Methanesulfonamide group at position-4 of the C-5-phenyl ring of 1,5-diarylpyrazole affords a potent class of cyclooxygenase-2 (COX-2) inhibitors

Sunil Kumar Singh; Saibaba Vobbalareddy; Samala Shivaramakrishna; A Krishnamraju; Shaikh Abdul Rajjak; Seshagiri Rao Casturi; Vangoori Akhila; Yeleswarapu Koteswar Rao

doi:10.1016/j.bmcl.2004.01.053

Methanesulfonamide group at position-4 of the C-5-phenyl ring of 1,5-diarylpyrazole affords a potent class of cyclooxygenase-2 (COX-2) inhibitors

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1683-8. doi: 10.1016/j.bmcl.2004.01.053.

Authors

Sunil Kumar Singh¹, Saibaba Vobbalareddy, Samala Shivaramakrishna, A Krishnamraju, Shaikh Abdul Rajjak, Seshagiri Rao Casturi, Vangoori Akhila, Yeleswarapu Koteswar Rao

Affiliation

¹ Discovery Chemistry, Discovery Research-Dr Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad 500 049, India. sunilkumarsingh@drredys.com

PMID: 15026050
DOI: 10.1016/j.bmcl.2004.01.053

Abstract

The effect of methanesulfonamide (MeSO(2)NH) group on COX-2 inhibitory activity of 1,5-diarylpyrazole is described. While this group being at position-4 of the N(1)-phenyl ring was found to be ineffective, its installation at position-4 of the C-5 phenyl ring offered several potent and selective inhibitors of COX-2 with IC(50) as low as 30 nM.

MeSH terms

Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemistry*
Cyclooxygenase Inhibitors / pharmacology
Humans
Isoenzymes / antagonists & inhibitors*
Isoenzymes / metabolism
Membrane Proteins
Prostaglandin-Endoperoxide Synthases / metabolism
Pyrazoles / chemistry*
Pyrazoles / pharmacology
Sulfonamides / chemistry*
Sulfonamides / pharmacology

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
Membrane Proteins
Pyrazoles
Sulfonamides
methanesulfonamide
Cyclooxygenase 2
PTGS2 protein, human
Prostaglandin-Endoperoxide Synthases