ACS Medicinal Chemistry Letters: Discovery of Sovleplenib, a Selective Inhibitor of Syk in Clinical Development for Autoimmune Diseases and Cancers

Hong Jia, Wei Deng, Baoyu Hao, Min Cai, Dong Guo, Yu Cai, Xiaoming Dai, Zhipeng Wu, Weigang He, Jian Wang, Guanglin Wang, Sumei Xia, Na Li, Weiguo Su, and Guangxiu Dai*

Abstract

Herein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (41) via a structure–activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-b]pyrazine scaffold. Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.

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Publication Date:April 18, 2024

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DOI: https://doi.org/10.1021/acsmedchemlett.3c00553

Link to article: https://pubs.acs.org/doi/10.1021/acsmedchemlett.3c00553