biostudies-literatureUnknown15(5)Jia HHerein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (<b>41</b>) via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-<i>b</i>]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.ACS medicinal chemistry letters595-601https://www.ebi.ac.uk/biostudies/studies/S-EPMC11089545biostudies-literatureDiscovery of Sovleplenib, a Selective Inhibitor of Syk in Clinical Development for Autoimmune Diseases and Cancers.PMC11089545Cai MJia HWang GXia SWang JDai XLi NWu ZHe WDai GCai YGuo DHao BDeng WSu WfalseDiscovery of Sovleplenib, a Selective Inhibitor of Syk in Clinical Development for Autoimmune Diseases and Cancers.Herein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (<b>41</b>) via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-<i>b</i>]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.2024-01-01T00:00:00Z2024 May2026-06-02T21:01:11.499Z2026-04-20T03:14:18.237ZS-EPMC110895453874689210.1021/acsmedchemlett.3c00553