Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective cyclooxygenase-2 inhibitors.

Abstract	GW406381 (8), currently undergoing clinical evaluation for the treatment of inflammatory pain is a member of a novel series of 2,3-diaryl-pyrazolo[1,5-b]pyridazine based cyclooxygenase-2 (COX-2) inhibitors, which have been shown to be highly potent and selective. Several examples of the series, in addition to possessing favourable pharmacokinetic profiles and analgesic activity in vivo, have also demonstrated relatively high brain penetration in the rat compared with the clinically available compounds, which may ultimately prove beneficial in the treatment of pain.
Authors	Paul Beswick, Sharon Bingham, Chas Bountra, Terry Brown, Kerry Browning, Ian Campbell, Iain Chessell, Nick Clayton, Sue Collins, John Corfield, Stephen Guntrip, Claudine Haslam, Paul Lambeth, Fiona Lucas, Neil Mathews, Graham Murkit, Alan Naylor, Neil Pegg, Elizabeth Pickup, Hazel Player, Helen Price, Alexander Stevens, Sharon Stratton, Joanne Wiseman
Journal	Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 14 Issue 21 Pg. 5445-8 (Nov 01 2004) ISSN: 0960-894X [Print] England
PMID	15454242 (Publication Type: Comparative Study, Journal Article)
Chemical References	Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Membrane Proteins Pyrazoles Pyridazines Freund's Adjuvant Cyclooxygenase 2 PTGS2 protein, human Prostaglandin-Endoperoxide Synthases
Topics	Administration, Oral Animals Arthritis, Experimental (chemically induced, drug therapy) Biological Availability Brain (metabolism) Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors (chemical synthesis, chemistry, pharmacokinetics) Freund's Adjuvant Humans Infusions, Intravenous Male Membrane Proteins Prostaglandin-Endoperoxide Synthases (chemistry, metabolism) Pyrazoles (chemical synthesis, chemistry, pharmacology) Pyridazines (chemical synthesis, chemistry, pharmacology) Rats Structure-Activity Relationship

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