PDE IV INHIBITING PYRIDINE DERIVATIVES

摘要

1. A compound having the formula wherein L is hydrogen; -A-B-is a bivalent radical of formula: -CR<4>=CR<5>- (a-1); or - CHR<4>-CHR<5>- (a-2); D is O or NR<6>; Q is a radical of the formula R<1> is hydrogen; R<2> is hydrogen; C1-6 alkyl or hydroxy; R<3> is hydrogen or C1-6 alkyl; R<4> and R<5> each independently selected from hydrogen or C1-4 alkyl; R<6> is hydrogen, C1-4 alkyl or cyano; R<7> and R<8> each independently is hydrogen; C1-6 alkyl; difluoromethyl; C3-6 cycloalkyl; a saturated 5-membered heterocycle containing one or two heteroatoms each independently selected from oxygen, sulfur or nitrogen; indanyl; or C1-10 alkyl substituted with one or two substituents each independently selected from aryl and C3-7 cycloalkyl; aryl is phenyl or phenyl substituted with one, two or three substituents each independently selected from halo, hydroxy, C1-4alkyl, C1-4alkyloxy, C3-6cycloalkyl, trifluoromethyl, amino, nitro, carboxyl, C1-4alkyloxycarbonyl and C1-4alkylcarbonylamino; an N-oxide form, a pharmaceutically acceptable acid or base addition salt and a stereochemically isomeric form thereof. 2. A compound according to claim 1, wherein R<7> and R<8> are each independently C1-6alkyl; C3-6cycloalkyl; difluoromethyl; a saturated 5-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; or C1-10alkyl substituted with aryl or C3-6cycloalkyl. 3. A compound according to any one of claims 1 to 2, wherein R<7> is cyclopentyl, tetrahydrofuranyl, cyclopropylmethyl, 5-phenylpentyl or indanyl; R<8> is hydrogen, methyl or difluoromethyl; R<2> is hydrogen or methyl; R<3> is hydrogen, hydroxy or methyl and R<4>, R<5> is hydrogen. 4. A compound according to claim 1, wherein the compound is: [1-[2-[6-(cyclopentyloxy)-5-methoxy-2-pyridinyl]propyl]-1,3-dihydro-2H-imidazol-2-ylidene]cyanamide; and [1-[2-[6-(cyclopentyloxy)-5-methoxy-2-pyridinyl]propyl]-1,3-dihydro-2H-imidazol-2-one, or an N-oxide, a stereochemically isomeric form or a pharmaceutically acceptable acid or base addition salt thereof. 5. A composition comprising a pharmaceutically acceptable carrier, and as active ingredient a therapeutically effective amount of a compound as claimed in any one of claims 1 to 4. 6. A process of preparing a composition as claimed in claim 5, characterized in that a pharmaceutically acceptable carrier is intimately mixed with a therapeutically effective amount of a compound as claimed in any one claims 1 to 4. 7. A compound as claimed in any one of claims 1 to 4 for use as a medicine for treating phosphodiesterase diseases. 8. Use of a compound as claimed in any one of claims 1 to 4 in the manufacture of a medicament useful for treating atonic or asthmatic diseases. 9. A process of preparing a compound as claimed in claim 1, characterized by a) cyclization of an intermediate of formula (II) or a functional derivative thereof, wherein R<1>-R<5>, D and Q are defined as in claim 1, in a reaction inert solvent and in the presence of a suitable acid; thus forming a compound of formula(I-a-1); if desired, converting compounds of formula (I) into each other following known transformations, and further, if desired, converting the compounds of formula (I), into a therapeutically active non-toxic acid addition salt by treatment with an acid, or into a therapeutically active non-toxic base addition salt by treatment with a base, or conversely, converting the acid addition salt form into the free base by treatment with alkali, or converting the base addition salt into the free acid by treatment with acid; and, if desired, preparing stereochemically isomeric forms or N-oxide forms thereof.