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The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors
Author(s) -
Sabatini Stefano,
Manfroni Giuseppe,
Barreca Maria Letizia,
Bauer Silke M.,
Gargaro Marco,
Cannalire Rolando,
Astolfi Andrea,
Brea Jose,
Vacca Carmine,
Pirro Matteo,
Massari Serena,
Tabarrini Oriana,
Loza Maria Isabel,
Fallarino Francesca,
Laufer Stefan A.,
Cecchetti Violetta
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12516
Subject(s) - chemotype , p38 mitogen activated protein kinases , protein kinase a , mapk/erk pathway , kinase , chemistry , mitogen activated protein kinase , biochemistry , computational biology , biology , chromatography , essential oil
The identification, synthesis, biological activity, and binding mode prediction of a series of pyrazolobenzothiazines as novel p38 α MAPK inhibitors are reported. Some of these compounds showed interesting activity in both p38 α MAPK and TNF ‐ α release assays. Derivative 6 emerged as the most interesting compound with IC 50 (p38 α ) = 0.457 μ m , IC 50 ( TNF ‐ α ) = 0.5 μ m and a promising kinase selectivity profile. The obtained results strongly indicate the pyrazolobenzothiazine core as a new p38 α inhibitor chemotype worthy of future chemical optimization efforts directed toward identifying a new generation of anti‐inflammatory agents.