Discovery of potent transient receptor potential vanilloid 1 antagonists: Design and synthesis of phenoxyacetamide derivatives |
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| Authors: | Eiki Takahashi Noriyuki Hirano Takashi Nagahara Satoru Yoshikawa Shinobu Momen Hiroshi Yokokawa Ryoji Hayashi |
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| Institution: | Pharmaceutical Research Laboratories, Toray Industries, Inc., 10-1-6 Tebiro, Kamakura, Kanagawa 248-8555, Japan |
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| Abstract: | We aimed to discover a novel type of transient receptor potential vanilloid 1 (TRPV1) antagonist because such antagonists are possible drug candidates for treating various disorders. We modified the structure of hit compound 7 (human TRPV1 IC50 = 411 nM) and converted its pyrrolidino group to a (hydroxyethyl)methylamino group, which substantially improved inhibitory activity (15d; human TRPV1 IC50 = 33 nM). In addition, 15d ameliorated bladder overactivity in rats in vivo. |
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| Keywords: | TRPV1 Transient receptor potential vanilloid 1 VR1 Antagonist |
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