Ciba-Geigy Corporation

Christof Angst

Hans Allgeier

Roland Heckendorn

Guido Bold

Peter Herold

Rudolf Duthaler

John G Dingwall

Antonio Togni

Derek E Brundish

Daniel Wallach

Graham E Fagg

Substituted 2-aminoalk-3-enoic acid derivative of formula I ##STR1## wherein R.sub.1 is an aliphatic hydrocarbon radical that is substituted by hydroxy, and R.sub.2 is free or esterified carboxy, and their salts exhibit NMDA-antagonistic properties and are useful as active ingredients of anticonvulsive medicaments.

4-substituted 2-aminoalk-3-enoic

Substituted 2-aminoalk-3-enoic acid derivative of formula I ##STR1## wherein R.sub.1 is an aliphatic hydrocarbon radical that is substituted by optionally acylated or aliphatically or araliphatically etherified hydroxy, by halogen, by optionally acylated and/or aliphatically substituted amino or by an aza-, diaza-, azoxa- or oxa-cycloaliphatic radical, or is an oxacycloaliphatic hydrocarbon radical bonded via a carbon atom, or is an optionally aliphatically N-substituted or N-acylated azacycloaliphatic hydrocarbon radical, and R.sub.2 is free or esterified carboxy, and their salts exhibit NMDA-antagonistic properties and are useful as active ingredients of anticonvulsive medicaments.

4-substituted 2-aminoalk-3-enoic acids

The invention relates to unsaturated amino acids of the formula I ##STR1## in which R.sup.1 represents hydroxy or etherified hydroxy, R.sup.2 represents hydrogen, alkyl, hydroxy or etherified hydroxy, R.sup.3 represents hydrogen, alkyl, haloalkyl, hydroxyalkyl, lower alkoxyalkyl, arylalkyl, lower alkenyl, halogen or aryl, R.sup.4 represents hydrogen, alkyl or aryl, R.sup.5 represents hydrogen or alkyl, R.sup.6 represents carboxy or esterified or amidated carboxy, R.sup.7 represents amino or amino substituted by alkyl or acyl, A represents unsubstituted or alkyl-substituted .alpha.,.omega.-alkylene having from 1 to 3 carbon atoms or represents a bond, and B represents methylene or a bond, with the proviso that A is other than a bond when B represents a bond, and salts thereof. They can be manufactured, for example, in accordance with the Michaelis-Arbuzov reaction and can be used as pharmacologically active substances.

Unsaturated amino acids

The invention relates to novel processes and intermediates for the preparation of 5-amino-4-hydroxyvaleric acid derivatives of the formula ##STR1## in which R.sup.1 represents hydrogen, optionally substituted alkyl, cycloalkyl, cycloalkyl-lower alkyl, aryl, aryl-lower alkyl or the radical of a natural amino acid, R.sup.2 represents hydrogen, optionally substituted alkyl, cycloalkyl, cycloalkyl-lower alkyl, aryl, aryl-lower alkyl, amino, hydroxy, mercapto, sulphinyl, sulphonyl or the radical of a natural amino acid, and R.sup.3 represents optionally substituted hydroxy or amino, by sigmatropic rearrangement of a suitable allyl ester, halolactonization of the resulting .gamma.,.delta.-unsaturated acid or of a suitable derivative thereof, exchange of halogen for a nitrogen-containing nucleophile, opening of the lactone ring and freeing of the amino group. Compounds of the formula I are starting materials for the preparation of renin-inhibitors which have an anti-hypertensive action.

Processes for the preparation of 5-amino-4-hydroxy-valeric acid

The invention relates to novel processes and intermediates for the preparation of 5-amino-4-hydroxyvaleric acid derivatives of the formula ##STR1## in which R.sup.1 represents hydrogen, optionally substituted alkyl, cycloalkyl, cycloalkyl-lower alkyl, aryl, aryl-lower alkyl or the radical of a natural amino acid, R.sup.2 represents hydrogen, optionally substituted alkyl, cycloalkyl, cycloalkyl-lower alkyl, aryl, aryl-lower alkyl, amino, hydroxy, mercapto, sulphinyl, sulphonyl or the radical of a natural amino acid, and R.sup.3 represents optionally substituted hydroxy or amino, by sigmatropic rearrangement of a suitable allyl ester, halolactonisation of the resulting .gamma.,.delta.-unsaturated acid or of a suitable derivative thereof, exchange of halogen for a nitrogen-containing nucleophile, opening of the lactone ring and freeing of the amino group. Compounds of the formula I are starting materials for the preparation of renin-inhibitors which have an anti-hypertensive action.

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Menlo Park, CA, United States of America

Christof Angst