-Butyl(2-oxo-2-pyran-5-yl)carbamate as the First Chameleon Diene Bearing an Electron-Donating Substituent.

The 2()-pyran-2-one bearing electron-donating -butylcarbamate (BocNH-) group at the 5- position is a "chameleon" diene and undergoes efficient Diels-Alder cycloadditions with alkene dienophiles with both electron-rich and electron-deficient substituents. Cycloadditions afford the 5-substituted bicyclic lactone cycloadducts regardless of the electronic nature of the dienophile. However, cycloadditions with electronically matched electron-deficient dienophiles proceed faster than those with electronically mismatched electron-rich dienophiles.

Further insight into the dual COX-2 and 15-LOX anti-inflammatory activity of 1,3,4-thiadiazole-thiazolidinone hybrids: The contribution of the substituents at 5th positions is size dependent.

Herin we report the design, synthesis, full characterization and biological investigation of new 15-LOX/COX dual inhibitors based on 1,3-thiazolidin-4-one (15-lipoxygenase pharmacophore) and 1,3,4-thiadiazole (COX pharmacophore) scaffolds. This series of molecular modifications is an extension of a previously reported series to further explore the structural activity relationship. Compounds 3a, 4e, 4n, 4q, 7 and 8 capable of inhibiting 15-LOX at (2.

Synthesis, biological evaluation and docking study of 1,3,4-thiadiazole-thiazolidinone hybrids as anti-inflammatory agents with dual inhibition of COX-2 and 15-LOX.

Selective inhibition of both cyclooxygenase-2 (COX-2) and 15-lipooxygenase (15-LOX) may provide good strategy for alleviation of inflammatory disorders while minimizing side effects associated with current anti-inflammatory drugs. The present study describes the synthesis, full characterization and biological evaluation of a series of thiadiazole-thiazolidinone hybrids bearing 5-alk/arylidene as dual inhibitors of these enzymes. Our design was based on merging pharmacophores that exhibit portent anti-inflammatory activities in one molecular frame.