Solvay Pharmaceuticals, B.v.

Adrianus Van Den Hoogenband

Wouter I Iwema Bakker

Gustaaf J M Van Scharrenburg

Andrew C McCreary

Hein K A C Coolen

Arnoldus H J Herremans

Martinus Th M Tulp

Jan H Van Maarseveen

The invention relates to hexahydro-pyrido[1,2-a]pyrazine derivatives having interesting neurokinin-NKreceptor antagonistic activity. The invention also relates to methods for the preparation of these compounds, to pharmaceutical compositions containing a pharmacologically active amount of at least one of these compounds as an active ingredient, as well as to the use of these compositions for the treatment of disorders in which neurokinin receptors are involved. The invention relates to compounds represented by the general formula (1) wherein the symbols have the meanings as given in the description.

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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, CF, OCH, halogen, cyano and 5-CF-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&#x2013;3C); n has the value 0&#x2013;3; m has the value 0&#x2013;2; Rrepresents NH, NH-alkyl (1&#x2013;3C), dialkyl (1&#x2013;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-piperazinyl; Ris hydrogen, alkyl (1&#x2013;4C) or phenyl, or Rtogether with (CH)wherein m is 1, and the intermediate carbon, nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; Rand Rindependently represent hydrogen or methyl, or Rand Rtogether 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 

Piperazine oxime dervatives having NK-1 receptor antagonistic activity

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Weesp, Netherlands

Adrianus Van Den Hoogenband