- Design and synthesis of a second series of triazole-based compounds as potent dual mPGES-1 and 5-lipoxygenase inhibitors
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Microsomal prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO) are pivotal enzymes in the biosynthesis of the pro-inflammatory PGE2 and leukotrienes, respectively. The design and synthesis of a second series of mPGES-1 inhibitors based on a triazole scaffold are described. Our studies allowed us to draw a tentative SAR profile and to optimize this series with the identification of compounds 10, 11 and 14-15 which displayed potent mPGES-1 inhibition in a cell-free assay. In addition, compounds 5, 10, 12 and 14-16 also blocked 5-LO activity in cell-free and cell-based test systems, emerging as very promising candidates for the development of safer and more effective anti-inflammatory drugs.
- Chini, Maria Giovanna,De Simone, Rosa,Bruno, Ines,Riccio, Raffaele,Dehm, Friederike,Weinigel, Christina,Barz, Dagmar,Werz, Oliver,Bifulco, Giuseppe
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experimental part
p. 311 - 323
(2012/09/08)
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