Amino acid derivatives, medicaments containing said compounds an

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...

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514616, 564153, 564155, 564157, 564158, 564 56, A01N 4728, A01N 3718, C07C23331, C07C27518

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active

059625309

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BRIEF SUMMARY
The present invention relates to new amino acid derivatives of general formula ##STR2## their tautomers, diastereomers, enantiomers, mixtures thereof and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, the use thereof and processes for preparing them.
Amino acid derivatives with NPY-antagonistic properties have already been described in WO 94/17035.
In general formula I above
R denotes a phenyl, 1-naphthyl or 2-naphthyl group, a 5-membered heteroaromatic ring linked via a carbon atom and containing a nitrogen, oxygen or sulphur atom or a nitrogen atom and an oxygen, a sulphur or a further nitrogen atom, whilst a nitrogen atom of an imino group may be substituted by an alkyl, alkoxycarbonylalkyl, carboxyalkyl, dialkylaminoalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl or alkoxycarbonyl group, or a 6-membered heteroaromatic ring linked via a carbon atom and containing 1, 2 or 3 nitrogen atoms, whilst a 1,4-butadienylene group may be attached both to the 5-membered and to the 6-membered heteroaromatic rings via two adjacent carbon atoms and the bicyclic heteroaromatic rings thus formed may also be bound via a carbon atom of the 1,4-butadienylene group and
the groups mentioned for R hereinbefore, including the mono- and bicyclic heteroaromatic rings in their carbon skeleton, may additionally be mono-, di- or at most trisubstituted by fluorine, chlorine or bromine atoms, by alkyl groups, cycloalkyl groups with 3 to 8 carbon atoms, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonylalkyl, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, a trifluoromethylsulphynyl or trifluoromethylsulphonyl groups, whilst the substituents may be identical or different and the abovementioned benzoyl, benzoylamino and benzoylmethylamino groups in turn may additionally be substituted in the phenyl moiety by a fluorine, chlorine or bromine atom, an alkyl, trifluoromethyl, amino or acetylamino group,
or the diphenylmethyl group, wherein disubstituted by fluorine, chlorine or bromine atoms, methyl, methoxy, hydroxycarbonylmethoxy, alkoxycarbonylmethoxy, hydroxy or trifluoromethyl groups, whilst the substituents in each case may be identical or different,
n denotes the numbers 0, 1 or 2,
U denotes a single bond, an oxygen atom or the --NH-- group,
R.sup.1 denotes a hydrogen atom,
a straight-chained or branched alkyl group with 1 to 8 carbon atoms which may be terminally substituted by a cycloalkyl group with 3 to 8 carbon atoms, or denotes a cycloalkyl group with 3 to 8 carbon atoms, whilst the abovementioned groups may in turn be substituted by an alkoxycarbonyl, phenylalkoxycarbonyl, carboxy, amino, monoalkylamino, dialkylamino or dialkylaminomethyl group,
a branched or unbranched alkylcarbonyl group containing 2 to 5 carbon atoms, which may be substituted in the alkyl moiety by an alkoxycarbonyl or phenylalkoxycarbonyl group, by a phenyl group or by a 5- or 6-membered heteroaromatic ring linked via a carbon atom, or a benzoyl group, wherein the phenyl moiety may also be replaced by a 5- or 6-membered heteroaromatic ring linked via a carbon atom, whilst the 5-membered heteroaromatic rings mentioned hereinbefore may contain a nitrogen, an oxygen or a sulphur atom or a nitrogen atom and an additional oxygen, sulphur or further nitrogen atom and may also be substituted by an alkyl group at a nitrogen atom, the 6-membered heteroaromatic rings may contain 1, 2 or 3 nitrogen atoms, and the phenyl groups mentioned hereinbefore may additionally be mono-, di- or at most tri-substituted, as may the heteroaromatic rings in their carbon skeleton, by fluorine, chlorine or bromine atoms, by alkyl groups, cycloalkyl groups with 3 to 8 carbon atoms, alkoxy, trifluoromethyl, alkoxycarbonylalkyl, carboxyalkyl, hydroxy, amin

REFERENCES:
patent: 5616620 (1997-04-01), Rudolf et al.
patent: 5807875 (1998-09-01), Rudolf et al.
Tsunematsu, H. et al; Chemical and Pharmaceutical Bulletin, "Beta-Naphthylamides of Guanidinophenyl Amino Acids As Substrates of Aminopeptidases"; (1988) 1205-9.36.3.
Tsunematsu, H.; et al J Biochem, Interactions of Derivatives of Guanidinophenylglycine and Guanidinophenylalanine with Trypsin and Related Enzymes (1980) 1773-1783, 88.
Hatanaka, Y.; Biochimica.et Biophysica Acta, "Interactions of Derivatives of Guanidinophenylalanine and Guanidinophenylglycine with Streptomyces griseus trypsin" (1985) 274-279, 832.

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