旨在避免代谢活化的新型苯溴马隆衍生物的合成。
Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation.
作者信息
Ohe Tomoyuki, Umezawa Ryutaro, Kitagawara Yumina, Yasuda Daisuke, Takahashi Kyoko, Nakamura Shigeo, Abe Akiko, Sekine Shuichi, Ito Kousei, Okunushi Kentaro, Morio Hanae, Furihata Tomomi, Anzai Naohiko, Mashino Tadahiko
机构信息
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, Japan.
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, Japan.
出版信息
Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3708-3711. doi: 10.1016/j.bmcl.2018.10.023. Epub 2018 Oct 15.
We synthesized six novel BBR derivatives that were designed to avoid metabolic activation via ipso-substitution and evaluated for their degree of toxicity and hURAT1 inhibition. It was found that all of the derivatives demonstrate lower cytotoxicity in mouse hepatocytes and lower levels of metabolic activation than BBR, while maintaining their inhibitory activity toward the uric acid transporter. We propose that these derivatives could serve as effective uricosuric agents that have much better safety profiles than BBR.
我们合成了六种新型黄连素衍生物，这些衍生物旨在通过本位取代避免代谢活化，并对其毒性程度和人尿酸转运蛋白1（hURAT1）抑制作用进行了评估。结果发现，所有衍生物在小鼠肝细胞中均表现出比黄连素更低的细胞毒性和更低水平的代谢活化，同时保持其对尿酸转运蛋白的抑制活性。我们认为，这些衍生物可作为有效的促尿酸排泄剂，其安全性比黄连素要好得多。
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