PDE IV INHIBITING PYRIDINE DERIVATIVES

• Main Authors: MATESANZ-BALLESTEROS, MARIA ENCARNACION, FREYNE, EDDY JEAN EDGARD, DIELS, GASTON STANISLAS MARCELLA, DIAZ-MARTINEZ, ADOLFO
• Format: Patent
• Language: English; French
• Published: 07.10.1999
• Edition: 6
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention concerns pyridine derivatives having formula (I), the N- oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein L is hydrogen; C1-6alkyl; C 1- 6alkyl carbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidyl; substituted piperidyl; C1-6alkylsulfonyl or arylsulfonyl; -A-B- is -CR4=CR5- or -CHR4-CHR5-; D is O or NR6; R1 is a hydrogen or C1-4alkyl; R2 is hydrogen; halo; C1-6alkyl; trifluoromethyl; C3- 6cycloalkyl; carboxyl; C1-4alkyl oxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; HET1; or substituted C1-6alkyl; or R2 is O-R9 or NH-R10; R3 is hydroge n, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; or R2 and R1, or R2 and R3 taken together may form a bivalent radical; Q is disubstituted pyridine; R7 and R8 each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cyclo alkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7- dihydro-5H-cyclopentapyridyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1- 10alkyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I), pharmaceutical compositions thereof and their use as a medicament. The present invention concerns pyridine derivatives having formula (I), the Noxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein L is hydrogen; C1-6alkyl; C16alkyl carbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidyl; substituted piperidyl; C1-6alkylsulfonyl or arylsulfonyl; -A-B- is -CR4=CR5- or -CHR4-CHR5-; D is O or NR6; R1 is a hydrogen or C1-4alkyl; R2 is hydrogen; halo; C1-6alkyl; trifluoromethyl; C36cycloalkyl; carboxyl; C1-4alkyl oxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; HET1; or substituted C1-6alkyl; or R2 is O-R9 or NH-R10; R3 is hydrogen, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; or R2 and R1, or R2 and R3 taken together may form a bivalent radical; Q is disubstituted pyridine; R7 and R8 each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cyclo alkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7dihydro-5H-cyclopentapyridyl; bicyclo¢2.2.1!-2-heptenyl; bicyclo¢2.2.1!heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C110alkyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I), pharmaceutical compositions thereof and their use as a medicament.