US 2006/0235069 A1Published application

Benzamide modulators of metabotropic glutamate receptors

AssigneeMerck & Co., Inc.

InventorsMark Duggan, Craig Lindsley, David Wisnoski

Life of this patent

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Abstract

The present invention is directed to compounds which are allosteric modulators of metabotropic glutamate receptors, including the mGluR5 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

Claims27

Dependent claims

A compound of the formula I:

wherein:
R1 is selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) C1-6alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(4) —OC1-6alkyl,
(5) —S(O)m—C1-6alkyl, wherein m is selected from 0, 1 and 2,
(6) —CO2R9, wherein R9 is independently selected from:
(a) hydrogen,
(b) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(c) benzyl, and
(d) phenyl,
(7) —NR10R11, wherein R10 and R11 are independently selected from:
(a) hydrogen,
(b) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(c) —C5-6cycloalkyl,
(d) benzyl,
(e) phenyl,
(f) —S(O)2—C1-6alkyl,
(g) —S(O)2-benzyl, and
(h) —S(O)2-phenyl,
(8) —S(O)2—NR10R11,
(9) phenyl, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl, and
(f) —OCF3;
R3 is selected from the group consisting of:
(1) C1-6alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(2) C3-7cycloalkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl, and
(3) phenyl, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with —NR10R11,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3;
(g) —CO2R9,
(h) —NR10R11,
(i) —C(O)NR10R11, and
(j) —NO2,
(4) heterocycle, wherein heterocycle is selected from:
benzoimidazolyl, benzimidazolonyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyrimidyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, azetidinyl, 1,4-dioxanyl, hexahydroazepinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, dihydrobenzoimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, and tetrahydrothienyl, and N-oxides thereof, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) phenyl,
(f) trifluoromethyl,
(g) —OCF3;
(h) —CO2R9,
(i) —NR10R11, and
(j) —CONR10R11;
R4 is selected from the group consisting of:
(1) C1-6alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(2) C3-7cycloalkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl, and
(3) phenyl, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3,
(g) —CO2R9,
(h) —NR10R11,
(i) —CONR10R11, and
(j) —NO2;
(4) heterocycle, wherein heterocycle is selected from:
benzoimidazolyl, benzimidazolonyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyrimidyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, azetidinyl, 1,4-dioxanyl, hexahydroazepinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, dihydrobenzoimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, and tetrahydrothienyl, and N-oxides thereof, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) phenyl,
(f) trifluoromethyl,
(g) —OCF3,
(h) —CO2R9,
(i) —NR10R11, and
(j) —CONR10R11;
or wherein R4 and R5 are joined together to form a phthalimidyl, succinimidyl or glutamidyl ring, which is unsubstituted or substituted with one or more substituents independently selected from the definitions of R1;
R5 and R6 are independently selected from the group consisting of:
(1) hydrogen, and
(2) C1-6alkyl;
n is an integer selected from 1, 2 and 3;
and pharmaceutically acceptable salts thereof and individual diastereomers thereof.

84 more elements

A compound which is selected from the group consisting of:

N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyrimidine-2-carboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide;
2-[({2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3-fluorophenyl}amino)carbonyl]phenyl;
N-{2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3-fluorophenyl}-2-hydroxybenzamide;
2-chloro-N-{2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3-fluorophenyl}benzamide;
N-{2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3-fluorophenyl}-2-fluorobenzamide;
N-{2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3-fluorophenyl}benzamide;
N-{2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3-fluorophenyl}-3,5-difluorobenzamide;
N-{2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methoxybenzamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-methylbenzamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-furamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-5-methylisoxazole-3-carboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}cyclohexanecarboxamide;
N-{5-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}cyclohexanecarboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-1-methyl-1H-imidazole-2-carboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-1,3-thiazole-4-carboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-hydroxypyridine-2-carboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}imidazo[2,1-b][1,3]thiazole-6-carboxamide;
N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-1,2,5-thiadiazole-3-carboxamide;
N-{2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-4-methoxyphenyl}pyridine-2-carboxamide;
N-{4-bromo-2-[(4-fluoro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-chloro-2-[(2,5-dioxo-3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-chloro-2-[(4-fluoro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-chloro-2-[(5,6-dimethyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-chloro-2-[(5-fluoro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-chloro-2-[(5-ethoxy-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{5-bromo-3-[(5,6-dichloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]pyridin-2-yl}pyridine-2-carboxamide;
N-{4-chloro-2-[(5-hydroxy-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-bromo-2-[(5-fluoro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-bromo-2-[(5-ethoxy-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-bromo-2-[(5,6-dichloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-bromo-2-[(4,6-dichloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{2-[(4,6-dichloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-4-fluorophenyl}pyridine-2-carboxamide;
N-{2-[(5,6-dichloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-4-fluorophenyl}pyridine-2-carboxamide;
N-{4-fluoro-2-[(5-nitro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{4-bromo-2-[(4-methyl-1,3-dioxo-3,4,5,6-tetrahydrocyclopenta[c]-pyrrol-2(1H)-yl)methyl]phenyl}pyridine-2-carboxamide;
N-{5-bromo-2-[(pyridin-2-ylcarbonyl)amino]benzyl}pyridine-2-carboxamide;
N-(4-bromo-2-{[(2-fluorobenzoyl)amino]methyl}phenyl)pyridine-2-carboxamide;
N-{5-bromo-2-[(pyridin-2-ylcarbonyl)amino]benzyl}pyridine-2-carboxamide;
N-[4-bromo-2-({[2-(trifluoromethyl)benzoyl]amino}methyl)phenyl]-pyridine-2-carboxamide;
N-(4-chloro-2-{[(3,5-dichlorobenzoyl)(ethyl)amino]methyl}phenyl)-pyridine-2-carboxamide;
N-(2-{[(4-butoxybenzoyl)(ethyl)amino]methyl}-4-chlorophenyl)-pyridine-2-carboxamide;
N-(4-chloro-2-{[(3,5-dimethoxybenzoyl)(ethyl)amino]methyl}phenyl)pyridine-2-carboxamide;
N-(4-chloro-2-{[(3,4-dichlorobenzoyl)(ethyl)amino]methyl}phenyl)pyridine-2-carboxamide;
N-(4-chloro-2-{[(3,5-dichlorobenzoyl)(isobutyl)amino]methyl}phenyl)pyridine-2-carboxamide;
N-(4-chloro-2-{[(3,5-dimethoxybenzoyl)(isobutyl)amino]methyl}phenyl)pyridine-2-carboxamide;
N-{5-fluoro-2-[(pyridin-2-ylcarbonyl)amino]benzyl}quinoxaline-2-carboxamide;
N-(2-{[(4-butoxybenzoyl)amino]methyl}-4-fluorophenyl)pyridine-2-carboxamide;
N-(4-bromo-2-{[(3-methoxybenzoyl)(methyl)amino]methyl}phenyl)pyridine-2-carboxamide;
N-(4-chloro-2-{[(3,5-dichlorobenzoyl)(methyl)amino]methyl}phenyl)pyridine-2-carboxamide;
N-(2-{[[3,5-bis(trifluoromethyl)benzoyl](methyl)amino]methyl}-4-chlorophenyl)pyridine-2-carboxamide;
N-[4-chloro-2-({(3,5-dichlorobenzoyl) [2-(dimethylamino)ethyl]amino}methyl)-phenyl]pyridine-2-carboxamide;
N-[2-(benzoylamino)-5-bromobenzyl]-N,3,5-trimethylbenzamide;
N-(4-bromo-2-{[(3,5-dichlorobenzoyl)(methyl)amino]methyl}-phenyl)pyridine-2-carboxamide;
N-(4-bromo-2-{[(3,4-difluorobenzoyl)(methyl)amino]methyl}phenyl)-pyridine-2-carboxamide;
N-(4-bromo-2-{[(2,4-difluorobenzoyl)(methyl)amino]methyl}phenyl)-pyridine-2-carboxamide;
N-(4-bromo-2-{[(3,4-dichlorobenzoyl)(methyl)amino]methyl}phenyl)-pyridine-2-carboxamide;
N-[4-chloro-2-({methyl[2-(trifluoromethyl)benzoyl]amino}methyl)-phenyl]pyridine-2-carboxamide;
N-(4-chloro-2-{[(3,4-dichlorobenzoyl)(methyl)amino]methyl}-phenyl)pyridine-2-carboxamide;
and pharmaceutically acceptable salts thereof.

60 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/550,968Filed 22 Mar 2004
Priority: 26 Mar 2003
Published: 19 Oct 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 417/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 13/10
Drugs for disorders of the urinary system: of the bladder

Family

Application60/457,734Us provisional application · filed 26 Mar 2003
US 7,507,836 B2Related patent
US 2006/0235069 A1This patent

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

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Abstract

A compound of the formula I:

wherein:
R1 is selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) C1-6alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(4) —OC1-6alkyl,
(5) —S(O)m—C1-6alkyl, wherein m is selected from 0, 1 and 2,
(6) —CO2R9, wherein R9 is independently selected from:
(a) hydrogen,
(b) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(c) benzyl, and
(d) phenyl,
(7) —NR10R11, wherein R10 and R11 are independently selected from:
(a) hydrogen,
(b) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(c) —C5-6cycloalkyl,
(d) benzyl,
(e) phenyl,
(f) —S(O)2—C1-6alkyl,
(g) —S(O)2-benzyl, and
(h) —S(O)2-phenyl,
(8) —S(O)2—NR10R11,
(9) phenyl, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl, and
(f) —OCF3;
R3 is selected from the group consisting of:
(1) C1-6alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(2) C3-7cycloalkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl, and
(3) phenyl, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with —NR10R11,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3;
(g) —CO2R9,
(h) —NR10R11,
(i) —C(O)NR10R11, and
(j) —NO2,
(4) heterocycle, wherein heterocycle is selected from:
benzoimidazolyl, benzimidazolonyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyrimidyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, azetidinyl, 1,4-dioxanyl, hexahydroazepinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, dihydrobenzoimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, and tetrahydrothienyl, and N-oxides thereof, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) phenyl,
(f) trifluoromethyl,
(g) —OCF3;
(h) —CO2R9,
(i) —NR10R11, and
(j) —CONR10R11;
R4 is selected from the group consisting of:
(1) C1-6alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(2) C3-7cycloalkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl, and
(3) phenyl, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3,
(g) —CO2R9,
(h) —NR10R11,
(i) —CONR10R11, and
(j) —NO2;
(4) heterocycle, wherein heterocycle is selected from:
benzoimidazolyl, benzimidazolonyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyrimidyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, azetidinyl, 1,4-dioxanyl, hexahydroazepinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, dihydrobenzoimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, and tetrahydrothienyl, and N-oxides thereof, which is unsubstituted or substituted with one or more substituents independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy,
(e) phenyl,
(f) trifluoromethyl,
(g) —OCF3,
(h) —CO2R9,
(i) —NR10R11, and
(j) —CONR10R11;
or wherein R4 and R5 are joined together to form a phthalimidyl, succinimidyl or glutamidyl ring, which is unsubstituted or substituted with one or more substituents independently selected from the definitions of R1;
R5 and R6 are independently selected from the group consisting of:
(1) hydrogen, and
(2) C1-6alkyl;
n is an integer selected from 1, 2 and 3;
and pharmaceutically acceptable salts thereof and individual diastereomers thereof.

84 more elements

Facts

Application

10/550,968Filed 22 Mar 2004

Priority

26 Mar 2003

Published

19 Oct 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 417/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 13/10
Drugs for disorders of the urinary system: of the bladder