Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
Email: lddd@benthamscience.org


Synthesis of 1,5-Diarylpyrazoles as Potential COX-2 Inhibitors with Nitric Oxide Releasing Ability

Author(s): Bolla Narasimha Rao, Meyyappan Muthuppalaniappan, Saketh Sriram Dinavahi, Srikant Viswanadha, Chandrakant Bagul, Kolupula Srinivas, Swaroop Kumar V. S. Vakkalanka, Krishnam Raju Atcha, Ahmed Kamal.


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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Article Details

Year: 2013
Page: [594 - 603]
Pages: 10
DOI: 10.2174/1570180811310070006
Price: $58