Novel molecular glue and application thereof

Abstract

The invention relates to a novel compound capable of being used as molecular glue or an enantiomer compound thereof, and a preparation method and application of the novel compound or the enantiomer compound.

Description

Technical Field

[0001] The invention relates to a novel compound capable of acting as molecular glue or its enantiomer, and a preparation method and use thereof. Background Art

[0002] Targeted Protein Degradation (TPD) refers to a mechanism that directly decomposes and eliminates pathogenic factors after translation into proteins, represented by targeted protein degradation chimeras (PROTACs). PROTACs consist of a protein of interest (POI) binding moiety (equivalent to the substrate protein connection region), a linker, and an E3 ligase binding moiety (equivalent to the enzyme connection region). The core of PROTAC technology is to allow the corresponding substrate of the TPD mechanism to directly meet the E3 ligase.

[0003] Molecular glue is a substance with different properties from PROTAC. It is a small molecule that can interact with various unpredictable target proteins. PROTAC is a divalent molecule composed of two parts, one part binds to POI and the other part binds to E3 ligase. These parts are connected by a linker and have a relatively large molecular weight, but molecular glue is smaller than PROTAC and has better pharmacological properties, higher membrane permeability, and better cell absorption rate than PROTAC.

[0004] Various types of molecular glues have been discovered, representative examples of which include thalidomide-related analogs, lenalidomide and pomalidomide targeting the E3 ligase hydroxycerebroside (CRBN).

[0005] Since safety and drug resistance are important considerations in the development of anticancer drugs, it is necessary to develop immunomodulators that minimize side effects and long-term complications while having a good safety profile. Traditional anticancer drugs, especially chemotherapy drugs and targeted therapy drugs, work by attacking tumor cells. Chemotherapeutic drugs (such as cisplatin and doxorubicin) mainly target rapidly dividing cells, so they affect not only cancer cells but also normal cells, causing serious side effects, while targeted therapy drugs (such as imatinib, a tyrosine kinase inhibitor) prevent cancer cell growth by inhibiting specific proteins, but there is a problem of drug resistance when used for a long time.

[0006] Since molecular glue works by eliminating the target protein itself rather than inhibiting its function, it has great potential to overcome the problem of mutation resistance. In addition, since it is the fundamental removal of the protein rather than simple inhibition, the therapeutic effect can be maintained continuously, and since it does not require the administration of high doses of drugs, molecular glue may be less toxic and safer than existing anti-cancer drugs. Summary of the invention

[0007] The present invention aims to provide a novel compound or an enantiomer compound thereof that can act as a molecular glue. Furthermore, the above compound can be used to prevent or treat cancer, more specifically, it is intended to be used to prevent or treat liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, rectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0008] [1] In one aspect of the present invention, the present invention relates to a compound represented by the following Chemical Formula 1 or an enantiomer compound thereof:

[0009] Chemical formula 1:

[0010] The above R 1 is an alkyl group, a saturated or unsaturated cycloalkyl group, an aromatic or non-aromatic heterocyclic group, an aryl group or an -alkyl-C(═O)—O-alkyl group,

[0011] The above alkyl group may be substituted by one or more alkoxy groups or hydroxy groups,

[0012] The above heterocyclic group or aryl group may be replaced by one or more alkyl, hydroxyl, halogen, alkoxy, -(C=0)-O-alkyl, -CF 3 、-OCF 3 , -S-alkyl, -S(O 2 )-alkyl or -S(O 2 )NH 2 Substituted or unsubstituted.

[0013] [2] In [1] above, R 1The group may be an alkyl group having 1 to 7 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an aromatic or non-aromatic heterocyclic group having a 5 to 12-membered ring containing a heteroatom selected from the group consisting of N, O and S, or an aryl group having 6 to 12 carbon atoms.

[0014] [3] In [1] above, R 1 It may be a substituted or unsubstituted alkyl group having 1 to 5 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 5 carbon atoms, a substituted or unsubstituted dihydrobenzofuran or pyridine, a substituted or unsubstituted phenyl group, or an -alkyl-(C=0)-O-alkyl group having 1 to 5 carbon atoms.

[0015] [4] In [1] above, the above R 1 It may be an alkyl group having 1 to 3 carbon atoms substituted with a hydroxyl group, an unsubstituted alkyl group having 3 to 5 carbon atoms, or a phenyl group substituted with a methoxy group.

[0016] [5] In the above [1], the compound represented by Chemical Formula 1 may be any one selected from the group consisting of:

[0017] 1) (3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester;

[0018] 2)(3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester;

[0019] 3) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione;

[0020] 4) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione;

[0021] 5) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentan-2-yl)amino)isoindoline-1,3-dione;

[0022] 6) 2-(2,6-dioxopiperidin-3-yl)-4-((3-methylbutan-2-yl)amino)isoindoline-1,3-dione;

[0023] 7) 4-((3,3-dimethylbutan-2-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0024] 8) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-methoxypropan-2-yl)amino)isoindoline-1,3-dione;

[0025] 9) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0026] 10) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0027] 11) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0028] 12) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0029] 13) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0030] 14) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0031] 15) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0032] 16) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0033] 17) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0034] 18) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0035] 19) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0036] 20) 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzenesulfonamide;

[0037] 21) methyl 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate;

[0038] 22) methyl 4-((1S)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate;

[0039] 23) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione;

[0040] 24) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(p-methylphenyl)ethyl)amino)isoindoline-1 ,3-diketone;

[0041] 25) 4-(((R)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0042] 26) 4-(((S)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0043] 27) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0044] 28) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0045] 29) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0046] 30) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0047] 31) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0048] 32) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0049] 33) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0050] 34) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0051] 35) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-ethoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0052] 36) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0053] 37) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0054] 38) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0055] 39) 4-(((R)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0056] 40) 4-(((S)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0057] 41) 4-(((R)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0058] 42) 4-(((S)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0059] 43) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione;

[0060] 44) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione;

[0061] 45) 4-(((R)-1-(3,5-dimethoxyphenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0062] 46) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0063] 47) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione;

[0064] 48) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione;

[0065] 49) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0066] 50) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0067] 51) 4-(((R)-1-(2,3-dihydrobenzofuran-5-yl)ethyl)amino)-2-(2,6-dioxopiperidine-3 -yl)isoindoline-1,3-dione; and

[0068] 52) 4-(((S)-1-Cyclopropylethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

[0069] [6] In the above [1], the compound represented by Chemical Formula 1 may be 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropane-2-yl)amino)isoindoline-1,3-dione, 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentane-2-yl)amino)isoindoline-1,3-dione, or 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione.

[0070] [7] In another aspect of the present invention, the present invention relates to a pharmaceutical composition for preventing or treating cancer, comprising the compound represented by Chemical Formula 1 or its enantiomer compound of the above-mentioned [1] as an active ingredient,

[0071] The cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0072] [8] In the above [7], the cancer may be a relapsed or refractory cancer.

[0073] [9] In the above [7], the cancer may be a drug-resistant cancer.

[0074]

[10] In the above [7], the above active ingredient may be any one selected from the group consisting of:

[0075] 1) (3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester;

[0076] 2)(3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester;

[0077] 3) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione;

[0078] 4) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione;

[0079] 5) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentan-2-yl)amino)isoindoline-1,3-dione;

[0080] 6) 2-(2,6-dioxopiperidin-3-yl)-4-((3-methylbutan-2-yl)amino)isoindoline-1,3-dione;

[0081] 7) 4-((3,3-dimethylbutan-2-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3 -dione;

[0082] 8) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-methoxypropan-2-yl)amino)isoindoline-1,3-dione;

[0083] 9) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0084] 10) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0085] 11) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0086] 12) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0087] 13) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0088] 14) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0089] 15) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0090] 16) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0091] 17) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0092] 18) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0093] 19) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0094] 20) 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino) ethyl)benzenesulfonamide;

[0095] 21) methyl 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate;

[0096] 22) methyl 4-((1S)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate;

[0097] 23) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione;

[0098] 24) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione;

[0099] 25) 4-(((R)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0100] 26) 4-(((S)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0101] 27) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0102] 28) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0103] 29) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0104] 30) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0105] 31) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0106] 32) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0107] 33) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0108] 34) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylthio)phenyl)ethyl)amino)isoindole 1,3-dione;

[0109] 35) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-ethoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0110] 36) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0111] 37) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0112] 38) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0113] 39) 4-(((R)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0114] 40) 4-(((S)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0115] 41) 4-(((R)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0116] 42) 4-(((S)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0117] 43) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione;

[0118] 44) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione;

[0119] 45) 4-(((R)-1-(3,5-dimethoxyphenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0120] 46) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0121] 47) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione;

[0122] 48) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione;

[0123] 49) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0124] 50) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0125] 51) 4-(((R)-1-(2,3-dihydrobenzofuran-5-yl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; and

[0126] 52) 4-(((S)-1-Cyclopropylethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

[0127]

[11] In the above [7], the active ingredient may be 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropane-2-yl)amino)isoindoline-1,3-dione, 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentane-2-yl)amino)isoindoline-1,3-dione, or 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione.

[0128]

[12] In the above [7], the above composition can be administered by intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal injection, oral administration, topical administration, intranasal injection, intrapulmonary injection or rectal administration.

[0129]

[13] In another aspect of the present invention, the present invention relates to a method for preventing or treating cancer in a subject, comprising the step of administering to the subject the compound represented by Chemical Formula 1 or its enantiomer compound of the above-mentioned [1],

[0130] The cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0131]

[14] In another aspect of the present invention, the present invention relates to a use of a compound represented by Chemical Formula 1 or an enantiomer compound of the above-mentioned [1] in the preparation of a drug for preventing or treating cancer,

[0132] The cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0133]

[15] In another aspect of the present invention, the present invention relates to a compound represented by Chemical Formula 1 of [1] or an enantiomer thereof for use in preventing or treating cancer,

[0134] The cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0135] The present invention relates to a novel compound or an enantiomer compound thereof that can act as a molecular glue. The compound is a molecular glue that can minimize side effects and long-term complications and can be effectively used to prevent or treat cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0136] Figure 1 The results of the Ames Test of the compounds of the present invention in TA98 and TA100 strains are shown.

[0137] Figure 2The results of hERG Related Cardiotoxicity test and Ligand Binding Assay of the compounds of the examples of the present invention are shown.

[0138] Figure 3 The figure shows the change in body weight after injection of the compound of the examples of the present invention in the MTD test.

[0139] Figure 4 The figure is used to confirm the cell death effect of the compounds of the examples of the present invention in liver cancer cell lines (Huh7, Hep3B, SNU 449 and SNU475).

[0140] Figure 5 Dose-response curves in various cancer cells are shown.

[0141] Figure 6 Shown are dose response curves in liver cancer cell lines (Huh7 and Hep3B).

[0142] Figure 7 Shown are dose response curves in non-small cell lung cancer cell lines (NCI-H460 and NCI-H1299).

[0143] Figure 8 Shown are dose response curves in pancreatic cancer cell lines (PANC-1 and Mia-Paca-2).

[0144] Fig. 9 Shown are dose response curves in colorectal cancer cell lines (HT29 and HCT116).

[0145] Fig.10 Shown are dose response curves in a gastric adenocarcinoma cell line (AGS).

[0146] Fig.11 Shown are dose response curves in a malignant melanoma cell line (A375).

[0147] Fig.12 Shown are dose response curves in an adenocarcinoma cell line (MDA-MB-231).

[0148] Fig.13 and Fig.14 The results of CRBN affinity test of the compounds of the examples of the present invention are shown.

[0149] Best Mode for Carrying Out the Invention

[0150] The terminology used in this specification is used to appropriately express the preferred embodiments of the present invention, and the definition of these terms should be based on the content of the full text of this specification. Throughout the specification, when a certain part "includes" a certain structural element, this means that it can also include other structural elements rather than excluding other structural elements, unless clearly stated to the contrary.

[0151] Unless otherwise defined, all technical terms used in the present invention have the same meanings as those generally understood by those skilled in the art in the relevant field of the present invention. In addition, preferred methods and samples are described in this specification, but similar or equivalent methods are also included in the scope of the present invention.

[0152] In one aspect, the present invention relates to a compound represented by the following Chemical Formula 1 or an enantiomer compound thereof:

[0153] Chemical formula 1:

[0154] The above R 1 is an alkyl group, a saturated or unsaturated cycloalkyl group, an aromatic or non-aromatic heterocyclic group, an aryl group or an -alkyl-C(═O)—O-alkyl group,

[0155] The above alkyl group may be substituted by one or more alkoxy groups or hydroxy groups,

[0156] The above heterocyclic group or aryl group may be replaced by one or more alkyl, hydroxyl, halogen, alkoxy, -(C=0)-O-alkyl, -CF 3 、-OCF 3 , -S-alkyl, -S(O 2 )-alkyl or -S(O 2 )NH 2 Substituted or unsubstituted.

[0157] In the present invention, unless otherwise specified, "alkyl" refers to a straight chain or branched saturated hydrocarbon residue. In one aspect of the present invention, the alkyl group may be C 1-7 Alkyl refers to an alkyl group having a skeleton consisting of 1 to 7 carbon atoms. 1-7 The alkyl group may be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, tert-pentyl, sec-pentyl, neopentyl, hexyl, heptyl, or the like.

[0158] In the present invention, "cycloalkyl" refers to a cyclic hydrocarbon residue, including saturated or unsaturated cycloalkyl. In one aspect of the present invention, the cycloalkyl may include a ring having a skeleton consisting of 3 to 7 carbons. Specifically, the cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl.

[0159] In the present invention, "aromatic or non-aromatic heterocyclic group" refers to a ring system containing one or more aromatic or non-aromatic rings containing one or more double bonds, wherein one or more atoms are heteroatoms independently selected from O, S, N and P, and the remaining ring atoms are carbon atoms. In one aspect of the present invention, the above-mentioned heterocyclic group can be an aromatic or non-aromatic heterocyclic group of 5 to 12 members containing a heteroatom selected from the group consisting of N, O and S. For example, the above-mentioned heterocyclic group can be benzofuran, dihydrobenzofuran, pyridine, pyrrolidine, piperidine or pyrimidine, but is not limited thereto.

[0160] In the present invention, a "saturated" compound refers to a compound in which all carbon-carbon bonds consist of only single bonds, and an "unsaturated" compound refers to a compound containing one or more double bonds or triple bonds.

[0161] In the present invention, "aryl" refers to a monocyclic aromatic group and / or a polycyclic aromatic group containing one or more aromatic hydrocarbon rings. In one aspect of the present invention, it may include a ring having a skeleton consisting of 6 to 12 carbons. Examples of aryl include, but are not limited to, phenyl, naphthyl, and azulenyl.

[0162] In the present invention, "halogen" refers to F, Cl, Br or I unless otherwise specified.

[0163] In the present invention, unless otherwise specified, "alkoxy" refers to a straight chain or branched alkyl-oxy residue. In one aspect of the present invention, the above-mentioned alkoxy may be "C 1-6 "Alkoxy" refers to an alkyl-oxy group having a skeleton consisting of 1 to 6 carbon atoms. Specifically, C 1-6 The alkoxy group may include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy, isopentoxy, tert-pentoxy, sec-pentoxy, neopentoxy, hexoxy and the like.

[0164] In the present invention, "substitution" means that a hydrogen atom bonded to a carbon atom in the structure is replaced by another substituent, and the substituted position is not limited to the position where the hydrogen atom is substituted, that is, there is no limitation on the substituent as long as it is any position that can be substituted, and if substituted at two or more positions, the two or more substituents may be the same or different from each other.

[0165] Furthermore, the compounds of the present invention may have a chiral carbon center and thus may exist as R or S isomers, racemic compounds, individual enantiomers or mixtures, individual diastereomers or mixtures, all of which stereoisomers and mixtures thereof may fall within the scope of the present invention.

[0166] In one embodiment of the present invention, the R 1It may be an alkyl group having 1 to 7 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an aromatic or non-aromatic heterocyclic group having a 5 to 12-membered ring containing a heteroatom selected from the group consisting of N, O and S, or an aryl group having 6 to 12 carbon atoms.

[0167] In one embodiment of the present invention, the R 1 It may be a substituted or unsubstituted alkyl group having 1 to 5 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 5 carbon atoms, a substituted or unsubstituted dihydrobenzofuran or pyridine, a substituted or unsubstituted phenyl group, or an -alkyl-(C=0)-O-alkyl group having 1 to 5 carbon atoms.

[0168] In one embodiment of the present invention, the R 1 It may be an alkyl group having 1 to 3 carbon atoms substituted with a hydroxyl group, an unsubstituted alkyl group having 3 to 5 carbon atoms, or a phenyl group substituted with a methoxy group.

[0169] In one embodiment of the present invention, the compound represented by Chemical Formula 1 may be any one selected from the group consisting of:

[0170] 1) (3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester;

[0171] 2)(3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester;

[0172] 3) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione;

[0173] 4) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione;

[0174] 5) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentan-2-yl)amino)isoindoline-1,3-dione;

[0175] 6) 2-(2,6-dioxopiperidin-3-yl)-4-((3-methylbutan-2-yl)amino)isoindoline-1,3-dione;

[0176] 7) 4-((3,3-dimethylbutan-2-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0177] 8) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-methoxypropan-2-yl)amino)isoindoline-1,3-dione;

[0178] 9) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0179] 10) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0180] 11) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0181] 12) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0182] 13) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0183] 14) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0184] 15) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0185] 16) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0186] 17) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0187] 18) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0188] 19) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0189] 20) 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzenesulfonamide;

[0190] 21) methyl 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate;

[0191] 22) methyl 4-((1S)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate;

[0192] 23) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione;

[0193] 24) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione;

[0194] 25) 4-(((R)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0195] 26) 4-(((S)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0196] 27) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0197] 28) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0198] 29) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0199] 30) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0200] 31) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0201] 32) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0202] 33) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylthio)phenyl)ethyl)amino)isoindole Indole-1,3-dione;

[0203] 34) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0204] 35) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-ethoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0205] 36) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0206] 37) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0207] 38) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0208] 39) 4-(((R)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0209] 40) 4-(((S)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0210] 41) 4-(((R)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0211] 42) 4-(((S)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0212] 43) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione;

[0213] 44) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione;

[0214] 45) 4-(((R)-1-(3,5-dimethoxyphenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0215] 46) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0216] 47) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione;

[0217] 48) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione;

[0218] 49) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0219] 50) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0220] 51) 4-(((R)-1-(2,3-dihydrobenzofuran-5-yl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; and

[0221] 52) 4-(((S)-1-Cyclopropylethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

[0222] In one embodiment of the present invention, the compound represented by Chemical Formula 1 of the present invention may be 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropane-2-yl)amino)isoindoline-1,3-dione, 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentane-2-yl)amino)isoindoline-1,3-dione, or 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione.

[0223] In one embodiment of the present invention, the compound represented by the chemical formula 1 of the present invention can act as a molecular glue. Specifically, the compound represented by the chemical formula 1 can be a molecular glue substance that binds to hydroxycerebroside (Cerebl on or CRBN) protein and exerts an anti-cancer effect through an immunomodulatory imidone drug (ImiD) mechanism.

[0224] In one embodiment of the present invention, the protein used as the endogenous target protein of the immunomodulator can be CRBN protein. CRBN protein forms an E3 ubiquitin ligase complex with DNA damage binding protein 1 (DD B1), Cullin-4A (CUL4A) and Cullin 1 regulatory factor (ROC1), which ubiquitinates many different proteins. CRBN protein is a substrate receptor of CRL4, one of the E3 ubiquitin ligases. CRL4 / CRBN can regulate the intracellular homeostasis of a variety of important intracellular proteins through ubiquitin-dependent degradation, and can directly bind to AMPK, which can cause a variety of metabolic diseases such as cancer. In addition, CRBN protein may also play a negative regulatory role in CD4+T cell activation. CRBN deficiency increases the activation of CD4+T cells and enhances the secretion of IL-2, inducing CD4+T cells to differentiate into Th17 cells. Enhanced T cell activation sometimes leads to T cell-mediated autoimmune diseases such as autoimmune encephalomyelitis and delayed-type hypersensitivity reactions.

[0225] In another aspect, the present invention relates to a pharmaceutical composition for preventing or treating cancer, comprising the compound represented by Chemical Formula 1 or its enantiomer compound as an effective ingredient, wherein the cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, rectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0226] In the present invention, "treatment" refers to all actions to improve or beneficially change the symptoms of a disease by administering the composition according to the present invention, "prevention" refers to all actions to inhibit or delay a disease by administering the composition according to the present invention, and "improvement" refers to all actions to improve the adverse conditions of a disease by administering the composition of the present invention to an individual or allowing the individual to ingest the composition of the present invention.

[0227] The disease to be "treated", "prevented" or "improved" in the present invention may be cancer. Cancer refers to a physiological condition in animals, usually characterized by abnormal or uncontrolled cell growth. Cancer and cancer pathology may be associated with, for example, metastasis, interference with the normal function of surrounding cells, release of cytokines or other secretory products at abnormal levels, suppression or enhancement of inflammation or immune response, neoplasia and premalignant lesions, and malignancies.

[0228] In one embodiment of the present invention, the cancer may be a relapsed or refractory cancer.

[0229] In one embodiment of the present invention, the cancer may be a drug-resistant cancer.

[0230] The pharmaceutical composition of the present invention can be administered with the therapeutically effective amount of the above-mentioned active ingredient. The above-mentioned therapeutically effective amount refers to the drug dosage that exerts an effective cancer prevention or treatment effect. The appropriate total daily usage can be determined by the attending physician within the scope of reasonable medical judgment. The specific therapeutically effective amount for a particular patient can be applied differently according to various factors and similar factors well-known in the medical field, including the type and degree of the reaction to be achieved, the type and amount of the drug to be administered in combination, the specific composition (including whether to use other preparations as appropriate), the patient's age, weight, general health, sex and diet, administration time, administration route, treatment cycle.

[0231] The pharmaceutical composition of the present invention can be administered to a subject or individual by any route of administration, for example, by intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal injection, oral administration, topical administration, intranasal injection, intrapulmonary injection or rectal administration. Preferably, the pharmaceutical composition of the present invention can be used for oral administration or intravenous administration.

[0232] In one embodiment of the present invention, the active ingredient of the pharmaceutical composition may be any one selected from the group consisting of:

[0233] 1) (3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester;

[0234] 2)(3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester;

[0235] 3) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione;

[0236] 4) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione;

[0237] 5) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentan-2-yl)amino)isoindoline-1,3-dione;

[0238] 6) 2-(2,6-dioxopiperidin-3-yl)-4-((3-methylbutan-2-yl)amino)isoindoline-1,3-dione;

[0239] 7) 4-((3,3-dimethylbutan-2-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0240] 8) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-methoxypropan-2-yl)amino)isoindoline-1,3-dione;

[0241] 9) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0242] 10) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0243] 11) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0244] 12) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindole 1,3-dione;

[0245] 13) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0246] 14) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0247] 15) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0248] 16) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0249] 17) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0250] 18) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0251] 19) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0252] 20) 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzenesulfonamide;

[0253] 21) methyl 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate;

[0254] 22) methyl 4-((1S)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate;

[0255] 23) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione;

[0256] 24) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione;

[0257] 25) 4-(((R)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0258] 26) 4-(((S)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0259] 27) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0260] 28) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0261] 29) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0262] 30) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0263] 31) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0264] 32) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0265] 33) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0266] 34) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0267] 35) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-ethoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0268] 36) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0269] 37) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione;

[0270] 38) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0271] 39) 4-(((R)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindole 1,3-dione;

[0272] 40) 4-(((S)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0273] 41) 4-(((R)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0274] 42) 4-(((S)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0275] 43) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione;

[0276] 44) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione;

[0277] 45) 4-(((R)-1-(3,5-dimethoxyphenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

[0278] 46) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione;

[0279] 47) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione;

[0280] 48) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione;

[0281] 49) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0282] 50) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione;

[0283] 51) 4-(((R)-1-(2,3-dihydrobenzofuran-5-yl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; and

[0284] 52) 4-(((S)-1-Cyclopropylethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

[0285] In one embodiment of the present invention, the above-mentioned active ingredient can be 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropane-2-yl)amino)isoindoline-1,3-dione, 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentane-2-yl)amino)isoindoline-1,3-dione, or 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione.

[0286] In another aspect, the present invention relates to a method for preventing or treating cancer in a subject, comprising the step of administering to the subject the compound represented by Chemical Formula 1 or its enantiomer compound, wherein the cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, rectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0287] In the present invention, the term "subject" is used synonymously with "individual", and the subject may be a mammal, such as a human, mouse, cow, horse, pig, dog, sheep, goat or cat.

[0288] The contents repeated with the aforementioned pharmaceutical composition of the present invention will be omitted.

[0289] In another aspect, the present invention relates to a use of the compound represented by Chemical Formula 1 or an enantiomer thereof in the preparation of a drug for preventing or treating cancer.

[0290] The cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0291] The contents repeated with the aforementioned pharmaceutical composition of the present invention will be omitted.

[0292] In another aspect, the present invention relates to a use of the compound represented by Chemical Formula 1 or an enantiomer compound thereof in preventing or treating cancer.

[0293] The cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

[0294] The contents repeated with the aforementioned pharmaceutical composition of the present invention will be omitted.

[0295] All matters mentioned in the compositions, methods of treatment and uses of the present invention are equally applicable unless they are inconsistent with each other.

[0296] Preferred embodiments are presented below to help understand the present invention. However, the following embodiments are merely illustrative of the present invention. It is obvious to those skilled in the art that various deformations and modifications can be made within the scope of the scope and technical idea of ​​the present invention, and these deformations and modifications naturally fall within the scope of the appended claims. DETAILED DESCRIPTION

[0297] Example

[0298] The novel compound of the present invention can be prepared according to the following reaction formula 1, but is not limited thereto.

[0299] Reaction 1:

[0300]

[0301] At room temperature, 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione (starting material 1, 1 equivalent, purchased from EOS, China), Amine (2 equivalents, purchased from Aldrich) and N,N-Diisopropylethylamine (DIPEA, 2 equivalents, purchased from Aldrich) were added to dimethyl sulfoxide (DMSO, purchased from Aldrich, 8 times the volume of starting material 1) solvent. Then the temperature was raised to 120°C, analyzed by HPLC, and stirred for about 5 to 8 hours until less than 5% of the starting material remained. After the reaction was completed, it was slowly cooled to room temperature, purified water (twice the amount of DMSO) was slowly added, and the resulting solid was filtered under reduced pressure. The obtained solid was recrystallized from isopropanol to obtain a solid with a purity of 98% or more.

[0302] As shown in Table 1 below, the compounds of the examples were prepared by the above method, and the type of amine in the above reaction formula 1 was changed during the process.

[0303] Table 1

[0304]

[0305]

[0306]

[0307]

[0308]

[0309]

[0310]

[0311]

[0312]

[0313]

[0314]

[0315]

[0316]

[0317]

[0318]

[0319]

[0320] Table 2 below shows the NMR and MS data for the compounds in Table 1 above.

[0321] Table 2

[0322]

[0323]

[0324]

[0325]

[0326]

[0327]

[0328]

[0329]

[0330]

[0331]

[0332]

[0333]

[0334]

[0335]

[0336]

[0337]

[0338]

[0339]

[0340]

[0341] Experimental example

[0342] Experimental Example 1: Microbial Mutagenicity Assay (Microbial Mutagenicity Assay) - Ames Test

[0343] In order to evaluate the safety of the compound (AST-DT-218) prepared in the example, the possibility of causing gene mutation was confirmed. First, TA98 and TA100 strains for detecting frameshift mutation and point mutation were cultured, AST-DT-218 was dissolved in a solvent and diluted to various concentrations (20.5μg / ml, 61.7μg / ml, 185.1μg / ml, 1555.5μg / ml, 1666.6μg / ml, 5000μg / ml), and an S9 mixture containing liver enzyme extract and auxiliary agents (metabolic activation system; concentration 30%) was prepared. According to the concentration of AST-DT-218, (i) TA98 strain without S9 mixture (TA98-S9), (ii) TA98 strain mixed with S9 mixture (TA98+S9), (iii) TA100 strain without S9 mixture (TA100-S9), (iv) TA100 strain mixed with S9 mixture (TA100+S9) were inoculated in histidine deficiency medium. As a negative control group, i.e., solvent control group (Solvent Control), only the solvent was inoculated into the histidine deficiency medium, and only the pure solvent was used in the absence of the compound. As a positive control group (Positive control), 2-nitrofluorene (2-NF), 2-aminoanthracene (2-AA), 4-nitroquinoline-1-oxide (4-NQO) were inoculated into the histidine deficiency medium. After culturing in each medium for 48 to 72 hours, the mutation rate was calculated by counting the number of clones generated, and the effect on metabolic activation was analyzed by comparing the mutation induction effect depending on the presence or absence of the S9 mixture. The results are shown in Tables 3 and Figure 1 shown.

[0344] Table 3

[0345]

[0346] It was observed that the number of mutant clones in the positive control group (2-NF, 2-AA and 4-NQO) increased significantly, while in the AST-DT-218-treated group, no significant increase in the number of mutant clones was observed within the concentration range of the experimental conditions, regardless of the presence or absence of the S9 mixture in the TA98 and TA100 strains. Therefore, it was confirmed that AST-DT-218 does not cause gene mutations.

[0347] Experimental Example 2: hERG Related Cardiotoxicity Test and Ligand Binding Assay

[0348] In order to evaluate the inhibitory effect of AST-DT-218 on hERG channels and confirm the possibility of causing cardiotoxicity, an hERG-Related Cardiotoxicity test was performed using an automated patch clamp. First, the hERG channel-expressing cell line (CHO) was cultured, and AST-DT-218 was dissolved in a solvent (DMSO) and diluted to a concentration (1 μM). The cells were mounted on a patch-clamp device, and the electrical activity of the hERG channel was recorded by measuring the voltage-dependent current. The inhibitory effect was calculated as the current reduction rate, and the IC was derived by creating a concentration-response curve. 50 value.

[0349] In addition, a ligand binding assay was performed to measure the binding affinity of AST-DT-218 to the hERG channel. First, the hERG channel expressing cell line (HEK293) was cultured, and then the cells were centrifuged to extract the cell membrane, and the membrane protein was prepared using a cell lysis reagent. Prepare the labeled hERG ligand, and dissolve AST-DT-218 in a solvent (DMSO) and dilute to a concentration (1 μM). After the cell membrane protein is dispensed into a 96-well plate or appropriate experimental equipment, a competitive binding experiment is performed by adding different concentrations of AST-DT-218 to each well and incubating for 1 to 2 hours. After the binding is completed, in order to separate the unbound ligand, it is washed with a recovery solution, and then the degree of ligand binding is measured using a radiometer or a fluorescence reader, and the signal intensity is analyzed to calculate the ligand binding inhibition rate. The degree of binding inhibition is plotted according to the AST-DT-218 concentration, and the IC is derived. 50 value.

[0350] hERG-Related Cardiotoxicity Test and Ligand Binding Assay Results Figure 2 This confirmed that AST-DT-218 has a low possibility of causing cardiotoxicity.

[0351] Experimental Example 3: Single-dose toxicity study Dose Toxicity Study

[0352] The toxicity of a single dose of AST-DT-218 was evaluated. First, healthy adult male and female rats were prepared and then fasted for 12 hours before the experiment. Solutions were prepared for each dose group (0 mg / kg, 500 mg / kg, 1000 mg / kg, 2000 mg / kg) with a final solution volume of 40 mL / kg. As shown in Table 4 below, rats were randomly divided into G1 to G4 (5 males / females per group), and then a single oral administration (po) was performed to each rat at a dose of 40 mL / kg.

[0353] Table 4

[0354]

[0355] 1 to 15 days after administration, clinical symptoms (such as stool color, hair loss, etc.), changes in body weight, changes in food consumption, changes in organ weights, ophthalmological examinations, and autopsies were observed. The results are shown in Table 5.

[0356] Table 5

[0357]

[0358] -: None

[0359] When AST-DT-218 was administered as a single dose, there were no toxicologically significant changes in clinical symptoms, body weight, food consumption, ophthalmic examinations, organ weights, or necropsy.

[0360] Experimental Example 4: Maximum Tolerated Dose (MTD) Test

[0361] The maximum tolerated dose (MTD) of AST-DT-218 in vivo was evaluated to determine the maximum dose that AST-DT-218 can be safely administered in experimental animals. First, the compound AST-DT-218 to be used in the experiment and the formulation solvent were prepared. 5% Tween 80, 40% PEG400, 10% DMSO, and 45% DPBS were mixed for use as solvents, and AST-DT-218 was prepared according to each dose, as shown in Table 6 below. Mice (n=5) to be used in the experiment were prepared and divided into 5 groups for the experiment. The control group was injected with only 0 mg / kg solvent, and the remaining groups were injected with 2.5 mg / kg, 5 mg / kg, 10 mg / kg, and 20 mg / kg of AST-DT-218 solution, respectively, and the injection volume was set to 0.1 mL per 20 g mouse.

[0362] Table 6

[0363]

[0364] From day 1 to day 5, the mice were injected at the same time every day, and the weight changes and abnormal behaviors of the mice were observed and data were collected during the experiment. Figure 3 As shown. Figure 3 As shown, it was non-toxic under solvent conditions and no weight loss or abnormal behavior was observed even at the highest treatment concentration of 20 mg / kg.

[0365] Experimental Example 5: Evaluation of the therapeutic potential of hepatocellular carcinoma

[0366] Indication expansion experiments were performed to evaluate the therapeutic potential of AST-DT-218 for hepatocellular carcinoma (HCC). First, HCC cell lines (Huh7, Hep3B, SNU449, SNU475) were prepared, and AST-DT-218 and sorafenib were diluted from the highest concentration of 50uM to 1 / 2 to prepare 10 concentrations (50μM, 2.5μM, 0.125μM, etc.). HCC cell lines (Huh7, Hep3B, SNU449, SNU475) were dispensed into 96-well plates, each well was treated with AST-DT-218 and sorafenib solution, and then the cells were cultured in an incubator for 24 hours. Then, the cell viability of each concentration was evaluated by measuring the cell number by nuclear staining, and a concentration-response curve of cell viability was created based on the data to derive the IC 50 value.

[0367] The experimental results are shown in Table 7 and Figure 4 It has been confirmed that AST-DT-218 is significantly more effective than Sorafenib in treating liver cancer.

[0368] Table 7

[0369]

[0370] Experimental Example 6: Dose Response Curve (DRC)

[0371] DRC was created to confirm whether AST-DT-218 effectively kills various cancer cells. First, liver cancer cell lines (Huh7 and Hep3B), non-small cell lung cancer cell lines (NCI-H460 and NCI-H1299), pancreatic cancer cell lines (PANC-1 and Mia-Paca-2), colorectal cancer cell lines (HT29 and HC T116), gastric adenocarcinoma cell lines (AGS), malignant melanoma cell lines (A375), and adenocarcinoma cell lines (MDA-MB-231) were prepared. Each cell line was cultured in a flask to prepare cells that reached the logarithmic growth phase, then washed with PBS, harvested with trypsin, centrifuged to adjust the cell density, and then resuspended in an appropriate culture medium and dispensed into a 96-well plate. The cells were cultured until they attached to the plate and stabilized, and then AST-DT-218, control groups (lenalidomide, pomalidomide) were prepared and diluted to different concentrations (from the highest concentration of 50uM to 1 / 2, 10 points (10-point)). The wells of the plate were treated with each concentration of each compound for 48 hours, and the cells were cultured to react with the compounds. After the culture was completed, cell viability was assessed by measuring the number of cells by nuclear staining. Data were collected by measuring cell viability at each concentration and then creating DRC (see Figures 5 to 12 ), and calculate IC 50 (See Table 8).

[0372] Table 8

[0373]

[0374] AST-DT-218 was confirmed to be effective in killing various cancer cells used in in vitro experiments ( Figure 5 ).

[0375] Experimental Example 7: CRBN affinity test

[0376] CRBN affinity experiments were performed to evaluate the binding affinity of AST-DT-135, AST-DT-218, and AST-DT-220 to CRBN protein. First, CRBN protein was expressed in Escherichia coli (E. coli) and purified, and then the purified CRBN protein was dissolved in a buffer solution (PBS). AST-DT-135, AST-DT-218, AST-DT-220, and lenalidomide hydrate were dissolved in a solvent, and the CRBN protein was dispensed into a 96-well plate, and then the CRBN protein was mixed and reacted with AST-DT-135, AST-DT-218, AST-DT-220, and lenalidomide hydrate, respectively. After the mixture was fully mixed and reacted, data was collected by measuring the binding intensity at each concentration to create a binding curve (see Fig.13 ), and derived KD values ​​(equilibrium dissociation constants) (see Tables 9 and Fig.14 ).

[0377] Table 9

[0378] Compound Kd(nM)on CRBN AST-DT-135 29 AST-DT-218 16 AST-DT-220 52 Lenalidomide hydrate 100

[0379] It has been confirmed that, compared with lenalidomide, the compounds of the examples of the present invention have very excellent binding affinity to the CRBN substrate.

Claims

1. A compound represented by the following chemical formula 1 or an enantiomer thereof, characterized in that: Chemical formula 1: The above R1 is an alkyl group, a saturated or unsaturated cycloalkyl group, an aromatic or non-aromatic heterocyclic group, an aryl group or an -alkyl-C(=O)-O-alkyl group, The above alkyl group may be substituted by one or more alkoxy groups or hydroxy groups, The above-mentioned heterocyclic group or aryl group may be substituted or unsubstituted by one or more alkyl groups, hydroxyl groups, halogen groups, alkoxy groups, -(C=0)-O-alkyl groups, -CF3, -OCF3, -S-alkyl groups, -S(O2)-alkyl groups or -S(O2)NH2 groups.

2. The compound according to claim 1, characterized in that R1 is an alkyl group having 1 to 7 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an aromatic or non-aromatic heterocyclic group having a 5 to 12-membered ring containing a heteroatom selected from the group consisting of N, O and S, or an aryl group having 6 to 12 carbon atoms.

3. The compound according to claim 1, characterized in that the above R1 is a substituted or unsubstituted alkyl group having 1 to 5 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 5 carbon atoms, a substituted or unsubstituted dihydrobenzofuran or pyridine, a substituted or unsubstituted phenyl group, or an -alkyl-(C=0)-O-alkyl group having 1 to 5 carbon atoms.

4. The compound according to claim 1, wherein R1 is a hydroxy-substituted alkyl group having 1 to 3 carbon atoms, an unsubstituted alkyl group having 3 to 5 carbon atoms, or a methoxy-substituted phenyl group.

5. The compound according to claim 1, wherein the compound represented by Chemical Formula 1 is any one selected from the group consisting of: 1) (3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester; 2)(3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester; 3) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione; 4) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione; 5) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentan-2-yl)amino)isoindoline-1,3-dione; 6) 2-(2,6-dioxopiperidin-3-yl)-4-((3-methylbutan-2-yl)amino)isoindoline-1,3-dione; 7) 4-((3,3-dimethylbutan-2-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 8) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-methoxypropan-2-yl)amino)isoindoline-1,3-dione; 9) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 10) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 11) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 12) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 13) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione; 14) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione; 15) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 16) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 17) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 18) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 19) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 20) 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzenesulfonamide; 21) methyl 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate; 22) methyl 4-((1S)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate; 23) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione; 24) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione; 25) 4-(((R)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 26) 4-(((S)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 27) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 28) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 29) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 30) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 31) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 32) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 33) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione; 34) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione; 35) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-ethoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 36) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 37) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 38) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 39) 4-(((R)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 40) 4-(((S)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 41) 4-(((R)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 42) 4-(((S)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 43) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione; 44) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione; 45) 4-(((R)-1-(3,5-dimethoxyphenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 46) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 47) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione; 48) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione; 49) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 50) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 51) 4-(((R)-1-(2,3-dihydrobenzofuran-5-yl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; and 52) 4-(((S)-1-Cyclopropylethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

6. The compound according to claim 1, wherein the compound represented by Chemical Formula 1 is 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropane-2-yl)amino)isoindoline-1,3-dione, 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentane-2-yl)amino)isoindoline-1,3-dione, or 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione.

7. A pharmaceutical composition for preventing or treating cancer, characterized in that it contains the compound represented by Chemical Formula 1 according to claim 1 or its enantiomer compound as an active ingredient, and the above cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, rectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

8. The pharmaceutical composition according to claim 7, wherein the cancer is a relapsed or refractory cancer.

9. The pharmaceutical composition according to claim 7, wherein the cancer is a drug-resistant cancer.

10. The pharmaceutical composition according to claim 7, wherein the active ingredient is any one selected from the group consisting of: 1) (3R)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester; 2)(3S)-3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyric acid methyl ester; 3) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione; 4) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropan-2-yl)amino)isoindoline-1,3-dione; 5) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentan-2-yl)amino)isoindoline-1,3-dione; 6) 2-(2,6-dioxopiperidin-3-yl)-4-((3-methylbutan-2-yl)amino)isoindoline-1,3-dione; 7) 4-((3,3-dimethylbutan-2-yl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 8) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-methoxypropan-2-yl)amino)isoindoline-1,3-dione; 9) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 10) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 11) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 12) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 13) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione; 14) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)amino)isoindoline-1,3-dione; 15) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 16) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 17) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 18) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 19) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 20) 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzenesulfonamide; 21) methyl 4-((1R)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate; 22) methyl 4-((1S)-1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethyl)benzoate; 23) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione; 24) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(p-tolyl)ethyl)amino)isoindoline-1,3-dione; 25) 4-(((R)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 26) 4-(((S)-1-(4-chlorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 27) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 28) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(2-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 29) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 30) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-fluoro-3-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 31) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 32) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(trifluoromethyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 33) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione; 34) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylthio)phenyl)ethyl)amino)isoindoline-1,3-dione; 35) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-ethoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 36) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 37) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluorophenyl)ethyl)amino)isoindoline-1,3-dione; 38) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 39) 4-(((R)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 40) 4-(((S)-1-(3,4-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 41) 4-(((R)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 42) 4-(((S)-1-(3,5-difluorophenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 43) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione; 44) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(6-methoxypyridin-3-yl)ethyl)amino)isoindoline-1,3-dione; 45) 4-(((R)-1-(3,5-dimethoxyphenyl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 46) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(3-fluoro-4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione; 47) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione; 48) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(5-methoxypyridin-2-yl)ethyl)amino)isoindoline-1,3-dione; 49) 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 50) 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-1-(4-(methylsulfonyl)phenyl)ethyl)amino)isoindoline-1,3-dione; 51) 4-(((R)-1-(2,3-dihydrobenzofuran-5-yl)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; and 52) 4-(((S)-1-Cyclopropylethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

11. The pharmaceutical composition according to claim 7, wherein the active ingredient is 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-hydroxypropane-2-yl)amino)isoindoline-1,3-dione, 2-(2,6-dioxopiperidin-3-yl)-4-(((S)-pentane-2-yl)amino)isoindoline-1,3-dione, or 2-(2,6-dioxopiperidin-3-yl)-4-(((R)-1-(4-methoxyphenyl)ethyl)amino)isoindoline-1,3-dione.

12. The pharmaceutical composition according to claim 7, characterized in that the composition is administered by intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, intrapulmonary administration or rectal administration.

13. A method for preventing or treating cancer in a subject, characterized in that it comprises the step of administering to the subject a compound represented by Chemical Formula 1 according to claim 1 or an enantiomer compound thereof, wherein the cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

14. Use of the compound represented by Chemical Formula 1 or its enantiomer compound according to claim 1 in the preparation of a drug for preventing or treating cancer, wherein: The cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

15. A use of the compound represented by Chemical Formula 1 or its enantiomer compound according to claim 1 in preventing or treating cancer, wherein: The cancer is any one selected from the group consisting of liver cancer, non-small cell lung cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric adenocarcinoma, gastric cancer, malignant melanoma, breast cancer, multiple myeloma, blood cancer and adenocarcinoma.

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