Design, synthesis and anti-necroptosis activity of fused heterocyclic MLKL inhibitors

In this study, with the covalent motif maintained, we aim to improve the activity by introducing the terminal fused heterocycles and meanwhile revealing the SAR on the part. As a result, compounds 9 and 14 showed the best activity (EC50 = 148.4 and 595.9 nM) against necroptosis among the analogues by covalently binding to MLKL. The SAR was also concluded to guide further structural optimization in this field.PMID:38442525 | DOI:10.1016/j.bmc.2024.117659

Source: Bioorganic and Medicinal Chemistry - March 5, 2024 Category: Chemistry Authors: Yining Tang Chunlin Zhuang Source Type: research