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1. A chemical entity of Formula I: wherein: X is —CH— or —N—; Y is —O— or —S—; M is 0-5; R1 is each independently selected from the group consisting of: H, halo, —CN, —C1-6alkyl, —C1-6haloalkyl, —C1-6thioalkyl, —C1-6alkoxy, —C1-6haloalkoxy, —SO2C1-6alkyl, aryl, heteroaryl, and heterocycloalkyl; R3 and R4 are each independently selected from the group consisting of —H, halo, —C1-6alkyl, —C1-6haloalkyl, —CH2OH, —C1-6alkoxy, —C1-6haloalkoxy, aryl, optionally substituted 5 or 6 membered heteroaryl, —(C1-C6alkyl)aryl, —(C1-C6 alkyl)heteroaryl, and —(CR10R11)1-3NR12R13; or R3 and R4 taken together with the carbons to which they are attached form a saturated or unsaturated monocylic ring system, having the following structure: or R3 is ((2R,6S)-2,6-dimethylmorpholin-4-yl)methyl, ((2S,6R)-2,6-dimethylmorpholin-4-yl)methyl, (1,4-oxazepan-4-yl)methyl, (1,4-oxazepan-4-ylmethyl), (2,2-dimethylmorpholino)methyl, (3-hydroxyazetidin-1-yl)methyl, (4-(methylsulfonyl)piperazin-1-yl)methyl, (4-acetyl-1,4-diazepan-1-yl)methyl, (4-acetylpiperazin-1-yl)methyl, (4-ethyl-3-oxopiperazin-1-yl)methyl, (4-methylpiperazin-1-yl)methyl, [3-(2-fluorophenoxy)azetidin-1-yl]methyl, [4-(2-fluorophenyl)piperazin-1-yl]methyl, [4-(3-fluorophenyl)piperazin-1-yl]methyl, [4-(4-fluorophenyl)piperazin-1-yl]methyl, [4-(morpholin-4-yl)piperidin-1-yl]methyl, [4-(pyridin-4-yloxy)piperidin-1-yl]methyl, {1,1-difluoro-5-azaspiro [2.4]heptan-5-yl}methyl, 2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl, 4-thiomorpholine-1,1-dione, 7-oxa-2-azaspiro[3.5]nonan-2-ylmethyl, or morpholinomethyl, and R4 is H or —CH3; or R3 and R4 taken together with the carbons to which they are attached form a six member monocyclic ring system, wherein D is —N(R9)—, and R9 is H, —C1-6alkyl, —C1-6haloalkyl, —SO2CH3, benzyl, benzoyl, (3-chlorobenzyl), (4-chlorobenzyl), (3-chlorobenzoyl), (4-chlorobenzoyl), (2-fluorobenzyl), (4-fluorobenzyl), (pyridin-2-yl), (pyridin-2-ylmethyl), (pyridin-4-ylmethyl), (pyrimidin-2-ylmethyl), (pyrimidin-4-ylmethyl), (pyrazine-2-carbonyl), cyclopropylmethyl, (cyclopropanecarbonyl), (2,2-difluorocyclopropanecarbonyl), (tetrahydro-2H-pyran-4-yl)methyl, (oxetan-3-yl), (3-methyloxetan-3-yl)methyl, (tetrahydrofuran-3-yl)methyl, (tetrahydrofuran-3-carbonyl), (tetrahydro-2H-pyran-2-yl)methyl, (tetrahydro-2H-pyran-4-yl)methyl, (tetrahydro-2H-pyran-3-yl)methyl, (1-methyl-1H-imidazol-2-yl)methyl, (4-methylthiazol-5-yl)methyl, (5-methyl-1,3,4-thiadiazol-2-yl)methyl, (1,1-dioxidothietan-3-yl), (1,4-dioxan-2-yl)methyl), (5-oxotetrahydrofuran-2-yl)methyl, (1-methylpyrrolidine-3-carbonyl), (pyrrolidine-3-carbonyl), or (morpholin-2-ylmethyl); D is —O—, —N(R9)—, or a bond; m and n are each independently 0-4, with the proviso that the sum of m and n is 1-5 when D is —O—, —N(R9)—, or is 2-6 when D is a bond; and with the proviso that when D is a bond, R1 is not —Cl in the para position; R5, R6, R7, R8, are each independently selected from the group consisting of: —H, —F, —C1-6alkyl, —C1-6haloalkyl, —OH, —C1-6alkoxy, —C1-6haloalkoxy; R9 is selected from the group consisting of —H, —C1-6alkyl, —C1-6thioalkyl, —C1-6haloalkyl, —CO2C1-6alkyl, —SO2(C1-6alkyl), —C1-6alkyl(aryl), —C1-6alkyl(C3-6cycloalkyl), —C1-6alkyl(heterocycloalkyl), —C1-6alkyl(heteroaryl), heteroaryl, —CO(aryl), —CO(heteroaryl), —CO(heterocycloalkyl), —CO(C3-6cycloalkyl), wherein each aryl, cycloalkyl, heterocycloalkyl, heteroaryl are optionally unsubstituted or substituted with a member each independently selected from the group consisting of —H, —Cl, —F, and —CH3; R10 and R11 are each independently selected from the group consisting of —H, —F, —C1-6alkyl, —CF3 and —OH; R12 and R13 are each independently selected from the group consisting of —H, —C1-6 alkyl, —C3-6cycloalkyl, —C1-6alkyl(aryl), —C1-6alkyl(heteroaryl), —C1-6alkyl(heterocycloalkyl), —CH2CON(C1-6alkyl)2; or R12 is H or —C1-6alkyl and R13 is —CH3, —CH2CON(CH3)2, cyclopropyl, benzyl, 3-pyridyl, oxan-4-ylmethyl, 2,2-dimethyloxan-4-yl, (3-methyloxetan-3-yl)methyl, (tetrahydrofuran-2-yl)methyl or (tetrahydrofuran-3-yl)methyl; or R12 is H, —C1-6alkyl, R13 is —CH3, —CH2CON(CH3)2, cyclopropyl, benzyl, 3-pyridyl, (tetrahydrofuran-2-yl)methyl, (tetrahydrofuran-3-yl)methyl, oxan-4-ylmethyl, 2,2-dimethyloxan-4-yl or (3-methyloxetan-3-yl)methyl; or R12 and R13 are taken together with the nitrogen to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more R14, where each R14 is independently selected from the group consisting of —H, —C1-6alkyl, —CH2OH, —OH, —COCH3, —SO2CH3, —O-pyridyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, —O-phenyl, —O-(2-fluorophenyl), -morpholino, 1,1-difluoro-cyclopropyl, or two R14 members are taken together to form a —C3-6heterocycloalkyl; or R12 and R13 are taken together with the nitrogen to which they are attached to form a heterocycloalkyl ring selected from (2R,6S)-2,6-dimethylmorpholine, (2S,6R)-2,6-dimethylmorpholine, (3R,5 S)-3,5-dimethylpiperazine, 1,1-difluoro-5-azaspiro[2.4]heptane, 1,4-oxazepane, 2-(methoxymethyl)pyrrolidine, 2,2-dimethylmorpholine, 2,6-dimethylmorpholine, 2-ethylmorpholine, 2-methylmorpholine, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-(2-fluorophenoxy)azetidine, 3,3,4-trimethylpiperazine, 3,4-dimethylpiperazine, 3-hydroxyazetidine, 3-methylmorpholine, 3-oxopiperazine, 4-(2-fluorophenyl)piperazine, 4-(3-fluorophenyl)piperazine, 4-(4-fluorophenyl)piperazine, 4-(methylsulfonyl)piperazine, 4-(morpholin-4-yl)piperidine, 4-(pyridin-4-yloxy)piperidine, 4-acetyl-1,4-diazepane, 4-acetylpiperazine, 4-ethyl-3-oxopiperazine, 4-hydroxypiperidine, 4-isopropylpiperazine, 4-methyl-piperazine, 4-thiomorpholine-1,1-dione, 8-oxa-3-azabicyclo[3.2.1]octane, isoindoline, morpholine, octahydropyrrolo[1,2-a]pyrazine, piperazine, and pyrrolidine; wherein the chemical entity is selected from the group consisting of compounds of Formula (I), and pharmaceutically acceptable salts of compounds of Formula (I). |
