US 2010/0137322 A1Published application

Novel n-(8-heteroaryltetrahydronaphtalene-2yl) or n-(5-heteroarylchromane-3-yl) carboxamide derivatives for the treatment of pain

AssigneeAstraZeneca AB

InventorsYevgeni Besidski, Inger Kers, Martin Nylof, Lars Sandberg, Karin Skogholm

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Abstract

The present invention relates to new compounds of formula (I) and to pharmaceutical composition containing said compounds and to the use of said compounds in therapy. The present invention further relates to processes for the preparation of said compounds and to new intermediates useful in the preparation thereof.

Claims22

Dependent claims

A compound of formula I or a pharmaceutically acceptable salt thereof, wherein:

formula I corresponds to:
X is O or CH2;
R1 is pyridinyl, pyrazolyl, isoxazolyl, pyrimidinyl, pyridazinyl, imidazopyridinyl, or pyrazinyl, wherein:
any such group may be independently mono-, di-, or tri-substituted with R11, R12, and/or R13;
R11, R12, and R13 are independently selected from halogen, C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, C1-6hydroxyalkyl, C3-6cycloalkyloxy, C3-6cycloalkylC1-6alkoxy, cyano, hydroxy, C1-6haloalkyl, C1-6haloalkoxy, C1-6haloalkoxyC1-6alkoxy, C1-6haloalkoxyC1-6alkyl, C1-6alkylsulfonic acid-, C1-6haloalkylsulfonic acid-, C3-6cycloalkylsulfonic acid-, C3-6halocycloalkylsulfonic acid-, C3-6cycloalkylC1-6alkylsulfonic acid-, C3-6halocycloalkylC1-6alkylsulfonic acid-, C1-6alkylsulfonyl-, C1-6haloalkylsulfonyl-, C3-6cycloalkylsulfonyl-, C3-6halocycloalkylsulfonyl-, C3-6cycloalkylC1-6alkylsulfonyl, C3-6halocycloalkylC1-6alkyl-sulfonyl, phenyl, phenylC1-6alkyl-, phenoxy, C1-6alkylphenyl-, C1-6alkoxyphenyl-, C1-6alkylamine, C1-6haloalkylamine, —C(O)NHC1-6 alkyl, —C(O)N(C1-6alkyl)2, and —C(O)NH2;
R2 is pyrazinyl, phenyl, pyridinyl, quinoxalinyl, triazolyl, pyridonyl, naphthyridinyl, pyrimidinyl, or quinolinyl, wherein:
any such group may be independently mono-, di-, or tri-substituted with R14, R15, and/or R16;
R14, R15, and R16 are independently selected from halogen, C1-6alkyl, C2-6alkenyl, C3-6alkynyl, C1-6alkoxy, C2-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkyl, C3-6heterocycloalkyl, C3-6cycloalkyloxy, C3-6heterocycloalkyloxy, C3-6cycloalkylC1-6alkoxy, C1-6alkyl-C3-6cycloalkylC1-6alkoxy, C3-6heterocycloalkylC1-6alkoxy, C1-6alkyl-C3-6heterocycloalkylC1-6alkoxy, C1-6alkoxyC1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6hydroxyalkyl, C1-6haloalkyl, C1-6haloalkoxy, C1-6haloalkoxyC1-6alkoxy, C1-6haloalkoxyC1-6alkyl, cyano, hydroxyl, NR4R5, C1-6alkylsulfonic acid-, C1-6haloalkylsulfonic acid-, C3-6cycloalkylsulfonic acid-, C3-6halocycloalkylsulfonic acid-, C3-6cycloalkylC1-6alkylsulfonic acid-, C3-6halocycloalkylC1-6alkylsulfonic acid-, C1-6alkylsulfonyl-, C1-6haloalkylsulfonyl-, C3-6cycloalkylsulfonyl-, C3-6halocycloalkylsulfonyl-, C3-6cycloalkyl-C1-6alkyl-sulfonyl, C3-6halocycloalkyl-C1-6alkyl-sulfonyl, phenyl, phenylC1-6alkyl-, phenoxy, C1-6alkylphenyl-, C1-6alkoxyphenyl-, —C(O)NR4R5, —C(O)C3-6cycloalkyl, —C(O)C3-6heterocycloalkyl, —C(O)C3-6cycloalkylC1-6alkoxy, —C(O)C3-6heterocycloalkylC1-6alkoxy, —C(O)C3-6cycloalkylC1-6alkyl, and —C(O)C3-6heterocycloalkylC1-6alkyl;
and
R4 and R5 are independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6alkoxyC1-6alkyl, C3-6cycloalkyl, C3-6halocycloalkyl, C3-6heterocycloalkyl, and C3-6heterocycloalkylC1-6alkyl.

7 more elements

A compound of formula I or a pharmaceutically acceptable salt thereof, wherein:

formula I corresponds to:
X is O or CH2;
R1 is pyridinyl, pyrazolyl, isoxazolyl, pyrimidinyl, pyridazinyl, imidazopyridinyl, or pyrazinyl, wherein:
any such group may be independently mono-, di-, or tri-substituted with R11, R12, and/or R13;
R11, R12, and R13 are independently selected from halogen, C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, C1-6hydroxyalkyl, C3-6cycloalkyloxy, C3-6cycloalkylC1-6alkoxy, cyano, hydroxy, C1-6haloalkyl, C1-6haloalkoxy, C1-6haloalkoxyC1-6alkoxy, C1-6haloalkoxy, C1-6alkyl, C1-6alkylsulfonic acid-, C1-6haloalkylsulfonic acid-, C3-6cycloalkylsulfonic acid-, C3-6halocycloalkylsulfonic acid-, C3-6cycloalkylC1-6alkylsulfonic acid-, C3-6halocycloalkylC1-6alkylsulfonic acid-, C1-6alkylsulfonyl-, C1-6haloalkylsulfonyl, C3-6cycloalkylsulfonyl-, C3-6halocycloalkylsulfonyl-, C3-6cycloalkylC1-6alkylsulfonyl, C3-6halocycloalkylC1-6alkyl-sulfonyl, phenyl, phenylC1-6alkyl-, phenoxy, C1-6alkylphenyl-, C1-6alkoxyphenyl-, C1-6alkylamine, C1-6haloalkylamine, —C(O)NHC1-6alkyl, —C(O)N(C1-6alkyl)2, —C(O)NH2;
R2 is pyrazinyl, phenyl, pyridinyl, quinoxalinyl, triazolyl, pyridonyl, naphthyridinyl, pyrimidinyl, or quinolinyl, wherein:
any such group is independently mono-, di-, or tri-substituted with R14, R15, and/or R16;
and
R14, R15, and R16 are independently selected from fluoro, iodo, chloro, bromo, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, all isomeric forms of pentyl and hexyl, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, t-butoxy, i-butoxy, propynyloxy, butynyloxy, pentynyloxy, methoxyethoxy, methoxypropoxy, ethoxymethoxy, ethoxyethoxy, ethoxypropoxy, propoxymethoxy, propoxyethoxy, propoxypropoxy, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, propoxymethyl, propoxyethyl, propoxypropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, fluoropropyl, difluoropropyl, trifluoropropyl, fluorobutyl, difluorobutyl, trifluorobutyl, bromopropyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, fluoropropoxy, difluoropropoxy, trifluoropropoxy, fluorobutoxy, difluorobutoxy, trifluorobutoxy, fluoropentoxy, difluoropentoxy, trifluoropentoxy, trifluoromethoxymethoxy, trifluoromethoxyethoxy, trifluoroethoxymethoxy, trifluoroethoxyethoxy, trifluoromethoxymethyl, trifluoromethoxyethyl, trifluoroethoxymethyl, trifluoroethoxyethyl, trifluoromethylamine, trifluoroethylamine, trifluoropropylamine, trifluoromethanesulfonic acid, difluoromethanesulfonic acid, fluoromethanesulfonic acid, methanesulfonyl, ethanesulfonyl, propanesulfonyl, butanesulfonyl, phenyl, cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, methylamide, ethylamide, propylamide, butylamide, pentylamide, dimethylamide, diethylamide, dipropylamide, N-methyl-N-ethylamide, N-methyl-N-propylamide, N-methyl-N-butylamide, N-methyl-N-pentylamide, N-ethyl-N-propylamide, N-ethyl-N-butylamide, N-ethyl-N-pentylamide, N-propyl-N-methylamide, N-propyl-N-ethylamide, N-propyl-N-butylamide, N-propyl-N-pentylamide, N-methoxymethylamide, N-methoxyethylamide, N-methoxypropylamide, N-methoxybutylamide, N-ethoxyethylamide, N-ethoxypropylamide, N-ethoxybutylamide, N-propoxymethylamide, N-propoxyethylamide, N-propoxypropylamide, N-propoxybutylamide, N-difluorocyclopropylamide, N-difluorocyclobutylamide, N-difluorocyclopentylamide, N-difluorocyclohexylamide, tetrahydropyranylamide, oxetanylamide, tetrahydrofuranylamide, oxepanylamide, dioxanylamide, trifluoromethylamide, trifluoroethylamide, trifluoropropylamide, trifluorobutylamide, N-trifluoromethyl-N-methylamide, N-trifluoromethyl-N-ethylamide, N-trifluoromethyl-N-propylamide, N-trifluoroethyl-N-methylamide, N-trifluoroethyl-N-ethylamide, N-trifluoroethyl-N-propylamide, N-trifluoropropyl-N-methylamide, N-trifluoropropyl-N-ethylamide, N-trifluoropropyl-N-propylamide, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, dioxanyl, oxetanyloxy, tetrahydrofuranyloxy, tetrahydropyranyloxy, oxepanyloxy, dioxanyloxy, oxetanylmethoxy, tetrahydrofuranylmethoxy, tetrahydropyranylmethoxy, oxepanylmethoxy, dioxanylmethoxy, cyclopropylmethoxy, cyclopropylethoxy, cyclobutylmethoxy, cyclobutylethoxy, cyclopropyloxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, pyrrolidinyl, pyrrolidinyl-carbonyl, thiazolyl, thiazolylmethoxy, thiazolylethoxy, methyl-thiazolylmethoxy, methyl-thiazolylmethyl, isoxazolylmethoxy, isoxazolylethoxy, methyl-isoxazolylmethoxy, methyl-isoxazolylmethyl, imidazolyl, imidazolylmethoxy, imidazolylethoxy, methyl-imidazolylmethoxy, methyl-imidazolylmethyl, pyridinyl, pyridinylmethoxy, pyridinylethoxy, methyl-pyridinylmethoxy, methyl-pyridinylmethyl, pyrazinyl, pyrazinylmethoxy, pyrazinylethoxy, methylpyrazinylmethoxy, and methylpyrazinylmethyl.

6 more elements

A compound or pharmaceutically acceptable salt thereof, wherein the compound is selected from:

N-[(3S)-5-Pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-4-(trifluoromethoxy)-benzamide;
4-Butoxy-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]benzamide;
4-{[(2R)-8-Pyridin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]carbamoyl}phenyl trifluoromethanesulfonate;
N-[(3S)-5-Pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-4-(trifluoromethoxy)-benzamide;
N-[(3S)-5-Pyridin-2-yl-3,4-dihydro-2H-chromen-3-yl]-4-(trifluoromethoxy)-benzamide;
N-[(2R)-8-(1-Methyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(trifluoromethoxy)-benzamide;
4-{[(2R)-8-(1-Methyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamoyl}phenyl trifluoromethanesulfonate;
5-Methyl-N-[(2R)-8-(1-methyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-2-phenyl-2H-1,2,3-triazole-4-carboxamide;
N-[(2R)-8-(3,5-Dimethyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(trifluoromethoxy)-benzamide;
N-[(2R)-8-(3,5-Dimethylisoxazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(trifluoromethoxy)-benzamide;
4-{[(2R)-8-(3,5-Dimethylisoxazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamoyl}phenyl trifluoromethanesulfonate;
N-[(2R)-8-pyridin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(2R)-8-pyridin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
6-isopropoxy-N-[(2R)-8-pyridin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]nicotin-amide;
6-(cyclopentyloxy)-N-[(2R)-8-pyridin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]nicotin-amide;
2,4-dimethoxy-N-[(2R)-8-pyridin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-benzamide;
5-methyl-2-phenyl-N-[(2R)-8-pyridin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-2H-1,2,3-triazole-4-carboxamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotin-amide;
6-isopropoxy-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotin-amide;
6-(cyclopentyloxy)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotin-amide;
2,4-dimethoxy-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]benzamide;
5-methyl-2-phenyl-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-2H-1,2,3-triazole-4-carboxamide;
6-isobutoxy-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotin-amide;
6-ethoxy-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotin-amide;
6-(2,2-difluoroethoxy)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotin-amide;
6-[2-fluoro-1-(fluoromethyl)ethoxy]-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotin-amide;
2-(cyclopentyloxy)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]pyrimidine-5-carboxamide;
6-(cyclobutyloxy)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotin-amide;
6-(cyclopropylmethoxy)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotin-amide;
N-[(2R)-8-(3,5-dimethylisoxazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-isopropoxy-nicotinamide;
6-(2,2-difluoroethoxy)-N-[(2R)-8-(3,5-dimethylisoxazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]nicotin-amide;
2-(cyclopentyloxy)-N-[(2R)-8-(3,5-dimethylisoxazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]pyrimidine-5-carboxamide;
6-(butylsulfonyl)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide.

31 more elements

A compound or pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

6-chloro-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
2-isopropoxy-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]pyrimidine-5-carboxamide;
5-methoxy-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]pyrazine-2-carboxamide;
5-isopropoxy-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]pyrazine-2-carboxamide;
N-[(2R)-8-(3-fluoropyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-isopropoxynicotinamide;
N-[(2R)-8-(3-fluoropyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]quinoxaline-2-carboxamide;
5-isopropoxy-N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]pyrazine-2-carboxamide;
N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-5-(3,3,3-trifluoropropoxy)pyrazine-2-carboxamide;
5-methoxy-N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]pyrazine-2-carboxamide;
N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-1,8-naphthyridine-2-carboxamide;
N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-1,5-naphthyridine-2-carboxamide;
2-methyl-N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-1,6-naphthyridine-3-carboxamide;
N-[(3S)-5-(6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-5-(3,3,3-trifluoropropoxy)pyrazine-2-carboxamide;
5-methoxy-N-[(3S)-5-(6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]pyrazine-2-carboxamide;
6-isopropoxy-N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
2-isobutyl-5-methyl-N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-2H-1,2,3-triazole-4-carboxamide;
6-isopropoxy-N-[(3S)-5-pyrimidin-5-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-pyrimidin-5-yl-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
6-isopropoxy-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
6-isopropoxy-N-[(3S)-5-(2-methoxypyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(2-methoxypyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
6-isopropoxy-N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
N-[(3S)-5-(2-fluoropyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]-6-isopropoxynicotinamide;
N-[(3S)-5-(2-fluoropyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]quinoxaline-2-carboxamide;
N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]quinoline-2-carboxamide;
6-isopropoxy-N-[(3S)-5-(3-methylpyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(6-fluoropyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-isopropoxynicotinamide;
N-[(3S)-5-(3-methylpyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
N-[(3S)-5-(6-fluoropyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
6-(2,4-dimethoxyphenyl)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-isopropoxy-N-[(3S)-5-(2-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(2-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
6-isopropoxy-N-[(2S)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]nicotinamide;
N-[(2R)-8-(2-fluoropyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-isopropoxynicotinamide;
N-[(2R)-8-pyridazin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
6-isopropoxy-N-[(3S)-5-(6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
6-isopropoxy-N-[(2R)-8-pyridazin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]nicotinamide;
N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-5-methoxypyrazine-2-carboxamide;
N-[(3S)-5-pyridazin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(3S)-5-pyridazin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
6-isopropoxy-N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]nicotinamide;
5-methoxy-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]pyrazine-2-carboxamide;
N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(2R)-8-(2-fluoropyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-4-methyl-2-(2,2,2-trifluoroethoxy)pyrimidine-5-carboxamide;
N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-methyl-2-(2,2,2-trifluoroethoxy)pyrimidine-5-carboxamide;
N-[(3S)-5-imidazo[1,2-a]pyridin-6-yl-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
2-isopropoxy-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-4-methylpyrimidine-5-carboxamide;
N-[(3S)-5-(2-ethoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
6-(cyclobutyloxy)-N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(2-ethylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(3S)-5-(2-cyclopropylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3-fluoropropoxy)nicotinamide;
N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3,3,3-trifluoropropoxy)nicotinamide;
N-[(3S)-5-(3,6-dimethoxypyridazin-4-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N-[(3S)-5-(6-methylpyrazin-2-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
6-(3-fluoropropoxy)-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(3-fluoropropoxy)-N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
2-isopropoxy-N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]isonicotinamide;
2-isopropoxy-N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]isonicotinamide;
6-(cyclobutyloxy)-N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(cyclobutyloxy)-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
2-isopropoxy-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]isonicotinamide;
N-[(3S)-5-(3,5-dimethylpyrazin-2-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(3-fluoropropoxy)nicotinamide;
N-[(3S)-5-(2-cyclopropylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2,2,2-trifluoroethoxy)nicotinamide;
N5-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2,N2-dipropylpyridine-2,5-dicarboxamide;
N5-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(3-methylbutyl)pyridine-2,5-dicarboxamide;
N2-isobutyl-N5-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-methylpyridine-2,5-dicarboxamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(pyrrolidin-1-ylcarbonyl)nicotinamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(1,3-thiazol-2-ylmethoxy)nicotinamide;
6-[(5-methylisoxazol-3-yl)methoxy]-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-[(1-methyl-1H-imidazol-2-yl)methoxy]-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(cyclopentylsulfonyl)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(pyridin-2-ylmethoxy)nicotinamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(pyridin-3-ylmethoxy)nicotinamide;
6-(pyrazin-2-ylmethoxy)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydrofuran-2-ylmethoxy)nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-2-ylmethoxy)nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-4-ylmethoxy)nicotinamide;
6-(but-2-yn-1-yloxy)-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N5-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(3,3,3-trifluoropropyl)pyridine-2,5-dicarboxamide;
6-(2-methoxyethoxy)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(oxetan-2-ylmethoxy)-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-{[(2R)-2-methoxypropyl]oxy}-N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-4-yloxy)nicotinamide;
N5-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-N2-(tetrahydro-2H-pyran-4-yl)pyridine-2,5-dicarboxamide;
N5-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-N2-(2,2,2-trifluoroethyl)pyridine-2,5-dicarboxamide;
N5-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-N2-(3,3,3-trifluoropropyl)pyridine-2,5-dicarboxamide;
N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-5-(tetrahydro-2H-pyran-4-yloxy)pyrazine-2-carboxamide;
N-[(3S)-5-(6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-4-yloxy)nicotinamide;
N-[(3S)-5-(6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-3-yloxy)nicotinamide;
N-[(3S)-5-pyridin-4-yl-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-3-yloxy)nicotinamide;
6-(2-methoxyethoxy)-N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
2-(2-methoxyethyl)-5-methyl-N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]-2H-1,2,3-triazole-4-carboxamide;
6-(oxetan-2-ylmethoxy)-N-[(3S)-5-pyridin-3-yl-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(2-methoxyethoxy)-N-[(3S)-5-(2-methoxypyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(2-methoxyethoxy)-N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(2-methoxyethoxy)-N-[(3S)-5-(3-methylpyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(6-fluoropyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(2-methoxyethoxy)nicotinamide;
N-[(2R)-8-(2-fluoropyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(2-methoxyethoxy)nicotinamide;
N-[(2R)-8-(2-fluoropyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(tetrahydro-2H-pyran-4-yloxy)nicotinamide;
N-[(2R)-8-pyridazin-4-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(tetrahydro-2H-pyran-3-yloxy)nicotinamide;
N-[(2R)-8-(6-methylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-2-(tetrahydro-2H-pyran-3-yloxy)pyrimidine-5-carboxamide;
1-butyl-N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-2-oxo-1,2-dihydropyridine-4-carboxamide;
N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-2-(tetrahydrofuran-3-yloxy)pyrimidine-5-carboxamide;
1-butyl-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-2-oxo-1,2-dihydropyridine-4-carboxamide;
N-[(3S)-5-(6-fluoro-5-methylpyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-3-yloxy)nicotinamide;
1-butyl-N-[(3S)-5-(6-fluoro-5-methylpyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-2-oxo-1,2-dihydropyridine-4-carboxamide;
N-[(3S)-5-(6-fluoro-5-methylpyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-2-(tetrahydro-2H-pyran-3-yloxy)pyrimidine-5-carboxamide;
N-[(2S)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(tetrahydro-2H-pyran-4-yloxy)nicotinamide;
N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-4-yloxy)nicotinamide;
N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(tetrahydro-2H-pyran-4-yloxy)nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-3-yloxy)nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydrofuran-3-yloxy)nicotinamide;
N-[(2R)-8-(2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(tetrahydrofuran-3-yloxy)nicotinamide;
N-[(2R)-8-(2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(tetrahydro-2H-pyran-3-yloxy)nicotinamide;
N-[(2R)-8-(2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-(tetrahydrofuran-2-ylmethoxy)nicotinamide;
N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
6-(1,4-dioxan-2-ylmethoxy)-N-[(2R)-8-(2-fluoropyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]nicotinamide;
6-(1,4-dioxan-2-ylmethoxy)-N-[(3S)-5-(2-methoxypyridin-4-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(1,4-dioxan-2-ylmethoxy)-N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N5-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-N2-(3,3,3-trifluoropropyl)pyridine-2,5-dicarboxamide;
6-(but-2-yn-1-yloxy)-N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]nicotinamide;
N-[(3S)-5-imidazo[1,2-a]pyridin-6-yl-3,4-dihydro-2H-chromen-3-yl]-6-(tetrahydro-2H-pyran-4-yloxy)nicotinamide;
N2-(4,4-difluorocyclohexyl)-N5-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]pyridine-2,5-dicarboxamide;
N5-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(4,4,4-trifluorobutyl)pyridine-2,5-dicarboxamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-2-[2-(2,2,2-trifluoroethoxy)ethoxy]isonicotinamide;
N2-methyl-N5-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(2,2,2-trifluoroethyl)pyridine-2,5-dicarboxamide;
N5-[(3S)-5-(2-ethylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(3,3,3-trifluoropropyl)pyridine-2,5-dicarboxamide;
N-{(3S)-5-[6-(methylsulfonyl)pyridin-3-yl]-3,4-dihydro-2H-chromen-3-yl}-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
N-[(3S)-5-(6-cyanopyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
N-[(3S)-5-(2-cyclopropylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
N-[(3S)-5-(2-ethylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
N5-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(3,3,3-trifluoropropyl)pyridine-2,5-dicarboxamide;
N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
6-(cyclopentylsulfonyl)-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N-[(3S)-5-(6-methylpyrazin-2-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
N5-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(3,3,3-trifluoropropyl)pyridine-2,5-dicarboxamide;
6-(2-isopropoxyethoxy)-N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
6-(2-isopropoxyethoxy)-N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]nicotinamide;
N2-(3-isopropoxypropyl)-N5-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]pyridine-2,5-dicarboxamide;
N2-(3-isopropoxypropyl)-N5-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]pyridine-2,5-dicarboxamide;
N5-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(4,4,4-trifluorobutyl)pyridine-2,5-dicarboxamide;
N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
N-[(2R)-8-(2-methoxypyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-2-[2-(2,2,2-trifluoroethoxy)ethoxy]isonicotinamide;
N5-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-methyl-N2-(2,2,2-trifluoroethyl)pyridine-2,5-dicarboxamide;
N5-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-methyl-N2-(2,2,2-trifluoroethyl)pyridine-2,5-dicarboxamide;
N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[(2,2,2-trifluoroethoxy)methyl]nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[(2,2,2-trifluoroethoxy)methyl]nicotinamide;
N-[(3S)-5-(2-methoxypyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-2-[(3,3,3-trifluoropropyl)amino]pyrimidine-5-carboxamide;
N5-[(3S)-5-(2-cyclopropylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-methyl-N2-(2,2,2-trifluoroethyl)pyridine-2,5-dicarboxamide;
N5-[(3S)-5-(2-cyclopropylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-(3,3,3-trifluoropropyl)pyridine-2,5-dicarboxamide;
N5-[(3S)-5-(2-cyclopropylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-N2-methyl-N2-(3,3,3-trifluoropropyl)pyridine-2,5-dicarboxamide;
N-[(3S)-5-(2-cyclopropylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine-4-carboxamide;
N-[(3S)-5-(5-fluoro-6-methoxypyridin-3-yl)-3,4-dihydro-2H-chromen-3-yl]-2-[(3,3,3-trifluoropropyl)amino]pyrimidine-5-carboxamide;
N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-2-[(3,3,3-trifluoropropyl)amino]pyrimidine-5-carboxamide;
N-[(3S)-5-(3,5-dimethylpyrazin-2-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
N-[(3S)-5-(2-methylpyrimidin-5-yl)-3,4-dihydro-2H-chromen-3-yl]-6-[(2,2,2-trifluoroethoxy)methyl]nicotinamide;
2-methoxy-N,N-dimethyl-5-[(3S)-3-({[6-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-yl]carbonyl}amino)-3,4-dihydro-2H-chromen-5-yl]nicotinamide;
5-[(3S)-3-{[(6-isopropoxypyridin-3-yl)carbonyl]amino}-3,4-dihydro-2H-chromen-5-yl]-2-methoxy-N-methylnicotinamide;
2-methoxy-N-methyl-5-[(3S)-3-({[6-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-yl]carbonyl}amino)-3,4-dihydro-2H-chromen-5-yl]nicotinamide;
5-[(3S)-3-{[(6-isopropoxypyridin-3-yl)carbonyl]amino}-3,4-dihydro-2H-chromen-5-yl]-2-methoxy-N,N-dimethylnicotinamide;
2-methoxy-N,N-dimethyl-5-[(3S)-3-({[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]carbonyl}amino)-3,4-dihydro-2H-chromen-5-yl]nicotinamide;
N,N-dimethyl-5-{(3S)-3-[({6-[2-(2,2,2-trifluoroethoxy)ethoxy]pyridin-3-yl}carbonyl)amino]-3,4-dihydro-2H-chromen-5-yl}pyrimidine-2-carboxamide;
N-{(3S)-5-[6-(hydroxymethyl)pyridin-3-yl]-3,4-dihydro-2H-chromen-3-yl}-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide;
6-(3-fluoropropoxy)-N-{(3S)-5-[6-(hydroxymethyl)pyridin-3-yl]-3,4-dihydro-2H-chromen-3-yl}nicotinamide;
N-{(3S)-5-[6-(hydroxymethyl)pyridin-3-yl]-3,4-dihydro-2H-chromen-3-yl}-6-(2,2,2-trifluoroethoxy)nicotinamide;
and
N-{(3S)-5-[5-(hydroxymethyl)pyrazin-2-yl]-3,4-dihydro-2H-chromen-3-yl}-6-[2-(2,2,2-trifluoroethoxy)ethoxy]nicotinamide.

177 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/596,878Filed 22 Apr 2008
Priority: 23 Apr 2007
Published: 3 Jun 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 405/14
Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having…:…
A61P 17/04
Drugs for dermatological disorders: antipruritics
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids

Family

Application60/913,312Us provisional application · filed 23 Apr 2007
US 8,143,408 B2Related patent
US 2010/0137322 A1This patent

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

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Abstract

A compound of formula I or a pharmaceutically acceptable salt thereof, wherein:

formula I corresponds to:
X is O or CH2;
R1 is pyridinyl, pyrazolyl, isoxazolyl, pyrimidinyl, pyridazinyl, imidazopyridinyl, or pyrazinyl, wherein:
any such group may be independently mono-, di-, or tri-substituted with R11, R12, and/or R13;
R11, R12, and R13 are independently selected from halogen, C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, C1-6hydroxyalkyl, C3-6cycloalkyloxy, C3-6cycloalkylC1-6alkoxy, cyano, hydroxy, C1-6haloalkyl, C1-6haloalkoxy, C1-6haloalkoxyC1-6alkoxy, C1-6haloalkoxyC1-6alkyl, C1-6alkylsulfonic acid-, C1-6haloalkylsulfonic acid-, C3-6cycloalkylsulfonic acid-, C3-6halocycloalkylsulfonic acid-, C3-6cycloalkylC1-6alkylsulfonic acid-, C3-6halocycloalkylC1-6alkylsulfonic acid-, C1-6alkylsulfonyl-, C1-6haloalkylsulfonyl-, C3-6cycloalkylsulfonyl-, C3-6halocycloalkylsulfonyl-, C3-6cycloalkylC1-6alkylsulfonyl, C3-6halocycloalkylC1-6alkyl-sulfonyl, phenyl, phenylC1-6alkyl-, phenoxy, C1-6alkylphenyl-, C1-6alkoxyphenyl-, C1-6alkylamine, C1-6haloalkylamine, —C(O)NHC1-6 alkyl, —C(O)N(C1-6alkyl)2, and —C(O)NH2;
R2 is pyrazinyl, phenyl, pyridinyl, quinoxalinyl, triazolyl, pyridonyl, naphthyridinyl, pyrimidinyl, or quinolinyl, wherein:
any such group may be independently mono-, di-, or tri-substituted with R14, R15, and/or R16;
R14, R15, and R16 are independently selected from halogen, C1-6alkyl, C2-6alkenyl, C3-6alkynyl, C1-6alkoxy, C2-6alkenyloxy, C3-6alkynyloxy, C3-6cycloalkyl, C3-6heterocycloalkyl, C3-6cycloalkyloxy, C3-6heterocycloalkyloxy, C3-6cycloalkylC1-6alkoxy, C1-6alkyl-C3-6cycloalkylC1-6alkoxy, C3-6heterocycloalkylC1-6alkoxy, C1-6alkyl-C3-6heterocycloalkylC1-6alkoxy, C1-6alkoxyC1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6hydroxyalkyl, C1-6haloalkyl, C1-6haloalkoxy, C1-6haloalkoxyC1-6alkoxy, C1-6haloalkoxyC1-6alkyl, cyano, hydroxyl, NR4R5, C1-6alkylsulfonic acid-, C1-6haloalkylsulfonic acid-, C3-6cycloalkylsulfonic acid-, C3-6halocycloalkylsulfonic acid-, C3-6cycloalkylC1-6alkylsulfonic acid-, C3-6halocycloalkylC1-6alkylsulfonic acid-, C1-6alkylsulfonyl-, C1-6haloalkylsulfonyl-, C3-6cycloalkylsulfonyl-, C3-6halocycloalkylsulfonyl-, C3-6cycloalkyl-C1-6alkyl-sulfonyl, C3-6halocycloalkyl-C1-6alkyl-sulfonyl, phenyl, phenylC1-6alkyl-, phenoxy, C1-6alkylphenyl-, C1-6alkoxyphenyl-, —C(O)NR4R5, —C(O)C3-6cycloalkyl, —C(O)C3-6heterocycloalkyl, —C(O)C3-6cycloalkylC1-6alkoxy, —C(O)C3-6heterocycloalkylC1-6alkoxy, —C(O)C3-6cycloalkylC1-6alkyl, and —C(O)C3-6heterocycloalkylC1-6alkyl;
and
R4 and R5 are independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6alkoxyC1-6alkyl, C3-6cycloalkyl, C3-6halocycloalkyl, C3-6heterocycloalkyl, and C3-6heterocycloalkylC1-6alkyl.

7 more elements

Facts

Application

12/596,878Filed 22 Apr 2008

Priority

23 Apr 2007

Published

3 Jun 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 405/14
Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having…:…
A61P 17/04
Drugs for dermatological disorders: antipruritics
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids