| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1377490 | Bioorganic & Medicinal Chemistry Letters | 2006 | 5 Pages |
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.
Graphical abstractTRPV1 antagonist activity of SB-705498 (15) and its in vitro and in vivo activity are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide
