US 2009/0156607 A1Published application

2-oxo-1-pyrrolidine derivatives

AssigneeUcb, S.A.

InventorsBenoit Kenda, Yannick Quesnel, Ali Ates, Philippe Michel, Laurent Turet, Joel Mercier

Life of this patent

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Abstract

The present invention concerns 2-oxo-1-pyrrolidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.

Claims18

Dependent claims

A compound having the structural formula I

or a geometric isomer, enantiomer, diastereoisomer, or a pharmaceutically acceptable salt thereof, wherein
R1 is hydrogen, C1-12 alkyl, aryl or heterocycle;
R2 is hydrogen;
or R1 and R2 are linked together to form a C3-6 cycloalkyl;
R3 is
a) an unsubstituted or substituted heterocycle linked to the rest of the molecule via one of its C atoms;
or
b) an unsubstituted or substituted heterocycle linked to the rest of the molecule via one of its N atoms selected from the group consisting of
1H-1,2,3-benzotriazol-1-yl;
1H-imidazo[4,5-b]pyridin-1-yl;
3H-imidazo[4,5-b]pyridin-3-yl;
7H-imidazo[4,5-c]pyridazin-7-yl;
1H-indol-1-yl;
2,3-dihydro-1H-indol-lyl;
9H-purin-9-yl;
1H-pyrazolo[3,4-b]pyridin-1-yl;
2H-pyrazolo[3,4-b]pyridin-2-yl;
1H-pyrrolo[2,3-b]pyridin-1-yl;
1H-pyrrolo[3,2-b]pyridin-1-yl;
3,4-dihydroquinolin-1(2H)-yl;
8H-isothiazolo[5,4-b]indol-8-yl;
1H-1,2,4-triazol-1-yl;
1H-1,2,3-triazol-1-yl;
1H-pyrrol-1-yl;
1H-tetrazol-1-yl;
and
2-chloro-1H-benzimidazol-1-yl;
R4 is hydrogen;
C1-12 alkyl optionally substituted by halogen, C1-4 alkoxy, C1-4 alkylthio, azido, nitrooxy or aryl;
C2-12 alkenyl;
C2-12 alkynyl;
aryl non-substituted by a cycloalkoxy;
azido;
alkoxy-carbonylamino;
arylsulfonyloxy;
or heterocycle;
R5 is hydrogen;
or R4 together with R5 forms an optionally substituted benzene ring such that the compound of structural formula (I) has the structure:
wherein
R6 is hydrogen or halogen;
R7 is hydrogen;
nitro;
halogen;
heterocycle;
amino;
aryl;
C1-12 alkyl optionally substituted by at least one halogen;
or C1-12 alkoxy optionally substituted by at least one halogen;
R8 is hydrogen, C1-12 alkyl or halogen;
and
R9 is hydrogen, C1-12 alkyl or halogen;
with the provisos that
R4 is not hydrogen when R1, R2 and R5 are hydrogen, and R3 is substituted or unsubstituted 3-pyridinyl;
unsubstituted 4-pyridinyl;
2-(phenylamino)pyrimidin-4-yl;
2-trifluoropyrimidin-4-yl;
isoxazol-5-yl 3-substituted by an aryl or an heterocycle;
a substituted 1H-pyrazol-5-yl;
a substituted 1H-pyrazol-3-yl;
a 3-substituted 1,2,4-oxadiazol-5-yl;
an unsubstituted or 1-substituted 1H-indol-3-yl;
2-[[4-[2-(1-methylethoxy)phenyl]-1-piperazinyl]methyl]thiazol-5-yl;
(2-(4-chlorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl);
5-(4-methoxyphenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl;
substituted or unsubstituted 1,2,4-triazol-3-yl;
substituted or unsubstituted 1,2,4-triazol-5-yl;
4,5,6,7-tetrahydro-2,1-benzisoxazol-3-yl;
substituted 4,5-dihydroisoxazol-5-yl;
substituted or unsubstituted 1H-1,2,3-benzotriazol-3-yl;
5-substituted 1,2,4-oxadiazol-3-yl;
unsubstituted 1H-imidazo[4,5-c]pyridin-2-yl;
1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-9H-purin-9-yl;
substituted or unsubstituted 2-thienyl;
substituted or unsubstituted 2-furyl;
substituted or unsubstituted 2-pyrrolyl;
substituted to unsubstituted 2-benzimidazol-2-yl;
or 1-substituted 1H-indol-2-yl;
R4 is not phenyl when R1, R2 and R5 are hydrogen, and R3 is a substituted 1,2,4-triazol-3-yl;
a substituted 1,2,4-triazol-5-yl;
or unsubstituted 1H-benzimidazol-2-yl;
R4 is not hydrogen or phenyl when R1 is hydrogen or C1′-2 alkyl, R2 and R5 are hydrogen, and R3 is a substituted or unsubstituted non aromatic heterocycle;
R4 is not hydrogen when R1 is C1′-2 alkyl, R2 and R5 are hydrogen, and R3 is a 3-substituted 1,2,4-oxadiazol-5-yl or unsubstituted 3-indolyl;
R4 is not hydrogen when R1 is phenyl, C1-12 alkyl or heterocycle, R2 and R5 are hydrogen, and R3 is unsubstituted 1,2,3-benzotriazol-1-yl or unsubstituted 1,2,4-triazol-1-yl;
R1 is not 1-pyrrolidin-2-one when R2, R4 and R5 are hydrogen, and R3 is 2-furyl;
and R1 is not 4-(2-pyrimidinyl)-1-piperazinyl when R2, R4 and R5 are hydrogen, and
R3 is 1-methyl-1H-pyrrol-2-yl.

83 more elements

A method of treatment or prevention of a condition comprising administering to a mammal in need thereof an effective amount of a compound having the structural formula (I)

or a geometric isomer, enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof,
wherein
R1 is hydrogen, C1-12 alkyl, aryl or 3-8 membered heterocycle;
R2 is hydrogen;
or R1 and R2 may be linked together in such a way to form a C3-6 cycloalkyl;
R3 is
(a) a heterocycle selected from the group consisting of:
1H-benzimidazol-6-yl;
1H-benzimidazol-7-yl;
imidazo[1,2-a]pyridin-3-yl;
imidazo[1,2-a]pyrimidin-3-yl;
imidazo[1,2-b][1,2,4]triazin-7-yl;
imidazo[1,2-b]pyridazin-3-yl;
5,6,7,8-tetrahydroimidazo[1,2-b]pyridazin-3-yl;
imidazo[2,1-b][1,3,4]thiadiazol-5-yl;
imidazo[2,1-b][1,3]thiazol-5-yl;
3H-imidazo[4,5-b]pyridin-7-yl;
1H-imidazol-4-yl;
1H-imidazol-5-yl;
1H-indol-2-yl;
1H-indol-3-yl;
1H-indol-4-yl;
1H-indol-7-yl;
isoxazol-4-yl;
1H-pyrazol-4-yl;
1H-pyrazol-5-yl;
1H-pyrazolo[1,5-a]pyrimidin-3-yl;
1H-pyrazolo[3,4-b]pyridin-3-yl;
pyridazin-4-yl;
pyridin-2-yl;
pyridin-3-yl;
pyridin-4-yl;
1H-pyrrolo[2,3-b]pyridin-3-yl;
1H-pyrrolo[2,3-b]pyridin-4-yl;
1H-pyrrolo[2,3-b]pyridin-5-yl;
1H-pyrrolo[2,3-c]pyridin-2-yl;
1H-pyrrolo[2,3-c]pyridin-3-yl;
1H-pyrrolo[3,2-b]pyridin-3-yl;
1H-pyrrolo[3,2-c]pyridin-2-yl;
1H-pyrrolo[3,2-c]pyridin-3-yl;
1,3,4-thiadiazol-2-yl;
1,3-thiazol-5-yl;
[1,2,4]triazolo[4,3-b]pyridazin-7-yl;
[1,2,4]triazolo[4,3-b]pyridazin-8-yl;
and
indolizin-3-yl;
or
(b) a heterocycle linked to the rest of the molecule via one of its N atoms selected from the group consisting of:
1H-1,2,3-benzotriazol-1-yl;
1H-imidazo[4,5-b]pyridin-1-yl;
3H-imidazo[4,5-b]pyridin-3-yl;
7H-imidazo[4,5-c]pyridazin-7-yl;
1H-indol-1-yl;
2,3-dihydro-1H-indol-lyl;
9H-purin-9-yl;
1H-pyrazolo[3,4-b]pyridin-1-yl;
2H-pyrazolo[3,4-b]pyridin-2-yl;
1H-pyrrolo[2,3-b]pyridin-1-yl;
1H-pyrrolo[3,2-b]pyridin-1-yl;
3,4-dihydroquinolin-1(2H)-yl;
8H-isothiazolo[5,4-b]indol-8-yl;
1H-1,2,4-triazol-1-yl;
1H-pyrrol-1-yl;
and
2-chloro-1H-benzimidazol-1-yl;
R4 is hydrogen;
C1-12 alkyl optionally substituted by halogen, C1-4 alkoxy, C1-4 alkylthio, azido, nitrooxy;
C2-12 alkenyl;
C2-12 alkynyl;
or alkoxycarbonylamino;
R5 is hydrogen;
or R4 together with R5 forms an optionally substituted benzene ring such that the compound of structural formula (I) has the structure:
wherein
R6 is hydrogen or halogen;
R7 is hydrogen;
nitro;
halogen;
heterocycle;
amino;
aryl;
C1-12 alkyl optionally substituted by at least one halogen;
or C1-12 alkoxy optionally substituted by at least one halogen;
R8 is hydrogen, C1-12 alkyl or halogen;
and
R9 is hydrogen, C1-12 alkyl or halogen;
wherein the condition is selected from the group consisting of epilepsy, epileptogenesis, seizure disorders, convulsions, Parkinson's disease, dyskinesia induced by dopamine replacement therapy, tardive dyskinesia induced by administration of neuroleptic drugs, Huntington Chorea, and other neurological disorders including bipolar disorders, mania, depression, anxiety, attention deficit hyperactivity disorder (ADHD), migraine, trigeminal and other neuralgia, chronic pain, neuropathic pain, cerebral ischemia, cardiac arrhythmia, myotonia, cocaine abuse, stroke, myoclonus, tremor, essential tremor, simple or complex tics, Tourette syndrome, restless leg syndrome and other movement disorders, neonatal cerebral haemorrhage, amyotrophic lateral sclerosis, spasticity and degenerative diseases, bronchial asthma, asthmatic status and allergic bronchitis, asthmatic syndrome, bronchial hyperreactivity and bronchospastic syndromes as well as allergic and vasomotor rhinitis and rhinoconjunctivitis.

83 more elements

A compound selected from the group consisting of:

methyl 3-(aminomethyl)hexanoate hydrochloride;
6-bromo-2-methylpyrazolo[1,5-a]pyrimidine;
6-bromo-2-(2-thienyl)pyrazolo[1,5-a]pyrimidine;
6-bromo-2-phenylpyrazolo[1,5-a]pyrimidine;
6-bromo-2-cyclopropylpyrazolo[1,5-a]pyrimidine;
6-bromo-2-tert-butylpyrazolo[1,5-a]pyrimidine;
6-chloro-2-phenylpyrazolo[1,5-a]pyrimidine;
6-bromo-2-methylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde;
2-methylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde;
6-bromo-2-(2-thienyl)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde;
6-bromo-2-cyclopropylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde;
2-(2-furyl)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde;
6-methyl-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde;
5-methyl-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde;
2-(2-thienyl)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde;
6-(4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde;
ethyl 3-(aminomethyl)hexanoate hydrochloride;
6-chloro-3-methyl-2-(trifluoromethyl)imidazo[1,2-b]pyridazine;
3-(bromomethyl)-6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazine;
4-(2,3,5-trifluorophenyl)pyrrolidin-2-one;
1-[2-(aminooxy)-2-oxoethyl]-4-propylpyrrolidin-2-one;
2-(2-oxo-4-propylpyrrolidin-1-yl)acetohydrazide;
4-phenyl-1-[(1-trityl-1H-imidazol-4-yl)methyl]pyrrolidin-2-one;
4-propyl-1-[(1-trityl-1H-imidazol-4-yl)methyl]pyrrolidin-2-one;
1-[(1-trityl-1H-imidazol-4-yl)methyl]pyrrolidin-2-one;
4-(2,3,5-trifluorophenyl)-1-[(1-trityl-1H-imidazol-4-yl)methyl]pyrrolidin-2-one;
1-[(1-methyl-1H-imidazol-5-yl)methyl]-4-(2,3,5-trifluorophenyl)pyrrolidin-2-one;
ethyl {5-[(2-oxo-4-propylpyrrolidin-1-yl)methyl]-1H-imidazol-1-yl}acetate;
{5-[(2-oxo-4-propylpyrrolidin-1-yl)methyl]-1H-imidazol-1-yl}acetic acid;
4-iodo-3-methyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrazole;
3,5-dimethyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrazole-4-carbaldehyde;
3-methyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrazole-4-carbaldehyde;
1-[(4-methylphenyl)sulfonyl]-1H-pyrazole-4-carbaldehyde;
1-[(4-methylphenyl)sulfonyl]-1H-pyrazole-5-carbaldehyde;
ethyl 4-amino-3-(2,3,5-trifluorophenyl)butanoate hydrochloride;
1-({3,5-dimethyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrazol-4-yl}methyl)-4-(2,3,5-trifluorophenyl)pyrrolidin-2-one;
1-({3-methyl-1-[(4-methylphenyl)sulfonyl]-1H-pyrazol-4-yl}methyl)-4-(2,3,5-trifluorophenyl)pyrrolidin-2-one;
ethyl 4-[(pyridazin-4-ylmethylene)amino]butanoate;
ethyl 4-[(pyridazin-4-ylmethyl)amino]butanoate;
5-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1H-indole;
3,3-dibromo-5-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1,3-dihydro-2H-indol-2-one;
1-[(6-chloro-9H-purin-9-yl)methyl]-4-propylpyrrolidin-2-one;
1-{[(3-nitropyridin-2-yl)amino]methyl}-4-propylpyrrolidin-2-one;
1-{[(3-aminopyridin-2-yl)amino]methyl}-4-propylpyrrolidin-2-one;
5-bromo-1H-pyrazolo[3,4-b]pyridine;
2-chloro-3-(2-oxopyrrolidin-1-yl)propanal;
S-ethyl 4-cyano-1-methyl-1H-imidazole-5-carbothioate;
5-formyl-1-methyl-1H-imidazole-4-carbonitrile;
1-(1H-imidazol-4-ylmethyl)-4-(2,3,5-trifluorophenyl)pyrrolidin-2-one;
ethyl 4-{[1-(1-trityl-1H-imidazol-4-yl)propyl]amino}butanoate;
ethyl 3-{[(2-methyl-1-trityl-1H-imidazol-5-yl)methyl]amino}propanoate;
ethyl 3-{[(4-methyl-1-trityl-1H-imidazol-5-yl)methyl]amino}propanoate;
1-(4-methoxy-1-methyl-1H-imidazol-5-yl)methanamine;
barium bis[(2-amino-5-chlorophenyl)acetate];
5-hydroxy-4-(2,2,2-trifluoroethyl)furan-2(5H)-one;
1-benzyl-5-hydroxy-4-(2,2,2-trifluoroethyl)-1,5-dihydro-2H-pyrrol-2-one;
1-benzyl-4-(2,2,2-trifluoroethyl)pyrrolidin-2-one;
4-(2,2,2-trifluoroethyl)pyrrolidin-2-one;
6-chloro-2-cyclopropylimidazo[1,2-b]pyridazine;
6-chloro-2-cyclobutylimidazo[1,2-b]pyridazine;
2-cyclopropyl-6-fluoroimidazo[1,2-a]pyridine;
6-chloro-2-cyclopropylimidazo[1,2-b]pyridazine-3-carbaldehyde;
6-chloro-2-cyclobutylimidazo[1,2-b]pyridazine-3-carbaldehyde;
2-cyclopropyl-6-fluoroimidazo[1,2-b]pyridazine-3-carbaldehyde;
6-chloro-2-cyclopropylimidazo[1,2-b]pyridazine-3-carbaldehyde;
(6-chloro-2-cyclopropylimidazo[1,2-b]pyridazin-3-yl)methanol;
[6-chloro-2-(4-methylphenyl)imidazo[1,2-b]pyridazin-3-yl]methanol;
(6-chloro-2-cyclobutylimidazo[1,2-b]pyridazin-3-yl)methanol;
(2-cyclopropyl-6-fluoroimidazo[1,2-a]pyridin-3-yl)methanol;
(2-cyclopropyl-6-chloroimidazo[1,2-a]pyridin-3-yl)methanol;
6-methyl-2-phenylpyrazolo[1,5-a]pyrimidine;
2-(2-thienyl)pyrazolo[1,5-a]pyrimidine;
2-(2-furyl)pyrazolo[1,5-a]pyrimidine;
2-(4-bromophenyl)pyrazolo[1,5-a]pyrimidine;
2-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine;
2-(4-chlorophenyl)-6-methylpyrazolo[1,5-a]pyrimidine;
2-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidine;
6-chloro-2-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidine;
6-fluoro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-7-ol;
2-cyclopropyl-5-methylpyrazolo[1,5-a]pyrimidin-7-ol;
7-chloro-6-fluoro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidine;
7-chloro-5,6-dimethyl-2-phenylpyrazolo[1,5-a]pyrimidine;
7-chloro-2-cyclopropyl-5-methylpyrazolo[1,5-a]pyrimidine;
6-fluoro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidine;
5,6-dimethyl-2-phenylpyrazolo[1,5-a]pyrimidine;
2-cyclopropyl-5-methylpyrazolo[1,5-a]pyrimidine;
4-(2,2-difluorovinyl)-1-(hydroxymethyl)pyrrolidin-2-one;
(6-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)methanol;
(5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)methanol;
[2-(2-thienyl)pyrazolo[1,5-a]pyrimidin-3-yl]methanol;
3-(chloromethyl)-6-methyl-2-phenylpyrazolo[1,5-a]pyrimidine;
3-(chloromethyl)-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidine;
3-(chloromethyl)-2-(2-thienyl)pyrazolo[1,5-a]pyrimidine;
1-[(6-hydroxy-2-phenylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]-4-propylpyrrolidin-2-one;
5-bromo-3-phenyl-1H-pyrazolo[3,4-b]pyridine;
5-bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine;
tert-butyl 5-bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine-1-carboxylate;
tert-butyl 5-bromo-3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate;
1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one;
2,5-dichloro-1H-indole;
1-[(6-chloro-9H-purin-9-yl)methyl]-4-propylpyrrolidin-2-one;
6-bromo-2-cyclopropyl-1H-imidazo[4,5-b]pyridine;
(5-chloro-2-imino-1,3-thiazol-3(2H)-yl)acetic acid hydrobromide;
methyl 3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridine-7-carboxylate;
methyl 1-(4-methoxybenzyl)-1H-imidazo[4,5-b]pyridine-7-carboxylate;
methyl 3-(4-methoxybenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine-7-carboxylate;
1-(4-methoxybenzyl)-2-methyl-1H-imidazo[4,5-b]pyridine-7-carboxylate;
[3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-7-yl]methanol;
[3-(4-methoxybenzyl)-2-methyl-3H-imidazo[4,5-b]pyridin-7-yl]methanol;
7-(chloromethyl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridine;
7-(chloromethyl)-3-(4-methoxybenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine;
1-{[3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
1-{[3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-phenylpyrrolidin-2-one;
1-{[3-(4-methoxybenzyl)-2-methyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
N-(4-methoxybenzyl)-2-nitroethylene-1,1-diamine;
ethyl 2-[(4-methoxybenzyl)amino]-3-nitro-6-(trifluoromethyl)isonicotinate;
ethyl 2-[(4-methoxybenzyl)amino]-3-nitro-6-phenylisonicotinate;
ethyl 2-[(4-methoxybenzyl)amino]-6-methyl-3-nitroisonicotinate;
ethyl 3-(4-methoxybenzyl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine-7-carboxylate;
ethyl 3-(4-methoxybenzyl)-5-phenyl-3H-imidazo[4,5-b]pyridine-7-carboxylate;
ethyl 3-(4-methoxybenzyl)-5-methyl-3H-imidazo[4,5-b]pyridine-7-carboxylate;
[3-(4-methoxybenzyl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-7-yl]methanol;
[3-(4-methoxybenzyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methanol;
[3-(4-methoxybenzyl)-5-methyl-3H-imidazo[4,5-b]pyridin-7-yl]methanol;
7-(chloromethyl)-3-(4-methoxybenzyl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
7-(chloromethyl)-3-(4-methoxybenzyl)-5-phenyl-3H-imidazo[4,5-b]pyridine;
7-(chloromethyl)-3-(4-methoxybenzyl)-5-methyl-3H-imidazo[4,5-b]pyridine;
1-{[3-(4-methoxybenzyl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
1-{[3-(4-methoxybenzyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
1-{[3-(4-methoxybenzyl)-5-methyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
methyl 6-bromo-1H-imidazo[4,5-b]pyridine-7-carboxylate;
methyl 6-bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridine-7-carboxylate;
[6-bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-7-yl]methanol;
6-bromo-7-(chloromethyl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridine;
1-{[6-bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
[3-(4-methoxybenzyl)-6-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methanol;
7-(chloromethyl)-3-(4-methoxybenzyl)-6-phenyl-3H-imidazo[4,5-b]pyridine;
1-{[3-(4-methoxybenzyl)-6-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
[3-(4-methoxybenzyl)-6-methyl-3H-imidazo[4,5-b]pyridin-7-yl]methanol;
7-(chloromethyl)-3-(4-methoxybenzyl)-6-methyl-3H-imidazo[4,5-b]pyridine;
1-{[3-(4-methoxybenzyl)-6-methyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
3-(4-methoxybenzyl)-7-methyl-2-phenyl-3H-imidazo[4,5-b]pyridine;
2-[3-(4-methoxybenzyl)-2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]-N,N-dimethylethylenamine;
3-(4-methoxybenzyl)-2-phenyl-3H-imidazo[4,5-b]pyridine-7-carbaldehyde;
1-{[3-(4-methoxybenzyl)-2-phenyl-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one;
6-chloro-8-methyl-3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazine;
6-chloro-7-methyl-3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazine;
8-methyl-3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazine;
7-methyl-3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazine;
N,N-dimethyl-2-[3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazin-7-yl]ethylenamine;
N,N-dimethyl-2-(3-phenyl[1,2,4]triazolo[4,3-b]pyridazin-7-yl)ethylenamine;
3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazine-7-carbaldehyde;
3-phenyl[1,2,4]triazolo[4,3-b]pyridazine-7-carbaldehyde;
N,N-dimethyl-2-[3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazin-8-yl]ethylenamine;
2-[6-chloro-3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazin-8-yl]-N,N-dimethylethylenamine;
3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine-8-carbaldehyde;
N,N-dimethyl-2-(3-phenyl[1,2,4]triazolo[4,3-b]pyridazin-8-yl)ethylenamine;
2-(6-chloro-3-phenyl[1,2,4]triazolo[4,3-b]pyridazin-8-yl)-N,N-dimethylethylenamine;
2-(6-chloro[1,2,4]triazolo[4,3-b]pyridazin-8-yl)-N,N-dimethylethylenamine;
3-phenyl[1,2,4]triazolo[4,3-b]pyridazine-8-carbaldehyde;
methyl 3-phenyl[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate;
6-chloro[1,2,4]triazolo[4,3-b]pyridazine-8-carbaldehyde;
methyl 6-chloro[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate;
(6-chloro-3-phenyl[1,2,4]triazolo[4,3-b]pyridazin-8-yl)(methoxy)methanol;
[6-chloro-3-(trifluoromethyl) [1,2,4]triazolo[4,3-b]pyridazin-8-yl] (methoxy)methanol;
1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde;
4-propyl-1-{[1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}pyrrolidin-2-one;
1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde;
4-propyl-1-{[1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]methyl}pyrrolidin-2-one;
1-(2-fluoroindolizin-3-yl)methanamine;
4-propyl-1-(1H-pyrrol-1-ylmethyl)pyrrolidin-2-one;
1-{[6-[(2,4-dimethoxybenzyl)amino]-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-propylpyrrolidin-2-one;
2-cyclopropyl-7-hydroxypyrazolo[1,5-a]pyrimidin-5(4H)-one;
5,7-dichloro-2-cyclopropylpyrazolo[1,5-a]pyrimidine;
5,7-dichloro-2-cyclopropyl-6-methylpyrazolo[1,5-a]pyrimidine;
5-chloro-2-cyclopropylpyrazolo[1,5-a]pyrimidine;
5-chloro-2-cyclopropyl-6-methylpyrazolo[1,5-a]pyrimidine;
1-(chloromethyl)-4-(2,2-difluorovinyl)pyrrolidin-2-one;
1-methyl-5-[(2-oxo-4-propylpyrrolidin-1-yl)methyl]-1H-imidazole-2-carboxylic acid;
ethyl 3-hydroxy-2-[(2-oxo-4-propylpyrrolidin-1-yl)methyl]propanoate;
ethyl 2-formyl-3-(2-oxo-4-propylpyrrolidin-1-yl)propanoate;
and
2-benzyl-4-[(2-oxo-4-propylpyrrolidin-1-yl)methyl]-2,4-dihydro-3H-pyrazol-3-one.

180 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/916,231Filed 31 May 2006
Priority: EP 05011779.51 Jun 2005
Published: 18 Jun 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification32 codes

C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…

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US 8,183,241 B2Related patent
US 2009/0156607 A1This patent

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Abstract

The present invention concerns 2-oxo-1-pyrrolidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.

A compound having the structural formula I

or a geometric isomer, enantiomer, diastereoisomer, or a pharmaceutically acceptable salt thereof, wherein
R1 is hydrogen, C1-12 alkyl, aryl or heterocycle;
R2 is hydrogen;
or R1 and R2 are linked together to form a C3-6 cycloalkyl;
R3 is
a) an unsubstituted or substituted heterocycle linked to the rest of the molecule via one of its C atoms;
or
b) an unsubstituted or substituted heterocycle linked to the rest of the molecule via one of its N atoms selected from the group consisting of
1H-1,2,3-benzotriazol-1-yl;
1H-imidazo[4,5-b]pyridin-1-yl;
3H-imidazo[4,5-b]pyridin-3-yl;
7H-imidazo[4,5-c]pyridazin-7-yl;
1H-indol-1-yl;
2,3-dihydro-1H-indol-lyl;
9H-purin-9-yl;
1H-pyrazolo[3,4-b]pyridin-1-yl;
2H-pyrazolo[3,4-b]pyridin-2-yl;
1H-pyrrolo[2,3-b]pyridin-1-yl;
1H-pyrrolo[3,2-b]pyridin-1-yl;
3,4-dihydroquinolin-1(2H)-yl;
8H-isothiazolo[5,4-b]indol-8-yl;
1H-1,2,4-triazol-1-yl;
1H-1,2,3-triazol-1-yl;
1H-pyrrol-1-yl;
1H-tetrazol-1-yl;
and
2-chloro-1H-benzimidazol-1-yl;
R4 is hydrogen;
C1-12 alkyl optionally substituted by halogen, C1-4 alkoxy, C1-4 alkylthio, azido, nitrooxy or aryl;
C2-12 alkenyl;
C2-12 alkynyl;
aryl non-substituted by a cycloalkoxy;
azido;
alkoxy-carbonylamino;
arylsulfonyloxy;
or heterocycle;
R5 is hydrogen;
or R4 together with R5 forms an optionally substituted benzene ring such that the compound of structural formula (I) has the structure:
wherein
R6 is hydrogen or halogen;
R7 is hydrogen;
nitro;
halogen;
heterocycle;
amino;
aryl;
C1-12 alkyl optionally substituted by at least one halogen;
or C1-12 alkoxy optionally substituted by at least one halogen;
R8 is hydrogen, C1-12 alkyl or halogen;
and
R9 is hydrogen, C1-12 alkyl or halogen;
with the provisos that
R4 is not hydrogen when R1, R2 and R5 are hydrogen, and R3 is substituted or unsubstituted 3-pyridinyl;
unsubstituted 4-pyridinyl;
2-(phenylamino)pyrimidin-4-yl;
2-trifluoropyrimidin-4-yl;
isoxazol-5-yl 3-substituted by an aryl or an heterocycle;
a substituted 1H-pyrazol-5-yl;
a substituted 1H-pyrazol-3-yl;
a 3-substituted 1,2,4-oxadiazol-5-yl;
an unsubstituted or 1-substituted 1H-indol-3-yl;
2-[[4-[2-(1-methylethoxy)phenyl]-1-piperazinyl]methyl]thiazol-5-yl;
(2-(4-chlorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl);
5-(4-methoxyphenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl;
substituted or unsubstituted 1,2,4-triazol-3-yl;
substituted or unsubstituted 1,2,4-triazol-5-yl;
4,5,6,7-tetrahydro-2,1-benzisoxazol-3-yl;
substituted 4,5-dihydroisoxazol-5-yl;
substituted or unsubstituted 1H-1,2,3-benzotriazol-3-yl;
5-substituted 1,2,4-oxadiazol-3-yl;
unsubstituted 1H-imidazo[4,5-c]pyridin-2-yl;
1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-9H-purin-9-yl;
substituted or unsubstituted 2-thienyl;
substituted or unsubstituted 2-furyl;
substituted or unsubstituted 2-pyrrolyl;
substituted to unsubstituted 2-benzimidazol-2-yl;
or 1-substituted 1H-indol-2-yl;
R4 is not phenyl when R1, R2 and R5 are hydrogen, and R3 is a substituted 1,2,4-triazol-3-yl;
a substituted 1,2,4-triazol-5-yl;
or unsubstituted 1H-benzimidazol-2-yl;
R4 is not hydrogen or phenyl when R1 is hydrogen or C1′-2 alkyl, R2 and R5 are hydrogen, and R3 is a substituted or unsubstituted non aromatic heterocycle;
R4 is not hydrogen when R1 is C1′-2 alkyl, R2 and R5 are hydrogen, and R3 is a 3-substituted 1,2,4-oxadiazol-5-yl or unsubstituted 3-indolyl;
R4 is not hydrogen when R1 is phenyl, C1-12 alkyl or heterocycle, R2 and R5 are hydrogen, and R3 is unsubstituted 1,2,3-benzotriazol-1-yl or unsubstituted 1,2,4-triazol-1-yl;
R1 is not 1-pyrrolidin-2-one when R2, R4 and R5 are hydrogen, and R3 is 2-furyl;
and R1 is not 4-(2-pyrimidinyl)-1-piperazinyl when R2, R4 and R5 are hydrogen, and
R3 is 1-methyl-1H-pyrrol-2-yl.

83 more elements

Facts

Application

11/916,231Filed 31 May 2006

Priority

EP 05011779.51 Jun 2005

Published

18 Jun 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification32 codes

C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…