery of SB-705498: A potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development
Author/Authors
Harshad K. Rami، نويسنده , , Mervyn Thompson، نويسنده , , Geoffrey Stemp، نويسنده , , Steve Fell، نويسنده , , Jeffrey C. Jerman، نويسنده , , Alexander J. Stevens، نويسنده , , Darren Smart، نويسنده , , Becky Sargent، نويسنده , , Dominic Sanderson، نويسنده , , Andrew D. Randall، نويسنده , , Martin J. Gunthorpe، نويسنده , , John B. Davis، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2006
Pages
5
From page
3287
To page
3291
Abstract
Small molecule antagonists of the vanilloid receptor TRPV1 (also known as VR1) are disclosed. Pyrrolidinyl ureas such as 8 and 15 (SB-705498) emerged as lead compounds following optimisation of the previously described urea SB-452533. Pharmacological studies using electrophysiological and FLIPR-Ca2+-based assays showed that compounds such as 8 and 15 were potent antagonists versus the multiple chemical and physical modes of TRPV1 activation (namely capsaicin, acid and noxious heat). Furthermore, 15 possessed suitable developability properties to enable progression of this compound into in vivo studies and subsequently clinical development.
Keywords
Electrophysiology , Capsaicin , Noxious heat , FCA , SB-705498 , TRPV1 antagonist , SB-366791 , TRPV1 , VR1 , pain , SB-452533
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2006
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
796975
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