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Updated: May 3, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
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Syntheses and structure-activity relationships for some triazolyl p38α MAPK inhibitors
Jean-Paul G Seerden1, Gabriela Leusink-Ionescu1, Robin Leguijt1
1Syncom B.V., Kadijk 3, Groningen 9747AT, The Netherlands.
Abstract:
The design, synthesis and biological evaluation of novel triazolyl p38α MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a 'click' reaction of functional azides with 2-alkynyl imidazoles and isosteric oxazoles to generate two small libraries of 1,4-disubstituted 1,2,3-triazolyl p38α MAPK inhibitors. Triazoles with low IC50 values and desired physicochemical properties were screened for in vitro downregulation of proinflammatory gene expression and were formulated in SAINT-O-Somes. Triazolyl p38α MAPK inhibitor 88 (IC50=0.096 μM) displayed the most promising in vitro activity.
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