Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation

Tomoyuki Ohe; Ryutaro Umezawa; Yumina Kitagawara; Daisuke Yasuda; Kyoko Takahashi; Shigeo Nakamura; Akiko Abe; Shuichi Sekine; Kousei Ito; Kentaro Okunushi; Hanae Morio; Tomomi Furihata; Naohiko Anzai; Tadahiko Mashino

doi:10.1016/j.bmcl.2018.10.023

Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation

Tomoyuki Ohe, Ryutaro Umezawa, Yumina Kitagawara, Daisuke Yasuda, Kyoko Takahashi, Shigeo Nakamura, Akiko Abe, Shuichi Sekine, Kousei Ito, Kentaro Okunushi, Hanae Morio, Tomomi Furihata, Naohiko Anzai, Tadahiko Mashino

薬科学科

研究成果: Article

1 引用（Scopus）

抜粋

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.

元の言語	English
ジャーナル	Bioorganic and Medicinal Chemistry Letters
DOI	https://doi.org/10.1016/j.bmcl.2018.10.023
出版物ステータス	Accepted/In press - 2018 1 1

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

文献にアクセス

10.1016/j.bmcl.2018.10.023

フィンガープリント Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

これを引用

Ohe, T., Umezawa, R., Kitagawara, Y., Yasuda, D., Takahashi, K., Nakamura, S., Abe, A., Sekine, S., Ito, K., Okunushi, K., Morio, H., Furihata, T., Anzai, N., & Mashino, T. (受理済み/印刷中). Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation. Bioorganic and Medicinal Chemistry Letters. https://doi.org/10.1016/j.bmcl.2018.10.023

Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation. / 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.

：: Bioorganic and Medicinal Chemistry Letters, 01.01.2018.

研究成果: Article

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. / Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation. ：: Bioorganic and Medicinal Chemistry Letters. 2018.

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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.",

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AU - Takahashi, Kyoko

AU - Nakamura, Shigeo

AU - Abe, Akiko

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AU - Morio, Hanae

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