کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1377490 | 981979 | 2006 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Discovery of SB-705498: A potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development Discovery of SB-705498: A potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development](/preview/png/1377490.png)
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.
TRPV1 antagonist activity of SB-705498 (15) and its in vitro and in vivo activity are reported.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 12, 15 June 2006, Pages 3287–3291