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The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors |
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| Authors: | Stefano Sabatini Giuseppe Manfroni Maria Letizia Barreca Silke M. Bauer Marco Gargaro Rolando Cannalire Andrea Astolfi Jose Brea Carmine Vacca Matteo Pirro Serena Massari Oriana Tabarrini Maria Isabel Loza Francesca Fallarino Stefan A. Laufer Violetta Cecchetti |
| Affiliation: | 1. Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy;2. Department of Pharmaceutical & Medicinal Chemistry, Institute of Pharmacy, Eberhard‐Karls University Tuebingen, Tuebingen, Germany;3. Department of Experimental Medicine, University of Perugia, Perugia, Italy;4. CIMUS Research Center, University of Santiago de Compostela, Santiago de Compostela, Spain;5. Department of Medicine, University of Perugia, Perugia, Italy |
| Abstract: | The identification, synthesis, biological activity, and binding mode prediction of a series of pyrazolobenzothiazines as novel p38α MAPK inhibitors are reported. Some of these compounds showed interesting activity in both p38α MAPK and TNF‐α release assays. Derivative 6 emerged as the most interesting compound with IC50 (p38 α ) = 0.457 μ m , IC50 (TNF‐ α ) = 0.5 μ m and a promising kinase selectivity profile. The obtained results strongly indicate the pyrazolobenzothiazine core as a new p38α inhibitor chemotype worthy of future chemical optimization efforts directed toward identifying a new generation of anti‐inflammatory agents. |
| Keywords: | anti‐TNF agents ligand efficiency molecular docking p38α MAPK inhibitors pyrazolobenzothiazines |