Discovery of 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole,FYX-051-a xanthine oxidoreductase inhibitor for the treatment of hyperuricemia |
| |
| Authors: | Takahiro Sato Naoki Ashizawa Koji Matsumoto Takashi Iwanaga Hiroshi Nakamura Tsutomu Inoue Osamu Nagata |
| |
| Institution: | 1. Research Laboratories 1, Research Department, Medical R&D Division, Fuji Yakuhin Co., Ltd, 3936-2 Sashiougi, Nishi-ku, Saitama-shi, Saitama 331-0047, Japan;2. Research Laboratories 2, Research Department, Medical R&D Division, Fuji Yakuhin Co., Ltd, 636-1 Iidashinden, Nishi-ku, Saitama-shi, Saitama 331-0068, Japan;3. Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane-shi, Chiba 283-8555, Japan |
| |
| Abstract: | Our previous study identified 2-2-(2-methoxy-ethoxy)-ethoxy]-5-5-(2-methyl-4-pyridyl)-1H-1,2,4]triazol-3-yl]-benzonitrile (2) as a safe and potent xanthine oxidoreductase (XOR) inhibitor for the treatment of hyperuricemia. Here, we synthesized a series of 3,5-dipyridyl-1,2,4-triazole derivatives and, in particular, examined their in vivo activity in lowering the serum uric acid levels in rats. As a result, we identified 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole (FYX-051, compound 39) to be one of the most potent XOR inhibitors; it exhibited an extremely potent in vivo activity, weak CYP3A4-inhibitory activity and a better pharmacokinetic profile than compound 2. Compound 39 is currently being evaluated in a phase 2 clinical trial. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
