New selective cyclooxygenase-2 inhibitors from cyclocoumarol: Synthesis, characterization, biological evaluation and molecular modeling
In this work, a serie of cyclocoumarol derivatives was designed, synthesized, characterized and studied for their potentialities as selective inhibitors of COX-2. All target compounds have been screened for their anti-inflammatory activity by the assay of PGE2 production. Among them, compound 5d exhibited the most potent inhibitory activity with a PGE2 inhibition compared to NS-398 (79% and 88% respectively) and showed non-inhibitory activity towards the COX-1 enzyme. Docking studies revealed the capacity of this compound to occupy the selective COX-2 cavity establishing additional hydrogen bonds between the oxygen of the methoxy group and the His90 and Arg513 of the binding site of the enzyme.
An asymmetric approach to coumarin anticoagulants via hetero-Diels-Alder cycloaddition
We have developed a general, two-step protocol for the synthesis of chiral non-racemic coumarin anticoagulants (e.g. warfarin, coumachlor and acenocoumarol). This approach features a one-pot three-component tandem Knoevenagel-hetero-Diels-Alder reaction between in situ generated 3-arylidene-2,4-chromanediones and iso-propenyl ether derived from (-)-menthol.
Cravotto, Giancarlo,Nano, Gian Mario,Palmisano, Giovanni,Tagliapietra, Silvia
p. 707 - 709
(2007/10/03)
High-yield synthesis of warfarin and its phenolic metabolites: New compounds
A novel synthesis of warfarin and phenolic warfarin metabolites is presented which results in higher yields than previous methods.