| 摘要 |
The present invention is concerned with aryl-isoxazole-4-carbonyl-pyrrole-2-carboxylic acid amide derivatives of formula (I) wherein R1 is hydrogen, halogen, lower alkoxy, phenyloxy or benzyloxy; R2 is lower alkyl, (CH2)n-O-lower alkyl or phenyl; R3 is hydrogen or lower alkyl; R4/R5 are independently from each other hydrogen, lower alkyl, lower alkyl substituted by halogen, lower alkynyl or-(CHR)n-aryl, unsubstituted or substituted by halogen, lower alkyl or lower alkoxy,-(CH2)n-non aromatic heterocyclic ring, unsubstituted or substituted by one or two lower alkyl groups,-(CH2)n-aromatic heterocyclic rings-(CR2)n-cycloalkyl, unsubstituted or substituted by one to three substituents, selected from the group consisting of hydroxy or lower alkyl,-(CHR)n-O-lower alkyl,-(CR2)n-OH,-(CHR)n-NR'R", or R4/R5 form together with the N-atom to which they are attached the ring-8-aza-bicyclo[3.2.1] octane, substituted by hydroxy, or-3,4-dihydro-lH-isoquinoline, or-a non aromatic heterocyclic ring, unsubstituted or substituted by one or two substituents, selected from the group consisting of C(O)O-lower alkyl, lower alkyl, lower alkyl substituted by halogen, cycloalkyl, hydroxy, halogen, N(R)C(O)-lower alkyl,-(C 2)n-O-lower alkyl, or by an aromatic heterocyclic ring; R is hydrogen, hydroxy, or lower alkyl, wherein R may be the same or different in case of R2; R'/R" are independently from each other hydrogen or lower alkyl; n is O, 1, 2, 3 or 4; m is 1, 2 or 3; and with their pharmaceutically acceptable acid addition salts. It has been found that this class of compounds show high affinity and selectivity for GABA AE5 receptor binding sites and might be useful as cognitive enhancer or for the treatment of cognitive disorders like Alzheimer's disease.
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