Key result
Tetrazole lumiracoxib derivative shows dual COX-2 inhibition and thromboxane A2 receptor antagonism in human blood.
Why the study?
The influence of isosteric substitution on balancing COX-2 inhibition and thromboxane A2 receptor antagonism in lumiracoxib derivatives was explored to design multitarget anti-inflammatory agents.
The identification of a tetrazole derivative of lumiracoxib with dual COX-2 inhibition and TP receptor antagonism provides a basis for designing new cardioprotective anti-inflammatory agents.
May guide design of dual COX-2/TP antagonists; leaves open clinical translation and safety in patients.
A series of lumiracoxib derivatives were designed to explore the influence of isosteric substitution on balancing COX-2 inhibition and thromboxane A(2) prostanoid (TP) receptor antagonism. The compounds were synthesized through a copper-catalyzed coupling procedure and characterized for their pK(a) values. TP receptor antagonism was assessed on human platelets; COX-2 inhibition was determined on human isolated monocytes and human whole blood. TPα receptor binding of the most promising compounds was evaluated through radioligand binding assays. Some of the isosteric substitutions at the carboxylic acid group afforded compounds with improved TP receptor antagonism; of these, a tetrazole derivative retained good COX-2 inhibitory activity and selectivity. The identification of this tetrazole acting as a balanced dual-acting compound in human whole blood, along with SAR analysis of the synthesized lumiracoxib derivatives, might contribute to the rational design of a new class of cardioprotective anti-inflammatory agents.
No takes yet. Share an insight, caveat, or question.
Bertinaria et al. (2012) studied this question. Lumiracoxib derivatives was evaluated on TP receptor antagonism and COX-2 inhibition. A tetrazole derivative of lumiracoxib demonstrated balanced dual-acting properties as a COX-2 inhibitor and thromboxane A2 receptor antagonist in human whole blood.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: