2,3-DIARYL-PYRAZOLO[1,5-B]PYRIDAZINES DERIVATIVES, THEIR PREPA RATION 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; 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.