1,3-DIHYDRO-2H-IMIDAZOL-2-ONE DERIVATIVES HAVING PDE IV AND CYTOKININ INHIBITING ACTIVITY

摘要

The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof, wherein R<1> and R<2> each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cycloalkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; R<3> is hydrogen, halo or C1-6alkyloxy; =C=X is a bivalent radical of formula =C=O; =C=CH-R<4>; =C=N-O-R<5>; or formula (a-4); Alk is C1-4alkanediyl; -A-B- is a bivalent radical of formula: -CR<6>=CR<7>- or -CHR<6>-CHR<7>-; L is hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; optionally substituted C3-6alkenyl; optionally substituted piperidinyl; C1-6alkylsulfonyl or arylsulfonyl; aryl is optionally substituted phenyl; Het<1> is morpholinyl or optionally substituted pyridinyl, -furanyl, -thienyl, -hydroxypyridinyl, -imidazolyl, -thiazolyl, -oxazolyl, -isoquinolinyl, -quinolinonyl, -piperidinyl, -piperazinyl; and Het<2> is morpholinyl or optionally substituted piperidinyl, -piperazinyl, -pyridinyl, -furanyl or -thienyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I) and pharmaceutical compositions thereof.