US 5,683,997 AGranted

Substituted benzazepinones

AssigneeCiba-Geigy Corporation

InventorsPeter Buhlmayer, Pascal Furet

Life of this patent

Estimating the term…

Abstract

The invention relates to substituted 3-amino-1-arylalkyl-benzazepin-2-ones of the general formula ##STR1## wherein the substituents are defined in the specification; or salts thereof; to processes for the preparation thereof; and to the use thereof as well as to pharmaceutical compositions that comprise compounds of formula (I) or pharmaceutically acceptable salts thereof.

Claims16

Dependent claims

A compound of the formula ##STR18## wherein Ar is aryl;

X is C.sub.1 -C.sub.2 alkylene or a direct bond;
R.sub.1 is selected from the group consisting of hydrogen;
lower alkyl;
aryl-lower alkyl;
and an acyl selected from the group consisting of lower alkanoyl, aryl-lower alkanoyl and aroyl, each of which is either unsubstituted or independently substituted by 1-3 substituents independently selected from the group consisting of lower alkyl, aryl-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy, aryl-lower alkoxy, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl-lower alkyl, nitro, halogen, trifluoromethyl, and amino, where said amino may be unsubstituted, mono- or independently di-substituted by lower alkyl, aryl-lower alkyl or aryl, or disubstituted by lower alkylene or lower alkyleneoxy-lower alkylene;
R.sub.2 is lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, aryl-lower alkoxy-lower alkyl, aryl-lower alkyl or C.sub.3 -C.sub.7 cycloalkyl-lower alkyl;
R.sub.3 is carboxy;
5-tetrazolyl, PO.sub.2 H.sub.2, PO.sub.3 H.sub.2 or SO.sub.3 H.sub.2 ;
alkoxycarbonyl;
lower alkoxy-lower alkoxycarbonyl;
aryl-lower alkoxycarbonyl;
aryloxycarbonyl;
carbamoyl;
carbamoyl that (i) is monosubstituted by hydroxy, lower alkanesulfonyl, halo-lower alkanesulfonyl or by arylsulfonyl, (ii) is monosubstituted or disubstituted, the substituents independently selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl and phenyl-lower alkyl, or (iii) is disubstituted by lower alkylene or by lower alkylene-X.sub.1 -lower alkylene, wherein X.sub.1 is selected from the group consisting of O, S and NH;
the ring A is unsubstituted or mono- or poly-substituted by substituents selected from the group consisting of:
lower alkyl, aryl-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy, aryl-lower alkoxy, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl-lower alkyl, nitro, halogen, trifluoromethyl, and amino, where said amino may be unsubstituted, mono- or independently di-substituted by lower alkyl, aryl-lower alkyl or by aryl, or disubstituted by lower alkylene or lower alkyleneoxy-lower alkylene;
"aryl" in each case above is an independently-selected "carbocyclic or heterocyclic aryl" which may be independently substituted by 1-3 substituents independently selected from the group consisting of lower alkyl, "carbocyclic or heterocyclic aryl"-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy, "carbocyclic or heterocyclic aryl"-lower alkoxy, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl-lower alkyl, nitro, halogen, trifluoromethyl, and amino, where said amino may be unsubstituted, mono- or independently di-substituted by lower alkyl, "carbocyclic or heterocyclic aryl"-lower alkyl or "carbocyclic or heterocyclic aryl", or disubstituted by lower alkylene or lower alkyleneoxy-lower alkylene:
and
"carbocyclic or heterocyclic aryl" is selected from the group consisting of phenyl, naphthyl, pyrrolyl, pyridyl, furyl, thienyl, imidazolyl, isoxazolyl, and thiazolyl;
a stereoisomer or a metal, mineral, ammonium, or organic salt thereof.

17 more elements

A compound selected from

3-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-nitrobenzyl)-2,3,4,5-tet rahydro-benzazepin-2-one;
3-(S)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-aminobenzyl)-2,3,4,5 -tetrahydro-benzazepin-2-one;
3-(S)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-tert-butylbenzyl)-2, 3,4,5-tetrahydro-benzazepin-2-one;
3-(R)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-tert-butylbenzyl)-2, 3,4,5-tetrahydro-benzazepin-2-one;
3-(S)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-methylbenzyl)-2,3,4, 5-tetrahydro-benzazepin-2-one;
3-(R)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-methylbenzyl)-2,3,4, 5-tetrahydro-benzazepin-2-one;
3-(S)-(1-(S)-carboxy-2-phenylethyl)-amino!-1-(p-isopropylbenzyl)-2,3,4,5-t etrahydro-benzazepin-2-one;
3-(R)-(1-(S)-carboxy-2-phenylethyl)-amino!-1-(p-isopropylbenzyl)-2,3,4,5-t etrahydro-benzazepin-2-one;
3-(S)-(1-(S)-carboxy-3-phenylpropyl)-amino!-1-(p-methylbenzyl)-2,3,4,5-tet rahydro-benzazepin-2-one;
3-(R)-(1-(S)-carboxy-3-phenylpropyl)-amino!-1-(p-methylbenzyl)-2,3,4,5-tet rahydro-benzazepin-2-one;
3-(S)-(1-(S)-N-hydroxy-carbamoyl-3-cyclohexylpropyl)-amino!-1-(p-isopropyl benzyl)-2,3,4,5-tetrahydro-benzazepin-2-one;
3-(S)-(1-(S)-carbamoyl-3-cyclohexylpropyl)-amino!-1-(p-isopropylbenzyl)-2, 3,4,5-tetrahydro-benzazepin-2-one;
3-(S)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-dimethylaminobenzyl) -2,3,4,5-tetrahydro-benzazepin-2-one;
3-(R)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-dimethylaminobenzyl) -2,3,4,5-tetrahydro-benzazepin-2-one;
3-(S)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(benzyl)-2,3,4,5-tetrah ydro-benzazepin-2-one;
3-(R)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(benzyl)-2,3,4,5-tetrah ydro-benzazepin-2-one;
3-(S)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-methoxybenzyl)-2,3,4 ,5-tetrahydro-benzazepin-2-one;
3-(R)-(1-(S)-carboxy-3-cyclohexyl-propyl)-amino!-1-(p-methoxybenzyl)-2,3,4 ,5-tetrahydro-benzazepin-2-one;
and
3-(S)-(1-(S)-carboxy-3-cyclohexyl-propyl)-N-acetylamino!-1-(p-isopropylben zyl)-2,3,4,5-tetrahydro-benzazepin-2-one;
or a salt thereof in each case.

18 more elements

Dependencies are inferred from the claim text.

patentgrep

Loading patent…

Abstract

A compound of the formula ##STR18## wherein Ar is aryl;

X is C.sub.1 -C.sub.2 alkylene or a direct bond;
R.sub.1 is selected from the group consisting of hydrogen;
lower alkyl;
aryl-lower alkyl;
and an acyl selected from the group consisting of lower alkanoyl, aryl-lower alkanoyl and aroyl, each of which is either unsubstituted or independently substituted by 1-3 substituents independently selected from the group consisting of lower alkyl, aryl-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy, aryl-lower alkoxy, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl-lower alkyl, nitro, halogen, trifluoromethyl, and amino, where said amino may be unsubstituted, mono- or independently di-substituted by lower alkyl, aryl-lower alkyl or aryl, or disubstituted by lower alkylene or lower alkyleneoxy-lower alkylene;
R.sub.2 is lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, aryl-lower alkoxy-lower alkyl, aryl-lower alkyl or C.sub.3 -C.sub.7 cycloalkyl-lower alkyl;
R.sub.3 is carboxy;
5-tetrazolyl, PO.sub.2 H.sub.2, PO.sub.3 H.sub.2 or SO.sub.3 H.sub.2 ;
alkoxycarbonyl;
lower alkoxy-lower alkoxycarbonyl;
aryl-lower alkoxycarbonyl;
aryloxycarbonyl;
carbamoyl;
carbamoyl that (i) is monosubstituted by hydroxy, lower alkanesulfonyl, halo-lower alkanesulfonyl or by arylsulfonyl, (ii) is monosubstituted or disubstituted, the substituents independently selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl and phenyl-lower alkyl, or (iii) is disubstituted by lower alkylene or by lower alkylene-X.sub.1 -lower alkylene, wherein X.sub.1 is selected from the group consisting of O, S and NH;
the ring A is unsubstituted or mono- or poly-substituted by substituents selected from the group consisting of:
lower alkyl, aryl-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy, aryl-lower alkoxy, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl-lower alkyl, nitro, halogen, trifluoromethyl, and amino, where said amino may be unsubstituted, mono- or independently di-substituted by lower alkyl, aryl-lower alkyl or by aryl, or disubstituted by lower alkylene or lower alkyleneoxy-lower alkylene;
"aryl" in each case above is an independently-selected "carbocyclic or heterocyclic aryl" which may be independently substituted by 1-3 substituents independently selected from the group consisting of lower alkyl, "carbocyclic or heterocyclic aryl"-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy, "carbocyclic or heterocyclic aryl"-lower alkoxy, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl-lower alkyl, nitro, halogen, trifluoromethyl, and amino, where said amino may be unsubstituted, mono- or independently di-substituted by lower alkyl, "carbocyclic or heterocyclic aryl"-lower alkyl or "carbocyclic or heterocyclic aryl", or disubstituted by lower alkylene or lower alkyleneoxy-lower alkylene:
and
"carbocyclic or heterocyclic aryl" is selected from the group consisting of phenyl, naphthyl, pyrrolyl, pyridyl, furyl, thienyl, imidazolyl, isoxazolyl, and thiazolyl;
a stereoisomer or a metal, mineral, ammonium, or organic salt thereof.

17 more elements