2,3-Diaryl-pyrazolo[1,5-b]pyridazines derivatives, their preparation and their use as cyclooxygenase 2(COX-2) inhibitors

US6451794B1 · kind B1 · utility

Assignee

• SmithKline Beecham Limited · US

Inventors

• Paul John Beswick · Hitchin, GB
• Ian Baxter Campbell
• Neil Mathews · Stevenage, GB
• Alan Naylor · Royston, GB

Key dates

• Filing date: Jun 13, 2000
• Grant date: Sep 17, 2002
• Expiry date: Jun 13, 2020

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention provides the compounds of formula (I) and pharmaceutically acceptable derivatives thereof in which: R0 is halogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy substituted by one or more fluorine atoms, or O(CH2)nNR4R5; R1 and R2 are independently selected from H, C1-6alkyl, C1-6alkyl, substituted by one or more fluorine atoms, C1-6alkoxy, C1-6hydroxyalkyl, SC1-6alkyl, C(O)H, C(O)C1-6alkyl, C1-6alkylsulphonyl, C1-6alkoxy substituted by one or more fluorine atoms, O(CH2)nCO2C1-6alkyl, O(CH2)nSC1-6alkyl, (CH2)nNR4R5, (CH2)nSC1-6alkyl or C(O)NR4R5; with the proviso that when R0 is at the 4-position and is halogen, at least one of R1 and R2 is C1-6alkylsulphonyl, C1-6alkoxy substituted by one or more fluorine atoms, O(CH2)nCO2C1-6alkyl, O(CH2)nSC1-6alkyl, (CH2)nNR4R5 or (CH2)nSC1-6alkyl, C(O)NR4R5; R3 is C1-6alkyl or NH2; R4 and R5 are independently selected from H, or C1-6alkyl or, together with the nitrogen atom to which they are attached, form a 4-8 membered saturated ring; and n is 1-4. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of the pain, fever, inflammation of a variety of conditions and diseases.