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US 2025/0019374 A1Published application
Protein tyrosine phosphatase inhibitors and methods of use thereof
AssigneesCalico Life Sciences LLC, AbbVie Inc.
InventorsAndrew Bogdan, Elliot P. Farney, Jennifer M. Frost, Philip R. Kym, Zhaoming Xiong, Naomi Anne Barton, Claire Anne Marie Cariou-Mumford, Christopher Patrick McMahon, Giuseppe Nano
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Abstract
The present invention provides for compounds of Formula (I) (I); wherein R2, X, and Z have any of the values defined herein, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of non-small cell lung cancer.
Claims16
A compound represented by Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- X is —O— or —N(Ra)—;
- Z is —O— or —N(R1)—;
- R1 is hydrogen or C1-6alkyl;
- R2 is selected from the group consisting of hydrogen, —C1-6alkyl, —C1-6alkylene-C3-6cycloalkyl, —C1-6alkylene-4-6 membered heterocyclyl, and —C1-6alkylene-phenyl;
- wherein —C1-6alkyl, —C1-6alkylene-C3-6cycloalkyl, —C1-6alkylene-4-6 membered heterocyclyl, and —C1-6alkylene-phenyl may optionally be substituted on one or more available carbons by one, two, three or more substituents each independently selected from Rg;
- wherein if —C1-6alkylene-4-6 membered heterocyclyl contains a substitutable ring nitrogen atom, that ring nitrogen atom may optionally be substituted by Rh;
- Rg is independently selected, for each occurrence, from the group consisting of halogen, hydroxyl, C1-6alkyl, phenyl, and C1-6alkoxy;
- wherein C1-6alkyl, phenyl, and C1-6alkoxy may optionally be substituted by one, two three or more substituents each independently selected from RP;
- Rh is C1-6alkyl-O—C(O)—;
- RP is independently selected, for each occurrence, from the group consisting of halogen, and hydroxyl;
- and
- Ra is selected from the group consisting of hydrogen and C1-6alkyl;
- wherein C1-6alkyl may optionally be substituted by one or more substituents each independently selected from the group consisting of halogen, cyano, oxo, hydroxyl, and C3-6cycloalkyl.
11 more elements
A compound selected from the group consisting of
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2S)-4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-(4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1-benzofuran-5-yl)-1′,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(2-cyclopentylethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(4-hydroxy-3,3-dimethylbutyl)amino]methyl}-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(3-hydroxy-3-methylbutyl)amino]methyl}-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-({[2-(3,3-difluorocyclobutyl)ethyl]amino}methyl)-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(4,4-difluorobutyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-({[2-(oxolan-3-yl)ethyl]amino}methyl)-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-4-fluoro-6-hydroxy-2-[(propylamino)methyl]-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-2-[(dipropylamino)methyl]-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-2-[(butylamino)methyl]-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-2-[(ethylamino)methyl]-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(cyclopentylmethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-({[(oxan-4-yl)methyl]amino}methyl)-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(2-methylbutyl)amino]methyl}-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(cyclopropylmethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[bis(cyclopropylmethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(cyclobutylmethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-({[(oxetan-3-yl)methyl]amino}methyl)-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-4-fluoro-6-hydroxy-2-[({2-[1-(hydroxymethyl)cyclobutyl]ethyl}amino)methyl]-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-4-fluoro-6-hydroxy-2-[({2-[1-(hydroxymethyl)cyclopentyl]ethyl}amino)methyl]-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-({[3-(2,2-difluoroethoxy)propyl]amino}methyl)-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- tert-butyl 4-[({[(2R)-4-fluoro-6-hydroxy-5-(1,1,4-trioxo-1λ6,2,5-thiadiazolidin-2-yl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amino)methyl]piperidine-1-carboxylate;
- 5-[(2R)-4-fluoro-6-hydroxy-2-({[2-(oxan-4-yl)ethyl]amino}methyl)-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-2-[({[(1RS,5SR)-bicyclo[3.1.0]hexan-6-yl]methyl}amino)methyl]-4-fluoro-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(3-phenylpropyl)amino]methyl}-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-({[2-(2,6,6-trimethylcyclohex-1-en-1-yl)ethyl]amino}methyl)-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-({[(3-phenylcyclobutyl)methyl]amino}methyl)-2,3-dihydro-1-benzofuran-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-4-fluoro-6-hydroxy-2-[({[4-(trifluoromethyl)cyclohexyl]methyl}amino)methyl]-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-4-fluoro-2-[({[1-(fluoromethyl)cyclopropyl]methyl}amino)methyl]-6-hydroxy-2,3-dihydro-1-benzofuran-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2S)-4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(2-ethylbutyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-4-fluoro-6-hydroxy-2-[(propylamino)methyl]-2,3-dihydro-1H-indol-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(2-methoxyethyl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(cyclobutylmethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-({[(oxan-4-yl)methyl]amino}methyl)-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(3-methylbutyl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(3,3-difluoropropyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(3,3,3-trifluoropropyl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(2-methylbutyl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-({[(3,3-difluorocyclobutyl)methyl]amino}methyl)-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[4-fluoro-6-hydroxy-2-({[2-(oxetan-3-yl)ethyl]amino}methyl)-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-(2-{[(4,4-difluorobutyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl)-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(cyclopentylmethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(cyclopropylmethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[(pentan-2-yl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-({[(2R)-butan-2-yl]amino}methyl)-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-2-[(butylamino)methyl]-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-(hydroxymethyl)-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(2-cyclopropylethyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-2-{[(3,3-dimethylbutyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-{(2R)-4-fluoro-6-hydroxy-2-[({[3-(propan-2-yl)cyclobutyl]methyl}amino)methyl]-2,3-dihydro-1H-indol-5-yl}-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-2-{[methyl(2-methylpropyl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- 5-[(2R)-4-fluoro-6-hydroxy-1-methyl-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- and
- 5-[(2R)-2-{[(3,3-difluoro-2-hydroxypropyl)amino]methyl}-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione;
- or a pharmaceutically acceptable salt thereof.
57 more elements
Dependencies are inferred from the claim text.