@article{a2105a77b1cb45a7a13d086f5aaaf72e,
title = "Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation",
abstract = "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.",
keywords = "Benzbromarone, Hepatotoxicity, Metabolic activation, URAT1",
author = "Tomoyuki Ohe and Ryutaro Umezawa and Yumina Kitagawara and Daisuke Yasuda and Kyoko Takahashi and Shigeo Nakamura and Akiko Abe and Shuichi Sekine and Kousei Ito and Kentaro Okunushi and Hanae Morio and Tomomi Furihata and Naohiko Anzai and Tadahiko Mashino",
note = "Funding Information: This work was supported by the Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Japan Agency for Medical Research and Development (AMED; 2012-2016), and the Platform Project for Supporting Drug Discovery and Life Science Research, AMED (2017-2018). This work was also supported by JSPS KAKENHI (Grant Number 16K08379) and a special grant generously provided by the Hoansha Foundation. Funding Information: This work was supported by the Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Japan Agency for Medical Research and Development (AMED; 2012-2016), and the Platform Project for Supporting Drug Discovery and Life Science Research , AMED (2017-2018). This work was also supported by JSPS KAKENHI (Grant Number 16K08379 ) and a special grant generously provided by the Hoansha Foundation. Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2018",
month = dec,
day = "15",
doi = "10.1016/j.bmcl.2018.10.023",
language = "English",
volume = "28",
pages = "3708--3711",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "23-24",
}