Substituerte 2-kinolyloksazoler som er anvendbare som PDE4-inhibitorer

Oppfinnelsen krever forbindelser med formel (I) er et 5-leddet heteroaryl; X er S eller 0; R1 er H, alkyl, sykloalkyl, syklo-alkylalkyl-, -CH2F, -CHF2, -CF3, -C(0)-alkyl eller -C (0) NR18R19; R3 og R4 er H, alkyl, hydroksyalkyl eller -C(0)0-alkyl; R5 og R6 er H, alkyl, hydroksyalkyl, alkoksyalkyl, merkaptoalkyl, -CH2F, -CHF2, -CF3, -C(O)OH eller -C(0)-O-alkyl; R7 er H, alkyl, alkenyl, hydroksyalkyl, sykloalkyl, alkoksyalkyl, aminoalkyl, (R17-fenyl) alkyl eller -CH2-C (0)-0-alkyl; og R8 omfatter alkyl, heteroaryl, fenyl eller sykloalkyl eller heterosykloalkyl, alle eventuelt substituert, eller sykloalkyl- eller heterosykloalkylsubsti-tuert amid; eller R7 og R8 og nitrogen-atomet som de er bundet til, danner til sammen en eventuelt substituert ring; og de gjenværende variabler er som The invention claims compounds of the formula wherein is a 5-membered heteroaryl; X is S or O; R1 is H, alkyl, cycloalkyl, cylcoalkylalkyl-, -CH2F, -CHF2, -CF3, -C(O)alkyl or -C(O)NR18R19; R3 and R4 H, alkyl, hydroxyalkyl or -C(O)Oalkyl; R5 and R6 are H, alkyl, hydroxyalkyl, alkoxyalkyl, mercaptoalkyl, -CH2F, -CHF2, -CF3, -C(O)OH or -C(O)Oalkyl; R7 is H, alkyl, alkenyl, hydroxyalkyl, cycloalkyl, alkoxyalkyl, aminoalkyl, (R17-phenyl)alkyl or -CH2-C(O)-O-alkyl; and R8 comprises alkyl, heteroaryl, phenyl or cycloalkyl, or heterocycloalkyl, all optionally substituted, or a cycloalkyl- or heterocycloalkyl-substituted amide; or R7 and R8 and the nitrogen to which they are attached together form an optionally substituted ring; and the remaining variables are as defined in the specification. Also claimed are pharmaceutical compositions, the use of the compounds as PDE4 inhibitors, and combinations with other actives.