In the 2-position heterocyclic substituted 4-aryl-5-carbamoyl-6-methyl-1,4-dihydropyridine-3-carboxylic acid compounds, the compounds for medical use, use of the compounds for the manufacture of a medicament for the treatment of allergic and inflammatory conditions , pharmaceutical compositions containing the compounds as well as the 2-acyl-3-aryl-propenoic acid esters for use as intermediates;

摘要

Platelet activating factor antagonists of formula (I): CHEM wherein R is phenyl or phenyl substituted by one or more substituents selected from nitro, halo, C1-C4 alkyl, C1-C4 alkoxy, aryl(C1-C4)alkoxy, fluoro(C1-C4)alkoxy, C1-C4 alkylthio, C1-C4 alkylsulphonyl, hydroxy, trifluoromethyl and cyano, or is phenyl fused to a dioxole ring; R1 and R2 are each independently H or C1-C6 alkyl, or R1 and R2 together complete a pyrrolidinyl, piperidino, morpholino, piperazinyl, N-(C1-C4 alkyl)piperazinyl or N-(C2-C4 alkanoyl-piperazinyl group; or R2 is H or C1-C4 alkyl and R1 is CN, C3-C7 cycloalkyl, aryl, heteroaryl or a C1-C4 alkyl group substituted by one or more substituents selected from C3-C7 cycloalkyl, C1-C4 alkoxycarbonyl, aryl or heteroaryl; Z is selected from C1-C6 alkoxy, aryl(C1-C4)alkoxy, hydroxy, and -NR4R5 wherein each of R4 and R5 is independently H or C1-C6 alkyl, or R4 and R5 together complete a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C1-C4 alkyl)piperazinyl group; Y is 1,4 phenylene or pyridine-2,5-diyl, and X is a 5 or 6 membered aromatic heterocyclic group containing one or more nitrogen atoms in its ring; which ring may be fused to a benzene ring or to a further 5- or 6-membered aromatic heterocyclic ring containing one or more nitrogen atoms, at least one of said heterocyclic rings optionally also containing an oxygen or sulphur atom, and being optionally substituted with one or more substituents selected from C1-C4 alkyl, C1-C4 alkoxy, halo, CF3 and CN; and their pharmaceutically acceptable salts.