Zhiwei Chen, Qi Zhang, Yun Chen, Yi Ning, Q-i Zhang, Mengxiao Zhang, Qiupei Liu, Yi Xue, Linjiang Tong, Jian Ding, Hua Xie and Wenhu Duan
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Design, synthesis and pharmacological evaluation of 3H-spiro[benzofuran-2,4′-piperidine] IRAK4 inhibitors for the treatment of diffuse large B-cell lymphoma
Interleukin-1 receptor-associated kinase 4 (IRAK4) has emerged as a promising target for the treatment of diffuse large B-cell lymphoma (DLBCL). Herein, we report the identification and structure–activity relationship studies of a new series of 3H-spiro[benzofuran-2,4′-piperidine] IRAK4 inhibitors designed to improve the pharmacokinetic properties of a previously identified series. The representative compound 13 showed strong inhibitory activity against IRAK4, significant antiproliferative effect against DLBCL cells, and improved pharmacokinetic properties. In addition, compound 13 effectively inhibited the activation of IRAK4 signaling pathway and induced DLBCL cell apoptosis. These results indicated that compound 13 was a promising lead compound for the development of anti-DLBCL agents.
期刊介绍：
Research and review articles in medicinal chemistry and related drug discovery science; the official journal of the European Federation for Medicinal Chemistry.
In 2020, MedChemComm will change its name to RSC Medicinal Chemistry. Issue 12, 2019 will be the last issue as MedChemComm.
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