Discovery of orally bioavailable inhibitors of MALT1 with in vivo activity for psoriasis

被引：2

作者：

Asaba, Ken Nunettsu ^{[1
]}

Okimura, Keiichi ^{[1
]}

Adachi, Yohei ^{[1
]}

Tokumaru, Kazuyuki ^{[1
]}

Goto, Yasufumi ^{[1
]}

Fujii, Shigeo ^{[1
]}

Watanabe, Akira ^{[1
]}

Sakai, Chizuka ^{[1
]}

Sakurada, Eri ^{[1
]}

Amikura, Kazutoshi ^{[1
]}

Aoki, Takumi ^{[1
]}

机构：

[1] Toray Industries Ltd, Pharmaceut Res Labs, 6-10-1 Tebiro, Kamakura, Kanagawa 2488555, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2023年 / 82卷

关键词：

MALT1; inhibitors; Structure activity relationship; Psoriasis; KAPPA-B ACTIVATION; PARACASPASE MALT1; LYMPHOMA; CLEAVAGE; CARD14;

D O I：

10.1016/j.bmcl.2023.129155

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the design, synthesis, and biological activity of a series of compounds that exhibit potent mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) inhibition. Structural transformation of the substructures of a starting compound gave amidomethyl derivatives and sulfonylguanidine derivatives that exhibited potent inhibition of MALT1. Compound 37 had good oral bioavailability and showed anti-psoriatic activity in an imiquimod-induced psoriasis mouse model after oral administration.

引用

页数：10

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