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

   
   

The invention provides the compounds of formula (I) ##STR1## and pharmaceutically acceptable derivatives thereof in which: R.sup.0 is halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted by one or more fluorine atoms, or O(CH.sub.2).sub.n NR.sup.4 R.sup.5 ; R.sup.1 and R.sup.2 are independently selected from H, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted by one or more fluorine atoms, C.sub.1-6 alkoxy, C.sub.1-6 hydroxyalkyl, SC.sub.1-6 alkyl, C(O)H, C(O)C.sub.1-6 alkyl, C.sub.1-6 alkylsulphonyl, C.sub.1-6 alkoxy substituted by one or more fluorine atoms, O(CH.sub.2).sub.n CO.sub.2 C.sub.1-6 alkyl, O(CH.sub.2).sub.n SC.sub.1-6 alkyl, (CH.sub.2).sub.n NR.sup.4 R.sup.5, (CH.sub.2).sub.n SC.sub.1-6 alkyl or C(O)NR.sup.4 R.sup.5 ; with the proviso that when R.sup.0 is at the 4-position and is halogen, at least one of R.sup.1 and R.sup.2 is C.sub.1-6 alkylsulphonyl, C.sub.1-6 alkoxy substituted by one or more fluorine atoms, O(CH.sub.2).sub.n CO.sub.2 C.sub.1-6 alkyl, O(CH.sub.2).sub.n SC.sub.1-6 alkyl, (CH.sub.2).sub.n NR.sup.4 R.sup.5 or (CH.sub.2).sub.n SC.sub.1-6 alkyl, C(O)NR.sup.4 R.sup.5 ; R.sup.3 is C.sub.1-6 alkyl or NH.sub.2 ; R.sup.4 and R.sup.5 are independently selected from H, or C.sub.1-6 alkyl 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.

A invenção fornece os compostos do ## do ## STR1 da fórmula (I) e pharmaceutically de derivatives aceitáveis disso em qual: R.sup.0 é halogênio, C.sub.1-6 alkyl, alkoxy C.sub.1-6 alkoxy, C.sub.1-6 substituído por um ou mais átomo do fluorine, ou O(CH.sub.2).sub.n NR.sup.4 R.sup.5; R.sup.1 e R.sup.2 são selecionados independentemente de H, C.sub.1-6 alkyl, alkyl C.sub.1-6 substituído por um ou mais átomo do fluorine, C.sub.1-6 alkoxy, C.sub.1-6 hydroxyalkyl, SC.sub.1-6 alkyl, C(O)H, C(O)C.sub.1-6 alkyl, C.sub.1-6 alkylsulphonyl, alkoxy C.sub.1-6 substituído por um ou mais átomo do fluorine, alkyl de O(CH.sub.2).sub.n CO.sub.2 C.sub.1-6, alkyl de O(CH.sub.2).sub.n SC.sub.1-6, (CH.sub.2).sub.n NR.sup.4 R.sup.5, (alkyl de CH.sub.2).sub.n SC.sub.1-6 ou C(O)NR.sup.4 R.sup.5; com o proviso que quando R.sup.0 for no 4-position e for halogênio, ao menos um de R.sup.1 e de R.sup.2 é C.sub.1-6 o alkylsulphonyl, alkoxy C.sub.1-6 substituído por um ou mais átomo do fluorine, alkyl de O(CH.sub.2).sub.n CO.sub.2 C.sub.1-6, alkyl de O(CH.sub.2).sub.n SC.sub.1-6, (CH.sub.2).sub.n NR.sup.4 R.sup.5 ou (alkyl de CH.sub.2).sub.n SC.sub.1-6, C(O)NR.sup.4 R.sup.5; R.sup.3 é o alkyl C.sub.1-6 ou o NH.sub.2; R.sup.4 e R.sup.5 são selecionados independentemente de H, ou o alkyl C.sub.1-6 ou, junto com o átomo do nitrogênio a que são unidos, dá forma a um 4-8 membered o anel saturated; e n é 1-4. Os compostos da fórmula (I) são inibidores potent e seletivos de COX-2 e são do uso no tratamento da dor, da febre, do inflammation de uma variedade das circunstâncias e das doenças.

 
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