Duphar International Research Bv

Solvay Pharmaceuticals, B.v.

Jan H Van Maarseveen

Cornelis G Kruse

Wouter I Iwema Bakker

Gustaaf J M Van Scharrenburg

Hein K A C Coolen

Andrew C McCreary

Peter H Hermkens

Johan W Scheeren

Arnoldus H J Herremans

Martinus Th M Tulp

Mayke B Hesselink

Adrianus Van Den Hoogenband

Dirk De Boer

Gijsbert D Kuil

The present invention relates to a group of unique diazabicyclo alkane derivatives having interesting neurokinin-NKreceptor antagonistic activity represented by the general formula (1) wherein: Rrepresents phenyl, 2-indolyl, 3-indolyl, 3-indazolyl or benzo[b]thiophen-3-yl, which groups may be substituted with halogen or alkyl (1&#x2013;3C), Rand Rindependently represent halogen, H, OCH, CHand CF, R, Rand Rindependently represent H, OH, O-alkyl(1&#x2013;4C), CHOH, NH, dialkyl(1&#x2013;3C)N, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or morpholin-4-yl substituted with one or two methyl or methoxymethyl groups, morpholin-4-ylamino, morpholin-4-ylmethyl, imidazol-1-yl, thiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl or 3-oxa-8-azabicyclo[3.2.1]oct-8-yl; Rand Rtogether may represent a keto, a 1,3-dioxan-2-yl or a 1,3-dioxolan-2-yl group, X represents either O or S, n has the value of 1, 2 or 3, a is the asymmetrical carbon atom 8a, 9a or 10a when n equals 1, 2 or 3 respectively The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions containing at least one of these compounds as an active ingredient 

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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

The invention relates to a method of preparing N-oxo-tetrahydro-.beta.-carbolines having formula 1. ##STR1## by an intramolecular ringclosure reaction of compounds of formula 2. ##STR2## wherein Z is an aldehyde function or acetal function, or is a functional group which can be converted into such a function during the ringclosure reaction. The eudistomin derivatives within the group of compounds having formula 1 have strong antiviral and antitumour activity.

Method of preparing N-oxo-tetrahydro-.beta.-carbolines

The invention relates to a method of preparing N-oxo-tetrahydro-.beta.-carbolines having formula 1. ##STR1## wherein R.sub.1 is lower alkyl or alkoxy, halogen, trifluoromethyl, lower alkylthio, hydroxy, amino, lower mono- or dialkyl- or acylamino.

Method of preparing n-oxo-tetrahydro-beta-carbolines

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Weesp, Netherlands

Jan H Van Maarseveen