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 a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt, solvate, ester or salt or solvate of such ester, of a compound of formula (I) in which: R⁰ is halogen, C_1-6alkyl, C_1-6alkoxy, C_1-6alkoxy substituted by one or more fluorine atoms, or O(CH₂)_nNR⁴R⁵; R¹ and R² are independently selected from H, C_1-6alkyl, C_1-6alkyl substituted by one or more fluorine atoms, C_1-6alkoxy, C_1-6hydroxyalkyl, SC_1-6alkyl, C(O)H, C(O)C_1-6alkyl, C_1-6alkylsulphonyl, C_1-6alkoxy substituted by one or more fluorine atoms, O(CH₂)_nCO₂C_1-6alkyl, O(CH₂)_nSC_1-6alkyl, (CH₂)_nNR⁴R⁵, (CH₂)_nSC_1-6alkyl 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 C_1-6alkylsulphonyl, C_1-6alkoxy substituted by one or more fluorine atoms, O(CH₂)_nCO₂C_1-6alkyl, O(CH₂)_nSC_1-6alkyl, (CH₂)_nNR⁴R⁵ or (CH₂)_nSC_1-6alkyl, C(O)NR⁴R⁵; R³ is C_1-6alkyl or NH₂; R⁴ and R⁵ are independently selected from H and C_1-6alkyl or, together with the nitrogen atom to which they are attached, form a 4-8 membered saturated ring; and n is 1-4; and an inhibitor of the release, or action, of tumour necrosis factor alpha.