PYRIDAZINE COMPOUNDS AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS.

摘要

Disclosed are pyridazine compounds of the formula I which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds: In formula (I) indicates a single bond or a double bond; X is O, S or N-R⁵; R¹, R² are independently selected from the group consisting of H, NH², NH-C₁-C₆-alkyl, OH, =O, (i.e. a carbonyl group), C₁-C₆-alkoxy, halogen, methyl, C₂-C₄-alkyl, C₃- C₄-cycloalkyl, C₃-C₄-alkenyl, fluorinated C₁-C₄-alkyl, fluorinated C₃-C₄-cycloalkyl, fluorinated C₃-C₄-alkenyl, formyl, C₁-C₃-alkylcarbonyl, and an aromatic radical Ar, R₁ and R₂ together with the carbon atoms, to which they are attached, form a fused, saturated or unsaturated 5-, 6- or 7-membered C-bound carbocyclic or heterocyclic ring comprising 1 heteroatom, selected from nitrogen, oxygen and sulfur as ring member and O, 1 or 2 further heteroatoms, independently selected from O, S and N, as ring members, wherein the fused ring is unsubstituted or may carry 1 , 2 or 3 substituents selected, independently of each other, from the group of radicals R⁴ as defined below; R³ is hydrogen OH, halogen, CN, nitro, C₁-C₆-alkyl, fluorinated C₁-C₆-alkyl, C₁-C₆- hydroxyalkyl, C₁-C₆-alkoxy-C₁-C₆- alkyl, C₂-C₆-alkenyl, fluorinated C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₇-cycloalkyl, fluorinated C₃-C₇-cycloalkyl, C₁-C₆-alkoxy, C₁-C₆- hydroxyalkoxy, C₁C₆-alkoxy-C₁-C₆-a lkoxy, fluorinated C₁-C₆-alkoxy, C₁-C₆- alkylthio, fluorinated-C₁-C₆ alkylthio, C₁C₆-alkylsulfinyl, fluorinated C₁-C₆- alkylsulfinyl, C₁-C₆-alkylsulfonyl, fluorinated C₁-C₆ alkylsulfonyl, C₁C₆- alkylcarbonyl, fluorinated C₁C₆-alkylcarbonyl, C₁ ^-C₆-alkylcarbonylamino, fluorinated C₁-C6-alkylcarbonylamino, carboxy, C1-C6-alkyloxycarbonyl, fluorinated C₁-C₆-alkoxycarbonyl, NR^aR^b, C(O)-NR^eR^f, NH-C(O)-N R^eR^f, NR^aR^b-C₁-C₆-alkylen e, O-NR^aR^b, etc. and wherein R⁴ and R⁵ are as defined in the specification and the claims.