| abstract |
The present invention relates to a group of novel piperazine oxime derivatives having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein: X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH 3 , CF 3 , OCH 3 , halogen, cyano and 5-CF 3 -tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza-indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1-3C); n has the value 0-3; m has the value 0-2; R 1 represents NH 2 , NH-alkyl (1-3C), dialkyl (1-3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH 3 -piperazinyl; R 2 is hydrogen, alkyl (1-4C) or phenyl, or R 2 together with (CH 2 ) m wherein m is 1, and the intermediate carbon nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R 3 and R 4 independently represent hydrogen or methyl, or R 3 and R 4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds with formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved. |