Patent NZ-501808-A (NZ)
Title: Arylpyridazinones and their use as prostaglandin endoperoxide H synthase biosynthesis inhibitors
Inventor: KORT MICHAEL E
IPC: C07D417/06
Filed: 1998-08-10
Abstract: A compound of formula (I); wherein: X is O, S, NR4, N-ORa, or N-NRbRc; R is H, alkyl, alkenyl, alkynyl, alkylcarbonylalkyl, alkylsulfonylalkyl, alkylsulfonylarylalkyl, alkoxy, alkoxyalkyl, carboxy, carboxyalkyl, cyanoalkyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, arylhaloalkyl, arylhydroxyalkyl, aryloxy, aryloxyhydroxyalkyl, aryloxyhaloalkyl, arylcarbonylalkyl, haloalkoxyhydroxyalkyl, heterocyclic, heterocyclic alkyl, heterocyclic alkoxy, heterocyclic oxy, -C(O)R5, (CH2)nC(O)R5, -R6-R7, -(CH2)nCH(OH)R5, -(CH2)nCH(ORd)R5, -(CH2)nC(NORd)R5, (CH2)nC(NRd)R5, -(CH2)nCH(NORd)R5, -(CH2)nCH(NRdRe)R5, -(CH2)nCºC-R7, (CH2)n[CH(CX'3)]m-(CH2)n-CX'3, -(CH2)n(CX'2)m-(CH2)n-CX'3, -(CH2)n[CH(CX'3)]m-(CH2)n-R8, (CH2)n(CHX'2)m-(CH2)nR8, -(CH2)n(CHX')m-(CH2)n-CX'3, -(CH2)n(CHX')m-(CH2)n-R8, and (CH2)nR20. At least one of R1, R2 and R3 is selected from formula (II) or (III), shown. The remaining two of the groups of R1 and R3, are independently H, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkylamino, alkenyloxy, alkylthio, alkylthioalkoxy, alkoxy, alkoxyalkyl, alkoxyalkylamino, alkoxyalkoxy, amido, amidoalkyl, haloalkyl, haloalkenyloxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkenylalkoxy, cycloalkylalkoxy, cycloalkylalkylamino, cycloalkylamino, cycloalkyloxy, cycloalkylidenealkyl, amino, aminocarbonyl, aminoalkoxy, aminocarbonylalkyl, alkylaminoaryloxy, dialkylamino, dialkylaminoaryloxy, arylamino, arylalkylamino, diarylamino, aryl, arylalkyl, arylalkylthio, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, heterocyclic, heterocyclic alkyl, heterocyclic(alkyl)amino, heterocyclic alkoxy, heterocyclic amino, heterocyclic oxy, heterocyclic thio, hydroxyalkylamino, hydroxyalkoxy, hydroxyalkylthio, mercaptoalkoxy, oxoalkoxy, cyano, nitro, aryloxyalkyl, alkylthioalkyl, arylthioalkyl, heterocyclic(alkyl) and Y, wherein Y is -OR14, -SR14, -C(R16)(R17)(R14), -C(O)NR21R14, -C(O)R14, -C(O)OR14, -NH(R14), -NC(O)R14,-N=CR21R14, -N-R19R14. R2 is H, hydroxy, hydroxyalkyl, halogen, alkyl, alkenyl, alkynyl, alkylamino, alkenyloxy, alkylthio, alkylthioalkoxy, alkoxy, alkoxyalkyl, alkoxyalkylamino, alkoxyalkoxy, amido, amidoalkyl, haloalkyl, haloalkenyloxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkenylalkoxy, cycloalkylalkoxy, cycloalkylalkylamino, cycloalkylamino, cycloalkyloxy, cycloalkylidenealkyl, amino, aminocarbonyl, aminoalkoxy, aminocarbonylalkyl, alkylaminoaryloxy, dialkylamino, dialkylaminoaryloxy, arylamino, arylalkylamino, diarylamino, aryl, arylalkyl, arylalkylthio, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, heterocyclic, heterocyclic alkyl, heterocyclic(alkyl)amino, heterocyclic alkoxy, heterocyclic amino, heterocyclic oxy, heterocyclic thio, hydroxyalkylamino, hydroxyalkoxy, hydroxyalkylthio, mercaptoalkoxy, oxoalkoxy, cyano, nitro and Y, wherein Y is -OR14, -SR14, -C(R16)(R17)(R14), -C(O)NR21R14, -C(O)R14, -C(O)OR14, -NH(R14), -NC(O)R14,-N=CR21R14, -NR19R14. Also described is a pharmaceutical composition comprising the compound of formula (I). The compounds of formula (I) are useful for inhibiting prostaglandin biosynthesis. The compounds of formula (I) are particularly useful for treating pain, fever, inflammation, rheumatoid arthritis, osteoarthritis and adhesions.