US 2009/0291983 A1Published application

3-Oxoisoindoline-1-Carboxamide Derivatives as Analgesic Agents

AssigneeAstraZeneca AB

InventorsYevgeni Besidski, Ylva Gravenfors, Inger Kers, Karin Skogholm, Mats Svensson

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Abstract

Compounds of formula I wherein R1, R2, R3, R4, R5 and R6 are as described in the specification, pharmaceutically acceptable salts, methods of making, pharmaceutical compositions containing and methods for using the same.

Claims9

Dependent claims

A compound of Formula I

or a pharmaceutically acceptable derivative thereof,
wherein
R1 and R2 represent independently, at each occurrence, halogen, C1-C12 alkyl, C1-C12 alkoxy, C1-C12 haloalkyl, C1-C12 haloalkoxy, cyano, SR7, N(R8a)R8b, C2-C6 alkynyl, aryl or Het1;
R3 represents hydrogen or C1-C12 alkyl;
R4 represents —(CH2)mR9 or —(CH2)nOR10;
further R3 and R4 may together represent a ring;
R5 represents hydrogen, C1-C12 alkyl group or C1-C12 alkoxy group (which C1-C12 alkyl and C1-C12 alkoxy groups are optionally substituted by one or more groups selected from halogen, C2-C6 alkenyl, C2-C6 alkynyl, cyano, oxo, aryl, Het4, —OR13, —SR14, —COXR15, —N(R16a)R16b, and —SO2R17);
R6 represents hydrogen, C1-C12 alkyl group or C1-C12 alkoxy group (which C1-C12 alkyl and C1-C12 alkoxy groups are optionally substituted by one or more groups selected from halogen, C2-C6 alkenyl, C2-C6 alkynyl, cyano, oxo, aryl, Het5, —OR18, —SR19, —COXR20, —N(R21a)R21b, —SO2R22);
Het1 to Het5 independently represent, at each occurrence, five- to twelve-membered heterocyclic groups containing one or more heteroatoms selected from oxygen, nitrogen and/or sulfur, which groups are optionally substituted by one or more substituents selected from —OH, oxo, halo, cyano, nitro, C1-6 alkyl, C1-6 alkoxy, aryl, aryloxy, —N(R23a)R23b, —C(O)R23c, —C(O)OR23d, —C(O)N(R23e)R23f, —N(R23g)C(O)R23h, —N(R23i)S(O)2R23j, OC(O)R23k and a further Het;
R7 and R8 represent independently, at each occurrence, hydrogen or C1-6 alkyl;
R9 and R10 represents aryl, Het2 (which aryl and Het2 optionally are substituted by one or more groups selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, cyano, SR1, N(R12a)R12b, C2-C6 alkenyl, aryl, and Het3;
R11, R12a, R12b, R13, R14, R15, R16a, R16b, R17, R18, R19, R20, R21a, R21b, R22, R23a, R23b, R23c, R23d, R23e R23f, R23g, R23h R23i, R23j and R23k represent independently, at each occurrence, hydrogen or C1-6 alkyl;
m represents an integer selected from 0, 1, 2 or 3;
n represents an integer selected from 1, 2 or 3;
X represents nitrogen or oxygen atom.

12 more elements

A compound selected from the following compounds:

N-(2,6-dimethylphenyl)-2-(2-ethoxybenzyl)-3-oxoisoindoline-1-carboxamide;
N-(2-chloro-6-methylphenyl)-2-(2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide;
N-(2,6-dichlorophenyl)-6-fluoro-2-(2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide;
2-(2,3-dihydro-1H-inden-1-yl)-N-(2,6-dimethylphenyl)-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-(2-isopropoxybenzyl)-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-6-fluoro-2-(2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-3-oxo-2-(1,2,3,4-tetrahydronaphthalen-1-yl)isoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-[1-(2-methoxyphenyl)ethyl]-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-(2-hydroxybenzyl)-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-3-oxo-2-[2-(trifluoromethoxy)benzyl]isoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-{2-[(2,6-dimethylpyridin-3-yl)oxy]ethyl}-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-{2-[4-fluoro-3-(trifluoromethyl)phenoxy]ethyl}-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-[(2R)-8-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-{1-methyl-2-[3-(trifluoromethyl)phenoxy]ethyl}-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-{2-[2-fluoro-5-(trifluoromethyl)phenoxy]ethyl}-3-oxoisoindoline-1-carboxamide;
N-(2,6-dichlorophenyl)-2-(2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide;
2-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-N-(2,6-dimethylphenyl)-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-[(2S)-8-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-[(3S)-5-methoxy-3,4-dihydro-2H-chromen-3-yl]-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-3-oxo-2-[(1R)-1-phenylethyl]isoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-(2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-(2-methylbenzyl)-3-oxoisoindoline-1-carboxamide;
2-[2-(4-chlorophenyl)propyl]-N-(2,6-dimethylphenyl)-3-oxoisoindoline-1-carboxamide;
2-(biphenyl-2-ylmethyl)-N-(2,6-dimethylphenyl)-3-oxoisoindoline-1-carboxamide;
N-(2-isopropyl-6-methylphenyl)-2-(2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide;
2-(2,4-difluorobenzyl)-N-(2-isopropyl-6-methylphenyl)-3-oxoisoindoline-1-carboxamide;
N-(2-isopropyl-6-methylphenyl)-2-[(3-methylpyridin-2-yl)methyl]-3-oxoisoindoline-1-carboxamide;
2-(2-fluorobenzyl)-N-mesityl-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-3-oxo-2-(pyridin-2-ylmethyl)isoindoline-1-carboxamide;
2-(3-chlorobenzyl)-N-(2-isopropyl-6-methylphenyl)-3-oxoisoindoline-1-carboxamide;
2-(3-chlorobenzyl)-N-mesityl-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-[2-(7-methyl-1H-indol-3-yl)ethyl]-3-oxoisoindoline-1-carboxamide;
2-(2,5-dimethoxybenzyl)-N-(2,6-dimethylphenyl)-3-oxoisoindoline-1-carboxamide;
N-(2-chloro-6-methylphenyl)-2-[2-(3-methoxyphenyl)ethyl]-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-(2-methoxybenzyl)-N-methyl-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethoxyphenyl)-2-(2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide;
N-(2,6-dimethylphenyl)-2-(4-fluoro-2-methoxybenzyl)-5-hydroxy-4-methyl-3-oxoisoindoline-1-carboxamide;
and
N-(2,6-dimethylphenyl)-2-(4-fluoro-2-methoxybenzyl)-3-oxoisoindoline-1-carboxamide;
or pharmaceutically acceptable derivative thereof.

37 more elements

Dependencies are inferred from the claim text.

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