Discovery of a potent orally available pyrazolopyridone derivative as a novel selective bromodomain and extra-terminal domain (BET)-first bromodomain (BD1) inhibitor

被引：1

作者：

Hagihara, Shuichi ^{[1
]}

Ishizawa, Kouhei ^{[1
]}

Soga, Kana ^{[1
]}

Honjo, Takashi ^{[1
]}

Takai, Shigeki ^{[1
]}

Kawano, Yuko ^{[1
]}

Kikuchi, Manami ^{[1
]}

Nishidate, Akiko ^{[1
]}

Matsumoto, Fumi ^{[1
]}

Murase, Mikako ^{[1
]}

Hashimoto, Naohiro ^{[1
]}

Sasaki, Chiduko ^{[1
]}

Miyaguchi, Ikuko ^{[1
]}

Okada, Okimasa ^{[1
]}

Akashi, Tomoya ^{[1
]}

Nakayama, Shinji ^{[1
]}

Ogasawara, Yuko ^{[1
]}

Endo, Junichi ^{[1
]}

机构：

[1] Mitsubishi Tanabe Pharm Corp, Sohyaku Innovat Res Div, 1000 Kamoshida Cho,Aoba Ku, Yokohama 2270033, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2024年 / 109卷

关键词：

BET family; BD1; selectivity; X-ray crystallography; Inflammation; Pyrazolopyridone; PROTEIN; CHROMATIN; BRD4;

D O I：

10.1016/j.bmcl.2024.129849

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Clinical studies have shown that inhibitors of bromodomain and extra-terminal domain (BET) proteins, particularly BRD4, have antitumor activity and efficacy. The BET protein has two domains, BD1 and BD2, and we previously focused on BD1 and reported orally bioavailable BD1-selective inhibitors. In this study, we obtained a BD1 inhibitor, a more potent and highly selective pyrazolopyridone derivative 13a, and confirmed its in vivo efficacy.

引用

页数：6

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