Synthesis and Cyclooxygenase-2 Inhibiting Property of 1,5-Diarylpyrazoles with Substituted Benzenesulfonamide Moiety as Pharmacophore: Preparation of Sodium Salt for Injectable Formulation

Pal, Manojit, Madan, Manjula, Padakanti, Srinivas, Pattabiraman, Vijaya R., Kalleda, Srinivas, Vanguri, Akhila, Mullangi, Ramesh, Mamidi, N. V. S. Rao, Casturi, Seshagiri R., Malde, Alpeshkumar, Gopalakrishnan, B. and Yeleswarapu Koteswar R. (2003) Synthesis and Cyclooxygenase-2 Inhibiting Property of 1,5-Diarylpyrazoles with Substituted Benzenesulfonamide Moiety as Pharmacophore: Preparation of Sodium Salt for Injectable Formulation. Journal of Medicinal Chemistry, 46 19: 3975-3984. doi:10.1021/jm020563g


Author Pal, Manojit
Madan, Manjula
Padakanti, Srinivas
Pattabiraman, Vijaya R.
Kalleda, Srinivas
Vanguri, Akhila
Mullangi, Ramesh
Mamidi, N. V. S. Rao
Casturi, Seshagiri R.
Malde, Alpeshkumar
Gopalakrishnan, B.
Yeleswarapu Koteswar R.
Title Synthesis and Cyclooxygenase-2 Inhibiting Property of 1,5-Diarylpyrazoles with Substituted Benzenesulfonamide Moiety as Pharmacophore: Preparation of Sodium Salt for Injectable Formulation
Journal name Journal of Medicinal Chemistry   Check publisher's open access policy
ISSN 0022-2623
Publication date 2003-08-13
Sub-type Article (original research)
DOI 10.1021/jm020563g
Volume 46
Issue 19
Start page 3975
End page 3984
Total pages 10
Place of publication Washington, D.C.
Publisher American Chemical Society
Language eng
Subject 030401 Biologically Active Molecules
030402 Biomolecular Modelling and Design
Abstract A series of 1,5-diarylpyrazoles having a substituted benzenesulfonamide moiety as pharmacophore was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Through SAR and molecular modeling, it was found that fluorine substitution on the benzenesulfonamide moiety along with an electron-donating group at the 4-position of the 5-aryl ring yielded selectivity as well as potency for COX-2 inhibition in vitro. Among such compounds 3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide 3 displayed interesting pharmacokinetic properties along with antiinflammatory activity in vivo. Among the sodium salts tested in vivo, 10, the propionyl analogue of 3, showed excellent antiinflammatory activity and therefore represents a new lead structure for the development of injectable COX-2 specific inhibitors.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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