US 2006/0148791 A1Published application

Glutamate receptor antagonists

AssigneeHoffmann-La Roche Inc.

InventorsGeo Adam, Alexander Alanine, Erwin Goetschi, Vincent Mutel, Thomas Woltering

Life of this patent

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Abstract

The present invention is a compound of formula wherein X is an ethynediyl group, R1, R2 and R3 are as defined in the specification.

Claims27

Dependent claims

A compound of formula I

wherein
X is a single bond;
R1 is phenyl substituted by halogen;
and
R3 is selected from the group consisting of
unsubstituted phenyl, unsubstituted pyridine, unsubstituted thiophenyl and unsubstituted thiazolyl, or
substituted phenyl, substituted pyridine, substituted thiophenyl and substituted thiazolyl, said substituted phenyl, said substituted pyridine, said substituted thiophenyl or said substituted thiazoyl being substituted by a substitutent selected from the group consisting of
halogen,
cyano,
nitro,
azido,
hydroxy,
carboxy,
morpholine-4-carbonyl,
carbamoyl,
thiocarbamoyl, N-hydroxycarbamoyl,
trimethylsilyl-ethynyl,
lower alkyl, lower alkynyl, lower alkoxy, halo-lower alkyl, 4-lower alkyl-piperazine-1-carbonyl, lower alkylaminocarbonyl, or
lower alkyl, lower alkynyl, lower alkoxy, halo-lower alkyl, 4-lower alkyl-piperazine-1-carbonyl, lower alkylaminocarbonyl substituted by a substitutent selected from the group consisting of amino, lower alkylamino, acylamino, oxo, hydroxy;
lower alkoxy, lower alkylthio, unsubstituted carboxy, esterified and amidated carboxy,
an unsubstituted 5-membered aromatic heterocycle,
a 5-membered aromatic heterocycle substituted by a substituent selected from the group consisting of
amino,
lower alkylamino,
acylamino,
oxo,
hydroxy,
lower alkoxy,
lower alkylthio,
carboxy,
carboxy esterified with lower alkyl,
carboxy amidated with lower alkylamino which is eventually substituted by hydroxy,
lower alkyl,
lower alkyl substituted by a substituent selected from the group consisting of halogen, hydroxy, amino, lower alkylamino, acylamino, amidino and amidino substituted by a substituent selected from the group consisting of lower alkyl,
—C(NRR′)═NR″ wherein R, R′ and R″ are hydrogen or lower alkyl,
hydroxy,
lower alkoxy,
lower alkylthio,
acyloxy,
lower alkylsulfinyl,
lower alkylsulfonyl,
lower alkoxy-lower alkylsulfanyl,
lower alkylsulfanyl,
cycloalkylsulfinyl,
cycloalkylsulfonyl,
hydroxyimino,
lower alkoxyimino,
lower alkoximino which is esterified or amidated,
lower alkenyl,
oxo,
cyano,
carbamoyloxy,
sulfamoyl and
sulfamoyl substituted by lower alkyl;
or a pharmaceutically acceptable acid addition salt thereof.

52 more elements

A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I

wherein
X is a single bond;
R1 is phenyl substituted by halogen;
and
R3 is selected from the group consisting of
unsubstituted phenyl, unsubstituted pyridine, unsubstituted thiophenyl and unsubstituted thiazolyl, or
substituted phenyl, substituted pyridine, substituted thiophenyl and substituted thiazolyl, said substituted phenyl, said substituted pyridine, said substituted thiophenyl or said substituted thiazoyl being substituted by a substitutent selected from the group consisting of
halogen,
cyano,
nitro,
azido,
hydroxy,
carboxy,
morpholine-4-carbonyl,
carbamoyl,
thiocarbamoyl, N-hydroxycarbamoyl,
trimethylsilyl-ethynyl,
lower alkyl, lower alkynyl, lower alkoxy, halo-lower alkyl, 4-lower alkyl-piperazine-1-carbonyl, lower alkylaminocarbonyl, or
lower alkyl, lower alkynyl, lower alkoxy, halo-lower alkyl, 4-lower alkyl-piperazine-1-carbonyl, lower alkylaminocarbonyl substituted by a substitutent selected from the group consisting of amino, lower alkylamino, acylamino, oxo, hydroxy;
lower alkoxy, lower alkylthio, unsubstituted carboxy, esterified and amidated carboxy,
an unsubstituted 5-membered aromatic heterocycle,
a 5-membered aromatic heterocycle substituted by a substituent selected from the group consisting of
amino,
lower alkylamino,
acylamino,
oxo,
hydroxy,
lower alkoxy,
lower alkylthio,
carboxy,
carboxy esterified with lower alkyl,
carboxy amidated with lower alkylamino which is eventually substituted by hydroxy,
lower alkyl,
lower alkyl substituted by a substituent selected from the group consisting of halogen, hydroxy, amino, lower alkylamino, acylamino, amidino and amidino substituted by a substituent selected from the group consisting of
lower alkyl,
—C(NRR′)═NR″ wherein R, R′ and R″ are hydrogen or lower alkyl,
hydroxy,
lower alkoxy,
lower alkylthio,
acyloxy,
lower alkylsulfinyl,
lower alkylsulfonyl,
lower alkoxy-lower alkylsulfanyl,
lower alkylsulfanyl,
cycloalkylsulfinyl,
cycloalkylsulfonyl,
hydroxyimino,
lower alkoxyimino,
lower alkoximino which is esterified or amidated,
lower alkenyl,
oxo,
cyano,
carbamoyloxy,
sulfamoyl and
sulfamoyl substituted by lower alkyl;
and
with the proviso that when X is a single bond and R3 is pyridinyl, R1 is not hydrogen or methyl,
or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier.

55 more elements

A compound selected from the group consisting of

3-[7-(4-Chloro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
3-[7-(3,4-Dichloro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
3-[7-(2-Chloro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
3-[7-(2,3-Difluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(4-Fluoro-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(3-[1,2,4]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(3-nitro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(2-imidazol-1-yl-pyridin-4-yl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-(3-Amino-phenyl)-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
N-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-acetamide;
N-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-methanesulfonamide;
8-(4-Fluoro-phenyl)-4-[3-(4-methyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(2-imidazol-1-yl-pyridin-4-yl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-2-methyl-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-2-hydroxy-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-[3-(2-methyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[3-(2-methyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
2-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-1H-benzo[b][1,4]diazepin-2-yl]-thiophene-3-carbonitrile;
2-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-1H-benzo[b][1,4]diazepin-2-yl]-thiophene-3-carbonitrile;
8-(4-Fluoro-phenyl)-4-(3-tetrazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(2-Fluoro-phenyl)-4-(3-tetrazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-[3-(2,4-Dimethyl-imidazol-1-yl)-phenyl]-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-(3-Chloro-thiophen-2-yl)-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(2-Fluoro-6-methoxy-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(2-Fluoro-phenyl)-4-(3-nitro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carbonitrile;
4-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carbonitrile;
3-[7-(3-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(3-Fluoro-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(3-[1,2,4]triazol-4-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
5-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiophene-2-carbonitrile;
4-[3-(2,4-Dimethyl-imidazol-1-yl)-phenyl]-8-(2-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-[3-(2-methoxymethylsulfanyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-Fluoro-3-[7-(2-fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
4-[7-(2,4-Difluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carbonitrile;
8-(2-Fluoro-phenyl)-4-[2-(4-methyl-imidazol-1-yl)-thiazol-4-yl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[2-(4-methyl-imidazol-1-yl)-thiazol-4-yl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydrobenzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(2-imidazol-1-yl-thiazol-4-yl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(2,4-Difluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(4-Fluoro-phenyl)-4-[3-(2-methylsulfanyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2,4-Difluoro-phenyl)-4-[3-(2-methyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2,4-Difluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(2-imidazol-1-yl-thiazol-4-yl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(2,5-Difluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(2,5-Difluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2,3-Difluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiobenzamide;
3-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiobenzamide;
4-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carbothioic acid amide;
8-(4-Fluoro-phenyl)-4-[3-(4-methyl-thiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid ethyl ester;
2-{3-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid ethyl ester;
2-{4-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridin-2-yl}-thiazole-4-carboxylic acid ethyl ester;
8-(4-Fluoro-phenyl)-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[2-(4-hydroxymethyl-thiazol-2-yl)-pyridin-4-yl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid;
2-{3-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid;
2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid (2-hydroxy-ethyl)-amide;
2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-4-methyl-thiazole-5-carboxylic acid (2-hydroxy-ethyl)-amide;
3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzoic acid;
4-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carboxylic acid;
8-(4-Fluoro-phenyl)-4-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-[3-(4,5-Dimethyl-4H-[1,2,4]triazol-3-yl)-phenyl]-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-N-hydroxy-benzamidine;
8-(4-Fluoro-phenyl)-4-{3-[5-(3-hydroxy-propyl)-[1,2,4]oxadiazol-3-yl]-phenyl}-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(2-hydroxy-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
and
4-(3-Chloro-2,4-dihydroxy-phenyl)-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one.

74 more elements

A pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisisting of

3-[7-(4-Chloro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
3-[7-(3,4-Dichloro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
3-[7-(2-Chloro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
3-[7-(2,3-Difluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(4-Fluoro-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(3-[1,2,4]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(3-nitro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(2-imidazol-1-yl-pyridin-4-yl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-(3-Amino-phenyl)-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
N-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-acetamide;
N-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-methanesulfonamide;
8-(4-Fluoro-phenyl)-4-[3-(4-methyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(2-imidazol-1-yl-pyridin-4-yl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-2-methyl-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-2-hydroxy-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-[3-(2-methyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[3-(2-methyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
2-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-1H-benzo[b][1,4]diazepin-2-yl]-thiophene-3-carbonitrile;
2-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-1H-benzo[b][1,4]diazepin-2-yl]-thiophene-3-carbonitrile;
8-(4-Fluoro-phenyl)-4-(3-tetrazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(2-Fluoro-phenyl)-4-(3-tetrazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-[3-(2,4-Dimethyl-imidazol-1-yl)-phenyl]-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-(3-Chloro-thiophen-2-yl)-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(2-Fluoro-6-methoxy-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(2-Fluoro-phenyl)-4-(3-nitro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carbonitrile;
4-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carbonitrile;
3-[7-(3-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(3-Fluoro-phenyl)-4-(3-imidazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(3-[1,2,4]triazol-4-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
5-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiophene-2-carbonitrile;
4-[3-(2,4-Dimethyl-imidazol-1-yl)-phenyl]-8-(2-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-[3-(2-methoxymethylsulfanyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
4-Fluoro-3-[7-(2-fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
4-[7-(2,4-Difluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carbonitrile;
8-(2-Fluoro-phenyl)-4-[2-(4-methyl-imidazol-1-yl)-thiazol-4-yl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[2-(4-methyl-imidazol-1-yl)-thiazol-4-yl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydrobenzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(2-imidazol-1-yl-thiazol-4-yl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(2,4-Difluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(4-Fluoro-phenyl)-4-[3-(2-methylsulfanyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2,4-Difluoro-phenyl)-4-[3-(2-methyl-imidazol-1-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2,4-Difluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-(2-imidazol-1-yl-thiazol-4-yl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(2,5-Difluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzonitrile;
8-(2,5-Difluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2,3-Difluoro-phenyl)-4-(3-[1,2,3]triazol-1-yl-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiobenzamide;
3-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-thiobenzamide;
4-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carbothioic acid amide;
8-(4-Fluoro-phenyl)-4-[3-(4-methyl-thiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid ethyl ester;
2-{3-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid ethyl ester;
2-{4-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridin-2-yl}-thiazole-4-carboxylic acid ethyl ester;
8-(4-Fluoro-phenyl)-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(2-Fluoro-phenyl)-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[2-(4-hydroxymethyl-thiazol-2-yl)-pyridin-4-yl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid;
2-{3-[7-(2-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid;
2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-thiazole-4-carboxylic acid (2-hydroxy-ethyl)-amide;
2-{3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-phenyl}-4-methyl-thiazole-5-carboxylic acid (2-hydroxy-ethyl)-amide;
3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-benzoic acid;
4-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-pyridine-2-carboxylic acid;
8-(4-Fluoro-phenyl)-4-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenyl]-1,3-dihydro— benzo[b][1,4]diazepin-2-one;
4-[3-(4,5-Dimethyl-4H-[1,2,4]triazol-3-yl)-phenyl]-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
3-[7-(4-Fluoro-phenyl)-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl]-N-hydroxy-benzamidine;
8-(4-Fluoro-phenyl)-4-{3-[5-(3-hydroxy-propyl)-[1,2,4]oxadiazol-3-yl]-phenyl}-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
8-(4-Fluoro-phenyl)-4-(2-hydroxy-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
and
4-(3-Chloro-2,4-dihydroxy-phenyl)-8-(4-fluoro-phenyl)-1,3-dihydro-benzo[b][1,4]diazepin-2-one;
and a pharmaceutically acceptable carrier.

75 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/363,351Filed 27 Feb 2006
Priority: EP 99120519.615 Oct 1999
Published: 6 Jul 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification28 codes

C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics
A61P 3/08
Drugs for disorders of the metabolism: for glucose homeostasis
A61P 9/08
Drugs for disorders of the cardiovascular system: vasodilators for multiple indications

Family

Application09/687,241Division · filed 13 Oct 2000
Application10/300,449Division · filed 20 Nov 2002
Application11/146,693Continuation · filed 7 Jun 2005
Application11/146,693Division · filed 7 Jun 2005
Application11/363,351Continuation · filed 27 Feb 2006
US 2003/0092677 A1Published application
US 2005/0234048 A1Published application
US 6,509,328 B1Related patent
US 6,960,578 B2Related patent
US 7,018,998 B2Related patent
US 7,151,098 B2Related patent
US 2006/0148791 A1This patent

From the US filing history. Foreign family members aren’t listed.

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A compound of formula I

wherein
X is a single bond;
R1 is phenyl substituted by halogen;
and
R3 is selected from the group consisting of
unsubstituted phenyl, unsubstituted pyridine, unsubstituted thiophenyl and unsubstituted thiazolyl, or
substituted phenyl, substituted pyridine, substituted thiophenyl and substituted thiazolyl, said substituted phenyl, said substituted pyridine, said substituted thiophenyl or said substituted thiazoyl being substituted by a substitutent selected from the group consisting of
halogen,
cyano,
nitro,
azido,
hydroxy,
carboxy,
morpholine-4-carbonyl,
carbamoyl,
thiocarbamoyl, N-hydroxycarbamoyl,
trimethylsilyl-ethynyl,
lower alkyl, lower alkynyl, lower alkoxy, halo-lower alkyl, 4-lower alkyl-piperazine-1-carbonyl, lower alkylaminocarbonyl, or
lower alkyl, lower alkynyl, lower alkoxy, halo-lower alkyl, 4-lower alkyl-piperazine-1-carbonyl, lower alkylaminocarbonyl substituted by a substitutent selected from the group consisting of amino, lower alkylamino, acylamino, oxo, hydroxy;
lower alkoxy, lower alkylthio, unsubstituted carboxy, esterified and amidated carboxy,
an unsubstituted 5-membered aromatic heterocycle,
a 5-membered aromatic heterocycle substituted by a substituent selected from the group consisting of
amino,
lower alkylamino,
acylamino,
oxo,
hydroxy,
lower alkoxy,
lower alkylthio,
carboxy,
carboxy esterified with lower alkyl,
carboxy amidated with lower alkylamino which is eventually substituted by hydroxy,
lower alkyl,
lower alkyl substituted by a substituent selected from the group consisting of halogen, hydroxy, amino, lower alkylamino, acylamino, amidino and amidino substituted by a substituent selected from the group consisting of lower alkyl,
—C(NRR′)═NR″ wherein R, R′ and R″ are hydrogen or lower alkyl,
hydroxy,
lower alkoxy,
lower alkylthio,
acyloxy,
lower alkylsulfinyl,
lower alkylsulfonyl,
lower alkoxy-lower alkylsulfanyl,
lower alkylsulfanyl,
cycloalkylsulfinyl,
cycloalkylsulfonyl,
hydroxyimino,
lower alkoxyimino,
lower alkoximino which is esterified or amidated,
lower alkenyl,
oxo,
cyano,
carbamoyloxy,
sulfamoyl and
sulfamoyl substituted by lower alkyl;
or a pharmaceutically acceptable acid addition salt thereof.

52 more elements

Facts

Application

11/363,351Filed 27 Feb 2006

Priority

EP 99120519.615 Oct 1999

Published

6 Jul 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification28 codes

C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics
A61P 3/08
Drugs for disorders of the metabolism: for glucose homeostasis
A61P 9/08
Drugs for disorders of the cardiovascular system: vasodilators for multiple indications

Family

Application09/687,241Division · filed 13 Oct 2000

Application10/300,449Division · filed 20 Nov 2002

Application11/146,693Continuation · filed 7 Jun 2005

Application11/146,693Division · filed 7 Jun 2005

Application11/363,351Continuation · filed 27 Feb 2006

US 2003/0092677 A1Published application

US 2005/0234048 A1Published application

US 6,509,328 B1Related patent

US 6,960,578 B2Related patent

US 7,018,998 B2Related patent

US 7,151,098 B2Related patent

US 2006/0148791 A1This patent

From the US filing history. Foreign family members aren’t listed.