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

摘要

The invention provides the compounds of formula (I)and pharmaceutically acceptable derivatives thereof in which:R<0 >is halogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy substituted by one or more fluorine atoms, or O(CH2)nNR<4>R<5>;R<1 >and R<2 >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)nNR<4>R<5>, (CH2)nSC1-6alkyl or C(O)NR<4>R<5>; with the proviso that when R<0 >is at the 4-position and is halogen, at least one of R<1 >and R<2 >is C1-6alkylsulphonyl, C1-6alkoxy substituted by one or more fluorine atoms, O(CH2)nCO2C1-6alkyl, O(CH2)nSC1-6alkyl, (CH2)nNR<4>R<5 >or (CH2)nSC1-6alkyl, C(O)NR<4>R<5>;R<3 >is C1-6alkyl or NH2;R<4 >and R<5 >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; andn 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.