Synthesis of 1,5-Diarylpyrazoles as Potential COX-2 Inhibitors with Nitric Oxide Releasing Ability
Bolla Narasimha Rao,
Saketh Sriram Dinavahi,
Swaroop Kumar V. S. Vakkalanka,
Krishnam Raju Atcha,
A few celecosib like 1,5-diarylpyrazoles conjugated with nitric oxide (NO) donating nitrate ester group were
synthesized and evaluated for their selective COX-2 inhibitory activity along with NO releasing ability of corresponding
nitrate esters. Most of the synthesized compounds exhibited improved COX-2 inhibition when compared with the reference
drug celecoxib. The nitrate ester derivatives (coxib prodrugs) 7 (nitrate ester of 1,5-diarylpyrazole with 2 carbon
linker), and 9 (nitrate ester of 1,5-diarylpyrazole with 3 carbon linker), upon incubation in human whole blood were partly
transformed into the corresponding alcohols 6, and 8 respectively. Molecular docking studies were performed on alcohol
derivatives and revealed additional H-bond interactions compared to celecoxib.
Keywords: CINODs, COX-2 inhibition, Coxib prodrugs, 1, 5-Diarylpyrazoles, Nitrate esters, NO-Donors.
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