Sulfur-containing compounds based on glutarimide skeleton and their applications

Abstract

The present invention relates to a compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof, and its application for treating tumors. The present invention also provides the application of a compound of general formula (II) or a pharmaceutically acceptable salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof for treating tumors. JPEG2022521746000207.jpg78135

Description

Technical field

[0001] The present invention generally relates to compounds represented by general formula (I) or salts, solvates, isotopically enriched analogs, tautomers, polymorphs, stereoisomers (including enantiomers), or stereoisomers thereof. It relates to a mixture of isomers and to its application in tumor therapy. JPEG2022521746000002.jpg87164 [Background technology]

[0002] Multiple myeloma (MM) is a malignant hematologic cancer that accounts for about 1% of all tumors and 10% of hematological malignancies. Clinical manifestations include anemia, renal dysfunction, recurrent infections, and osteolytic bone destruction, often occurring in middle-aged and elderly people. Chemotherapy and early autologous stem cell transplantation are the mainstays of treatment for multiple myeloma, but these treatments have a poor prognosis and a high recurrence rate. Recent study results show that immunomodulatory agents are an important cornerstone of multiple myeloma treatment schedules and have a significant impact on improving clinical remission rates and prolonging patient survival. there is

[0003] Thalidomide, a first-generation immunomodulatory drug, was used to treat morning sickness in pregnant women throughout the 1950s and 1960s, but was banned because of the birth of malformed fetuses after taking it. However, as Singhal et al. first used thalidomide as a single agent for the treatment of patients with refractory multiple myeloma, it showed good clinical efficacy. Since then, there have been many clinical trials of thalidomide alone or in combination with dexamethasone to treat refractory or relapsed multiple myeloma. The discovery of thalidomide's immunomodulatory and anti-tumor activity has brought renewed widespread attention to this type of drug. To enhance its immunomodulatory functions and anticancer activity, and reduce toxicity and side effects, scientists have used thalidomide as a lead compound to develop a series of phthalimide-substituted derivatives, pomalidomide, lenalidomide. was synthesized. Lenalidomide, a less toxic but more active derivative, was ratified by the FDA in 2006 for the treatment of relapsed or refractory multiple myeloma in combination with dexamethasone. In 2013, pomalidomide, a third-generation immunomodulatory agent, was ratified for the treatment of patients with relapsed / refractory multiple myeloma containing at least two agents, lenalidomide and bortezomib. Its detailed mechanism of action has not been clarified so far, but according to a study in 2010, a biochemical method was used to affinity purify proteins that interact with thalidomide, and the major components of thalidomide and its analogues were identified. Cereblon was identified as the target site, and research in related fields was becoming increasingly active. Subsequently, the mechanism of treatment of multiple myeloma with this class of drugs in the treatment of multiparticulate bone swelling, namely, CRL4A, because immunomodulatory agents can bind to intracellular CRBN proteins CRBN It has been disclosed that ubiquitination ligases ubiquitinate and degrade the transcription factors IKZF1 and IKZF3. These two transcription factors were critical for B-cell development and survival. In 2014, Prof. Harper discovered five endogenous ligase substrates, GRINL1A, MBOAT7, OTUD7B, C6orf141 and MEIS2, by protein chip ubiquitination analysis. Among them, MEIS2 as a transcription factor plays an important role in the normal development of the human body. Increased expression of MEIS2 may lead to shortened toes in chicken embryos. have been shown to be potential downstream molecules that Thalidomide and MEIS2 competitively bound to CRBN because the MEIS2 molecule matched the binding site of thalidomide on CRBN. In 2015, Professor Kronke reported that lenalidomide is also an effective method for the treatment of myelodysplastic syndrome (MDS) caused by chromosomal 5q deletions, by stable isotopes of amino acids in cell culture (SILAC) quantitative mass spectrometry. When applying labels to assess global changes in ubiquitination and protein levels in the del(5q) myeloid cell line KG-1, by comparison, lenalidomide can specifically degrade CK1α protein, whereas pomalidomide, None of the thalidomide was found to play any role (see Figure 1).

[0004] In summary, thalidomides and their derivatives play an important role in the treatment of other related malignancies such as multiple myeloma, but currently there are no reports of heteroatom-substituted compounds of this class. There is a need to further improve bioactivity. Therefore, there is an urgent need to design and synthesize a series of highly active thalidomide analogs to achieve better therapeutic effects. [Outline of the invention]

[0005] One aspect of the invention is a compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer (including enantiomer) or stereoisomer thereof to provide a mixture of JPEG2022521746000003.jpg81129 where A is CH 2 or represents C(O), B, U, V and W are the same or different and each independently represents CH or N, wherein B, U, V and W are not N at the same time, Y represents O or S, R represents SH, and L and X 1 does not exist or R represents S, L represents an optionally substituted linear or branched alkyl, and X 1 does not exist or R is S(O) or S(O) 2 , L represents an optionally substituted straight or branched chain alkyl or amino, and X 1 does not exist and R is S, S(O) or S(O) 2 represents

[0006] L represents optionally substituted linear or branched alkylene, wherein said linear or branched alkylene is O, C(O), S, S(O), S(O) 2 , C(O)N(R 1 ), N(R 2 )C(O), N(R 3 ), N(R 4 )C(O)N(R 5 ), optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene, or any combination thereof, or interrupted arbitrarily one or more times by multiple, R 1 , R 2 , R 3 , R 4 and R 5 is independently H or C 1-3 represents an alkyl, and

[0007] X 1 is NR 6 R. 7 , C(O)NR e R. f , NHC(O)R 8 , NHC(O)NR 9 R. 10 , quaternary ammonium base, OR h , SH, optionally substituted (especially optionally substituted with one or more fluorine) linear or branched alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl or optionally substituted heteroaryl, where R 6 , R 7 , R e , R f , R h , R 9 and R 10 each independently represents H, optionally substituted straight or branched chain alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl or optionally substituted heteroaryl and the condition is R 6 , R 7 is not H at the same time, and R 8 represents a straight or branched chain alkyl, aryl, heteroaryl or heterocyclyl, or R e and R f together with the nitrogen atoms attached to them form a 5- to 8-membered heterocyclyl, or X 1 represents a group of formula (G1), JPEG2022521746000004.jpg83170 In formula (G1), A 1 is CH 2 or represents C(O), B. 1 , U 1 , V 1 , W 1 are the same or different and each independently represents CH or N, where B 1 , U 1 , V 1 and W 1 is not N at the same time, Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents However, the following compounds: 2-(2,6-dioxopiperidin-3-yl)-4-mercaptoisoindoline-1,3-dione; 3-(4-mercapto-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(methylsulfinyl)isoindoline-1,3-dione; 3-(4-(methylsulfinyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(methylsulfonyl)isoindoline-1,3-dione; and Does not contain 3-(4-(methylsulfonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione.

[0008] Another object of the present invention is to provide compounds of formula (I') or salts, solvates, isotopically enriched analogues, tautomers, polymorphs, stereoisomers (including enantiomers), or The object is to provide a mixture of stereoisomers. JPEG2022521746000005.jpg80162 where A, B, U, V, W, Y are as defined in Formula (I) herein; R is S, S(O) or S(O) 2 represents

[0009] L represents optionally substituted linear or branched alkylene, wherein said linear or branched alkylene is O, C(O), S, S(O), S(O) 2 , S(O) 2 N(R 1 ), N(R 2 )S(O) 2 , C(O)N(R 1 ), N(R 2 )C(O), N(R 3 ), N(R 4 )C(O)N(R 5 ), optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene, or any combination thereof, or interrupted arbitrarily one or more times by multiple, R 1 , R 2 , R 3 , R 4 and R 5 is independently H or C 1-3 represents an alkyl, and

[0010] L. 1 represents H, then X 1 is NHC(O)R i or SR j in which R i and R i are independent of each other, and C 1-6 Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 represents cycloalkyl optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof, or X 1 is C 1-6 Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 represents cycloalkyl optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; or

[0011] L. 1 is C 1-3 if it is alkyl, then X 1 is NR 6 R. 7 and R 6 is H or C 1-6 represents alkyl and R 7 is C 1-6 Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 represents cycloalkyl optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; or

[0012] C. 1-6 Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 represents heterocyclyl optionally substituted with substituents selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof.

[0013] In some embodiments, the present invention further provides compounds of formula (I), compounds of formula (I'), or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, tautomers thereof, A pharmaceutical composition is provided that includes an isomer, polymorph, stereoisomer (including enantiomers), or mixture of stereoisomers, and at least one pharmaceutically acceptable carrier.

[0014] In some embodiments, the present invention further provides a compound of formula (I), a compound of formula (I'), or a pharmaceutically acceptable salt, solvate, isotopically enriched analogue thereof, of the present invention. , tautomers, polymorphs, stereoisomers (including enantiomers), or mixtures of stereoisomers, or a reagent or pharmaceutical kit comprising said pharmaceutical composition of the invention.

[0015] In some embodiments, the present invention further provides a compound of formula (I), or a compound of formula (I'), or a pharmaceutically acceptable salt, solvate, or isotopic enrichment thereof for use as a medicament. Analogs, tautomers, polymorphs, stereoisomers (including enantiomers), or mixtures of stereoisomers are provided.

[0016] In some embodiments, the compound of formula (I) or the compound of formula (I') according to the present invention, or a pharmaceutically acceptable salt, solvate, isotopically enriched analog, tautomer Forms, polymorphs, stereoisomers (including enantiomers), or mixtures of stereoisomers, or said pharmaceutical compositions of the invention are used in the treatment of cancer or tumors.

[0017] In some embodiments, the present invention further provides compounds of formula (I), compounds of formula (I'), or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, tautomers thereof, Use of the isomers, polymorphs, stereoisomers (including enantiomers), or mixtures of stereoisomers or said pharmaceutical compositions of the present invention in the manufacture of a medicament for treating cancer or tumors.

[0018] In some embodiments, the present invention further provides a compound of formula (I), or a compound of formula (I'), or a pharmaceutically acceptable salt, solvate, isotopically enriched analog, mutual For the treatment of cancer or tumors, comprising administering to a subject a therapeutically effective amount of a mutant, polymorph, stereoisomer (including enantiomer), or mixture of stereoisomers, or said pharmaceutical composition. provide a method of [Brief description of the drawing]

[0019]

Figure 1

[0020] Thus, according to one aspect of the present invention, embodiment 1): compounds of formula (I) or salts, solvates, isotopically enriched analogues, tautomers, polymorphs, stereoisomers (enantiomers) thereof stereoisomers), or mixtures of stereoisomers. JPEG2022521746000006.jpg71152 where A is CH 2 or represents C(O), B, U, V, W are the same or different and each independently represent CH or N, B, U, V and W are not N at the same time, Y represents O or S, R represents SH, and L sums X 1 does not exist; or R represents S, L represents an optionally substituted linear or branched alkyl, and X 1 does not exist; or R is S(O) or S(O) 2 , L represents an optionally substituted straight or branched chain alkyl or amino, and X 1 does not exist; or R is S, S(O) or S(O) 2 represents

[0021] L is optionally substituted linear or branched alkylene, wherein said linear or branched alkylene is O, C(O), S, S(O), S(O) 2 , C(O)N(R 1 ), N(R 2 )C(O), N(R 3 ), N(R 4 )C(O)N(R 5), optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene or any combination thereof. arbitrarily interrupted one or more times by R 1 , R 2 , R 3 , R 4 and R 5 are each independently H or alkyl (preferably C 1-3 alkyl), and

[0022] X 1 is NR 6 R. 7 , C(O)NR e R. f , NHC(O)R 8 , NHC(O)NR 9 R. 10 , quaternary ammonium base, OR h , SH, optionally substituted (especially optionally substituted with one or more fluorine) linear or branched alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted represents heterocyclyl or optionally substituted heteroaryl, where R 6 , R 7 , R e , R f , R h , R 9 and R 10 each independently represents H, optionally substituted straight or branched chain alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl or optionally substituted heteroaryl and the condition is R 6 , R 7 is not H at the same time, and where R 8 represents a straight or branched chain alkyl, aryl, heteroaryl or heterocyclyl, or R e and R f together with the nitrogen atoms attached to them form a 5- to 8-membered heterocyclyl, or X 1 represents a group of formula (G1), JPEG2022521746000007.jpg68128 In formula (G1), A 1 is CH 2 or represents C(O), B. 1 , U 1 , V 1 , W 1 are the same or different and each independently represents CH or N, and B 1 , U 1 , V 1 Sum W 1 is not N at the same time, Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents However, the following compounds: 2-(2,6-dioxopiperidin-3-yl)-4-mercaptoisoindoline-1,3-dione; 3-(4-mercapto-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(methylsulfinyl)isoindoline-1,3-dione; 3-(4-(methylsulfinyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-(2,6-dioxopiperidin-3-yl)-4-(methylsulfonyl)isoindoline-1,3-dione; and Does not contain 3-(4-(methylsulfonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione.

[0023] Embodiment 2): For a compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof , wherein the ring-constituting atoms B, U, V and W in formula (I) are the same and all are CH.

[0024] Embodiment 3): For a compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , wherein one of the ring-constituting atoms B, U, V and W in formula (I) is N and the others are CH.

[0025] Embodiment 4): For a compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof , wherein two of the ring-constituting atoms B, U, V and W in formula (I) are N and the others are CH.

[0026] Embodiment 5): For a compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , wherein three of the ring-constituting atoms B, U, V and W in formula (I) are N and the others are CH.

[0027] Embodiment 6): for a compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof is also a compound of formula (Ia). JPEG2022521746000008.jpg61145 where A, R, L, X 1 , Y are as defined in embodiment 1).

[0028] Embodiment 7): For a compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof is also a compound of formula (Ib). JPEG2022521746000009.jpg66135 where bases A, R, L, X 1 , Y are as defined in embodiment 1).

[0029] Embodiment 8): For a compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof is also a compound of formula (Ic). JPEG2022521746000010.jpg80158 where bases A, R, L, X 1 , Y are as defined in embodiment 1).

[0030] Embodiment 9): A compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof Accordingly, it is also a compound of formula (Id). JPEG2022521746000011.jpg94168 where bases A, R, L, X 1 , Y are as defined in embodiment 1).

[0031] Embodiment 10): for a compound of formula (I) according to embodiment 1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or mixture of stereoisomers thereof is also a compound of formula (Ie). JPEG2022521746000012.jpg61135 where bases A, R, L, X 1 , Y are as defined in embodiment 1).

[0032] Embodiment 11): A compound of formula (I) according to any one of embodiments 1)-10) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where Y represents O.

[0033] Embodiment 12): A compound of formula (I) according to any one of embodiments 1)-10) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, wherein Y in formula (I) represents S.

[0034] Embodiment 13): A compound of formula (I) according to any one of embodiments 1)-11) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, wherein A in formula (I) represents C(O).

[0035] Embodiment 14): A compound of formula (I) according to any one of embodiments 1)-11) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, wherein A in formula (I) is CH 2 represents

[0036] Embodiment 15): A compound of formula (I) according to any one of embodiments 1)-14) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, wherein R in formula (I) represents S, L represents an optionally substituted straight or branched chain alkyl, and X 1 does not exist. In one sub-embodiment, R represents S and L is optionally substituted linear or branched C 1-40 Alkyl (especially C 1-30 alkyl), and X 1 does not exist. In one sub-embodiment, R represents S, L is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, represents heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl or pentadecyl, and X1 does not exist.

[0037] Embodiment 16): A compound of formula (I) according to any one of embodiments 1)-14) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, wherein R in formula (I) is S(O) or S(O) 2 , L represents an optionally substituted straight or branched chain alkyl or amino, and X 1 does not exist. In one subembodiment, R is S(O) or S(O) 2 and L is an optionally substituted linear or branched C 1-40 Alkyl (especially C 1-30 alkyl) or amino, and X 1 does not exist. In one subembodiment, R is S(O) or S(O) 2 where L is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl , dodecyl, tridecyl, tetradecyl, pentadecyl or amino, and X 1 does not exist.

[0038] Embodiment 17): A compound of formula (I) according to any one of embodiments 1)-14) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where R represents SH and L and X 1 does not exist.

[0039] Embodiment 18): A compound of formula (I) according to any one of embodiments 1)-14) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where: R is S, S(O) or S(O) 2 represents

[0040] L is optionally substituted linear or branched C 1-40 represents alkylene, in which said linear or branched C 1-40 Alkylene is O, C(O), S, S(O), S(O) 2 , C(O)N(R 1 ), N(R 2 )C(O), N(R 3 ), N(R 4 )C(O)N(R 5 ), optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene or any combination thereof. optionally interrupted one or more times by groups, where R 1 , R 2 , R 3 , R 4 and R 5 is independently H or C 1-3 represents an alkyl, and

[0041] X 1 is NR 6 R. 7 , C(O)NR e R. f , NHC(O)R 8 , NHC(O)NR 9 R. 10 , OR h , SH, quaternary ammonium base, optionally substituted (especially optionally substituted with one or more fluorine) straight or branched chain C 1-10 represents alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl or optionally substituted heteroaryl, where R 6 , R 7 , R e , R f , R h , R 9 and R 10 are each independently H, an optionally substituted linear or branched C 1-10 represents alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl or optionally substituted heteroaryl, where R 6 , R 7 is not H at the same time, and where R 8 is straight or branched C 1-8 represents alkyl, aryl, heteroaryl or heterocyclyl, or where R e and R f together with the nitrogen atoms attached to them form a 5- to 8-membered heterocyclyl, or X 1 represents a group of formula (G1), JPEG2022521746000013.jpg68137 In formula (G1), A 1 is CH 2 or represents C(O), B. 1 , U 1 , V 1 , W 1 are the same or different and each independently represent CH or N, where B 1 , U 1 , V 1 and W 1 is not N at the same time, Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents

[0042] Embodiment 19): A compound of formula (I) according to any one of embodiments 1)-14) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where: R is S, S(O) or S(O) 2 represents

[0043] L is optionally substituted linear or branched C 1-40 represents alkylene, wherein said linear or branched C 1-40 Alkylene is O;C(O);S;S(O);S(O) 2 ;C(O)N(R 1 );N(R 2 )C(O);N(R 3 );N(R 4 )C(O)N(R 5 ); halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy or C 1-5 arylene optionally substituted with a substituent selected from the group consisting of alkyl; halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo group or C 1-5 heterocyclylene optionally substituted with a substituent selected from the group consisting of alkyl; halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy or C 1-5 heteroarylene optionally substituted with a substituent selected from the group consisting of alkyl; halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy or C 1-5 cycloalkylene optionally substituted with a substituent selected from the group consisting of alkyl; or optionally interrupted one or more times by one or more selected from the group consisting of any combination thereof, wherein , R 1 , R 2 , R 3 , R 4 and R 5 is independently H or C 1-3 represents an alkyl, and

[0044] X 1 is NR 6 R. 7 ;C(O)NR e R. f ;NHC(O)R 8 ;NHC(O)NR 9 R. 10 ;OR h ;SH; quaternary ammonium base; linear or branched C optionally substituted with one or more fluorine 1-10 Alkyl; halogen, oxo group, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C 1-6 cycloalkyl optionally substituted with substituents selected from the group consisting of alkyl or any combination thereof; halogen, oxo group, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C 1-6 aryl optionally substituted with substituents selected from the group consisting of alkyl or any combination thereof; halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 Alkoxy, C 1-6 alkylsulfonyl, di(C 1-6 alkyl)phosphoryl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo group, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, optionally substituted 5- or 6-membered heteroaryl, C 1-6 heterocyclyl optionally substituted with a substituent selected from the group consisting of alkyl or any combination thereof; or halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3alkoxy, di(C 1-6 Alkyl)phosphoryl, C 1-6 alkylsulfonyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C 1-6 a substituent selected from the group consisting of alkyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, optionally substituted 5- or 6-membered heteroaryl or any combination thereof represents heteroaryl optionally substituted with, where R 6 , R 7 , R e , R f , R h , R 9 and R 10 are each independently H, an optionally substituted linear or branched C 1-10 represents alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, or optionally substituted heteroaryl, with the proviso that R 6 , R 7 is not H at the same time, and R in it 8 is straight or branched C 1-6 represents alkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl, or where R e and R f together with the nitrogen atoms attached to them form an optionally substituted 5- to 8-membered heterocyclyl.

[0045] Embodiment 20): A compound of formula (I) according to embodiment 1) or 19) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof where L is the following optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof) group: linear or branched C 1 -C 40 Alkylene;*-((CH 2 ) n1 O) m1 -(CH 2 ) n2 -;*-((CH 2 ) n1 O) m1 -(CH 2 ) n2 -O-(CH 2 ) n3 -;*-(CH 2 ) n1 -O-(CH 2 ) n2 -;*-((CR 11 R. 12 ) n1 O) m1 -(CR 13 R. 14 ) n2 -;*-((CR 15 R. 16 ) n1 O) m1 -(CR 17 R. 18 ) n2 -O-(CR 19 R. 20 ) n3 -;*-(CH 2 ) n1 -S-(CH 2 ) n2 -;*-(CH 2 ) n1 -S(O)-(CH 2 ) n2 -;*-(CH 2 ) n1 -S(O) 2 -(CH 2 ) n2 -;*-(CH 2 ) n1 -N(R 21 )-(CH 2 ) n2 -;*-(CH 2 ) n1 -N(R 22 )C(O)-(CH 2 ) n2 -;*-(CH 2 ) n1 -C(O)N(R 23 )-(CH 2 ) n2 -;*-(CH 2 ) n1 -N(R 24 )C(O)N(R 25 )-(CH 2 ) n2 -;*-(CH 2 ) n1 -(N(R 26 )C(O)-(CH 2 ) n2 ) m1 -;*-(CH 2 ) n1 -piperazinylene-(CH 2 ) n2 -;*-(CH 2 ) n1 -Phenylene-(CH 2 ) n2 -;*-(CH 2 ) n1 -Phenylene-(CH 2 ) n2 -N(R 21 )-(CH 2 ) n3 -;*-(CH 2 ) n1 -furanylene-(CH 2 ) n2 -;*-(CH 2 ) n1 -furanylene-(CH 2 ) n2 -N(R 21 )-(CH 2 ) n3 -;*-(CH 2 ) n1 -thiazolylene-(CH 2 ) n2 -;*-(CH 2 ) n1 -thiazolylene-C(O)N(R 23 )-(CH 2 ) n2 -;*-(CH 2 ) n1 -thiazolylene-(CH 2 ) n2 -N(R 21 )-(CH 2 ) n3 -;C(O), N(R 21 ), C(O)N(R 23 ), N(R 22 )C(O), optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene or optionally substituted heteroarylene or any combination thereof straight or branched alkylene optionally interrupted one or more times by one or more substituents; or carbon chain C(O), optionally substituted cycloalkylene, optionally substituted arylene *-(( CH 2 ) n1 O) m1 -(CH 2 ) n2 - represents where * is the point of attachment with the group R, R. 21 , R 22 , R 23 , R 24 , R 25 and R 26 are independently H and C 1-3 selected from alkyl,

[0046] R. 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 and R 20 each independently H, linear or branched C 1 -C 10 alkyl or C 3 -C 10 represents cycloalkyl in which, when in the same group L, R 11 , R 12 , R 13 , R 14 ; or R 15 , R 16 , R 17 , R 18 , R 19 , R 20 is not H at the same time, and

[0047] n1, n2, n3, m1 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or Represents 20 integers.

[0048] Embodiment 21): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is an optionally substituted linear or branched C 1 -C 40 represents alkylene. In one sub-embodiment, L is halogen, C 1-5 linear or branched C optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof 1 -C 40 represents alkylene.

[0049] Embodiment 22): A compound of formula (I) according to embodiment 20) or 21) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof for mixtures of where L is the following: halogen, C 1-5 A group optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof: -CH 2 -;-(CH 2 ) 2 -;-(CH 2 ) 3 -;-(CH 2 ) 4 -;-(CH 2 ) 5 -;-(CH 2 ) 6 -;-(CH 2 ) 7 -;-(CH 2 ) 8 -;-(CH 2 ) 9 -;-(CH 2 ) 10 -;-(CH 2 ) 11 -;-(CH 2 ) 12 -;-(CH 2 ) 13 -;-(CH 2 ) 14 -;-(CH 2 ) 15 -;-(CH 2 ) 16 -;-(CH 2 ) 17 -;-(CH 2 ) 18 -;-(CH 2 ) 19 -; or -(CH 2 ) 20 - represents In one subembodiment, L is -CH 2 -;-(CH 2 ) 2 -;-(CH 2 ) 3 -;-(CH 2 ) 4 -;-(CH 2 ) 5 -;-(CH 2 ) 6 -;-(CH 2 ) 7 -;-(CH 2 ) 8 -;-(CH 2 ) 9 -;-(CH 2 ) 10 -;-(CH 2 ) 11 -;-(CH 2 ) 12 -;-(CH 2 ) 13 -;-(CH 2 ) 14 -;-(CH 2 ) 15 -;-(CH 2 ) 16 -;-(CH 2 ) 17 -;-(CH 2 ) 18 -;-(CH 2 ) 19 -; or -(CH 2 ) 20 - represents

[0050] Embodiment 23): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is the following optionally substituted (e.g., halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-((CH 2 ) n1 O) m1 -(CH 2 ) n2 -,*-((CH 2 ) n1 O) m1 -(CH 2 ) n2 -O-(CH 2 ) n3 -,*-(CH 2 ) n1 -O-(CH 2 ) n2 -,*-((CR 11 R. 12 ) n1 O) m1 -(CR 13 R. 14 ) n2 -,*-((CR 15 R. 16 ) n1 O) m1 -(CR 17 R. 18 ) n2 -O-(CR 19 R. 20 ) n3 - represents, in which * represents the connection point with the group R, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 each independently H, linear or branched C 1 -C 10 alkyl or C 3 -C 10 represents cycloalkyl, where in the same group L, R 11 , R 12 , R 13 , R 14 ; or R 15 , R 16 , R 17 , R 18 , R 19 , R 20 is not H at the same time, and n1, n2, n3, m1 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 , 17, 18, 19 or 20 integers.

[0051] Embodiment 24): A compound of formula (I) according to embodiment 20) or 23) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof where L is the following optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-CH 2 CH 2 O(CH 2 ) 2 -;*-(CH 2 CH 2 O) 2 -(CH 2 ) 2 -;*-(CH 2 CH 2 O) 3 -(CH 2 ) 2 -;*-(CH 2 CH 2 O) 4 -(CH 2 ) 2 -;*-(CH 2 CH 2 O) 5 -(CH 2 ) 2 -;*-(CH 2 CH 2 O) 6 -(CH 2 ) 2 -;*-(CH 2 CH 2 O) 7 -(CH 2 ) 2 -;*-(CH 2 CH 2 O) 8 -(CH 2 ) 2 -;*-(CH 2 CH 2 O) 9 (CH 2 ) 2 -;*-(CH 2 CH 2 O) 10 (CH 2 ) 2 -;*-CH 2 CH 2 OCH 2 -;*-(CH 2 CH 2 O) 2 -CH 2 -;*-(CH 2 CH 2 O) 3 -CH 2 -;*-(CH 2 CH 2 O) 4 -CH 2 -;*-(CH 2 CH 2 O) 5 -CH 2 -;*-(CH 2 CH 2 O) 6 -CH 2 -;*-(CH 2 CH 2 O) 7 -CH 2 -;*-(CH 2 CH 2 O) 8 -CH 2 -;*-(CH 2 CH 2 O) 9 -CH 2 -;*-(CH 2 CH 2 O) 10 -CH 2 -;*-CH2 CH 2 O(CH 2 ) 3 -;*-(CH 2 CH 2 O) 2 -(CH 2 ) 3 -;*-(CH 2 CH 2 O) 3 -(CH 2 ) 3 -;*-(CH 2 CH 2 O) 4 -(CH 2 ) 3 -;*-(CH 2 CH 2 O) 5 -(CH 2 ) 3 -;*-(CH 2 CH 2 O) 6 -(CH 2 ) 3 -;*-(CH 2 CH 2 O) 7 -(CH 2 ) 3 -;*-(CH 2 CH 2 O) 8 -(CH 2 ) 3 -;*-(CH 2 CH 2 O) 9 (CH 2 ) 3 -;*-(CH 2 CH 2 O) 10 (CH 2 ) 3 -;*-CH 2 CH 2 OCH 2 CH 2 CH 2 OCH 2 -;*-CH 2 CH 2 OCH 2 CH 2 CH 2 O-(CH 2 ) 2 -;*-CH 2 CH 2 OCH 2 CH 2 CH 2 O-(CH 2 ) 3 -;*-(CH 2 CH 2 O) 2 (CH 2 CH 2 CH 2 O)(CH 2 ) 3 -;*-(CH 2 CH 2 O) 2 (CH 2 CH 2 CH 2 O) 2 (CH 2 ) 3 -;*-(CH 2 ) 1 O(CH 2 ) 1 -;*-(CH 2 ) 1 O(CH 2 ) 2 -;*-(CH 2 ) 2 O(CH 2 ) 2 -;*-(CH 2 ) 2 O(CH 2 ) 1 -;*-(CH 2 ) 2 O(CH 2 ) 3 -;*-(CH 2 ) 2 O(CH 2 ) 4 -;*-(CH 2 ) 2 O(CH 2 ) 5 -;*-(CH 2 ) 2 O(CH 2 ) 6 -;*-(CH 2 ) 3 O(CH 2 ) 1 -;*-(CH 2 ) 3 O(CH 2 ) 2 -;*-(CH 2 ) 3 O(CH 2 ) 3 -;*-(CH 2 ) 4 O(CH 2 ) 1 -;*-(CH 2 ) 4 O(CH 2 ) 2 -;*-(CH 2 ) 4 O(CH 2 ) 3 -;*-(CH 2 ) 5 O(CH 2 ) 1 -;*-(CH 2 ) 5 O(CH 2 ) 2 -;*-(CH 2 ) 5 O(CH 2 ) 3 -;*-(CH 2 ) 5 O(CH 2 ) 4 -; or *-(CH 2 ) 5 O(CH 2 ) 5 represents -, in which * represents the point of attachment to the group R;

[0052] Embodiment 25): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted)*-(CH 2 ) n1 -N(R 21 )-(CH 2 ) n2 - represents, in which * represents the connection point with the group R, R 21 is H and C 1-3 selected from alkyl, n1 and n2 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 integers.

[0053] Embodiment 26): A compound of formula (I) according to embodiment 20) or 25) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof where L is optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) 1 -NH-(CH 2 ) 1 -, *-(CH 2 ) 2 -NH-(CH 2 ) 1 -, *-(CH 2 ) 2 -NH-(CH 2 ) 2 -, *-(CH 2 ) 2 -NH-(CH 2 ) 3 -, *-(CH 2 ) 2 -NH-(CH 2 ) 4 -, *-(CH 2 ) 2 -NH-(CH 2 ) 5 -, *-(CH 2 ) 2 -NH-(CH 2 ) 6 -, *-(CH 2 ) 2 -NH-(CH 2 ) 7 -, *-(CH 2 ) 2 -NH-(CH 2 ) 8 -, *-(CH 2 ) 2 -NH-(CH 2 ) 9 -, *-(CH 2 ) 2 -NH-(CH 2 ) 10 -, *-(CH 2 ) 2 -NH-(CH 2 ) 11 -, *-(CH 2 ) 2 -NH-(CH 2 ) 12 -, *-(CH 2 ) 3 -NH-(CH 2 ) 1 -, *-(CH 2 ) 3 -NH-(CH 2 ) 2 -, *-(CH 2 ) 3 -NH-(CH 2 ) 3 -, *-(CH 2 ) 4 -NH-(CH 2 ) 1-, *-(CH 2 ) 4 -NH-(CH 2 ) 2 -, *-(CH 2 ) 5 -NH-(CH 2 ) 3 -, *-(CH 2 ) 5 -NH-(CH 2 ) 1 -, *-(CH 2 ) 5 -NH-(CH 2 ) 2 -, *-(CH 2 ) 8 -NH-(CH 2 ) 2 -, *-(CH 2 ) 5 -NH-(CH 2 ) 3 -, *-(CH 2 ) 5 -NH-(CH 2 ) 4 -, *-(CH 2 ) 5 -NH-(CH 2 ) 5 -, *-(CH 2 ) 1 -N(CH 3 )-(CH 2 ) 8 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 3 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 4 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 5 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 6 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 2 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 3 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 4 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 5 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 6 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 7 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 8 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 9 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 10 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 11 -, or *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 12 represents -, in which * represents the point of attachment to the group R;

[0054] Embodiment 27): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted)*-(CH 2 ) n1 -N(R 22 )C(O)-(CH 2 ) n2 - represents, in which * represents the connection point with the group R, R 22 is H and C 1-3 is selected from alkyl, n1 and n2 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, Represents 19 or 20 integers.

[0055] Embodiment 28): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof according to embodiment 20) or 27) where L is optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) 2 -NHC(O)-CH 2 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 2 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 3 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 4 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 5 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 6 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 7 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 8 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 9 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 10 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 11 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 12 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 13 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 14 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 15 -, *-(CH 2 ) 3 -NHC(O)-CH 2 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 2 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 3 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 4 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 5 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 6 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 7 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 8 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 9 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 10 -, *-(CH 2) 3 -NHC(O)-(CH 2 ) 11 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 12 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 13 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 14 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 15 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 1 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 2 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 3 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 4 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 5 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 6 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 7 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 8 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 9 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 10 -, *-(CH 2 ) 5 NHC(O)(CH 2 ) 1 -, *-(CH 2 ) 8 NHC(O)(CH 2 ) 2 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-CH 2 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 2 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 3 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 4 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 5 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 6 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 7 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 8 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 9 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 10 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 11 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 12 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 13 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 14 -, or *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 15 represents -, in which * represents the point of attachment to the group R;

[0056] Embodiment 29): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) n1 -C(O)N(R 23 )-(CH 2 ) n2 - represents, in which * represents the connection point with the group R, R 23 is H and C 1-3 is selected from alkyl, n1 and n2 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, Represents 19 or 20 integers.

[0057] Embodiment 30): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof according to embodiment 20) or 29) where L is optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) 2 -C(O)NH-CH 2 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 2 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 3 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 4 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 5 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 6 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 7 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 8 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 9 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 10 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 11 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 12 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 13 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 14 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 15 -, *-(CH 2 ) 3 -C(O)NH-CH 2 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 2 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 3 -, *-(CH2 ) 3 -C(O)NH-(CH 2 ) 4 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 5 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 6 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 7 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 8 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 9 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 10 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 11 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 12 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 13 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 14 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 15 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 1 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 2 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 3 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 4 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 5 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 6 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 7 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 8 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 9 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 10 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-CH 2 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 2 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 3 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 4 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 5 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 6 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 7 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 8 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 9 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 10 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 11 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 12 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 13 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 14 -, or *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 15 represents -, in which * represents the point of attachment to the group R;

[0058] Embodiment 31): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted)*-(CH 2 ) n1 -N(R 24 )C(O)N(R 25 )-(CH 2 ) n2 - represents, in which * represents the connection point with the group R, R 24 Sum R 25 are independently H and C 1-3 is selected from alkyl and n1 and n2 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 integers.

[0059] Embodiment 32): A compound of formula (I) according to embodiment 20) or 31) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof where L is optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) 2 -NHC(O)NH-(CH 2 ) 4 -, *-(CH 2 ) 4 -NHC(O)NH-(CH 2 ) 2 -, *-CH 2 -NHC(O)NH-(CH 2 ) 2 -, *-(CH 2 ) 2 -NHC(O)NH-CH 2 -, *-(CH 2 ) 2 -NHC(O)NH-(CH 2 ) 2 -, *-(CH 2 ) 2 -NHC(O)NH-(CH 2 ) 3 -, or *-(CH 2 ) 3 -NHC(O)NH-(CH 2 ) 2 - represents

[0060] Embodiment 33): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is *-(CH 2 ) n1 -piperazinylene-(CH 2 ) n2 - represents, in which * represents the point of attachment to the group R, said piperazinylene is halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or C 1-5optionally substituted with a substituent selected from the group consisting of alkyl (especially methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl), or any combination thereof, n1 and n2 are each independently represents an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0061] Embodiment 34): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof according to embodiment 20) or 33) for mixtures of where L is *-CH 2 -piperazinylene-CH 2 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 5 -, *-(CH 2 ) 3 -piperazinylene-CH 2 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 4 -piperazinylene-CH 2 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -piperazinylene-CH 2 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 4 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 5 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 6 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 7 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 8 -, *-CH 2 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 5 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 6 -piperazinylene-(CH 2 ) 8 -, or *-(CH 2 ) 7 -piperazinylene-(CH 2 ) 8 -, in which * represents the point of attachment to the group R, and said piperazinylene is halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or C 1-5 substituted with substituents selected from the group consisting of alkyl (particularly methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl) or any combination thereof. In one subembodiment, L is *-CH 2 -piperazinylene-CH 2 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 5 -, *-(CH 2 ) 3 -piperazinylene-CH 2 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 4 -piperazinylene-CH 2 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -piperazinylene-CH 2 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 4 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 5 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 6 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 7 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 8 -, *-CH 2 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 5 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 6 -piperazinylene-(CH 2 ) 8 -, or *-(CH 2 ) 7 -piperazinylene-(CH 2 ) 8 represents -, in which * represents the point of attachment to the group R;

[0062] Embodiment 35): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is *-(CH 2 ) n1 -Phenylene-(CH 2 ) n2 -, in which * represents the point of attachment to the group R, said phenylene being halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or C 1-5substituted with a substituent selected from the group consisting of alkyl (especially methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl) or any combination thereof, n1 and n2 are each independently 1, Represents an integer of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

[0063] Embodiment 36): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof according to embodiment 20) or 35) for mixtures of where L is *-CH 2 -phenylene-CH 2 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 5 -, *-(CH 2 ) 3 -phenylene-CH 2 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 4 -phenylene-CH 2 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 5 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 6 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 7 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -phenylene-CH 2 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 5 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 6 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 7 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 8 -, *-CH 2 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 5 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 6 -Phenylene-(CH 2 ) 8 -, or *-(CH 2 ) 7 -Phenylene-(CH 2 ) 8 -, in which * represents the point of attachment to the group R, and said phenylene is halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or C 1-5 optionally substituted with substituents selected from the group consisting of alkyl (especially methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl) or any combination thereof. In one subembodiment, L is *-CH 2 -phenylene-CH 2 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 5 -, *-(CH 2 ) 3 -phenylene-CH 2 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 4 -phenylene-CH 2 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 5 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 6 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 7 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -phenylene-CH 2 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 5 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 6 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 7 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 8 -, *-CH 2 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 5 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 6 -Phenylene-(CH 2 ) 8 -, or *-(CH 2 ) 7 -Phenylene-(CH 2 ) 8 represents -, in which * represents the point of attachment to the group R;

[0064] Embodiment 37): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) n1 -S-(CH 2 ) n2 -represents, in which * represents a connection point with the group R, n1 and n2 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Represents an integer of 13, 14, 15, 16, 17, 18, 19 or 20.

[0065] Embodiment 38): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof according to embodiment 20) or 37) where L is optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) 1 S(CH 2 ) 1 -, *-(CH 2 ) 2 S(CH 2 ) 2 -, *-(CH 2 ) 2 S(CH 2 ) 1 -, *-(CH 2 ) 1 S(CH 2 ) 2 -, *-(CH 2 ) 1 S(CH 2 ) 3 -, *-(CH 2 ) 1 S(CH 2 ) 4 -, *-(CH 2 ) 2 S(CH 2 ) 3 -, *-(CH 2 ) 2 S(CH 2 ) 4 -, *-(CH 2 ) 2 S(CH 2 ) 5 -, *-(CH 2 ) 3 S(CH 2 ) 1 -, *-(CH 2 ) 3 S(CH 2 ) 2 -, *-(CH 2 ) 3 S(CH 2 ) 3 -, *-(CH 2 ) 4 S(CH 2 ) 1 -, *-(CH 2 ) 4 S(CH 2 ) 2 -, *-(CH 2 ) 4 S(CH 2 ) 3 -, *-(CH 2 ) 5 S(CH 2 ) 1 -, *-(CH 2 ) 5 S(CH 2 ) 2 -, *-(CH 2 ) 5 S(CH 2 ) 3 -, *-(CH 2 ) 6 S(CH 2 ) 1 -, *-(CH 2 ) 6 S(CH 2 ) 2 -, *-(CH 2 ) 6 S(CH 2 ) 3 -, *-(CH 2 ) 7 S(CH 2 ) 1 -, *-(CH 2 ) 7 S(CH 2 ) 2 -, *-(CH 2 ) 7 S(CH 2 ) 3 -, *-(CH 2 ) 8 S(CH 2 ) 1 -, *-(CH 2 ) 8 S(CH 2 ) 2 -, *-(CH 2 ) 8 S(CH 2 ) 3 -, *-(CH 2 ) 9 S(CH 2 ) 1 -, *-(CH 2 ) 9 S(CH 2 ) 2 -, or *-(CH 2 ) 9 S(CH 2 ) 3 represents -, in which * represents the point of attachment to the group R;

[0066] Embodiment 39): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) n1 -S(O)-(CH 2 ) n2 -represents, in which * represents a connection point with the group R, n1 and n2 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Represents an integer of 13, 14, 15, 16, 17, 18, 19 or 20.

[0067] Embodiment 40): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof according to embodiment 20) or 39) where L is optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) 1 S(O)(CH 2 ) 1 -, *-(CH 2 ) 2 S(O)(CH 2 ) 2 -, *-(CH 2 ) 2 S(O)(CH 2 ) 1 -, *-(CH 2 ) 1 S(O)(CH 2 ) 2 -, *-(CH 2 ) 1 S(O)(CH 2 ) 3 -, *-(CH 2 ) 1 S(O)(CH 2 ) 4 -, *-(CH 2 ) 2 S(O)(CH 2 ) 3 -, *-(CH 2 ) 2 S(O)(CH 2 ) 4 -, *-(CH 2 ) 2 S(O)(CH 2 ) 5 -, *-(CH 2 ) 3 S(O)(CH 2 ) 1 -, *-(CH 2 ) 3 S(O)(CH 2 ) 2 -, *-(CH 2 ) 3 S(O)(CH 2 ) 3 -, *-(CH 2 ) 4 S(O)(CH 2 ) 1 -, *-(CH 2 ) 4 S(O)(CH 2 ) 2 -, *-(CH 2 ) 4 S(O)(CH 2 ) 3 -, *-(CH 2 ) 5 S(O)(CH 2 ) 1 -, *-(CH 2 ) 5 S(O)(CH 2 ) 2 -, *-(CH 2 ) 5 S(O)(CH 2 ) 3 -, *-(CH 2 )6 S(O)(CH 2 ) 1 -, *-(CH 2 ) 6 S(O)(CH 2 ) 2 -, *-(CH 2 ) 6 S(O)(CH 2 ) 3 -, *-(CH 2 ) 7 S(O)(CH 2 ) 1 -, *-(CH 2 ) 7 S(O)(CH 2 ) 2 -, *-(CH 2 ) 7 S(O)(CH 2 ) 3 -, *-(CH 2 ) 8 S(O)(CH 2 ) 1 -, *-(CH 2 ) 8 S(O)(CH 2 ) 2 -, *-(CH 2 ) 8 S(O)(CH 2 ) 3 -, *-(CH 2 ) 9 S(O)(CH 2 ) 1 -, *-(CH 2 ) 9 S(O)(CH 2 ) 2 -, or *-(CH 2 ) 9 S(O)(CH 2 ) 3 represents -, in which * represents the point of attachment to the group R;

[0068] Embodiment 41): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) n1 -S(O) 2 -(CH 2 ) n2 - represents, in which * represents the point of connection with the group R; Represents an integer of 13, 14, 15, 16, 17, 18, 19 or 20.

[0069] Embodiment 42): A compound of formula (I) according to embodiment 20) or 41) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof where L is optionally substituted (e.g. halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) 1 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 1 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 1 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 1 S(O) 2 (CH 2 ) 4 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 4 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 5 -, *-(CH 2 ) 3 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 3 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 3 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 4 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 4 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 4 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 5 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 5 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 5 S(O)(CH 2 ) 3 -, *-(CH 2 ) 6 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 6 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 6 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 7 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 7 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 7 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 8 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 8 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 8 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 9 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 9 S(O) 2 (CH 2 ) 2 -, or *-(CH 2 ) 9 S(O) 2 (CH 2 ) 3 represents -, in which * represents the point of attachment to the group R;

[0070] Embodiment 43): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted with a substituent selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof) group: *-(CH 2 ) 1 -NH-(CH 2 ) 1 -, *-(CH 2 ) 2 -NH-(CH 2 ) 1 -, *-(CH 2 ) 2 -NH-(CH 2 ) 2 -, *-(CH 2 ) 2 -NH-(CH 2 ) 3 -, *-(CH 2 ) 2 -NH-(CH 2 )4 -, *-(CH 2 ) 2 -NH-(CH 2 ) 5 -, *-(CH 2 ) 2 -NH-(CH 2 ) 6 -, *-(CH 2 ) 2 -NH-(CH 2 ) 7 -, *-(CH 2 ) 2 -NH-(CH 2 ) 8 -, *-(CH 2 ) 2 -NH-(CH 2 ) 9 -, *-(CH 2 ) 2 -NH-(CH 2 ) 10 -, *-(CH 2 ) 2 -NH-(CH 2 ) 11 -, *-(CH 2 ) 2 -NH-(CH 2 ) 12 -, *-(CH 2 ) 3 -NH-(CH 2 ) 1 -, *-(CH 2 ) 3 -NH-(CH 2 ) 2 -, *-(CH 2 ) 3 -NH-(CH 2 ) 3 -, *-(CH 2 ) 4 -NH-(CH 2 ) 1 -, *-(CH 2 ) 4 -NH-(CH 2 ) 2 -, *-(CH 2 ) 5 -NH-(CH 2 ) 3 -, *-(CH 2 ) 5 -NH-(CH 2 ) 1 -, *-(CH 2 ) 5 -NH-(CH 2 ) 2 -, *-(CH 2 ) 8 -NH-(CH 2 ) 2 -, *-(CH 2 ) 5 -NH-(CH 2 ) 3 -, *-(CH 2 ) 5 -NH-(CH 2 ) 4 -, *-(CH 2 ) 5 -NH-(CH 2 ) 5 -, *-(CH 2 ) 1 -N(CH 3 )-(CH 2 ) 8 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 3 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 4 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 5 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 6 -N(CH 3 )-(CH 2 ) 1 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 2 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 3 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 4 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 5 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 6 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 7 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 8 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 9 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 10 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 11 -, *-(CH 2 ) 2 -N(CH 3 )-(CH 2 ) 12 -, *-(CH 2 ) 2 -NHC(O)-CH 2 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 2 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 3 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 4 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 5 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 6 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 7 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 8 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 9 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 10 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 11 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 12 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 13 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 14 -, *-(CH 2 ) 2 -NHC(O)-(CH 2 ) 15 -, *-(CH 2 ) 3 -NHC(O)-CH 2 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 2 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 3 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 4 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 5 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 6 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 7 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 8 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 9-, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 10 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 11 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 12 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 13 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 14 -, *-(CH 2 ) 3 -NHC(O)-(CH 2 ) 15 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 1 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 2 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 3 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 4 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 5 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 6 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 7 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 8 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 9 -, *-(CH 2 ) 4 NHC(O)(CH 2 ) 10 -, *-(CH 2 ) 5 NHC(O)(CH 2 ) 1 -, *-(CH 2 ) 8 NHC(O)(CH 2 ) 2 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-CH 2 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 2 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 3 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 4 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 5 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 6 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 7 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 8 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 9 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 10 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 11 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 12 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 13 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 14 -, *-(CH 2 ) 2 -N(CH 3 )C(O)-(CH 2 ) 15 -, *-(CH 2 ) 2 -C(O)NH-CH 2 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 2 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 3 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 4 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 5 -, *-(CH 2 ) 2 -C(O)NH-(C H. 2 ) 6 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 7 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 8 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 9 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 10 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 11 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 12 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 13 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 14 -, *-(CH 2 ) 2 -C(O)NH-(CH 2 ) 15 -, *-(CH 2 ) 3 -C(O)NH-CH 2 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 2 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 3 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 4 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 5 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 6 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 7 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 8 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 9 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 10 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 11 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 )12 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 13 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 14 -, *-(CH 2 ) 3 -C(O)NH-(CH 2 ) 15 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 1 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 2 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 3 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 4 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 5 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 6 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 7 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 8 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 9 -, *-(CH 2 ) 4 C(O)NH(CH 2 ) 10 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-CH 2 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 2 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 3 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 4 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 5 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 6 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 7 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 8 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 9 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 10 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 11 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 12 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 13 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 14 -, *-(CH 2 ) 2 -C(O)N(CH 3 )-(CH 2 ) 15 -, *-(CH 2 ) 2 -NHC(O)NH-(CH 2 ) 4 -, *-(CH 2 ) 4 -NHC(O)NH-(CH 2 ) 2 -, *-CH 2 -NHC(O)NH-(CH 2 ) 2 -, *-(CH 2 ) 2 -NHC(O)NH-CH 2 -, *-(CH 2 ) 2 -NHC(O)NH-(CH 2 ) 2 -, *-(CH 2 ) 2 -NHC(O)NH-(CH 2 ) 3 -, *-(CH 2 ) 3 -NHC(O)NH-(CH 2 ) 2 -, *-CH 2 -piperazinylene-CH 2 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 5 -, *-(CH 2 ) 3 -piperazinylene-CH 2 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 4 -piperazinylene-CH 2 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -piperazinylene-CH 2 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 2 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 4 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 5 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 6 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 7 -, *-(CH 2 ) 8 -piperazinylene-(CH 2 ) 8 -, *-CH 2 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 2 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 3 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 4 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 5 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 6 -piperazinylene-(CH 2 ) 8 -, *-(CH 2 ) 7 -piperazinylene-(CH2 ) 8 -, *-CH 2 -phenylene-CH 2 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 5 -, *-(CH 2 ) 3 -phenylene-CH 2 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 4 -phenylene-CH 2 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 5 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 6 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 7 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -phenylene-CH 2 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 5 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 6 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 7 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 8 -, *-CH 2 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 5 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 6 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 7 -Phenylene- (CH 2 ) 8 -, *-(CH 2 ) 1 S(CH 2 ) 1 -, *-(CH 2 ) 2 S(CH 2 ) 2 -, *-(CH 2 ) 2 S(CH 2 ) 1 -, *-(CH 2 ) 1 S(CH 2 ) 2 -, *-(CH 2 ) 1 S(CH 2 ) 3 -, *-(CH 2 ) 1 S(CH 2 ) 4 -, *-(CH 2 ) 2 S(CH 2 ) 3 -, *-(CH 2 ) 2 S(CH 2 ) 4 -, *-(CH 2 ) 2 S(CH 2 ) 5 -, *-(CH 2 ) 3 S(CH 2 ) 1 -, *-(CH 2 ) 3 S(CH 2 ) 2 -, *-(CH 2 ) 3 S(CH 2 ) 3 -, *-(CH 2 ) 4 S(CH 2 ) 1 -, *-(CH 2 ) 4 S(CH 2 ) 2 -, *-(CH 2 ) 4 S(CH 2 ) 3 -, *-(CH 2 ) 5 S(CH 2 ) 1 -, *-(CH 2 ) 5 S(CH 2 ) 2 -, *-(CH 2 ) 5 S(CH 2 ) 3 -, *-(CH 2 ) 6 S(CH 2 ) 1 -, *-(CH 2 ) 6 S(CH 2 ) 2 -, *-(CH 2 ) 6 S(CH 2 ) 3 -, *-(CH 2 ) 7 S(CH 2 ) 1 -, *-(CH 2 ) 7 S(CH 2 ) 2 -, *-(CH 2 ) 7 S(CH 2 ) 3 -, *-(CH 2 ) 8 S(CH 2 ) 1 -, *-(CH 2 ) 8 S(CH 2 ) 2 -, *-(CH 2 ) 8 S(CH 2 ) 3 -, *-(CH 2 ) 9 S(CH 2 ) 1 -, *-(CH 2 ) 9 S(CH 2 ) 2 -, *-(CH 2 ) 9 S(CH 2 ) 3 -, *-(CH 2 ) 1 S(O)(CH 2 ) 1 -, *-(CH 2 ) 2 S(O)(CH 2 ) 2 -, *-(CH 2 ) 2 S(O)(CH 2 ) 1 -, *-(CH 2 ) 1 S(O)(CH 2 ) 2 -, *-(CH 2 ) 1 S(O)(CH 2 ) 3 -, *-(CH 2 ) 1 S(O)(CH 2 ) 4 -, *-(CH 2 ) 2 S(O)(CH 2 ) 3 -, *-(CH 2 ) 2 S(O)(CH 2 ) 4-, *-(CH 2 ) 2 S(O)(CH 2 ) 5 -, *-(CH 2 ) 3 S(O)(CH 2 ) 1 -, *-(CH 2 ) 3 S(O)(CH 2 ) 2 -, *-(CH 2 ) 3 S(O)(CH 2 ) 3 -, *-(CH 2 ) 4 S(O)(CH 2 ) 1 -, *-(CH 2 ) 4 S(O)(CH 2 ) 2 -, *-(CH 2 ) 4 S(O)(CH 2 ) 3 -, *-(CH 2 ) 5 S(O)(CH 2 ) 1 -, *-(CH 2 ) 5 S(O)(CH 2 ) 2 -, *-(CH 2 ) 5 S(O)(CH 2 ) 3 -, *-(CH 2 ) 6 S(O)(CH 2 ) 1 -, *-(CH 2 ) 6 S(O)(CH 2 ) 2 -, *-(CH 2 ) 6 S(O)(CH 2 ) 3 -, *-(CH 2 ) 7 S(O)(CH 2 ) 1 -, *-(CH 2 ) 7 S(O)(CH 2 ) 2 -, *-(CH 2 ) 7 S(O)(CH 2 ) 3 -, *-(CH 2 ) 8 S(O)(CH 2 ) 1 -, *-(CH 2 ) 8 S(O)(CH 2 ) 2 -, *-(CH 2 ) 8 S(O)(CH 2 ) 3 -, *-(CH 2 ) 9 S(O)(CH 2 ) 1 -, *-(CH 2 ) 9 S(O)(CH 2 ) 2 -, *-(CH 2 ) 9 S(O)(CH 2 ) 3 -, *-(CH 2 ) 1 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 1 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 1 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 1 S(O) 2 (CH 2 ) 4 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 4 -, *-(CH 2 ) 2 S(O) 2 (CH 2 ) 5 -, *-(CH 2 ) 3 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 3 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 3 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 4 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 4 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 4 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 5 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 5 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 5 S(O)(CH 2 ) 3 -, *-(CH 2 ) 6 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 6 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 6 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 7 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 7 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 7 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 8 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 8 S(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 8 S(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 9 S(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 9 S(O) 2 (CH 2 ) 2 -, or *-(CH 2 ) 9 S(O) 2 (CH 2 ) 3 represents -, in which * represents the point of attachment to the group R;

[0071] Embodiment 44): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted with substituents selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof:

[0072] -(CH 2 ) 6 -NH-(CH 2 ) 1 -, *-(CH 2 ) 6 -NH-(CH 2 ) 3 -, *-(CH 2 ) 6 -NH-(CH 2 ) 4 -, *-(CH 2 ) 6 -NH-(CH 2 ) 5 -, *-(CH2 ) 7 -NH-(CH 2 ) 1 -, *-(CH 2 ) 7 -NH-(CH 2 ) 2 -, *-(CH 2 ) 7 -NH-(CH 2 ) 3 -, *-(CH 2 ) 7 -NH-(CH 2 ) 4 -, *-(CH 2 ) 6 -NH-CH(CH 3 )-, *-(CH 2 ) 5 -NH-CH(CH 3 )-, *-(CH 2 ) 4 -NH-CH(CH 3 )-, *-(CH 2 ) 3 -NH-CH(CH 3 )-, *-(CH 2 ) 2 -NH-CH(CH 3 )-, *-(CH 2 ) 7 -NH-CH(CH 3 )-, *-(CH 2 ) 8 -NH-CH(CH 3 )-, *-(CH 2 ) 7 -NH-CH(CF 3 )-, *-(CH 2 ) 6 -NH-CH(CF 3 )-, *-(CH 2 ) 5 -NH-CH(CF 3 )-, *-(CH 2 ) 4 -NH-CH(CF 3 )-, *-(CH 2 ) 3 -NH-CH(CF 3 )-, *-(CH 2 ) 2 -NH-CH(CF 3 )-, *-(CH 2 ) 8 -NH-CH(CF 3 )-, *-CH 2 -C(O)NH-(CH 2 ) 4 -, *-CH 2 -C(O)NH-(CH 2 ) 2 -, *-CH 2 -C(O)NH-(CH 2 ) 3 -, *-CH 2 -C(O)NH-(CH 2 ) 5 -, *-(CH 2 ) 1 -Phenylene-(CH 2 ) 1 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 1 -, *-(CH 2 ) 1 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 1 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 1 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 1 -, *-(CH 2 ) 1 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 2 -, *-CH 2 -phenylene-CH 2 -NH-CH(CH 3 )-, *-CH 2 -Phenylene-(CH 2 ) 2 -NH-CH(CH 3 )-, *-CH 2 -phenylene-CH 2 -NH-CH 2 -, *-CH 2 -Phenylene-(CH 2 ) 2 -NH-CH 2 -, *-(CH 2 ) 1 -C(O)NH-(CH 2 ) 4 -, *-(CH 2 ) 1 -furanylene-(CH 2 ) 1 -, *-(CH 2 ) 1 -furanylene-(CH 2 ) 2 -, *-(CH 2 ) 1 -furanylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -furanylene-(CH 2 ) 1 -, *-(CH 2 ) 2 -furanylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -furanylene-(CH 2 ) 1 -, *-(CH 2 ) 3 -furanylene-(CH 2 ) 2 -, *-(CH 2 ) 1 -thiazolylene-(CH 2 ) 1 -, *-(CH 2 ) 1 -thiazolylene-(CH 2 ) 2 -, *-(CH 2 ) 1 -thiazolylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -thiazolylene-(CH 2 ) 1 -, *-(CH 2 ) 2 -thiazolylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -thiazolylene-(CH 2 ) 1 -, *-(CH 2 ) 3 -thiazolylene-(CH 2 ) 2 -, or *-CH 2 -thiazolylene-CH 2 -NH-CH 2 represents -, in which * represents the point of attachment to the group R;

[0073] Embodiment 45): For a compound of formula (I) according to embodiment 20) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where L is optionally substituted (e.g., halogen, C 1-5 optionally substituted with substituents selected from the group consisting of alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or any combination thereof: JPEG2022521746000014.jpg112170 in which * represents the connection point with the group R.

[0074] Embodiment 46): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is C(O)NH 2 , piperidine-1-carbonyl, N,N-diisopropylcarbamoyl, NHC(O)CH 3 , SH, adamantyl-O- (especially adamantan-1-yl-O- or adamantan-2-yl-O-), norcamphanyl-O-, 1,7,7-trimethylbiscyclo[2.2.1] Represents heptanyl-O- (especially (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl-O-) or OH.

[0075] Embodiment 47): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is cyclohexyl-O- (e.g. 2-isopropyl-5-methylcyclohexyl-O-), adamantan-1-yl-O-, adamantan-2-yl-O-, adamantyl-NHC(O)-, 3,5- dimethyladamantan-1-yl-NHC(O)-, adamantan-2-yl-NHC(O)-, or NHC(O)CH 3 represents

[0076] Embodiment 48): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is a linear or branched C optionally substituted with one or more fluorine 1-10 represents alkyl.

[0077] Embodiment 49): For a compound of formula (I) according to embodiment 48) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where X 1 is CF 2 CF 3 or CF 3 represents

[0078] Embodiment 50): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 are halogen, cyano, C 1-3 Alkyl, C 1-3 alkoxy, trifluoromethyl, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy or C 1-5 represents cycloalkyl optionally substituted with substituents selected from the group consisting of alkyl or any combination thereof.

[0079] Embodiment 51): For a compound of formula (I) according to embodiment 50) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where X 1 represents cyclobutyl, 3,3-difluorocyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.2.1]heptan-2-yl or adamantyl.

[0080] Embodiment 52): For a compound of formula (I) according to embodiment 50) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where X 1 represents cyclopropyl, 2,3-dihydro-1H-indenyl or 4-cyano-2,3-dihydro-1H-indenyl.

[0081] Embodiment 53): For a compound of formula (I) according to embodiment 50) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where X 1 is adamantan-1-yl, adamantan-2-yl, 3,5-dimethyladamantan-1-yl or (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl represents

[0082] Embodiment 54): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is the formula N + R. a R. b R. c X - represents a quaternary ammonium base in which R a , R b , R c are independently C 1-20 represents alkyl, and X - is F - , Cl - , Br - , or I - or R in it a and R b form a 5- to 8-membered heterocyclyl together with the N atoms connected thereto, and the ring-constituting atoms of said 5- to 8-membered heterocyclyl are optionally heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur. Including R c is C 1-20 represents alkyl, and X - is F - , Cl - , Br - , or I - represents

[0083] Embodiment 55): For a compound of formula (I) according to embodiment 54) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where R a , R b , R c are independently C 1-10 represents alkyl (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl or decyl) .

[0084] Embodiment 56): For a compound of formula (I) according to embodiment 54) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where R a , R b each independently represents methyl, ethyl, propyl, isopropyl or butyl, and R c represents ethyl, and X - is Cl - represents

[0085] Embodiment 57): A compound of formula (I) according to embodiment 54) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where R a , R b , R c both represent ethyl, and X - is Cl - or where R a , R b , R c both represent methyl, and X - is Cl - represents

[0086] Embodiment 58): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is the formula N + R. a R. b R. c X - represents a quaternary ammonium base in which R a and R b form a 5- to 8-membered heterocyclyl together with the N atoms connected thereto, and the ring-constituting atoms of the 5- to 8-membered heterocyclyl are optionally heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur. Including R c is C 1-20 represents alkyl, and X - is F - , Cl - , Br - , or I - represents

[0087] Embodiment 59): For a compound of formula (I) according to embodiment 58) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where X 1 teeth Represents JPEG2022521746000015.jpg44132.

[0088] Embodiment 60): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is halogen, halogenated C 1-3 alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C 1-5 Represents aryl optionally substituted with substituents selected from the group consisting of alkyl or any combination thereof.

[0089] Embodiment 61): For a compound of formula (I) according to embodiment 58) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where X 1 represents optionally substituted phenyl or naphthyl.

[0090] Embodiment 62): For a compound of formula (I) according to embodiment 58) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where X 1 represents phenyl, 4-fluorophenyl, 4-chlorophenyl, 3,5-difluorophenyl, 4-(bromomethyl)-2-fluorophenyl or 3,4,5-trifluorophenyl.

[0091] Embodiment 63): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 represents optionally substituted heterocyclyl or optionally substituted heteroaryl, wherein the substituents of said optionally substituted heterocyclyl are C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, oxo group, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 selected from the group consisting of alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl, or any combination thereof , and the optionally substituted heteroaryl substituents are C 1-6 Alkyl (e.g. C 1-3alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 selected from the group consisting of alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof .

[0092] Embodiment 64: For a compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof according to embodiment 63), wherein said optionally substituted 5- or 6-membered heterocyclyl substituents are C 1-6 Alkyl (e.g. C 1-3 alkyl), cyano, halogenated C 1-3 A substituent of said optionally substituted 6-membered aryl selected from the group consisting of alkyl, amino, hydroxy, or halogen or any combination thereof, is C 1-6 Alkyl (e.g. C 1-3 alkyl), halogenated C 1-3 The substituents of said optionally substituted 5- or 6-membered heteroaryl are selected from the group consisting of alkyl, amino, hydroxy, or halogen or any combination thereof, and are C 1-6 Alkyl (e.g. C 1-3 alkyl), halogenated C 1-3 selected from the group consisting of alkyl, amino, hydroxy, or halogen or any combination thereof.

[0093] Embodiment 65: A compound of formula (I) according to embodiment 63) or 64) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or stereoisomer thereof For mixtures, where X 1 was arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, oxo group, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 morpholinyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, oxo group, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 piperidinyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, oxo group, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 piperazinyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, oxo group, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof)1, 4-diazacycloheptan-1-yl, optionally substituted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, oxo group, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof)3, 8-diazabicyclo[3.2.1]octan-3-yl, optionally substituted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, oxo group, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof)2, 5-diazabicyclo[2.2.2]octan-2-yl, optionally substituted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 pyrrolidinyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 quinazolinyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 pyridyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 pyrimidyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 thiazolyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 quinolyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C1-6 Alkyl)phosphoryl, C 1-6 indolyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 )benzothienyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof , or arbitrarily permuted (e.g. C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 )benzofuranyl substituted with alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof; show.

[0094] Embodiment 66: A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or stereoisomer thereof according to embodiment 63) or 64) For mixtures, where X 1 optionally substituted groups: 2-azabicyclo[3.2.1]octyl, 1,4-diazacyclobicyclo[3.2.1]octyl, tetrahydro-2H-pyranyl, azacycloheptyl, azacyclooctyl, isoindolyl , thiomorpholino, 5-azaspiro[2.4]heptyl, 6-azaspiro[2.5]octyl, 2-oxa-7-azaspiro[3.5]nonyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[4.1. 0]heptyl, 5,7-dihydro-6H-pyrrolo[3,4-b]pyridyl, 3-azaspiro[5.5]undecane-3-yl, hexahydro-1H-isoindol-2(3H)-yl, ( 3aR,7aS)-hexahydro-1H-isoindol-2(3H)-yl, (3aR,7aS)-octahydro-2H-isoindol-2-yl, azacyclobutyl or [1,4'-dipiperidine ]-1′-yl, in which the substituents of said group are C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, cyano, amino, hydroxy, oxo group, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 optionally selected from alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl or any combination thereof.

[0095] Embodiment 67: For a compound of formula (I) according to embodiment 65) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, where X 1 is morpholinyl, piperidinyl, piperazinyl, N-methylpiperazinyl, (N-methylpiperazinyl)piperidinyl, 3,5-dimethylpiperazinyl, 1,4-diazacycloheptan-1-yl, 4-methyl -1,4-diazacyclohept-1-yl, 1-methyl-1,4-diazacycloheptan-1-yl, 8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl , 5-methyl-2,5-diazabicyclo[2.2.2]octan-2-yl, 4-(4-fluorophenyl)piperazin-1-yl, 4-(3,4-difluorophenyl)piperazin-1-yl , 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2,6-dioxopiperidin-3-yl, pyridyl, pyrimidyl, thiazolyl, quinolyl, 6,7-difluoroquinazolin-4-yl, 3-Cyano-quinolyl, indolyl, 1-methyl-1H-indol-7-yl, benzothionyl, benzofuranyl, quinazolinyl, 6,7-difluoroquinazolin-4-yl, pyrrolidinyl, 4-(pyridin-3-yl)pyrimidine -2-yl or 4,4-difluoropiperidinyl.

[0096] Embodiment 68: A compound of formula (I) according to embodiment 65) or 66) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer or stereoisomer thereof For mixtures, where X 1 is 2-oxopiperidin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, 4-(ethylsulfonyl)piperazin-1-yl, 1,4-diazacyclobicyclo[3.2.1]octane-4 -yl, 8,8-difluoro-2-azabicyclo[3.2.1]octan-2-yl, 3-fluoro-4-hydroxypyrrolidin-1-yl, 3-methyl-4-(trifluoromethyl)pyrrolidine-1 -yl, 4,4-dimethylpiperidin-1-yl, 3,5-dimethylpiperidin-1-yl, 4,4-difluoropiperidin-1-yl, 4-methylpiperazin-1-yl, tetrahydro-2H-pyran -2-yl, pyrrolidin-1-yl, 3-cyanoazacyclobutyl, 3-hydroxyazacyclobutyl, 3-hydroxy-3-methylazacyclobutyl, 3-hydroxy-2-methylazetidin-1-yl, 3-(trifluoromethoxy)azetidin-1-yl, azacycloheptan-1-yl, azacyclooctan-1-yl, 7-fluoro-5-azaspiro[2.4]heptan-5-yl, 1,1-difluoro -5-azaspiro[2.4]heptan-5-yl, 1,1-difluoro-6-azaspiro[2.5]octan-6-yl, 6-azaspiro[2.5]octan-6-yl, 2-oxa-7-azaspiro [3.5]nonan-7-yl, 3-azabicyclo[3.1.0]hexan-3-yl, 6-(difluoromethyl)-3-azabicyclo[4.1.0]heptan-3-yl, 3-fluoro-5,7 -dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, 3-(trifluoromethyl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, iso indol-2-yl, thiomorpholino, [1,4'-dipiperidin]-1'-yl, JPEG2022521746000016.jpg31166 in which * represents the connection point with the group R.

[0097] Embodiment 69: A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof, or for a mixture of stereoisomers, where X 1 represents optionally substituted cycloalkyl or optionally substituted aryl, wherein the substituents of said optionally substituted cycloalkyl are C 1-6 Alkyl, Halogen, C 1-3 alkoxycarbonyl or any combination thereof, wherein said optionally substituted aryl substituents are halogenated C 2-4 selected from the group consisting of alkenyl, halogen or any combination thereof.

[0098] Embodiment 70: For a compound of formula (I) according to embodiment 69) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, where X 1 is (2-bromovinyl)phenyl or Represents JPEG2022521746000017.jpg53137.

[0099] Embodiment 71: A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof, or for a mixture of stereoisomers, where X 1 is NR 6 R. 7 in which R 6 and R 7 each independently H or an optionally substituted linear or branched C 1-10 Represents an alkyl, and the condition is R 6 , R 7 is not H at the same time.

[0100] Embodiment 72: For a compound of formula (I) according to embodiment 71) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, where X 1 is NHCH 3 , N(CH 3 ) 2 , N(CH 2 CH 3 ) 2 , or N(CH(CH 3 ) 2 ) 2 represents

[0101] Embodiment 73: A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof, or for a mixture of stereoisomers, where X 1 is NR 6 R. 7 in which R 6 represents H, and R 7 represents substituted ethyl in which the substituent is 2,6-dichloro-3-fluorophenyl.

[0102] Embodiment 74: A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof, or for a mixture of stereoisomers, where X 1 is NR 6 R. 7 in which R 6 represents H or methyl, and R 7 represents optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, or optionally substituted heteroaryl, wherein R 7 The substituents of said groups represented by are optionally halogen, C 1-5 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 selected from alkylsulfonyl, oxo group, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, optionally substituted 5- or 6-membered heteroaryl, or cyano, wherein said Optionally substituted 5- or 6-membered heterocyclyl substituents are C 1-6 Substituents of said optionally substituted 6-membered aryl selected from alkyl or halogen are C 1-6 The substituents of said optionally substituted 5- or 6-membered heteroaryl are selected from alkyl or halogen and are C 1-6 selected from alkyl or halogen.

[0103] Embodiment 75: For a compound of formula (I) according to embodiment 74) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, where X 1 is NR 6 R. 7 in which R 6 represents H or methyl, and R 7 is pyrimidyl, pyrrolidinyl (especially pyrrolidin-1-yl), pyridyl, quinazolinyl, 6,7-difluoroquinazolin-4-yl, phenyl, 3-chloro-4-methylphenyl, 4-fluorophenyl, 3,5-difluorophenyl , 3,4,5-trifluorophenyl, 2-(dimethylphosphoryl)phenyl, 2-(isopropylsulfonyl)phenyl, 4-(pyridin-3-yl)pyrimidin-2-yl, indolyl, 1-methyl-1H- indol-7-yl, benzothienyl, benzo[b]thiophen-7-yl, benzofuran-7-yl, benzofuranyl, 3-cyano-quinolin-4-yl, quinolyl, thiazolyl, adamantyl, adamantan-1-yl, adamantane -2-yl, 3,5-dimethyladamantan-1-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 4-(4-methylpiperazin-1-yl)piperidine-1 -yl, cyclohexyl, dimethylcyclohexyl (e.g. 4,4-dimethylcyclohexyl), C 7-12 Spirocyclic alkyl (e.g. spiro[5.5]undecane-3-yl, spiro[3.3]heptyl, spiro[3.3]heptan-2-yl), azacycloheptanyl (e.g. azacycloheptan-1-yl), aza cyclooctanyl (e.g. azacyclooctan-1-yl), piperidinyl, dimethylpiperidinyl (e.g. 4,4-dimethylpiperidinyl, 3,5-dimethylpiperidinyl), or azaspirocyclic alkyl (e.g. 3-azaspiro [5.5]Undecane-3-yl).

[0104] Embodiment 76: A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof, or for a mixture of stereoisomers, where X 1 is NR 6 R. 7 in which R 6 represents H, methyl, ethyl, isopropyl or cyclohexyl, and R 7 is an optionally substituted group:

[0105] adamantyl, noradamantyl, norcamphanyl, cyclohexyl, cyclopentyl, cyclopropyl, cyclobutyl, ethyl, isopropyl, tert-butyl, methyl, 2,4-dimethylpentan-3-yl, bicyclopropylmethyl, spiro[3.3]heptyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, 4,4-dimethylcyclohexyl, oxacyclobutyl, oxazolyl, 2,3-dihydro-1H-indenyl, quinuclidine group, 1,7,7-trimethylbicyclo represents [2.2.1]heptyl, 7,7-dimethylbicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptyl or 1-cyclopropylethyl.

[0106] Embodiment 77: For a compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof according to embodiment 76), where R 7 teeth,

[0107] Bicyclo[1.1.1]pentan-1-yl, 4,4-dimethylcyclohexyl, 2-methoxycyclopropyl, 3-fluorocyclobutyl, 3,3-difluorocyclobutyl, 3,3-difluoro-1-(2- (Trifluoromethyl)phenyl)cyclobutyl, 3-(2-(trifluoromethyl)phenyl)oxacyclobutan-3-yl, 3,3-difluorocyclopentyl, 3-hydroxycyclohexyl, (1S,3S)-3-hydroxycyclohexyl , 3-cyano-bicyclo[1.1.1]pentan-1-yl, bicyclo[2.2.2]octan-1-yl, 4-hydroxybicyclo[2.2.2]octan-1-yl, 2-isopropyl-5- methylcyclohexyl, 5-methyloxazol-2-yl, 4-cyano-2,3-dihydro-1H-inden-1-yl, 2,4-dimethylpentan-3-yl, bicyclopropylmethyl, quinuclidin-3-yl , (S)-quinuclidin-3-yl, (R)-quinuclidin-3-yl, adamantan-1-yl, 3-hydroxyadamantyl, 3-hydroxyadamantan-1-yl, 3-chloroadamantan-1-yl, 4-chloroadamantan-1-yl, 2-chloroadamantan-1-yl, adamantan-2-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 7,7-dimethylbicyclo[ 2.2.1]heptan-1-yl, 7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl 3,5-dimethyladamantyl, 3,5-dimethyladamantan-1-yl, hexahydro- 2,5-methanopentalen-3a(1H)-yl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptan-2-yl, 1-cyclopropylethyl, or Represents JPEG2022521746000018.jpg44131.

[0108] Embodiment 78: A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof, or for a mixture of stereoisomers, where X 1 is NR 6 R. 7 in which R 6 represents H, and R 7 represents a substituted thiazolyl in which the substituent has the structural formula C(O)NHR d in which R d is C 1-5 represents alkyl or 2-chloro-6-methylphenyl.

[0109] Embodiment 79): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is NR 6 R. 7 in which R 6 represents H, and R 7 represents pyrimidin-4-yl, pyridin-4-yl or quinazolin-4-yl; or therein X 1 is NR 6 R. 7 in which R 6 and R 7 represents phenyl.

[0110] Embodiment 80): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is NHC(O)NR 9 R. 10 in which R 9 represents H, and R 10 represents adamantyl, adamantan-1-yl, adamantan-2-yl, 3,5-dimethyladamantan-1-yl, phenyl, or 3-chloro-4-methylphenyl.

[0111] Embodiment 81): A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where X 1 is C(O)NH 2 , piperidine-1-carbonyl, N,N-diisopropylcarbamoyl.

[0112] Embodiment 82): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1is OH, adamantyl-O-, norcamphanyl-O-, or 1,7,7-trimethylbiscyclo[2.2.1]heptanyl-O- (e.g. (1S,2R,4S)-1,7,7- represents trimethylbiscyclo[2.2.1]heptanyl-O-).

[0113] Embodiment 83): A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where X 1 is optionally substituted (e.g. substituted with one or more fluoro) linear or branched C 1-10 represents alkyl. In one sub-embodiment, X 1 is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl, decyl, CF 2 CF 3 or CF 3 represents

[0114] Embodiment 84): A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where X 1 is NHC(O)R 8 in which R 8 is straight or branched C 1-6 It represents alkyl, aryl, heteroaryl or heterocyclyl. In one sub-embodiment, X 1 is NHC(O)CH 3 represents

[0115] Embodiment 85): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is NHC(O)NR 9 R. 10 in which R 9 and R 10 are each independently H, an optionally substituted linear or branched C 1-10 represents alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl or optionally substituted heteroaryl, wherein R 9 and R 10 is not arbitrarily H at the same time.

[0116] Embodiment 86): A compound of formula (I) according to any one of embodiments 18) to 45) or 85) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph thereof, For a stereoisomer, or a mixture of stereoisomers, where X 1 is NHC(O)NR 9 R. 10 in which R 9 and R 10 each independently H or the following optionally substituted groups: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl, decyl, phenyl, naphthyl, pyrimidyl, pyridyl, quinazolinyl, quinolyl, isoquinolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, indazolyl, benzimidazolyl, benzotriazolyl , naphthyridinyl, cinnolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl , 1H-pyrrolo[2,3-b]pyridyl, 4H-fluoro[3,2-b]pyrrolyl, adamantyl, adamantan-1-yl, adamantan-2-yl, 3,5-dimethyladamantan-1-yl, represents phenyl or 3-chloro-4-methylphenyl.

[0117] Embodiment 87): A compound of formula (I) according to any one of embodiments 18) to 45), 85) or 86) or a salt, solvate, isotopically enriched analogue, tautomer thereof, For polymorphs, stereoisomers, or mixtures of stereoisomers, where X 1 is NHC(O)NR 9 R. 10 in which R 9 represents H, and R 10 represents adamantyl, adamantan-1-yl, adamantan-2-yl, 3,5-dimethyladamantan-1-yl, phenyl, or 3-chloro-4-methylphenyl.

[0118] Embodiment 88): A compound of formula (I) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments 18) to 45) , or a mixture of stereoisomers, where X 1 is an optionally substituted cycloalkyl (e.g. C 3 -C 12 cycloalkyl or C 3 -C 10 cycloalkyl). In one subembodiment, said cycloalkyl is optionally halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, an oxo group, C 1-3 Alkyl, C 1-3 substituted with alkoxy, cyano, or trifluoromethyl. In one sub-embodiment, X 1 represents cyclobutyl, 3,3-difluorocyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.2.1]heptan-2-yl or adamantyl. In one sub-embodiment, X 1 is adamantan-1-yl, adamantan-2-yl, 3,5-dimethyladamantan-1-yl, or (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2- represents a file.

[0119] Embodiment 89): A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where X 1 represents optionally substituted aryl (eg 5- to 14-membered aryl). In one subembodiment, said aryl is optionally halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or C 1-3 substituted with alkyl. In one sub-embodiment, X 1 represents phenyl, 3-chloro-4-methylphenyl, naphthyl or fluorenyl. In one sub-embodiment, X 1 represents phenyl, 4-fluorophenyl, 3,5-difluorophenyl or 3,4,5-trifluorophenyl.

[0120] Embodiment 90): A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where X 1 represents optionally substituted heterocyclyl (eg 3- to 12-membered heterocyclyl). In one subembodiment, said heterocyclyl is C 1-6 Alkyl, oxo group, di(C 1-6 Alkyl)phosphoryl, C 1-6 alkylsulfonyl, optionally substituted 5- or 6-membered heteroaryl, halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy, oxo group, C 1-3 alkoxy, cyano, trifluoromethyl, optionally substituted aryl (e.g. optionally substituted 6-membered aryl, e.g. phenyl or 4-fluorophenyl), optionally substituted heterocyclyl (e.g. optionally substituted 5- or 6-membered heterocyclyl, eg piperazinyl, N-methylpiperazinyl), optionally substituted with amino or hydroxy. In one subembodiment, the optionally substituted 5- or 6-membered heterocyclyl substituents are C 1-6 Substituents of said optionally substituted 6-membered aryl selected from alkyl or halogen are C 1-6 The substituents of said optionally substituted 5- or 6-membered heteroaryl are selected from alkyl or halogen and are C 1-6 selected from alkyl or halogen. In one sub-embodiment, X 1 is the following optionally substituted heterocyclyl: azacyclobutyl, oxacyclobutyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, acridinyl, triazolyl, tetrahydrofuranyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydrothiapyranyl, oxazolealkyl, thiazolidinyl, piperidinyl, piperazinyl , morpholinyl, thiomorpholinyl, dioxacyclohexyl, 1,4-diazacycloheptan-1-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, or 2,5-diazabicyclo[2.2.2]octane -2-yl, in which the substituents are halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy, an oxo group, C 1-3 Alkyl, C 1-3 be selected from alkoxy, cyano, trifluoromethyl, optionally substituted aryl (especially phenyl, 4-fluorophenyl), optionally substituted heterocyclyl (e.g. piperazinyl, N-methylpiperazinyl), amino or hydroxy can be done. In one sub-embodiment, X 1is morpholinyl, piperidinyl, piperazinyl, N-methylpiperazinyl, (N-methylpiperazinyl)piperidinyl, 3,5-dimethylpiperazin-1-yl, 1,4-diazacycloheptan-1-yl, 4- Methyl-1,4-diazacyclohept-1-yl, 1-methyl-1,4-diazacycloheptan-1-yl, 4-(4-fluorophenyl)piperazin-1-yl, 4-(3 ,4-difluorophenyl)piperazin-1-yl, 4,4-difluoropiperidin-1-yl, 2-oxopiperidin-1-yl, pyrrolidinyl, 2-oxopyrrolidin-1-yl, 2,6-dioxopiperidine -3-yl, 1-methyl-1,4-diazacycloheptan-1-yl, 8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl or 5-methyl-2,5- represents diazabicyclo[2.2.2]octan-2-yl.

[0121] Embodiment 91): A compound of formula (I) according to any one of embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where X 1 represents optionally substituted heteroaryl (eg 5- to 10-membered heteroaryl). In one subembodiment, said heteroaryl is optionally C 1-6 Alkyl, oxo group, di(C 1-6 Alkyl)phosphoryl, C 1-6 alkylsulfonyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl, halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy or p -toluenesulfonyloxy, oxo group, C 1-3 substituted with alkoxy, cyano, or trifluoromethyl. In one subembodiment, the optionally substituted 5- or 6-membered heterocyclyl substituents are C 1-6 the substituents of said optionally substituted 6-membered aryl selected from alkyl or halogen are C 1-6 The substituents of said optionally substituted 5- or 6-membered heteroaryl are selected from alkyl or halogen and are C 1-6 selected from alkyl or halogen. In one sub-embodiment, X 1 optionally substituted quinazolinyl, optionally substituted pyridyl, optionally substituted pyrimidyl, optionally substituted thiazolyl, optionally substituted quinolyl, optionally substituted indolyl, optionally substituted benzothienyl , or optionally substituted benzofuranyl, in which the substituents are as defined above. In one sub-embodiment, X 1 is pyridyl, pyrimidyl, thiazolyl, quinolyl, 6,7-difluoroquinazolin-4-yl, 3-cyano-quinolyl, indolyl, 1-methyl-1H-indol-7-yl, benzothienyl, benzofuranyl, quinazolinyl, 6,7 - represents difluoroquinazolin-4-yl or 4-(pyridin-3-yl)pyrimidin-2-yl.

[0122] Embodiment 92): The compound of formula (I) according to any one of Embodiments 18) to 45) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof isomers, or mixtures of stereoisomers, where X 1 represents a group of formula (G1), JPEG2022521746000019.jpg90164 In formula (G1), A 1 is CH 2 or represents C(O), Ring-constituting atom B 1 , U 1 , V 1 , W 1 are the same, both are CH, or Ring-constituting atom B 1 , U 1 , V 1 , W 1 one of which is N and the other is CH, or Ring-constituting atom B 1 , U 1 , V 1 , W 1 two of which are N and the others are CH, or Ring-constituting atom B 1 , U 1 , V 1 , W 1 three of which are N and the others are CH, or Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents

[0123] Embodiment 93): A compound of formula (I) according to any one of embodiments 18) to 45) or 92) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph thereof, For a stereoisomer, or a mixture of stereoisomers, where X 1 is the expression (G 2 ) represents the group of JPEG2022521746000020.jpg71139(G 2 ), A 1 is CH 2 or represents C(O) and Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents

[0124] Embodiment 94): A compound of formula (I) according to any one of embodiments 18) to 45) or 92) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph thereof, For a stereoisomer, or a mixture of stereoisomers, where X 1 is the expression (G 3 ) represents the group of JPEG2022521746000021.jpg71145(G 3 ), A 1 is CH 2 or represents C(O) and Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents

[0125] Embodiment 95): A compound of formula (I) according to any one of embodiments 18) to 45) or 92) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph thereof, For a stereoisomer, or a mixture of stereoisomers, where X 1 is the expression (G 4 ) represents the group of JPEG2022521746000022.jpg70129(G 4 ), A 1 is CH 2 or represents C(O) and Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents

[0126] Embodiment 96): A compound of formula (I) according to any one of embodiments 18) to 45) or 92) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph thereof, For a stereoisomer, or a mixture of stereoisomers, where X 1 is the expression (G 5 ) represents the group of JPEG2022521746000023.jpg78146(G 5 ), A 1 is CH 2 or represents C(O) and Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents

[0127] Embodiment 97): A compound of formula (I) according to any one of embodiments 18) to 45) or 92) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph thereof, For a stereoisomer, or a mixture of stereoisomers, where X 1 is the expression (G 6 ) represents the group of JPEG2022521746000024.jpg91170(G 6 ), A 1 is CH 2 or represents C(O) and Y 1 represents O or S, and Z is S, S(O) or S(O) 2 represents

[0128] Embodiment 98): A compound of formula (I) according to any one of embodiments 92) to 97) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof , or a mixture of stereoisomers, where A 1 is CH 2 or represents C(O) and Y 1 represents O and Z represents S.

[0129] On the other hand, the present invention provides embodiment A1): compounds of formula (I') or salts, solvates, isotopically enriched analogs, tautomers, polymorphs, stereoisomers (including enantiomers) thereof , or to provide a mixture of stereoisomers, JPEG2022521746000025.jpg77149 here, A, B, U, V, W, Y are as defined in any one of embodiments 1)-14); R is S, S(O) or S(O) 2 represents

[0130] L represents optionally substituted linear or branched alkylene, wherein said linear or branched alkylene is O, C(O), S, S(O), S(O) 2 , S(O) 2 N(R 1 ), N(R 2 )S(O) 2 , C(O)N(R 1 ), N(R 2 )C(O), N(R 3 ), N(R 4 )C(O)N(R 5), optionally substituted cycloalkylene, optionally substituted arylene, optionally substituted heterocyclylene, optionally substituted heteroarylene or any combination thereof. arbitrarily interrupted one or more times by R 1 , R 2 , R 3 , R 4 and R 5 is independently H or C 1-3 represents an alkyl, and

[0131] L. 1 represents H, then X 1 is NHC(O)R i or SR j in which R i and R i are independently C 1-6 Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 represents cycloalkyl optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy or any combination thereof, or X 1 is C 1-6 Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 represents cycloalkyl optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; or

[0132] L. 1 is C 1-3 if it is alkyl, then X 1 is NR 6 R. 7 and R 6 is H or C 1-6 represents alkyl and R 7 is C 1-6 Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 represents cycloalkyl optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; or

[0133] C. 1-6 Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 represents heterocyclyl optionally substituted with substituents selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof.

[0134] Embodiment A2): A compound of formula (I') according to embodiment A1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , where A is CH 2 or represents C(O), and B, U, V, and W all represent CH.

[0135] Embodiment A3): A compound of formula (I') according to embodiment A1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof where L is an optionally substituted linear or branched C 1-40 represents alkylene, in which said linear or branched C 1-40 Alkylene is O;C(O);S;S(O);S(O) 2 ;S(O) 2 N(R 1 );N(R 2 )S(O) 2 ;C(O)N(R 1 );N(R 2 )C(O);N(R 3 );N(R 4 )C(O)N(R 5 ); halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy or C 1-5 arylene optionally substituted with a substituent selected from the group consisting of alkyl; halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo group or C 1-5 heterocyclylene optionally substituted with a substituent selected from the group consisting of alkyl; halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy or C 1-5 heteroarylene optionally substituted with a substituent selected from the group consisting of alkyl; halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy or C 1-5 cycloalkylene optionally substituted with a substituent selected from the group consisting of alkyl; or optionally interrupted one or more times by one or more selected from the group consisting of any combination thereof, wherein , R 1 , R 2 , R 3 , R 4 and R 5 is independently H or C 1-3 represents alkyl.

[0136] Embodiment A4): A compound of formula (I') according to embodiment A1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof , wherein L is the following optionally substituted groups: linear or branched C 1 -C 40 Alkylene,*-(CH 2 ) n1 -N(R 22 )S(O) 2 -(CH 2 ) n2 -, *-(CH 2 ) n1 -S(O) 2 N(R 23 )-(CH 2 ) n2 -, or *-(CH 2 ) n1 -Phenylene-(CH 2 ) n2 - represents, in which * represents the connection point with the group R, R 22 , R 23 are independently H and C 1-3 is selected from alkyl and n1 and n2 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 integers.

[0137] Embodiment A5): A compound of formula (I') according to embodiment A1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof for, where L is the following optionally substituted groups:

[0138] -CH 2 -, -(CH 2 ) 2 -, -(CH 2 ) 3 -, -(CH 2 ) 4 -, -(CH 2 ) 5 -, -(CH 2 ) 6 -, -(CH 2 ) 7 -, -(CH 2 ) 8 -, -(CH 2 ) 9 -, -(CH 2 ) 10 -, -(CH 2 ) 11 -, -(CH 2 ) 12 -, -(CH 2 ) 13 -, -(CH 2 ) 14 -, -(CH 2 ) 15 -, -(CH 2 ) 16 -, -(CH 2 ) 17 -, -(CH 2 ) 18 -, -(CH 2 ) 19 -, -(CH 2 ) 20 -, *-(CH 2 ) 2 -NHS(O) 2 -CH 2 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 2 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 3 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 4 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 5 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 6 -, *-(CH 2 ) 2 -NHS(O)2 -(CH 2 ) 7 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 8 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 9 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 10 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 11 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 12 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 13 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 14 -, *-(CH 2 ) 2 -NHS(O) 2 -(CH 2 ) 15 -, *-(CH 2 ) 3 -NHS(O) 2 -CH 2 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 2 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 3 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 4 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 5 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 6 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 7 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 8 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 9 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 10 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 11 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 12 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 13 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 14 -, *-(CH 2 ) 3 -NHS(O) 2 -(CH 2 ) 15 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 4 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 5 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 6 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 7 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 8 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 9 -, *-(CH 2 ) 4 NHS(O) 2 (CH 2 ) 10 -, *-(CH 2 ) 5 NHS(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 6 NHS(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 7 NHS(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 8 NHS(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 8 NHS(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 9 NHS(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 10 NHS(O) 2 (CH 2 ) 1 -, *-(CH 2 ) 5 NHS(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 6 NHS(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 7 NHS(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 8 NHS(O) 2 (CH 2 ) 3 -, *-(CH 2 ) 9 NHS(O) 2 (CH 2 ) 2 -, *-(CH 2 ) 10 NHS(O) 2 (CH 2 ) 2 -, *-CH 2 -phenylene-CH 2 -, *-(CH 2 ) 1 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 1 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 1 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 1 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 2 -Phenylene-(CH2 ) 5 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 1 -, *-(CH 2 ) 3 -phenylene-CH 2 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 4 -phenylene-CH 2 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 5 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 6 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 7 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -phenylene-CH 2 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 2 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 3 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 4 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 5 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 6 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 7 -, *-(CH 2 ) 8 -Phenylene-(CH 2 ) 8 -, *-CH 2 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 2 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 3 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 4 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 5 -Phenylene-(CH 2 ) 8 -, *-(CH 2 ) 6 -Phenylene-(CH 2 ) 8 -, or *-(CH 2 ) 7 -Phenylene-(CH 2 ) 8 represents -, in which * represents the point of attachment to the group R;

[0139] Embodiment A6): A compound of formula (I') according to embodiment A1) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof for, where L is the following optionally substituted groups: Represents JPEG2022521746000026.jpg13398.

[0140] Embodiment A7): A compound of formula (I') or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof according to any one of embodiments A1) to A6) isomers, or mixtures of stereoisomers, where: L. 1 represents H, and X 1 is an optionally substituted group:

[0141] represents adamantyl-C(O)NH-, adamantyl-S-, or norcamphanyl, in which the substituents of said group are C 1-6 Alkyl (e.g. C 1-3 alkyl), oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof.

[0142] Embodiment A8): A compound of formula (I') according to embodiment A7) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof for, where X 1 is adamantan-1-yl-C(O)NH-, 3-hydroxyadamantyl-C(O)NH-, 3-hydroxyadamantan-1-yl-C(O)NH-, 3-chloroadamantan-1-yl -C(O)NH-, 4-chloroadamantan-1-yl-C(O)NH-, 2-chloroadamantan-1-yl-C(O)NH-, adamantan-2-yl-C(O) NH-, adamantan-1-yl-S-, 3-hydroxyadamantyl-S-, 3-hydroxyadamantan-1-yl-S-, 3-chloroadamantan-1-yl-S-, 4-chloroadamantane-1 -yl-S-, 2-chloroadamantan-1-yl-S-, adamantan-2-yl-S-, bicyclo[2.2.1]heptan-2-yl, 1,7,7-trimethylbicyclo[2.2. 1]heptan-2-yl, 7,7-dimethylbicyclo[2.2.1]heptan-1-yl, or 7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl.

[0143] Embodiment A9): A compound of formula (I') according to any one of embodiments A1) to A6) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof isomers, or mixtures of stereoisomers, where: L. 1 is C 1-3 When representing alkyl, X 1 teeth NR 6 R. 7 and R 6 is H or C 1-3 represents alkyl and R 7 is an optionally substituted group:

[0144] represents adamantyl, cyclohexyl, spirocycloalkyl or norcamphanyl, in which the substituents of said groups are C 1-6 Alkyl (e.g. C 1-3 alkyl), oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof.

[0145] Embodiment A10): A compound of formula (I') according to any one of embodiments A1) to A6) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof isomers, or mixtures of stereoisomers, where R 7 is adamantane-1-yl, 3-hydroxyadamantyl, 3-hydroxyadamantan-1-yl, 3-chloroadamantan-1-yl, 4-chloroadamantan-1-yl, 2-chloroadamantan-1-yl, adamantane- 2-yl, bicyclo[2.2.1]heptan-2-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 7,7-dimethylbicyclo[2.2.1]heptane-1- yl, or 7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl.

[0146] Embodiment A11): A compound of formula (I') according to any one of embodiments A1) to A6) or a salt, solvate, isotopically enriched analogue, tautomer, polymorph, stereoisomer thereof isomers, or mixtures of stereoisomers, where L 1 is C 1-3 When representing alkyl, X 1 represents an optionally substituted piperidinyl, wherein the substituents of said optionally substituted piperidinyl are C 1-6 Alkyl (e.g. C 1-3 alkyl), halogen, oxo group, cyano, amino, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, halogenated C 1-3 Alkyl, di(C 1-6 Alkyl)phosphoryl, C 1-6 selected from the group consisting of alkylsulfonyl or any combination thereof;

[0147] Particularly preferred are the compounds in Table 1 of the present invention and salts thereof (especially pharmaceutically acceptable salts thereof, such as hydrochloride salts), enantiomers, diastereomers, solvates and polymorphs thereof. Table 1 Compounds of the Invention JPEG2022521746000027.jpg13398JPEG2022521746000028.jpg13296JPEG2022521746000029.jpg12297JPEG2022521746000030.jpg12797JPEG2022521746000031.jpg13397JPEG2022521746000032.jpg12796JPEG2022521746000033.jpg12697JPEG2022521746000034.jpg13397JPEG2022521746000035.jpg13397JPEG2022521746000036.jpg13397JPEG2022521746000037.jpg12996JPEG2022521746000038.jpg13297JPEG2022521746000039.jpg13097JPEG2022521746000040.jpg13297JPEG2022521746000041.jpg13396JPEG2022521746000042.jpg12696JPEG2022521746000043.jpg13397JPEG2022521746000044.jpg13297JPEG2022521746000045.jpg13296JPEG2022521746000046.jpg12697JPEG2022521746000047.jpg12697JPEG2022521746000048.jpg12396JPEG2022521746000049.jpg12697JPEG2022521746000050.jpg13396JPEG2022521746000051. jpg13397JPEG2022521746000052.jpg13397JPEG2022521746000053.jpg13297JPEG2022521746000054.jpg13296JPEG2022521746000055.jpg13097JPEG2022521746000056.jpg12397JPEG2022521746000057.jpg13097JPEG2022521746000058.jpg12697JPEG2022521746000059.jpg12997JPEG2022521746000060.jpg13397JPEG2022521746 000061.jpg13397JPEG2022521746000062.jpg13097JPEG2022521746000063.jpg12397JPEG2022521746000064.jpg11997JPEG2022521746000065.jpg13397JPEG2022521746000066.jpg12697JPEG2022521746000067.jpg13397JPEG2022521746000068.jpg12696JPEG2022521746000069.jpg12996JPEG2022521746000070.jpg13297JPEG2022521746000071.jpg13297JPEG2022521746000072.jpg13397JPEG2022521746000073.jpg12397JPEG2022521746000074.jpg12697JPEG2022521746000075.jpg12396JPEG2022521746000076.jpg12697JPEG2022521746000077.jpg12396JPEG2022521746000078.jpg13297JPEG2022521746000079.jpg13397JPEG2022521746000080.jpg13397JPEG2022521746000081.jpg12397JPEG2022521746000082.jpg13297JPEG2022521746000083.jpg13297JPEG2022521746000084.jpg13297JPEG2022521746000085. jpg12697JPEG2022521746000086.jpg13396JPEG2022521746000087.jpg13397JPEG2022521746000088.jpg12397JPEG2022521746000089.jpg12397JPEG2022521746000090.jpg13297JPEG2022521746000091.jpg12397JPEG2022521746000092.jpg13397JPEG2022521746000093.jpg13397JPEG2022521746000094.jpg13397JPEG2022521746000095.jpg1339 7JPEG2022521746000096.jpg13398JPEG2022521746000097.jpg13398JPEG2022521746000098.jpg12696JPEG2022521746000099.jpg13297JPEG2022521746000100.jpg13397JPEG2022521746000101.jpg13097JPEG2022521746000102.jpg13397JPEG2022521746000103.jpg13397JPEG2022521746000104.jpg12797JPEG2022521746000105.jpg13397JPEG2022521746000106.jpg13397JPEG2022521746000107.jpg12797JPEG2022521746000108.jpg12697JPEG2022521746000109.jpg12997JPEG2022521746000110.jpg13396JPEG2022521746000111.jpg13397JPEG2022521746000112.jpg13296JPEG2022521746000113.jpg13396JPEG2022521746000114.jpg12697JPEG2022521746000115.jpg12796JPEG2022521746000116.jpg13297JPEG2022521746000117.jpg13397JPEG2022521746000118.jpg13097JPEG2022521746000119.jpg13296JPEG2022521746000120. jpg8097

[0148] The compounds of formulas (I), (Ia), (Ib), (Ic), (Id), and formula (I') of the present invention can have spatial configuration and thus one or more stereoisomeric forms. It should be recognized that it can exist in the form The present invention also provides compounds in essentially pure isomeric form (e.g. greater than about 90% ee, such as greater than about 95% ee or 97% ee, or greater than 99% ee), and It relates to mixtures thereof (including racemates). These isomers can be prepared using methods conventional in the art, such as asymmetric synthesis (eg using chiral intermediates) or by chiral separation.

[0149] One aspect of the present invention also provides a compound of formula (I) or a compound of formula (I') according to the present invention as an active ingredient, or a pharmaceutically acceptable salt, racemate, enantiomer, dia Stereoisomers, solvates or polymorphs as well as pharmaceutical compositions containing a pharmaceutically acceptable carrier are provided. The pharmaceutical composition according to the present invention further comprises at least one additional drug for treating or preventing cancer or tumor.

[0150] In one embodiment, the cancer or tumor is multiple myeloma, myelodysplastic syndrome (MDS), previously treated myelodysplastic syndrome, plasma cell myeloma, transplant-related cancer, myelofibrosis, plasma cell myeloma, myeloma, neutropenia; leukemia, acute myelocyte leukemia, anemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, acute myeloid leukemia (AML), CD20 positive, primary lymphoma , B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent primary mediastinal (thymic) large B-cell, recurrent transformed non-Hodgkin's lymphoma , refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell, refractory transformed non-Hodgkin's lymphoma, smoldering myeloma (smoldering myeloma), smoldering multiple myeloma, Richter's syndrome.

[0151] The pharmaceutical composition containing the active ingredient according to the present invention can be administered through an appropriate administration route (nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural administration, peritoneal administration, vaginal administration, intramuscular administration). including, but not limited to, intradermal, subcutaneous, transdermal, epidural, intrathecal and intravenous administration. It can be made into such things as tablets, dragees, troches, powders, granules, powder injections, or liquid formulations (eg suspensions, solutions, emulsions or syrups).

[0152] In another aspect of the invention, compounds of formula (I) or compounds of formula (I') according to the invention, or pharmaceutically acceptable salts, racemates, enantiomers, diastereomers, solvents thereof Solutes or polymorphs are used as medicaments.

[0153] In another aspect of the invention, compounds of formula (I) or compounds of formula (I') according to the invention, or pharmaceutically acceptable salts, racemates, enantiomers, diastereomers, solvents thereof Solutes or polymorphs are used to prevent and / or treat cancers or tumors. In one embodiment, the cancer or tumor is multiple myeloma, myelodysplastic syndrome (MDS), previously treated myelodysplastic syndrome, plasma cell myeloma, transplant-related cancer, myelofibrosis, plasma cell myeloma, myeloma, neutropenia; leukemia, acute myelocyte leukemia, anemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, acute myeloid leukemia (AML), CD20 positive, primary lymphoma , B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent primary mediastinal (thymic) large B-cell, recurrent transformed non-Hodgkin's lymphoma , refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell, refractory transformed non-Hodgkin's lymphoma, smoldering myeloma , smoldering multiple myeloma, and Richter's syndrome.

[0154] Another aspect of the invention is a compound of formula (I) or a compound of formula (I') according to the invention, or a pharmaceutically acceptable salt, racemate, enantiomer, diastereomer, solvent Use of the compound or polymorph in the manufacture of a medicament for preventing and / or treating cancer or tumor is provided. In one embodiment, the cancer or tumor is multiple myeloma, myelodysplastic syndrome (MDS), previously treated myelodysplastic syndrome, plasma cell myeloma, transplant-related cancer, myelofibrosis, plasma cell myeloma, myeloma, neutropenia; leukemia, acute myelocyte leukemia, anemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, acute myeloid leukemia (AML), CD20 positive, primary lymphoma , B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent primary mediastinal (thymic) large B-cell, recurrent transformed non-Hodgkin's lymphoma , refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell, refractory transformed non-Hodgkin's lymphoma, smoldering myeloma , smoldering multiple myeloma, and Richter's syndrome.

[0155] Another aspect of the invention further provides compounds of formula (I) or compounds of formula (I') according to the invention, or pharmaceutically acceptable salts, racemates, enantiomers, diastereomers thereof , solvates or polymorphs, or pharmaceutical compositions of the present invention, to a subject.

[0156] In one embodiment, in the method for treating or preventing cancer or tumor according to the present invention, said cancer or tumor is multiple myeloma, myelodysplastic syndrome (MDS), previously treated myelodysplastic syndrome, Cellular myeloma, transplant-related cancer, myelofibrosis, plasma cell myeloma, bone marrow disease, neutropenia; leukemia, acute mammary cell leukemia, anemia, chronic granulocytic leukemia, B-cell chronic lymphoma acute myeloid leukemia (AML), CD20-positive, primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent primary mediastinum (thymic) large B-cell, recurrent transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large cell Selected from the group consisting of type B-cell, refractory transformed non-Hodgkin's lymphoma, smoldering myeloma, smoldering multiple myeloma, Richter's syndrome.

[0157] A compound of formula (I) or a compound of formula (I') according to the present invention, or a pharmaceutically acceptable salt, racemate, enantiomer thereof, in a method for treating or preventing cancer or a tumor according to the present invention. Isomers, diastereoisomers, solvates or polymorphs, or said pharmaceutical compositions are administered at least through nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, intrapleural administration, peritoneal administration, It is administered to the subject by at least one administration method selected from the group consisting of vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural administration, intrathecal administration and intravenous administration. definition Unless otherwise specified, the following terms, phrases and symbols used herein generally have the following meanings. Herein, the general formula for compounds of formula (I) may be used interchangeably with general formula (I-1) below, JPEG2022521746000121.jpg71143

[0158] where A, B, U, V, W, R, L, X 1 and Y and all substituents are as defined in Formula (I). For the same reason, Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), and Formula (Ie) may be interchanged with general formulas that are 180° inverted. Also, herein, the general formula of formula (I') may also be used interchangeably with the following general formula (I'-1), JPEG2022521746000122.jpg76148 where A, B, U, V, W, R, L, X 1 , L 1 and Y and all substituents are as defined in formula (I'). Unless otherwise specified, the singular forms "one," "that," and "the" include the plural forms. Herein, a bond interrupted by a wavy line represents the point at which the represented group is attached to the rest of the molecule. For example, the base of formula (G1) represented by JPEG2022521746000123.jpg76152 shows that Z in the group of formula (G1) is connected to group L of the compound of formula (I).

[0159] In this specification, the symbol "*" in the group L represents the connection point between the group L and the group R, but in the present invention the symbol "*" in the group L is the group L and the group X 1 Also included is an implementation that represents a connection point with

[0160] In the present invention, the terms "halogen atom" or "halogen" used alone or in combination refer to fluorine, chlorine, bromine or iodine, and are preferably F, Cl or Br.

[0161] The term "alkyl" used in the present invention, alone or in combination, refers to straight or branched chain alkyl. The term "C x -C y alkyl” or “C x-y "Alkyl" (where x and y are each an integer) refers to a straight or branched chain alkyl containing x to y carbon atoms. In the present invention, the term "C 1-10 "Alkyl" refers to a straight or branched chain alkyl containing from 1 to 10 carbon atoms. C in the present invention 1-10 Alkyl is C 1-9 preferably alkyl, C 1-8 more preferably alkyl, C 2-8 more preferably alkyl, C 1-7 More preferably it is alkyl and thus C 1-6 Alkyl, C 1-5 alkyl or C 1-4 Alkyl is more preferred. Representative examples are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl and decyl. include. The term "C 1-3 "Alkyl" refers to alkyl containing 1-3 carbon atoms, representative examples of which include methyl, ethyl, n-propyl and isopropyl. In the present invention, the "alkyl" is optionally substituted, and the substituents are halogen, cyano, C 1-3 Alkyl, C 1-3 Preferred are one or more substituents selected from the group consisting of alkoxy, trifluoromethyl, heterocyclyl or any combination thereof.

[0162] In the present invention, the term "alkylene" (which may be used interchangeably with "alkylene chain") used alone or in combination means a linear or branched divalent saturated carbon chain consisting of carbon and hydrogen atoms. A hydrogen group. The term "C x -C y "Alkylene" (where x and y are each an integer) refers to a straight or branched chain alkylene containing x to y carbon atoms. C of the present invention 1 -C 30 Alkylene is preferably C 1 -C 29 Alkylene, C 1 -C 28 Alkylene, C 1 -C 27 Alkylene, C 1 -C 26 Alkylene, C 1 -C 25 Alkylene, C 1 -C 24 Alkylene, C 1 -C 23 Alkylene, C 1 -C 22 Alkylene, C 1 -C 21 Alkylene, C 1 -C 20 Alkylene, C 1 -C 19 Alkylene, C 1 -C 18 Alkylene, C 1 -C 17 Alkylene, C 1 -C 16 Alkylene, C 1 -C15 Alkylene, C 1 -C 14 Alkylene, C 1 -C 13 Alkylene, C 1 -C 12 Alkylene, C 1 -C 11 Alkylene, C 1 -C 10 Alkylene, C 1 -C 9 Alkylene, C 1 -C 8 Alkylene, C 1 -C 7 Alkylene, C 1 -C 6 Alkylene, C 1 -C 5 Alkylene, C 1 -C 4 Alkylene, C 1 -C 3 Alkylene, or C 1 -C 2 is alkylene. Representative examples are methylene, ethylene, propylene, isopropylidene, butylene, isobutylene, sec-butylene, tert-butylene, n-pentylene, isopentylene, neopentylene, tert-pentylene, hexylene, heptylene, octylene, nonylene, decylene, undecylene. , dodecylene, tridecylene, tetradecylene, pentadecylene, hexadecylene, heptadecylene, octadecylene, nonadecylene, eicosylene, heneicosylene, docosylene, tricosylene, tetracosylene, pentacosylene, hexacosylene, heptacosylene, octacosylene, nonacosylene and triacontylene. is not limited to In the present invention, the "alkylene" is optionally substituted, and the substituents are halogen, cyano, C 1-3 Alkyl, C 1-3 Preferred are one or more substituents selected from the group consisting of alkoxy, trifluoromethyl, heterocyclyl or any combination thereof.

[0163] In the present invention, the term "aryl" used alone or in combination means an aromatic hydrocarbon group containing 5 to 14 carbon atoms and optionally containing one or more condensed rings (e.g. phenyl, naphthyl or fluorenyl). In the present invention, said "aryl" is optionally substituted aryl. Substituted aryl refers to aryl substituted one to three times with substituents, wherein the substituents are C 1-6 Alkyl (e.g. C 1-3 alkyl), alkenyl halide, C halide 1-3 alkoxy, cyano, C 1-3 alkoxy, halogenated C 1-3 It is preferably selected from the group consisting of alkyl(trifluoromethyl), heterocyclyl, halogen, amino or hydroxy.

[0164] In the present invention, the term "arylene" used alone or in combination means a divalent aromatic hydrocarbon group containing 5 to 14 carbon atoms and optionally containing one or more condensed rings (e.g. , phenylene, naphthylene or fluorenylene). In the present invention, the "arylene" is optionally substituted arylene. Substituted arylene refers to arylene substituted one to three times with substituents, wherein the substituents are C 1-3 Alkyl, alkenyl halide, C halide 1-3 alkoxy, cyano, C 1-3 alkoxy, halogenated C 1-3 is selected from the group consisting of alkyl(trifluoromethyl), heterocyclyl, halogen, amino or hydroxy.

[0165] In the present invention, the term "alkoxy", used alone or in combination, refers to straight or branched chain alkoxy, whose structural formula is -O-alkyl. Preferably, the alkyl portion of alkoxy can contain 1-10 carbon atoms. Representative examples of "alkoxy" include methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy, 2-pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, 2- Including, but not limited to, hexyloxy, 3-hexyloxy, 3-methylpentyloxy, and the like. The term "C 1 -C 3 alkoxy” or “C 1-3 "Alkoxy" refers to a straight or branched chain alkoxy containing 1-3 carbon atoms. C. 1-3 Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy and isopropoxy. Methoxy and ethoxy are preferred.

[0166] In the present invention, the term "cycloalkyl" used alone or in combination means 3 to 12 carbon atoms (e.g., 3-12, 3-11, 3-10, 3-8, 3- 7, 3-6 carbon atoms) and partially unsaturated (e.g. containing one or more double bonds but not fully conjugated) monocyclic or bicyclic or polycyclic It refers to a cyclic hydrocarbon group. The term "C 3-10 "Cycloalkyl" means a saturated and partially unsaturated (e.g., containing one or more double bonds but not fully conjugated) monocyclic or bicyclic or polycyclic ring having 3 to 10 carbon atoms. It refers to a cyclic hydrocarbon group. The term "cycloalkyl" includes monocyclic, bicyclic or tricyclic alkyls having 3 to 12 carbon atoms. Representative examples of monocyclic cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentynyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Bicyclic and tricyclic cycloalkyls are bridged cyclic alkyls, fused cyclic and spirocycloalkyls (decalinyl, octahydrocyclopentadiene, octahydro-1H-indenyl, 2,3-dihydro-1H-indenyl, spirocycloalkyl, adamantyl , noradamantyl, norcamphanyl (systematic name is biscyclo[2.2.1]heptyl).In the present invention, said “cycloalkyl” is optionally single or polysubstituted such as, but not limited to, 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexyl. Alkyl” substituents are halogen, cyano, C 1-3 Alkyl, C 1-3 alkoxy, halogenated C 1-3 One or more substituents selected from the group consisting of alkyl (eg, trifluoromethyl), amino, hydroxy, heterocyclyl, or any combination thereof.

[0167] In the present invention, the term "cycloalkylene" used alone or in combination means 3 to 12 carbon atoms (e.g., 3-12, 3-11, 3-10, 3-8, 3- saturated and partially unsaturated (e.g. containing one or more double bonds but not fully conjugated) monocyclic or bicyclic or polycyclic rings with 7, 3-6 carbon atoms) Refers to the divalent radicals of hydrocarbons. The term "C 3 -C 10 "Cycloalkylene" means a saturated and partially unsaturated (e.g., containing one or more double bonds, but not fully conjugated) monocyclic or bicyclic or polycyclic ring having 3 to 10 carbon atoms. Refers to the divalent radicals of hydrocarbons. The term "cycloalkylene" includes monocyclic, bicyclic or tricyclic hydrocarbon divalent radicals having from 3 to 12 carbon atoms. Representative examples of monocyclic cycloalkylenes include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene. Bicyclic and tricyclic cycloalkylenes include bridged cyclic alkylenes, fused cyclic alkylenes and spirocyclic alkylenes, such as decarinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, 2,3-dihydro-1H. -Indenylene, spirocycloalkylene, adamantanilen, noradamantanylene, norcamphanylene (systematic name is biscyclo[2.2.1]heptyl), including but not limited to. In the present invention, said "cycloalkylene" is optionally singly or polysubstituted, for example 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-di It includes, but is not limited to, substituted cyclohexyl. The substituents of said substituted "cycloalkylene" are preferably halogen, cyano, C 1-3 Alkyl, C 1-3 alkoxy, halogenated C 1-3 One or more substituents selected from the group consisting of alkyl (eg, trifluoromethyl), amino, hydroxy, heterocyclyl, or any combination thereof.

[0168] In the present invention, the term "C x-y spirocyclic alkyl” or “C x-y A "spirocyclic group" (where x and y are each an integer) refers to a spirocyclic alkyl having x to y carbon atoms. The term "C" used alone or in combination in the present invention 7-12 "Spirocyclic alkyl" refers to spirocyclic alkyl having 7 to 12 carbon atoms. The term "C 7-11 Representative examples of "spirocyclic alkyl" include spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[5.5]undecyl but not limited to these. "C 7-12 Spirocyclic alkyl” further includes halogen, cyano, C 1-3 Alkyl, C 1-3 alkoxy, halogenated C 1-3substituted with one or more substituents selected from the group consisting of alkyl (eg trifluoromethyl), amino, oxo groups, hydroxy, heterocyclyl or any combination thereof.

[0169] In the present invention, the term "heteroaryl" used alone or in combination means one or more independently selected from the group consisting of oxygen, nitrogen and sulfur (e.g., 1 to 6, 1 to 5 5- to 10-membered monocyclic or bicyclic aromatic ring groups containing 1, 1 to 4, or 1 to 3 heteroatoms. Representative examples of such heteroaryl groups are furanyl, oxazolyl, isoxazolyl, oxadiazole, thienyl, thiazolyl, isothiazolyl, thiadiazole, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl. , isobenzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzo[2,1,3]oxadiazole, benzo[ 2,1,3]thiadiazole, benzo[1,2,3]thiadiazole, quinolyl, isoquinolyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a] pyrimidyl, imidazo[1,2-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, 4H-fluoro[3,2-b]pyrrolyl, pyrrolo[ Including, but not limited to, 2,1-b]thiazolyl and imidazo[2,1-b]thiazolyl. By definition, heteroaryl may be unsubstituted or substituted. Substituted heteroaryl refers to heteroaryl substituted one to three times with substituents, wherein the substituents are C 1-3 Alkyl, C 1-3 It is preferably selected from the group consisting of alkoxy, cyano, trifluoromethyl, heterocyclyl, halogen, amino or hydroxy.

[0170] In the present invention, the term “heteroarylene” used alone or in combination means one or more independently selected from the group consisting of oxygen, nitrogen and sulfur (e.g., 1 to 6, 1 to 5 5- to 10-membered monocyclic or bicyclic divalent aromatic ring group containing 1, 1 to 4, or 1 to 3 heteroatoms. Representative examples of the heteroarylene include furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, iso indolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzisoxazolylene, benzothiazolylene, benzoisothiazolylene, benzotriazolylene, benzo[2,1, 3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolylene, isoquinolylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2-a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, 4H-fluoro[3, Including, but not limited to, 2-b]pyrrolylene, pyrrolo[2,1-b]thiazolylene and imidazo[2,1-b]thiazolylene. By definition, heteroarylene may be unsubstituted or substituted. Substituted heteroarylene refers to heteroarylene substituted one to three times with substituents, wherein the substituents are preferably C 1-3 Alkyl, C 1-3 It is preferably selected from the group consisting of alkoxy, cyano, trifluoromethyl, heterocyclyl, halogen, amino or hydroxyl.

[0171] In the present invention, the term "heterocyclyl" or "heterocyclo" used alone or in combination means one or more independently selected from the group consisting of oxygen, nitrogen and sulfur (e.g., 1 to 5 or 3- to 12-membered monocyclic, bicyclic or tricyclic saturated or partially unsaturated (for example, containing one or more double bonds but not fully conjugated) containing 1 to 4 heteroatoms. not) refers to a cyclic hydrocarbon group. In some embodiments, "heterocyclyl" preferably refers to a 3- to 6-membered monocyclic saturated or heterocyclic ring containing one or more heteroatoms independently selected from the group consisting of sulfur, oxygen and nitrogen. Refers to a partially unsaturated (eg, containing one or more double bonds but not fully conjugated) cyclic hydrocarbon group. Representative examples are azacyclobutyl, oxacyclobutyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, acridinyl, triazolyl, tetrahydrofuranyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydrothiapyranyl, oxazolealkyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl. , dioxacyclohexyl, 1,4-diazacycloheptan-1-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, 2,5-diazabicyclo[2.2.2]octan-2-yl, and azaspiro (especially 3-azaspiro[5.5]undecane-3-yl). Said heterocyclyl may be unsubstituted or substituted as defined, wherein the substituents are C 1-6 Alkyl (e.g. C 1-3 alkyl), C 1-3 It is preferably selected from the group consisting of alkoxy, cyano, trifluoromethyl, heterocyclyl, halogen, amino or hydroxy.

[0172] In the present invention, the term "heterocyclylene" used alone or in combination means one or more independently selected from the group consisting of sulfur, oxygen and nitrogen (e.g., 1 to 5 or 1 to 5). 3- to 12-membered monocyclic, bicyclic or tricyclic saturated or partially unsaturated (i.e., containing one or more double bonds but fully conjugated) heteroatoms (including 4). not) refers to a divalent cyclic hydrocarbon group. In some embodiments, "heterocyclylene" preferably refers to a 3- to 6-membered monocyclic ring containing one or more heteroatoms independently selected from the group consisting of sulfur, oxygen and nitrogen. Refers to a saturated or partially unsaturated (eg, containing one or more double bonds but not fully conjugated) divalent cyclic hydrocarbon group. Representative examples of said heterocyclylenes are azetidinylene, oxetanylene, pyrrolidinylene, imidazolidylene, pyrazolidylene, triazolylene, tetrahydrofuranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomol Including, but not limited to, polynylene and dioxanylene. Said heterocyclylene may be unsubstituted or substituted as specifically defined, wherein the substituents are preferably C 1-3 Alkyl, C 1-3 selected from the group consisting of alkoxy, cyano, trifluoromethyl, heterocyclyl, halogen, amino or hydroxyl;

[0173] The term "quaternary ammonium base" as used herein, alone or in combination, refers to the formula N + R. a R. b R. c X - refers to the quaternary ammonium base of, where R a , R b , R c are independently C 1-20 represents alkyl, and X - is F - , Cl - , Br - , or I - or where R a and R b forms a 4- to 8-membered heterocyclyl (especially a 5- to 8-membered heterocyclyl, or a 5- to 6-membered heterocyclyl) together with the N atoms connected thereto, and the ring-constituting atoms of the 5- to 8-membered heterocyclyl are further optionally containing a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur; c is C 1-20 represents alkyl, and X - is F - , Cl - , Br - , or I - represents The heterocyclyl in said 5- to 8-membered heterocyclyl is as defined in the above sentence, and the heteroatom of heterocyclyl optionally further comprises an oxygen atom, a nitrogen atom and / or a sulfur atom. Exemplary heterocyclyls include, but are not limited to piperidinyl, morpholinyl, imidazolyl, triazolyl, piperazinyl. Exemplary heterocyclo quaternary ammonium bases are Including but not limited to JPEG2022521746000124.jpg42122.

[0174] As used herein, "norcamphane" (also referred to as 1,7,7-trimethylbicyclo[2.2.1]heptane; camphane; vinylane) has the definition known to those skilled in the art, and its structural formula is They are as follows. JPEG2022521746000125.jpg59157

[0175] As used herein, “adamantane” (Tricyclo[3.3.1.1 3,7 ]decane) has a definition known to those skilled in the art, and its structural formula is, for example: JPEG2022521746000126.jpg44105

[0176] As used herein, "noradamantane" (also referred to as noradamantane) has the definition known to those skilled in the art, and its structural formula is, for example: JPEG2022521746000127.jpg49124

[0177] As used herein, "adamantanamine" has the definition known to those skilled in the art. An example of "adamantanamine" is adamantane-1-amine (its corresponding English chemical name is adamantan-1-amine or Tricyclo[3.3.1.1 3,7 ]decan-1-amine; CAS:768-94-5) and has the following structural formula: JPEG2022521746000128.jpg44114

[0178] The term "about" is used herein to mean approximately, roughly, approximately, or... left to right. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the stated numerical values. In general, the term “about” modifies values ​​above and below the stated value by varying (increase or decrease) up or down, eg, 10%, 5%, 2%, 1%.

[0179] Compound salts of formula I or compound salts of formula (I′) according to the present invention, or pharmaceutically acceptable salts, solvates, isotopically enriched analogs, tautomers, polymorphs, stereos thereof Mixtures of isomers or stereoisomers are also included within the scope of the invention.

[0180] In all embodiments of the present invention, the chemical salt of Formula I or the chemical salt of Formula (I') or a pharmaceutically acceptable salt thereof is a non-toxic, inorganic or organic acid and / or alkali salt. refers to the salt added by Examples include sulfate, hydrochloride, citrate, maleate, sulfonate, citrate, lactate, tartrate, fumarate, phosphate, dihydrohydrochloride, pyrophosphate, metaphosphate, oxalate acid salts, malonates, benzoates, mandelic acids, succinates, glycolates, paratoluenesulfonates, and the like.

[0181] "Pharmaceutically acceptable carrier" means a pharmaceutically acceptable substance such as a filler, stabilizer, dispersing agent, suspending agent, diluent, excipient, thickener, solvent or encapsulant. Point. Compounds useful in the present invention can perform their desired function by being loaded or transported into the body of a patient. Generally, such constructs are loaded or transported from one organ or part of the body to another organ or part of the body. Carriers must be "acceptable" as compatible with the other ingredients of the formulation (including the compounds useful in the invention) and not injurious to the patient. Some examples of substances used as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn and potato starch; celluloses such as sodium carboxymethylcellulose, ethylcellulose and cellulose acetate. and derivatives thereof; excipients such as powdered tragacanth, malt, gelatin, talc, cocoa butter and suppository wax; oils such as peanut, cottonseed, safflower, sesame, olive, corn and soybean; polyols such as glycerol, sorbitol, mannitol and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; salt buffers; and other common non-toxic compatibilizers used in drug formulations.

[0182] The term "treatment" or "treatment" refers to a compound of formula I, or a compound of formula (I'), or a pharmaceutically acceptable salt thereof, according to the present invention, or a compound of formula I, or a compound of formula By administering a pharmaceutical composition containing the compound of (I') or a pharmaceutically acceptable salt thereof to a subject, it is possible to slow down (alleviate) the development of an unwanted disease or condition, such as cancer or tumor. Point. Beneficial effects or desired clinical outcomes of the present invention include relief of symptoms, reduction in severity of disease, stabilization of disease status, slowing or slowing of disease progression, amelioration or alleviation of disease, and remission of disease. Including but not limited to.

[0183] A "therapeutically effective amount" of a compound according to the present invention will depend on the patient's age, sex and weight, the patient's current medical condition and the progress of the patient's cancer being treated. Appropriate dosages can be determined by those of ordinary skill in the art based on these and other factors.

[0184] The choice of active compound(s) and / or composition and dosage thereof should be based on individual circumstances (generally, individual circumstances) to achieve the best effect. ) should be understood. Administration and dosing regimens should be within the capabilities of those skilled in the art, and appropriate dosages depend on many factors, including physicians, veterinarians and researchers of ordinary skill (Wells et al. eds. , Pharmacotherapy Handbook, 2nd Edition, Appleton and Lange, Stamford, Conn. (2000); PDR Pharmacopoeia, Tarascon Pocket Pharmacopoeia 2000, Deluxe Edition, Tarascon Publishing, Loma Linda, Calif. (2000)). The term "room temperature" in the present invention refers to ambient temperature, for example, temperature of 20 to 30°C. Example

[0185] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. The invention may be practiced without some or all of these given details. In other instances, well known process operations have not been described in detail so as not to unnecessarily obscure the invention. While the invention is illustrated by certain examples, it should be understood that the invention is not intended to be limited by these examples. The following abbreviations are used in all descriptions and examples. JPEG2022521746000129.jpg246170

[0186] In the present invention, 1 H NMR spectra were measured with a Bruker-500 MHz nuclear magnetic resonance spectrometer, CD 3 CD as an internal standard when using OD 3 using OD (δ=3.31 ppm) or CDCl with 0.1% TMS as solvent 3 When using 1 H NMR spectra were obtained with CDCl as an internal standard 3 (δ=7.26 ppm) or DMSO-d with 0.03% TMS as solvent 6 When using 1 H NMR spectra were obtained with DMSO-d as an internal standard. 6 (δ=2.50 ppm) was used. High resolution mass spectrometry data were measured by AB Triple 4600 mass spectrometer, preparative HPLC was measured by SHIMADZU LC-20AP, and HPLC purity was measured by SHIMADZU LC-30AP or Waters 1525. Measured by Unless otherwise specified, all reactions were performed in an air atmosphere, followed by TLC or LC-MS after the reaction, intermediates were separated and purified by column chromatography on ISCO or Biotage, and the final product designed and synthesized was Waters 2767. separated and purified in a preparative liquid phase of the type Solvents and reagents are as follows.

[0187] DCM, DMF, anhydrous EtOH and anhydrous MeOH used as solvents for the reaction were all purchased from Chinese Sinopharm Group. For preparative HPLC, preparative grade CH 3 CN and deionized water were used. All other reagents and pharmaceuticals were purchased from the manufacturer and used as received unless otherwise specified. In addition, the manufacturing methods of the starting materials SIAIS171092, SIAIS171134, SIAIS171123, SIAIS213132, and SIAIS213134 used in some of the examples below are the manufacturing methods of Chinese Patent Application No. 201910279248.9, such as intermediate preparation examples 29, 35, 31, 42 and 43 production methods can be referred to.

[0188] "Norcamphanilamine" ((1R,2S,4R)-born-2-ylamine; (1R,2S,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptane used in the examples of the present invention -2-amine, CAS No. 32511-34-5) has a definition known to those skilled in the art, and its structural formula is for example as shown below. JPEG2022521746000130.jpg55119General composition method General method for preparing thio-substituted pomalidomide carbon chain carboxylic acid series compounds: JPEG2022521746000131.jpg411702-(2,6-dioxopiperidin-3-yl)-4-mercaptoisoindoline-1,3-dione (SIAIS151014) production:

[0189] Pomalidomide (2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione) (20 g, 72.4 mmol) was placed in a 250 mL egg-shaped flask, followed by anhydrous N, N-dimethylcarboxamide (150 mL) was charged and sodium sulfide nonahydrate (28 g, 108.6 mmol) was added batchwise while stirring at room temperature, followed by stirring at room temperature for 6 h. Next, the reaction solution was gradually poured into 400 mL of ice-water mixture, and the pH of the reaction solution was slowly adjusted to 2-3 with 6N hydrochloric acid aqueous solution while stirring. A large amount of solid precipitated. Stir at room temperature for 0.5 h, suction filter, and wash the filter cake three times with water. The filter cake was then slurried with 100 mL of anhydrous acetone, suction filtered, and the filter cake was washed with acetone three times and dried under reduced pressure to yield the intermediate compound (SIAIS151014) (off-white solid, 14 g, 67% yield). ). Preparation of target compounds (thio-substituted pomalidomide alkyl carbon chain carboxylic acid series compounds):

[0190] Intermediate compound SIAIS151014 (3.4 mmol, 1 equiv) was placed in a 100 mL egg-shaped flask, then anhydrous N,N-dimethylcarboxamide (10 mL) and anhydrous potassium carbonate (6.8 mmol, 2 equiv) were added and stirred at room temperature. Slowly the corresponding brominated substrate (4.1 mmol, 1.2 equiv) was added dropwise. After the dropping was completed, the mixture was stirred at room temperature for 0.5 hours. After the starting material reaction was completed, the reaction mixture was poured into 50 mL of water, extracted with ethyl acetate (2x50 mL), the organic phases were combined, washed with water (3x20 mL), washed with saturated brine (50 mL), dried Dry over sodium sulfate, evaporate the solvent under reduced pressure and purify the crude product by column chromatography (eluent (v / v):dichloromethane / ethyl acetate=20:1), rotary evaporate to dryness, The corresponding t-butanol ester intermediate was obtained. The corresponding t-butanol ester intermediate was placed in a 25 mL egg-shaped flask, then 88% formic acid (10 mL) was added, stirred at room temperature for 12 h, the solvent was distilled off under reduced pressure, water was added and lyophilized. to obtain the corresponding target compounds (thio-substituted pomalidomido alkyl carbon chain carboxylic acid series compounds). Thio-substituted pomalidomide PEG chain carboxylic acid series compound general preparation method: JPEG2022521746000132.jpg40170

[0191] Intermediate compound SIAIS151014 (0.724 mmol, 1 equiv) was placed in a 50 mL egg-shaped flask, then anhydrous N,N-dimethylcarboxamide (10 mL) and anhydrous potassium carbonate (1.448 mmol, 2 equiv) were added and gradually stirred at room temperature. The corresponding tosylate-substituted substrate (0.869 mmol, 1.2 equiv) was added dropwise. After the dropping was completed, the mixture was stirred at room temperature for 0.5 hours. After the raw material reaction is completed, the insoluble matter is removed by filtration, and the sample is loaded as it is on a reversed-phase C18 column for separation (eluent: acetonitrile: water 10%-100% (v1: v2)), and the pressure is reduced. Removal of the solvent below gave the corresponding intermediate t-butanol ester. The corresponding intermediate compound t-butanol ester was placed in a 25 mL egg-shaped flask, followed by dichloromethane (1 mL) and trifluoroacetic acid (3 mL), and reacted for 1 h at room temperature with stirring. Evaporate the solvent under reduced pressure, add water and freeze-dry to obtain the corresponding target product. General preparation method for terminal primary amine-substituted thiopomaridomide carbon chain series compounds: JPEG2022521746000133.jpg42170

[0192] Compound SIAIS151014 (2.8 mmol, 1 equiv) was placed in a 100 mL egg-shaped flask, followed by anhydrous N,N-dimethylcarboxamide (20 mL) and anhydrous potassium carbonate (5.6 mmol, 2 equiv) and stirred at room temperature. Then the corresponding brominated substrate (3.4 mmol, 1.2 equiv) was slowly added dropwise, and after the addition was complete, the mixture was stirred at room temperature for 1 h. After the starting material reaction was completed, the reaction mixture was poured into 50 mL of water, extracted with ethyl acetate (3x50 mL), the organic phases were combined, washed with water (3x20 mL), washed with saturated brine (50 mL), dried Dry over sodium sulfate, evaporate the solvent under reduced pressure and separate the crude product on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%). was evaporated under reduced pressure and lyophilized to give the corresponding Boc-protected alkylation product. The resulting Boc-protected alkylated product was placed in a 25 mL egg-shaped flask, then anhydrous dichloromethane (5 mL) and trifluoroacetic acid (0.5 mL) were added and stirred at room temperature for 12 h. Evaporate the solvent under reduced pressure, separate the crude product on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%), remove the solvent under reduced pressure. Evaporation and lyophilization gave the corresponding end-substituted primary amine target product. Thio-Substituted Lenalidomide Carbon Chain Carboxylic Acid Series Compounds General Preparation Method: JPEG2022521746000134.jpg701703-(4-(Benzylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS171088) Preparation:

[0193] Sodium thiosulfate pentahydrate (53.7 g, 216.3 mmol), benzyl chloride (27.4 g, 216.3 mmol), copper sulfate pentahydrate (77.4 mg, 0.31 mmol) with bipyridine (0.72 g, 4.6 mmol) were dissolved in methanol. (120 mL) and water (120 mL) in a 500 mL egg-shaped flask, then gradually heated to 80° C. and stirred for 2 h. The reaction was then allowed to cool to room temperature and 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione (i.e. lenalidomide) (8.0 g, 30.9 mmol) was added, Finally, t-butyl nitrite (4.78 g, 46.4 mmol) was slowly added dropwise. After the dropping was completed, the temperature was raised to 80°C again and the mixture was stirred for 8 hours. After completion of the reaction, the reaction was allowed to cool to room temperature, water (200 mL) was added, extracted with ethyl acetate (2x200 mL), the organic phases were combined, washed with water (2x50 mL) and saturated brine (50 mL). ), dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the crude product was purified by column chromatography (eluent (v / v): petroleum ether / ethyl acetate=1:2) to give the desired compound. (SIAIS171088) (white solid, 6.8 g, 60% yield) was obtained. Preparation of 3-(4-mercapto-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS171095):

[0194] Anhydrous aluminum chloride (2.61 g, 19.6 mmol) and anhydrous toluene (70 mL) were placed in a 250 mL egg-shaped flask and compound (SIAIS171088) (1.8 g, 4.9 mmol) was slowly added with stirring. After the addition was complete, it was stirred overnight at 35°C. After completion of the reaction, a 20% aqueous citric acid solution was gradually added with stirring, and a large amount of solid precipitated. Thereafter, suction filtration was performed, the filter cake was washed with water and ethyl acetate respectively, and the filter cake was dried to obtain the target compound (SIAIS171095) (white solid, 1.15 g, yield 85%). Preparation of Desired Products of the Thio-Substituted Lenalidomide Carbon Chain Carboxylic Acid Series by Compound SIAIS171095:

[0195] Compound SIAIS171095 (0.36 mmol, 1 equiv), the corresponding brominated substrate (0.43 mmol, 1.2 equiv) were placed in a 10 mL egg-shaped flask with anhydrous potassium carbonate (0.72 mmol, 2 equiv), followed by anhydrous N,N-dimethylcarboxamide ( 2 mL) was added and stirred at room temperature for 2 h. After the reaction was completed, it was poured into 50 mL of water, extracted with ethyl acetate (2x50 mL), the organic phases were combined, washed with water (2x30 mL), washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and reduced pressure. The solvent was evaporated under low temperature and the crude product was separated on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%) and the corresponding t-butanol ester An intermediate product was obtained. The corresponding t-butanol ester intermediate was then placed in a 10 mL egg-shaped flask, added with 88% formic acid (3 mL) and stirred at room temperature for 12 h. Evaporate the solvent under reduced pressure, add water and lyophilize to obtain the corresponding target compound. Thio-Substituted Lenalidomide PEG Chain Carboxylic Acid Series Compound General Preparation Method: JPEG2022521746000135.jpg56170

[0196] Compound SIAIS171095 (0.724 mmol, 1 equiv) was placed in a 50 mL egg-shaped flask, then anhydrous N,N-dimethylcarboxamide (10 mL) and anhydrous potassium carbonate (1.448 mmol, 2 equiv) were added, and gradually stirred at room temperature. The corresponding tosylate substrate (0.869mmol, 1.2equiv) was added dropwise. After completion of dropping, the mixture was stirred at room temperature for 0.5 hours. After the raw material reaction is completed, insoluble matter is removed by filtration, and the sample is loaded as it is on a reversed-phase C18 column for separation (acetonitrile:water 10%-100% (v1:v2) as eluent), Removal of the solvent under reduced pressure gave the corresponding intermediate t-butanol ester. The corresponding intermediate compound t-butanol ester was placed in a 25 mL egg-shaped flask, followed by dichloromethane (1 mL) and trifluoroacetic acid (3 mL), and reacted for 1 h at room temperature with stirring. Evaporate the solvent under reduced pressure, add water and freeze-dry to obtain the corresponding target product. A general method for preparing terminally substituted thiolenalidomide carbon chain series compounds with primary amines: JPEG2022521746000136.jpg44170

[0197] Compound SIAIS171095 (0.36 mmol, 1 equiv) was placed in a 10 mL reaction bottle, then anhydrous N,N-dimethylcarboxamide (2 mL) and anhydrous potassium carbonate (0.72 mmol, 2 equiv) were added, and the mixture was gradually added with stirring at room temperature. bromide (0.43 mmol, 1.2 equiv) was added. After completion of dropping, the mixture was stirred at room temperature for 1 hour. After the starting material reaction is finished, the crude product is separated on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10% -100%), and the solvent is distilled off under reduced pressure. Evaporation and lyophilization gave the Boc-protected alkylated intermediate product.

[0198] The Boc-protected alkylated intermediate product obtained in step 1 was placed in a 10 mL reaction bottle followed by anhydrous dichloromethane (2 mL) and trifluoroacetic acid (2 mL) and stirred at room temperature for 12 h. Evaporate the solvent under reduced pressure, separate the crude product on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10% -100%), and evaporate the solvent under reduced pressure. Evaporation and freeze-drying gave the corresponding target compound. A general method for preparing a terminally substituted thiolenalidomide PEG chain series compound with a primary amine: JPEG2022521746000137.jpg56170

[0199] Intermediate compound SIAIS171095 (0.36 mmol, 1 equiv) was placed in a 10 mL egg-shaped flask, then anhydrous N,N-dimethylcarboxamide (2 mL) and anhydrous potassium carbonate (0.72 mmol, 2 equiv) were added and gradually stirred at room temperature. The corresponding brominated substrate (0.43mmol, 1.2equiv) was added dropwise and after the addition was completed, it was stirred at room temperature for 1h. After the raw material reaction is completed, separate on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%), remove the solvent under reduced pressure, Lyophilization afforded the Boc-protected alkylated intermediate product.

[0200] The Boc-protected alkylated intermediate product obtained in step 1 was placed in a 10 mL reaction bottle followed by anhydrous dichloromethane (2 mL) and trifluoroacetic acid (2 mL) and stirred at room temperature for 12 h. Evaporate the solvent under reduced pressure, separate the crude product on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%), remove the solvent under reduced pressure. Evaporation and freeze-drying gave the corresponding target compound. A general method for preparing the alkyl-substituted thiopomalidomid series of compounds: JPEG2022521746000138.jpg67157

[0201] The compound SIAIS151014 (0.344 mmol, 1 equiv) prepared according to Scheme 1, potassium carbonate (0.688 mmol, 2 equiv) and DMF (5 mL) were placed in a 50 mL two-necked flask, protected by argon gas replacement, and then treated with the corresponding halogen-substituted substrate. (0.413mmol, 1.2equiv) was added. After that, the mixture was stirred at room temperature and reacted for 1 hour. After completion of the reaction, insoluble matter was removed by filtration, and then separated on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%), and Removal of the solvent gave the target compound. A general method for preparing the alkyl-substituted thiolenalidomide series of compounds: JPEG2022521746000139.jpg66158 In scheme 9, the group X represents halogen and R 1 is the group X in the compound of formula (I) according to the present invention 1 has the same definition as

[0202] According to Scheme 9, the compound SIAIS171095 (0.344 mmol, 1 equiv) prepared in Scheme 4, potassium carbonate (0.688 mmol, 2 equiv) and DMF (5 mL) were placed in a 50 mL two-neck flask and protected by argon gas replacement. Halogen-substituted substrate (0.413 mmol, 1.2 equiv) was added. After that, the mixture was stirred at room temperature and reacted for 1 hour. After completion of the reaction, remove insoluble matter by filtration, then separate with a reversed-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%), and The target compound was obtained by removing the solvent at . A general method for preparing the sulfoxide or sulfone substituted pomalidomide or lenalidomide series of compounds: JPEG2022521746000140.jpg49170

[0203] Put compound SIAIS151014 or compound SIAIS171095 (0.164 mmol, 1 equiv) and DCM (10 mL) into a 50 mL two-necked flask, add mCPBA (0.328 mmol, 2 equiv) while stirring, replace with argon gas three times, and cool at room temperature. The mixture was stirred and reacted for 2 hours. Add saturated sodium bicarbonate to quench the reaction, extract with DCM, dry over anhydrous sodium sulfate and concentrate to give a colorless oil, add 2 mL of acetonitrile and separate on a reverse phase C18 column ( Eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%), the solvent was removed under reduced pressure to obtain the desired compounds of sulfoxides and sulfones. A general method for preparing compounds of the thiolenalidomide carbon chain series with terminally substituted tertiary or secondary amines: JPEG2022521746000141.jpg57170 in scheme 11, NHR 4 R. 5 represents a linear or branched alkyl secondary amine, or a primary amine or an azacyclo-containing substrate.

[0204] According to Scheme 11, the corresponding terminally bromine-substituted thiolenalidomide compound (0.05 mmol, 1 equiv), potassium carbonate (0.10 mmol, 2 equiv) and DMF (2 mL) are placed in a 15 mL sample vial and reacted with the corresponding secondary amine or A primary amine or azacyclo containing substrate (0.10 mmol, 2 equiv) was added and heated at 40° C. to react overnight. Insolubles were removed by filtration, followed by separation by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), acetonitrile was rotary evaporated, Freeze-drying gave the corresponding target compound. A general method for preparing the terminal diethylamino-substituted thiolenalidomide carbon chain series of compounds: JPEG2022521746000142.jpg47170 In scheme 12, n may be an integer in the range 1-20.

[0205] According to Scheme 12, the corresponding terminally bromine-substituted thiolenalidomide compound (0.05 mmol, 1 equiv) and DMF (2 mL) were put into a 15 mL sample bottle, and diethylamine (0.10 mmol, 2 equiv) was added while stirring, and heated at 40°C. and allowed to react overnight. Filter to remove insolubles, followed by preparative HPLC separation (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), rotary evaporate the acetonitrile and freeze. After drying, the desired compound was obtained. A general method for preparing the terminal nitromethyl-substituted thiolenalidomide carbon chain series of compounds: JPEG2022521746000143.jpg50170

[0206] The corresponding NH-terminated thiolenalidomide (0.033 mmol, 1 equiv), sodium cyanoborohydride (1.0 mmol, 3 equiv) and methanol (2 mL) were placed in a 15 mL sample vial, and formaldehyde (0.066 mmol, 2 equiv) was added with stirring. was added and allowed to react overnight with stirring at room temperature. After filtration, separation by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), rotary evaporation of the acetonitrile and lyophilization followed by A compound was obtained. Example 1: Preparation of 3-(4-(benzylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS171088)

[0207] The method of Scheme 4 provided compound SIAIS171088 (white solid, 6.8 g, 60% yield) under suitable conditions as understood in the art. 1 H NMR (500 MHz, CDCl 3 ) δ 8.07 (s, 1H), 7.75 (t, J = 7.3 Hz, 1H), 7.55 (dd, J = 7.4, 6.8 Hz, 1H), 7.49 - 7.41 (m, 1H), 7.27 - 7.17 (m, 5H), 5.20 - 5.17 (m, 1H), 4.22 (d, J = 16.5 Hz, 1H), 4.15 - 4.04 (m, 2H), 3.92 (d, J = 16.5 Hz, 1H), 2.95 - 2.74 (m , 2H), 2.32 - 2.22 (m, 1H), 2.17 - 2.11 (m, 1H). HRMS (ESI) m / z: calculated value C 20 H. 19 N. 2 O 3 S. +[M+H] + , 367.1111; found 367.1402. Intermediate Example 1: 3-(4-Mercapto-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS171095)

[0208] The method of Scheme 4 provided compound SIAIS171095 (white solid, 1.15 g, 85% yield) under appropriate conditions as understood in the art. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.82 - 7.39 (m, 3H), 5.73 (s, 1H), 5.21 - 5.04 (m, 1H), 4.40 - 4.20 (m, 2H), 2.99 - 2.85 (m, 1H), 2.67 - 2.56 (m, 1H), 2.47 - 2.30 (m, 1H), 2.05 - 1.95 (m, 1H). HRMS (ESI) m / z: calculated value C 13 H. 13 N. 2 O 3 S. + [M+H] + , 277.0641; found 276.8348.

[0209] Intermediate Example 2: Preparation of 3-(4-((5-Aminopentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS171132)

[0210] The method of Scheme 6 prepared compound SIAIS171132 under suitable conditions understood in the art, the difference being that the brominated substrate used was tert-butyl (5-bromopentyl)carbamate. The target compound SIAIS171132 (pale yellow solid, 95 mg, 73% combined yield for two steps) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.00 (s, 1H), 7.85 - 7.45 (m, 6H), 5.21 - 5.07 (m, 1H), 4.42 - 4.16 (m, 2H), 3.16 - 3.05 (m, 2H ), 2.92 - 2.85 (m, 1H), 2.84 - 2.71 (m, 2H), 2.64 - 2.60 (m, 1H), 2.45 - 2.40 (m, 1H), 2.07 - 1.93 (m, 1H), 1.66 - 1.58 (m, 2H), 1.54 - 1.50 (m, 2H), 1.49 - 1.44 (m, 2H). HRMS (ESI) m / z: calculated value C 18 H. 24 N. 3 O 3 S. + [M+H] + , 362.1533; found 362.1537.

[0211] Intermediate Example 3: Preparation of 3-(4-((8-Aminooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS171136)

[0212] The method of Scheme 6 prepared compound SIAIS171136 under suitable conditions understood in the art, the difference being that the brominated substrate used was tert-butyl (8-bromooctyl)carbamate. The target compound SIAIS171136 (white solid, 100 mg, 68% combined yield for two steps) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.75 - 7.47 (m, 6H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.28 (dd, J = 70.1, 17.4 Hz, 2H), 3.13 - 3.00 (m, 2H), 2.98 - 2.84 (m, 1H), 2.78 - 2.74 (m, 2H), 2.64 - 2.59 (m, 1H), 2.47 - 2.38 (m, 1H), 2.06 - 1.93 (m, 1H), 1.68 - 1.54 (m, 2H), 1.52 - 1.48 (m, 2H), 1.45 - 1.34 (m, 2H), 1.30 - 1.20 (m, 6H). HRMS (ESI) m / z: calculated value C 21 H. 30 N. 3 O 3 S. + [M+H] + , 404.2002; observed 404.1996. Example 2: Preparation of 2-(2,6-dioxopiperidin-3-yl)-4-(methylthio)isoindoline-1,3-dione (SIAIS1210073)

[0213] The method of Scheme 8 prepared compound SIAIS1210073 under suitable conditions understood in the art, the difference being that the halogenated substrate used was methyl iodide. The target compound SIAIS1210073 (yellow solid, 58 mg, 55% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.14 (s, 1H), 7.81 (dd, J = 7.9, 7.5 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 7.2 Hz , 1H), 5.12 (dd, J = 12.9, 5.4 Hz, 1H), 2.95 - 2.82 (m, 1H), 2.64 - 2.56 (m, 4H), 2.55 - 2.51 (m, 1H), 2.10 - 2.02 (m , 1H). HRMS (ESI) m / z: calculated value C 14 H. 13 N. 2 O 4 S. + [M+H] + , 305.0591; found 305.0617. Example 3: Preparation of 3-(4-(methylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1210071)

[0214] The method of Scheme 9 prepared compound SIAIS1210071 under suitable conditions understood in the art, the difference being that the halogenated substrate used was methyl iodide. The target compound SIAIS1210071 (white solid, 134 mg, 64% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.58 - 7.50 (m, 3H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.34 (d, J = 17.4 Hz, 1H) , 4.20 (d, J = 17.3 Hz, 1H), 2.97 - 2.86 (m, 1H), 2.60 (d, J = 9.8 Hz, 4H), 2.49 - 2.40 (m, 1H), 2.04 - 1.95 (m, 1H ). HRMS (ESI) m / z: calculated value C 14 H. 15 N. 2 O 3 S. + [M+H] + , 291.0798; found 291.0752. Example 4: Preparation of 3-(4-(ethylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1213073)

[0215] The method of Scheme 9 prepared compound SIAIS1213073 under suitable conditions understood in the art, the difference being that the halogenated substrate used was bromoethane. The target compound SIAIS1213073 (orange solid, 15 mg, 45% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.59 - 7.50 (m, 2H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.3 Hz, 1H), 4.22 (d, J = 17.4 Hz, 1H), 3.10 (q, J = 7.3 Hz, 2H), 2.95 - 2.86 (m, 1H), 2.63 - 2.56 (m, 1H), 2.49 - 2.40 (m, 1H), 2.05 - 1.96 (m, 1H), 1.26 (t, J = 7.3 Hz, 3H). HRMS (ESI) m / z: calculated value C 15 H. 17 N. 2 O 3 S. + [M+H] + , 305.0954; found 305.0904. Example 5: Preparation of 3-(1-oxo-4-(propylthio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1213071)

[0216] The method of Scheme 9 prepared compound SIAIS1213071 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1-bromopropane. The target compound SIAIS1213071 (pale yellow solid, 15 mg, 43% yield) was obtained. 1H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.57 (dd, J = 7.5, 1.2 Hz, 1H), 7.54 (d, J = 7.5 Hz, 1H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.4 Hz, 1H), 4.22 (d, J = 17.4 Hz, 1H), 3.06 (t, J = 7.0Hz,2H), 2.96 - 2.85 (m, 1H), 2.63 - 2.56 (m, 1H), 2.48 - 2.40 (m, 1H), 2.04 - 1.97 (m, 1H), 1.66 - 1.58 (m, 2H) , 0.99 (t, J = 7.3 Hz, 3H). HRMS (ESI) m / z: calculated value C 16 H. 19 N. 2 O 3 S. + [M+H] + , 319.1111; found, 319.1164. Example 6: Preparation of 3-(4-(isopropylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1213075)

[0217] The method of Scheme 9 prepared compound SIAIS1213075 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 2-bromopropane. The target compound SIAIS1213075 (pale yellow solid, 12 mg, 34% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.69 (dd, J = 7.7, 0.9 Hz, 1H), 7.63 (dd, J = 7.5, 0.9 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.38 (d, J = 17.5 Hz, 1H), 4.24 (d, J = 17.5 Hz, 1H), 3.69 - 3.60 (m, 1H), 2.96 - 2.85 (m, 1H), 2.63 - 2.56 (m, 1H), 2.48 - 2.40 (m, 1H), 2.04 - 1.98 (m, 1H), 1.27 (dd, J = 6.6, 2.8Hz, 6H). HRMS (ESI) m / z: calculated value C 16 H. 19 N. 2 O 3 S. + [M+H] + , 319.1111; found 318.1144. Example 7: Preparation of 3-(1-oxo-4-(pentylthio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1213195)

[0218] The method of Scheme 9 prepared compound SIAIS1213195 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1-bromopentane. The target compound SIAIS1213195 (pale yellow solid, 29 mg, 76% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.59 - 7.49 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.08 (t, J = 7.3 Hz, 2H), 2.96 - 2.86 (m, 1H), 2.62 - 2.55 (m, 1H), 2.49 - 2.42 (m, 1H), 2.04 - 1.97 (m, 1H), 1.64 - 1.55 (m, 2H), 1.42 - 1.34 (m, 2H), 1.33 - 1.25 (m, 2H) ), 0.85 (t, J = 7.3 Hz, 3H). HRMS (ESI) m / z: calculated value C 18 H. 23 N. 2 O 3 S. + [M+H] + , 347.1424; found 347.1455. Example 8: Preparation of 3-(1-oxo-4-(pentylthio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1216025)

[0219] The method of Scheme 9 prepared compound SIAIS1216025 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1-bromooctane. The target compound SIAIS1216025 (white solid, 22.4 mg, 58% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.62 (dd, J = 7.5, 1.1 Hz, 1H), 7.58 - 7.50 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.08 (t, J = 7.3 Hz, 2H), 2.96 - 2.87 (m, 1H), 2.62 - 2.56 (m, 1H), 2.49 - 2.40 (m, 1H), 2.04 - 1.97 (m, 1H), 1.62 - 1.55 (m, 2H), 1.44 - 1.35 (m, 2H), 1.28 - 1.20 (m, 8H) ), 0.84 (t, J = 6.9 Hz, 3H). HRMS (ESI) m / z: calculated value C 21 H. 29 N. 2 O 3 S. + [M+H] + , 389.1893; found 389.1901.

[0220] Example 9: Preparation of 3-(4-((3-hydroxypropyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216189)

[0221] The method of Scheme 9 prepared compound SIAIS1216189 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 3-bromo-1-propyl alcohol. The target compound SIAIS1216189 (pale yellow solid, 20 mg, 60% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.64 (dd, J = 7.4, 1.2 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.62 (t, J = 5.2 Hz, 1H), 4.36 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.50 (dd, J = 11.4, 6.0 Hz, 2H), 3.12 (t, J = 7.3 Hz, 2H), 2.96 - 2.88 (m, 1H), 2.63 - 2.55 (m, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.96 (m, 1H) , 1.77 - 1.70 (m, 2H). HRMS (ESI) m / z: calculated value C 16 H. 19 N. 2 O 4 S. + [M+H] + , 335.1060; found 335.1015.

[0222] Example 10: Preparation of 3-(4-((5-hydroxypentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220069)

[0223] The method of Scheme 9 prepared compound SIAIS1220069 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 5-bromo-1-pentanol. The target compound SIAIS1220069 (white solid, 16 mg, 44% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.56 (dd, J = 7.5, 1.2 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.12 (dd, J = 13.3, 5.2 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.37 (t, J = 5.8 Hz, 2H), 3.08 (t, J = 7.3 Hz, 2H), 2.95 - 2.87 (m, 1H), 2.62 - 2.56 (m, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 2.98 (m , 1H), 1.64 - 1.56 (m, 2H), 1.44 - 1.40 (m, 4H). HRMS (ESI) m / z: calculated value C 18 H. 23 N. 2 O 4 S. + [M+H] + , 363.1373; found 363.1376.

[0224] Example 11: Preparation of 3-(4-((8-hydroxyoctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS264006)

[0225] The method of Scheme 9 prepared compound SIAIS264006 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 8-bromo-1-octanol. The target compound SIAIS264006 (white solid, 40 mg, 55% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.62 (dd, J = 7.5, 1.1 Hz, 1H), 7.56 (dd, J = 7.5, 1.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.31 (t, J = 5.2 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.39 - 3.35 (m, 2H), 3.07 (t, J = 7.3 Hz, 2H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 17.4 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.63 - 1.56 (m, 2H), 1.42 - 1.35 (m, 4H), 1.29 - 1.22 (m, 6H). HRMS (ESI) m / z: calculated value C 21 H. 29 N. 2 O 4 S. + [M+H] + , 405.1843; found 405.1849.

[0226] Example 12: Preparation of 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)acetamide (SIAIS1213145)

[0227] The method of Scheme 9 prepared compound SIAIS1213145 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 2-iodoacetamide. The target compound SIAIS1213145 (white solid, 14 mg, 39% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.00 (s, 1H), 7.64 (dd, J = 7.7, 0.9 Hz, 1H), 7.58 (dd, J = 7.5, 0.9 Hz, 1H), 7.53 (t, J = 7.6 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.40 (d, J = 17.4 Hz, 1H), 4.26 (d, J = 17.4 Hz, 1H), 3.74 (s, 2H) , 2.96 - 2.87 (m, 1H), 2.64 - 2.57 (m, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H). HRMS (ESI) m / z: calculated value C 15 H. 16 N. 3 O 4 S. + [M+H] + , 334.0856; found 334.0820.

[0228] Intermediate Example 4: Preparation of 3-(4-((5-bromopentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216049) JPEG2022521746000144.jpg53160

[0229] The method of Scheme 9 prepared compound SIAIS1216049 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,5-dibromopentane. The target compound SIAIS1216049 (white solid, 298 mg, 35% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.64 (dd, J = 7.5, 0.9 Hz, 1H), 7.59 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.52 (t, J = 6.6 Hz, 2H), 3.10 (t, J = 7.1 Hz, 2H) , 2.95 - 2.87 (m, 1H), 2.63 - 2.55 (m, 1H), 2.48 - 2.41 (m, 1H), 2.03 - 1.97 (m, 1H), 1.86 - 1.76 (m, 2H), 1.66 - 1.58 ( m, 2H), 1.57 - 1.48 (m, 2H). HRMS (ESI) m / z: calculated value C 18 H. 22 BrN 2 O 3 S. + [M+H] + , 425.0529; found 425.0535.

[0230] Intermediate Example 5: Preparation of 3-(4-((6-bromohexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216133) JPEG2022521746000145.jpg59157

[0231] The method of Scheme 9 prepared compound SIAIS1216133 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,6-dibromohexane. The target compound SIAIS1216133 (white solid, 339 mg, 38% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.13 (dd, J =13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.52 (t, J = 6.7 Hz, 2H), 3.08 (t, J = 7.2 Hz, 2H) , 2.96 - 2.87 (m, 1H), 2.59 (d, J = 17.4 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.82 - 1.74 (m, 2H), 1.63 - 1.56 (m, 2H), 1.46 - 1.36 (m, 4H). HRMS (ESI) m / z: calculated value C 19 H. 24 BrN 2 O 3 S. + [M+H] + , 439.0686; found 439.0680.

[0232] Intermediate Example 6: Preparation of 3-(4-((7-bromoheptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216135) JPEG2022521746000146.jpg52154

[0233] The method of Scheme 9 prepared compound SIAIS1216135 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,7-dibromoheptane. The target compound SIAIS1216135 (white solid, 212 mg, yield 23%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 7.63 (dd, J = 7.5, 0.9 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.52 (t, J = 6.7 Hz, 2H), 3.08 (t, J = 7.2 Hz, 2H) , 2.96 - 2.87 (m, 1H), 2.63 - 2.56 (m, 1H), 2.49 - 2.40 (m, 1H), 2.04 - 1.97 (m, 1H), 1.82 - 1.73 (m, 2H), 1.63 - 1.56 ( m, 2H), 1.44 - 1.27 (m, 6H).HRMS (ESI) m / z: calculated value C 20 H. 26 BrN 2 O 3 S. + [M+H] + , 453.0842; found 453.0840.

[0234] Intermediate Example 7: Preparation of 3-(4-((8-bromooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216137) JPEG2022521746000147.jpg52119

[0235] The method of Scheme 9 prepared compound SIAIS1216137 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,8-dibromooctane. The target compound SIAIS1216137 (white solid, 351 mg, 38% yield) was obtained. 1H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.20 (d, J = 17.4 Hz, 1H), 3.51 (t, J = 6.7 Hz, 2H), 3.08 (t, J = 7.3 Hz, 2H) , 2.95 - 2.87 (m, 1H), 2.63 - 2.55 (m, 1H), 2.49 - 2.41 (m, 1H), 2.03 - 1.97 (m, 1H), 1.81 - 1.73 (m, 2H), 1.64 - 1.55 ( m, 2H), 1.44 - 1.32 (m, 4H), 1.31 - 1.23 (m, 4H). HRMS (ESI) m / z: calculated value C 21 H. 28 BrN 2 O 3 S. + [M+H] + , 467.0999; found 467.0996.

[0236] Intermediate Example 8: Preparation of 3-(4-((9-bromomonyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220059) JPEG2022521746000148.jpg52143

[0237] The method of Scheme 9 prepared compound SIAIS1220059 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,9-dibromononane. The target compound SIAIS1220059 (white solid, 400 mg, 42% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.00 (s, 1H), 7.62 (dd, J = 7.5, 0.9 Hz, 1H), 7.59 - 7.50 (m, 2H), 5.13 (dd, J =13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.51 (t, J = 6.7 Hz, 2H), 3.07 (t, J = 7.2 Hz, 2H) , 2.95 - 2.86 (m, 1H), 2.59 (d, J = 17.4 Hz, 1H), 2.49 - 2.40 (m, 1H), 2.04 - 1.97 (m, 1H), 1.81 - 1.72 (m, 2H), 1.63 - 1.56 (m, 2H), 1.42 - 1.31 (m, 4H), 1.28 - 1.22 (m, 6H). HRMS (ESI) m / z: calculated value C 22 H. 30 BrN 2 O 3 S. + [M+H] + , 481.1155; found 481.1152.

[0238] Intermediate Example 9: Preparation of 3-(4-((10-bromodecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220013) JPEG2022521746000149.jpg47132

[0239] The method of Scheme 9 prepared compound SIAIS1220013 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,10-dibromodecane. The target compound SIAIS1220013 (pale yellow solid, 329 mg, 33% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.62 (d, J = 7.5 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H) , 4.35 (d, J = 17.4 Hz, 1H), 4.20 (d, J = 17.4 Hz, 1H), 3.52 (t, J = 6.7 Hz, 2H), 3.08 (t, J = 7.2 Hz, 2H), 2.95 - 2.87 (m, 1H), 2.62 - 2.56 (m, 1H), 2.49 - 2.42 (m, 1H), 2.03 - 1.97 (m, 1H), 1.81 - 1.73 (m, 2H), 1.62 - 1.55 (m, 2H), 1.43 - 1.32 (m, 4H), 1.24 (s, 8H). HRMS (ESI) m / z: calculated value C 23 H. 32 BrN 2 O 3 S. + [M+H] + , 495.1312; found 495.1310.

[0240] Intermediate Example 10: Preparation of 3-(4-((11-bromoundecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220015) JPEG2022521746000150.jpg42137

[0241] The method of Scheme 9 prepared the compound SIAIS1220015 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,11-dibromoundecane. The target compound SIAIS1220015 (white solid, 276 mg, yield 27%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.64 - 7.60 (m, 1H), 7.58 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 ( d, J = 17.4 Hz, 1H), 4.20 (d, J = 17.4 Hz, 1H), 3.52 (t, J = 6.7 Hz, 2H), 3.08 (t, J = 7.2 Hz, 2H), 2.96 - 2.86 ( m, 1H), 2.63 - 2.56 (m, 1H), 2.49 - 2.40 (m, 1H), 2.03 - 1.96 (m, 1H), 1.82 - 1.73 (m, 2H), 1.62 - 1.54 (m, 2H), 1.42 - 1.32 (m, 4H), 1.24 (s, 10H). HRMS (ESI) m1 / z: calculated value C 24 H. 34 BrN 2 O 3 S. + [M+H] + , 509.1468; found 509.1466. Example 13: Preparation of 3-(4-(methylsulfonyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1210083)

[0242] The method of Scheme 10 prepared compound SIAIS1210083 under suitable conditions understood in the art, the difference being that the substrate used was thiolenalidomide SAIIS171095. The target compound SIAIS1210083 (white solid, 16 mg, yield 72%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.05 (s, 1H), 8.13 (dd, J = 7.8, 0.8 Hz, 1H), 8.10 (dd, J = 7.6, 0.7 Hz, 1H), 7.84 (t, J = 7.7 Hz, 1H), 5.17 (dd, J = 13.3, 5.1 Hz, 1H), 4.83 (d, J = 18.6 Hz, 1H), 4.68 (d, J = 18.5 Hz, 1H), 3.34 (s, 3H) , 2.96 - 2.86 (m, 1H), 2.65 - 2.57 (m, 1H), 2.49 - 2.42 (m, 1H), 2.07 - 2.00 (m, 1H). HRMS (ESI) m / z: calculated value C 14 H. 15 N. 2 O 5 S. + [M+H] + , 323.0696; found 323.0717.

[0243] Example 14: 3-(4-((5-Morpholinopentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216061)

[0244] The method of Scheme 11 prepared compound SIAIS1216061 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((5-bromopentyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216049) and morpholine. The hydrochloride salt of the target compound SIAIS1216061 (pale yellow solid, 7.3 mg, 34% yield) was obtained. 1H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 10.44 (s, 1H), 7.65 (d, J = 7.0 Hz, 1H), 7.60 - 7.52 (m, 2H), 5.14 (dd, J = 13.3, 5.0 Hz, 1H), 4.36(d, J = 17.4 Hz,, 1H), 4.21 (d, J = 17.4 Hz, 1H), 4.05 - 3.65(m, 4H), 3.41 (t, J = 5.5 Hz , 2H), 3.15 - 2.97 (m, 6H), 2.96 - 2.88 (m, 1H), 2.63 - 2.57 (m, 1H), 2.49 - 2.40 (m, 1H), 2.04 - 1.97 (m, 1H), 1.75 - 1.57 (m, 4H), 1.44 (s, 2H). HRMS (ESI) m / z: calculated value C 22 H. 30 N. 3 O 4 S. + [M+H] + , 432.1952; found, 432.1963.

[0245] Example 15: 3-(1-oxo-4-((5-(piperazin-1-yl)pentyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1216063)

[0246] The method of Scheme 11 prepared compound SIAIS1216063 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((5-bromopentyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216049) and piperazine. The hydrochloride salt of the target compound SIAIS1216063 (pale yellow solid, 12 mg, 56% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 9.02 (s, 2H), 7.64 (dd, J = 7.6, 1.0 Hz, 1H), 7.59 - 7.52 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.50 - 3.48 (m, 4H), 3.43 - 3.39 (m, 2H ), 3.341 - 3.20 (m, 4H), 3.11 - 3.08 (m, 2H), 2.95 - 2.90 (m, 1H), 2.60 (d, J = 17.3 Hz, 1H), 2.48 - 2.40 (m, 1H), 2.05 - 1.98 (m, 1H), 1.67 - 1.55 (m, 4H), 1.44 - 1.39 (m, 2H),. HRMS (ESI) m / z: Calculated value C 22 H. 31 N. 4 O 3 S. + [M+H] + , 431.2111; found, 431.2114.

[0247] Example 16: 3-(4-((5-(methylamino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216141)

[0248] The method of Scheme 11 prepared the compound SIAIS1216141 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((5-bromopentyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216049) and methylamine hydrochloride. The hydrochloride salt of the target compound SIAIS1216141 (white solid, 5 mg, 13% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.25 (s, 2H), 7.64 (dd, J = 7.6, 1.1 Hz, 1H), 7.58 (dd, J = 7.5, 1.0 Hz, 1H) , 7.56 - 7.52 (m, 1H), 5.14 (dd, J = 13.4, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.12 - 3.07 (m, 2H), 2.96 - 2.88 (m, 1H), 2.87 - 2.82 (m, 2H), 2.63 - 2.57 (m, 1H), 2.54 (dd, J = 7.0, 4.6 Hz, 3H), 2.48 - 2.40 (m, 1H), 2.04 - 1.98 (m, 1H), 1.65 - 1.54 (m, 4H), 1.47 - 1.41 (m, 2H). HRMS (ESI) m / z: calculated value C 19 H. 26 N. 3 O 3 S. + [M+H] + , 376.1986; observed 376.1982.

[0249] Example 17: 3-(4-((5-((2-(diethylamino)ethyl)amino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220035)

[0250] The method of Scheme 11 prepared compound SIAIS1220035 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((5-bromopentyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216049) and N1,N1-diethylethane-1,2-diamine. The hydrochloride salt of the target compound SIAIS1220035 (white solid, 20 mg, yield 43%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 10.74 (s, 1H), 9.36 (s, 2H), 7.65 (d, J = 7.4 Hz, 1H), 7.58 (d, J = 7.0 Hz , 1H), 7.54 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.3 Hz, 1H), 4.22 (d, J = 17.4 Hz , 1H), 3.44 - 3.39 (m, 2H), 3.38 - 3.32 (m, 2H), 3.30 (t, J = 7.1 Hz, 2H), 3.20 - 3.15 (m, 4H), 3.09 - 3.05 (m, 1H) ), 2.96 - 2.91 (m, 2H), 2.59 (d, J = 16.4 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.98 (m, 1H), 1.94 - 1.86 (m, 2H), 1.69 - 1.60 (m, 4H), 1.25 (t, J = 7.2 Hz, 6H). HRMS (ESI) m / z: calculated value C 24 H. 37 N. 4 O 3 S. + [M+H] + , 461.2581; found 461.2517.

[0251] Example 18: 3-(4-((6-morpholinohexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220027)

[0252] The method of Scheme 11 prepared compound SIAIS1220027 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((6-bromohexyl)thio)-1-oxoiso Indolin-2-yl)piperidine-2,6-dione (SIAIS1216133) and morpholine. The hydrochloride salt of the target compound SIAIS1220027 (white solid, 17 mg, yield 39%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 10.71 (s, 1H), 7.64 (dd, J = 7.5, 1.0 Hz, 1H), 7.57 (d, J = 6.4 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.3 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.93 (d, J = 11.9 Hz, 2H), 3.76 (t, J = 12.0 Hz, 2H), 3.42 - 3.37 (m, 2H), 3.12 - 3.07 (m, 2H), 3.05 - 2.96 (m, 4H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 17.7 Hz, 1H), 2.50 - 2.41 (m, 1H), 2.05 - 1.98 (m, 1H), 1.69 - 1.58 (m, 4H), 1.48 - 1.40 (m, 2H), 1.34 - 1.27 (m, 2H). HRMS (ESI) m / z: calculated value C 23 H. 32 N. 3 O 4 S. + [M+H] + , 446.2108; found 446.2091.

[0253] Example 19: 3-(4-((7-morpholinoheptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220031)

[0254] The method of Scheme 11 prepared compound SIAIS1220031 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135) and morpholine. The hydrochloride salt of the target compound SIAIS1220031 (white solid, 30 mg, 65% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 2H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.4, 1.0 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.4 Hz,, 1H), 4.22 (d, J = 17.4 Hz, 1H), 3.98 - 3.88 (m , 2H), 3.79 (s, 2H), 3.35 (s, 2H), 3.11 - 3.06 (m, 2H), 3.00 (s, 4H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 17.5 Hz, 1H), 2.49 - 2.42 (m, 1H), 2.04 - 1.97 (m, 1H), 1.67 (s, 2H), 1.63 - 1.57 (m, 2H), 1.45 - 1.37 (m, 2H), 1.33 - 1.24 (m, 4H). HRMS (ESI) m / z: calculated value C 24 H. 34 N. 3 O 4 S. + [M+H] + , 460.2265; found 460.2253.

[0255] Example 20: 3-(4-((8-Morpholinooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216143)

[0256] The method of Scheme 11 prepared the compound SIAIS1216143 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and morpholine. The hydrochloride salt of the target compound SIAIS1216143 (pale yellow solid, 16 mg, 68% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 10.59 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.94 (dd, J = 12.6, 2.8 Hz, 2H), 3.75 ( t, J = 11.4 Hz, 2H), 3.38 (d, J = 12.2 Hz, 2H), 3.11 - 3.06 (m, 2H), 3.05 - 2.97 (m, 4H), 2.96 - 2.88 (m, 1H), 2.63 - 2.56 (m, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.69 - 1.63 (m, 2H), 1.63 - 1.57 (m, 2H), 1.45 - 1.35 (m, 2H), 1.30 - 1.22 (s, 6H). 13 CMR (126 MHz, DMSO) δ 173.35, 171.47, 168.28, 141.39, 132.58, 132.52, 130.69, 120.63, 120.65, 52.11, 47.16, 31.69, 31.69, 31.69 : calculated value C 25 H. 36 N. 3 O 4 S. + [M+H] + , 474.2421; found 474.2420.

[0257] Example 21: 3-(1-oxo-4-((8-(piperazin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1216145)

[0258] The method of Scheme 11 prepared compound SIAIS1216145 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and piperazine. The hydrochloride salt of the target compound SIAIS1216145 (pale yellow solid, 15 mg, 63% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 9.36 (s, 3H), 7.63 (dd, J = 7.6, 0.9 Hz, 1H), 7.58 (dd, J = 7.5, 0.9 Hz, 1H) , 7.53 (t, J = 7.5 Hz, 1H), 5.14 (dd, J = 13.3, 5.3 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.49 (t, J = 6.6 Hz, 2H), 3.15 - 3.06 (m, 6H), 2.96 - 2.87 (m, 1H), 2.60 (d, J = 16.5 Hz, 1H), 2.48 - 2.42 (m, 1H ), 2.04 - 1.98 (m, 1H), 1.62 - 1.57 (m, 4H), 1.42- 1.36 (m, 2H), 1.30 - 1.24 (m, 10H).HRMS (ESI) m / z: calculated value C 25 H. 37 N. 4 O 3 S. + [M+H] + , 473.2581; found 473.2587.

[0259] Example 22: 3-(4-((8-(3,5-dimethylpiperazin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220057)

[0260] The method of Scheme 11 prepared compound SIAIS1220057 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and 2,6-dimethylpiperazine. The hydrochloride salt of the target compound SIAIS1220057 (white solid, 30 mg, yield 60%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.88 (s, 1H), 10.99 (s, 1H), 10.01 (s, 2H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.4, 1.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.79 - 3.64 (m, 4H), 3.12 - 2.98 (m, 6H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 17.5 Hz, 1H), 2.49 - 2.42 (m, 1H), 2.04 - 1.98 (m, 1H), 1.71 (s, 2H), 1.63 - 1.56 (m, 2H), 1.43 - 1.38 (m, 2H), 1.33 - 1.26 (m, 12H). HRMS (ESI) m / z: calculated value C 27 H. 41 N. 4 O 3 S. + [M+H] + ,501.2894; found 501.2891.

[0261] Example 23: 3-(1-oxo-4-((8-(piperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220009)

[0262] The method of Scheme 11 prepared compound SIAIS1220009 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and piperidine. The hydrochloride salt of the target compound SIAIS1220009 (white solid, 38 mg, yield 81%) was obtained. 1H NMR (500 MHz, DMSO) δ 11.71 (s, 1H), 11.02 (s, 1H), 7.63 (d, J = 7.4 Hz, 1H), 7.60 - 7.50 (m, 2H), 5.14 (dd, J = 13.3, 5.0 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.62 - 3.20 (m, 8H), 3.14 - 3.02 (m, 4H), 2.96 - 2.87 (m, 1H), 2.81 (s, 2H), 2.63 - 2.77 (m, 1H), 2.48 - 2.39 (m, 1H), 2.05 - 1.96 (m, 1H), 1.72 - 1.56 (m, 4H) ), 1.45 - 1.35 (m, 2H), 1.27 (s, 6H). HRMS (ESI) m / z: calculated value C 26 H. 38 N. 3 O 3 S. + [M+H] + , 472.2628; found 472.2663.

[0263] Example 24: 3-(4-((8-(4,4-difluoropiperidin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220055)

[0264] The method of Scheme 11 prepared compound SIAIS1220055 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and 4,4-difluoropiperidine. The hydrochloride salt of the target compound SIAIS1220055 (white solid, 12 mg, 40% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 10.86 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.59 - 7.51 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.57 (d, J = 12.4 Hz, 2H), 3.12 - 3.03 ( 2.96 - 2.87 (m, 1H), 2.63 - 2.57 (m, 1H), 2.49 - 2.28 (m, 5H), 2.04 - 1.97 (m, 1H), 1.72 - 1.68 (m, 2H), 1.63 - 1.56 (m, 2H), 1.44 - 1.36 (m, 2H), 1.27 (s, 6H). HRMS (ESI) m / z: calculated value C 26 H. 36 F. 2 N. 3 O 3 S. + [M+H] + , 508.2440; found 508.2415.

[0265] Example 25: 3-(4-((8-(1,4-diazacycloheptan-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione ( SIAIS1220017)

[0266] The method of Scheme 11 prepared compound SIAIS1220017 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and homopiperazine. The hydrochloride salt of the target compound SIAIS1220017 (white solid, 33 mg, yield 67%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 2H), 9.37 (s, 1H), 9.22 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.59 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.75 - 3.42 (m, 6H), 3.25 - 3.15 (m, 2H), 3.13 - 3.00 (m, 4H), 2.96 - 2.87 (m, 1H), 2.62 - 2.56 (m, 1H), 2.49 - 2.41 (m, 1H), 2.20 - 2.07 (m , 2H), 2.04 - 1.98 (m, 1H), 1.71 - 1.62 (m, 2H), 1.62 - 1.55 (m, 2H), 1.45 - 1.35 (m, 2H), 1.27 (s, 6H). HRMS (ESI) m / z: calculated value C 26 H. 39 N. 4 O 3 S. + [M+H] + , 487.2737; found 487.2733.

[0267] Example 26: 3-(1-oxo-4-((8-(4-(piperazin-1-yl)piperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6- Zeon (SIAIS1220019)

[0268] The method of Scheme 11 prepared compound SIAIS1220019 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidin-2,6-dione (SIAIS1216137) and 1-(piperidin-4-yl)piperazine. The hydrochloride salt of the target compound SIAIS1220019 (white solid, 39 mg, yield 70%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 9.44 (s, 1H), 8.72 (s, 2H), 7.63 (dd, J = 7.6, 1.0 Hz, 1H), 7.58 (dd, J = 7.4, 1.0 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.56 - 3.58 (m, 2H), 3.20 - 3.11 (m, 5H), 3.10 - 3.06 (m, 2H), 3.02 - 2.95 (m, 2H), 2.94 - 2.88 (m, 1H), 2.88 - 2.83 (m, 2H), 2.83 - 2.67 (m, 4H), 2.59 (d, J = 17.5 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.06 - 1.95 (m, 3H) , 1.73 - 1.63 (m, 2H), 1.63 - 1.55 (m, 4H), 1.45 - 1.35 (m, 2H), 1.27 (s, 6H). HRMS (ESI) m / z: calculated value C 30 H. 46 N. 5 O 3 S. + [M+H] + , 556.3316; found 556.3313.

[0269] Example 27: 3-(4-((8-(methylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216151)

[0270] The method of Scheme 11 prepared the compound SIAIS1216151 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and methylamine hydrochloride. The hydrochloride salt of the target compound SIAIS1216151 (white solid, 7 mg, 17% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 8.63 (s, 2H), 7.63 (d, J = 7.5 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.08 (t, J = 6.8 Hz, 2H), 2.96 - 2.87 (m, 1H), 2.86 - 2.78 (m, 2H), 2.71 (d, J = 4.9 Hz, 3H), 2.59 (d, J = 16.1 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.04 - 1.97 (m , 1H), 1.63 - 1.53 (m, 4H), 1.44 - 1.36 (m, 2H), 1.29 - 1.23 (m, 6H). HRMS (ESI) m / z: calculated value C 22 H. 32 N. 3 O 3 S. + [M+H] + , 418.2159; found 418.2153.

[0271] Example 28: 3-(4-((8-((2-(diethylamino)ethyl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220037)

[0272] The method of Scheme 11 prepared compound SIAIS1220037 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and N1,N1-diethylethane-1,2-diamine. The hydrochloride salt of the target compound SIAIS1220037 (white solid, 16 mg, 36% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 10.56 (s, 1H), 9.14 (s, 2H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.5, 1.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.3 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.41 - 3.35 (m, 4H), 3.22 - 3.15 (m, 4H), 3.08 (td, J = 7.0, 1.2 Hz, 2H), 2.97 - 2.87 (m, 3H), 2.59 (d, J = 17.5 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.65 - 1.56 (m, 4H), 1.45 - 1.37 (m, 2H), 1.32 - 1.25 (m, 6H), 1.24 (t, J = 7.1 Hz, 6H). HRMS (ESI) m / z: calculated value C 27 H. 43 N. 4 O 3 S. + [M+H] + , 503.3050; found 503.3044.

[0273] Example 29: 3-(4-((8-(4-methylpiperazin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220011)

[0274] The method of Scheme 11 prepared the compound SIAIS1220011 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and 1-methylpiperazine. The hydrochloride salt of the target compound SIAIS1220011 (white solid, 12 mg, yield 80%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 9.60 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.59 - 7.51 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.38 (d, J = 12.1 Hz, 2H), 3.12 - 3.06 ( 2.98 - 2.90 (m, 3H), 2.84 - 2.75 (m, 2H), 2.63 - 2.55 (m, 1H), 2.48 - 2.40 (m, 1H), 2.05 - 1.96 (m, 1H), 1.77 (d, J = 11.1 Hz, 2H), 1.74 - 1.50 (m, 7H), 1.45 - 1.15 (m, 10H). HRMS (ESI) m / z: calculated value C 26 H. 39 N. 4 O 3 S. + [M+H] + , 487.2737; found 487.2732.

[0275] Example 30: 3-(4-((9-morpholinomonyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220065)

[0276] The method of Scheme 11 prepared compound SIAIS1220065 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((9-bromomonyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1220059) and morpholine. The hydrochloride salt of the target compound SIAIS1220065 (white solid, 7 mg, 17% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 2H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.4, 0.9 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.3 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.93 (dd, J = 12.5, 2.7 Hz, 2H), 3.80 (t, J = 11.4 Hz, 2H), 3.35 (s, 2H), 3.08 (t, J = 7.1 Hz, 2H), 3.02 - 2.88 (m, 4H), 2.96 - 2.87 (m, 1H), 2.59 (d, J = 17.7 Hz, 1H), 2.49 - 2.42 (m, 1H), 2.04 - 1.97 (m, 1H), 1.67 (s, 2H), 1.63 - 1.57 (m, 2H), 1.43 - 1.37 (m, 2H), 1.26 (s, 8H). HRMS (ESI) m / z: calculated value C 26 H. 38 N. 3 O 4 S. + [M+H] + ,488.2578; found 488.2576.

[0277] Example 31: 3-(4-((10-morpholinodecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220023)

[0278] The method of Scheme 11 prepared compound SIAIS1220023 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((10-bromodecyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1220013) and morpholine. The hydrochloride salt of the target compound SIAIS1220023 (pale yellow solid, 24 mg, 60% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.06 (s, 1H), 11.02 (s, 1H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.59 - 7.51 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.93 (dd, J = 12.5, 2.9 Hz, 2H), 3.80 ( t, J = 11.4 Hz, 2H), 3.37 (d, J = 12.2 Hz, 2H), 3.08 (t, J = 7.2 Hz, 2H), 3.04 - 2.96 (m, 4H), 2.97 - 2.88 (m, 1H ), 2.63 - 2.56 (m, 1H), 2.50 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.71 - 1.63 (m, 2H), 1.63 - 1.55 (m, 2H), 1.44 - 1.35 (m, 2H), 1.25 (s, 10H). HRMS (ESI) m / z: calculated value C 27 H. 40 N. 3 O 4 S. + [M+H] + , 502.2734; found 502.2728.

[0279] Example 32: 3-(4-((11-Morpholinoundecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220045)

[0280] The method of Scheme 11 prepared compound SIAIS1220045 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((11-bromoundecyl)thio)-1-oxoiso Indolin-2-yl)piperidine-2,6-dione (SIAIS1220015) and morpholine. The hydrochloride salt of the target compound SIAIS1220045 (white solid, 35 mg, yield 85%) was obtained. 1H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 10.66 (s, 1H), 7.62 (dd, J = 7.5, 0.9 Hz, 1H), 7.57 (d, J = 6.6 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.93 (d, J = 12.2 Hz, 2H), 3.76 (t, J = 11.3 Hz, 2H), 3.37 (s, 2H), 3.07 (t, J = 7.2 Hz, 2H), 3.01 (s, 4H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 17.9 Hz, 1H), 2.49 - 2.42 (m, 1H), 2.05 - 1.97 (m, 1H), 1.66 (s, 2H), 1.63 - 1.55 (m , 2H), 1.43 - 1.35 (m, 2H), 1.30 - 1.21 (m, 12H). HRMS (ESI) m / z: calculated value C 28 H. 42 N. 3 O 4 S. + [M+H] + , 516.2890; found 516.2899.

[0281] Example 33: 3-(4-((5-(diethylamino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216139)

[0282] The method of Scheme 12 prepared the compound SIAIS1216139 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((5-bromopentyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216049). The hydrochloride salt of the target compound SIAIS1216139 (pale yellow solid, 21 mg, 71% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 9.13 (s, 1H), 7.64 (dd, J = 7.6, 0.9 Hz, 1H), 7.59 - 7.52 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.37 - 4.33 (m, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.71 - 3.30 (m, 10H), 3.14 - 3.05 (m, 4H), 2.92 (dd, J = 11.2, 6.2 Hz, 1H), 2.60 (d, J = 17.1 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.03 - 1.99 (m, 1H), 1.62 (dd, J = 14.7 , 7.3 Hz, 4H), 1.44 (dd, J = 14.4, 7.3 Hz, 2H). HRMS (ESI) m / z: calculated value C 22 H. 32 N. 3 O 3 S. + [M+H] + , 418.2159; found 418.2155.

[0283] Example 34: 3-(4-((6-(diethylamino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220029)

[0284] The method of Scheme 12 prepared compound SIAIS1220029 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((6-bromohexyl)thio)-1-oxoiso It is indolin-2-yl)piperidine-2,6-dione (SIAIS1216133). The hydrochloride salt of the target compound SIAIS1220029 (white solid, 23 mg, yield 53%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 9.84 (s, 1H), 7.64 (dd, J = 7.5, 1.1 Hz, 1H), 7.59 - 7.52 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.12 - 3.03 (m, 6H), 2.98 - 2.87 (m, 3H ), 2.59 (d, J = 16.5 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.65 - 1.56 (m, 4H), 1.47 - 1.40 (m, 2H), 1.35 - 1.27 (m, 2H), 1.18 (t, J = 7.2 Hz, 6H). HRMS (ESI) m / z: calculated value C 23 H. 34 N. 3 O 3 S. + [M+H] + , 432.2315; found 432.2314.

[0285] Example 35: 3-(4-((7-(diethylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220033)

[0286] The method of Scheme 12 prepared compound SIAIS1220033 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135). The hydrochloride salt of the target compound SIAIS1220033 (white solid, 18 mg, 40% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 9.88 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.5, 1.1 Hz, 1H) , 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.11 - 3.04 (m, 6H), 2.99 - 2.93 (m, 2H), 2.93 - 2.87 (m, 1H), 2.59 (d, J = 17.5 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.98 (m, 1H), 1.64 - 1.57 (m, 4H), 1.44 - 1.38 (m, 2H), 1.34 - 1.26 (m, 4H), 1.19 (t, J = 7.3 Hz, 6H). HRMS (ESI) m / z: calculated value C 24 H. 36 N. 3 O 3 S. + [M+H] + , 446.2472; found 446.2469.

[0287] Example 36: 3-(4-((8-(diethylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216147)

[0288] The method of Scheme 12 prepared compound SIAIS1216147 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137). The hydrochloride salt of the target compound SIAIS1216147 (white solid, 16 mg, yield 70%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 10.02 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.58 - 7.52 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.09 - 3.04 (m, 6H), 2.97 - 2.92 (m, 3H ), 2.63 - 2.56 (m, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.62 - 1.58 (m, 4H), 1.44 - 1.37 (m, 2H), 1.28 (s , 6H), 1.19 (t, J = 3.6 Hz, 6H). HRMS (ESI) m / z: calculated value C 25 H. 38 N. 3 O 3 S. + [M+H] + , 460.2628; found 460.2623.

[0289] Example 37: 3-(4-((9-(diethylamino)nonyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220067)

[0290] The method of Scheme 12 prepared compound SIAIS1220067 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((9-bromomonyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1220059). The hydrochloride salt of the target compound SIAIS1220067 (white solid, 19 mg, yield 79%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 11.16 (s, 1H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.10 - 3.02 (m, 6H), 2.98 - 2.86 (m, 3H ), 2.59 (d, J = 17.5 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.05 - 1.97 (m, 1H), 1.65 - 1.55 (m, 4H), 1.43 - 1.36 (m, 2H), 1.27 (s, 8H), 1.19 (t, J = 7.3 Hz, 6H). HRMS (ESI) m / z: calculated value C 26 H. 40 N. 3 O 3 S. + [M+H] + ,474.2785; found 474.2790.

[0291] Example 38: 3-(4-((10-(diethylamino)decyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220025)

[0292] The method of Scheme 12 prepared compound SIAIS1220025 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((10-bromodecyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1220013). The hydrochloride salt of the target compound SIAIS1220025 (pale yellow solid, 23 mg, 59% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 10.00 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.10 - 3.03 (m, 6H), 2.98 - 2.86 (m, 3H ), 2.63 - 2.55 (m, 1H), 2.49 - 2.40 (m, 1H), 2.04 - 1.97 (m, 1H), 1.64 - 1.55 (m, 4H), 1.44 - 1.36 (m, 2H), 1.26 (d , J = 8.1 Hz, 10H), 1.19 (t, J = 7.3 Hz, 6H). HRMS (ESI) m / z: calculated value C 27 H. 42 N. 3 O 3 S. + [M+H] + ,488.2941; found 488.2929.

[0293] Example 39: 3-(4-((11-(diethylamino)undecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220047)

[0294] The method of Scheme 12 prepared compound SIAIS1220047 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((11-bromoundecyl)thio)-1-oxoiso It is indolin-2-yl)piperidine-2,6-dione (SIAIS1220015). The hydrochloride salt of the target compound SIAIS1220047 (white solid, 19 mg, 48% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 9.66 (s, 1H), 7.62 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.5, 1.1 Hz, 1H) , 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.07 (t, J = 7.0 Hz, 6H), 2.99 - 2.87 (m, 3H), 2.59 (d, J = 17.3 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H ), 1.62 - 1.56 (m, 4H), 1.43 - 1.55 (m, 2H), 1.28 - 1.23 (m, 12H), 1.18 (t, J = 7.3 Hz, 6H). HRMS (ESI) m / z: calculated value C 28 H. 44 N. 3 O 3 S. + [M+H] + ,502.3098; found 502.3097.

[0295] Example 40: 3-(4-((5-(dimethylamino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216089)

[0296] The method of Scheme 13 prepared compound SIAIS1216089 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((5-aminopentyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS171132). The hydrochloride salt of the target compound SIAIS1216089 (pale yellow solid, 7 mg, 54% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.00 (s, 1H), 9.82 (s, 1H), 7.65 (dd, J = 7.5, 1.1 Hz, 1H), 7.58 (dd, J = 7.5, 1.1 Hz, 1H) , 7.54 (t, J = 7.5 Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.3 Hz, 1H), 4.22 (d, J = 17.3 Hz, 1H) , 3.13 - 3.07 (m, 2H), 3.02 - 2.96 (m, 2H), 2.95 - 2.87 (m, 1H), 2.72 (d, J = 4.9 Hz, 6H), 2.63 - 2.57 (m, 1H), 2.47 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.67 - 1.59 (m, 4H), 1.46 - 1.39 (m, 2H). HRMS (ESI) m / z: calculated value C 20 H. 28 N. 3 O 3 S. + [M+H] + , 390.1846; found 390.1849.

[0297] Example 41: 3-(4-((8-(dimethylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216149)

[0298] The method of Scheme 13 prepared compound SIAIS1216149 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-aminooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS171136). The hydrochloride salt of the target compound SIAIS1216149 (white solid, 14 mg, 63% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 9.98 (s, 1H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.59 - 7.51 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.12 - 3.06 (m, 2H), 3.00 - 2.93 (m, 2H ), 2.93 - 2.87 (m, 1H), 2.71 (d, J = 2.8 Hz, 6H), 2.62 - 2.56 (m, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.64 - 1.55 (m, 4H), 1.44 - 1.36 (m, 2H), 1.30 - 1.20 (s, 6H). HRMS (ESI) m / z: calculated value C 23 H. 34 N. 3 O 3 S. + [M+H] + , 432.2315; found 432.2324.

[0299] Example 42: 3-(4-((8-(4-methyl-1,4-diazacycloheptan-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2, 6-dione (SIAIS1220051)

[0300] The method of Scheme 13 prepared compound SIAIS1220051 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-(1,4-diazacycloheptane-1 -yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220017). The hydrochloride salt of the target compound SIAIS1220051 (white solid, 12 mg, yield 62%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.40 (s, 1H), 11.15 (s, 1H), 10.99 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (d, J = 6.5 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.85 - 3.42 (m, 8H), 3.11 - 3.02 (m, 4H), 2.95 - 2.88 (m, 1H), 2.77 (s, 3H), 2.59 (d, J = 17.5 Hz, 1H ), 2.49 - 2.41 (m, 1H), 2.18 (d, J = 47.5 Hz, 2H), 2.05 - 1.98 (m, 1H), 1.72 - 1.63 (m, 2H), 1.63 - 1.56 (m, 2H), 1.44 - 1.36 (m, 2H), 1.27 (s, 6H). HRMS (ESI) m / z: calculated value C 27 H. 41 N. 4 O 3 S. + [M+H] + , 501.2894; found 501.2891.

[0301] Example 43: 3-(4-((8-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2 ,6-dione (SIAIS1220049)

[0302] The method of Scheme 13 prepared compound SIAIS1220049 under suitable conditions understood in the art, the difference being that the substrate used was 3-(1-oxo-4-((8-(4-(piperazine-1 -yl)piperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220019). The hydrochloride salt of the target compound SIAIS1220049 (white solid, 5 mg, yield 63%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 10.28 (s, 1H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.57 (dd, J = 7.4,1.0 Hz, 1H) , 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.60 - 3.52 (m, 5H), 3.25 - 3.15 (m, 3H), 3.11 - 3.05 (m, 3H), 3.00 - 2.84 (m, 7H), 2.79 (s, 3H), 2.59 (d, J = 18.0 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.25 - 2.08 (m, 2H), 2.04 - 1.90 (m, 3H), 1.65 (s, 2H), 1.63 - 1.56 (m, 2H), 1.43 - 1.37 (m, 2H), 1.27 (s, 6H). HRMS (ESI) m / z: calculated value C 31 H. 48 N. 5 O 3 S. + [M+H] + , 570.3472; found 570.3484.

[0303] Intermediate Example 11: Preparation of 3-(4-((3-(bromomethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1227123) JPEG2022521746000151.jpg53126

[0304] The method of Scheme 9 prepared compound SIAIS1227123 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,3-di(bromomethyl)benzene. The target compound SIAIS1227123 (pale yellow oil, 357 mg, 39% yield) was obtained. HRMS (ESI) m / z: calculated value C 21 H. 20 BrN 2 O 3 S. + [M+H] + , 459.0373; found 459.0379. Example 44: Preparation of 3-(4-(tert-butylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1213167) JPEG2022521746000152.jpg82170 Step 1:

[0305] Methyl 3-bromo-2-methylbenzoate (458 mg, 2.0 mmol), NBS (427 mg, 2.4 mmol) and BPO (24 mg, 0.1 mmol) were placed in a 50 mL one-necked flask and replaced with argon gas three times. Then, the mixture was heated to 80°C in an oil bath and reacted overnight. After removing insoluble matter by filtration, after adding a small amount of acetonitrile, the sample was loaded on a reversed-phase C18 column and separated (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%- 100%) and the solvent was removed under reduced pressure to give compound SIAIS1213017 (pale yellow solid, 437 mg, 71% yield). Step 2:

[0306] Methyl 3-bromo-2-bromomethylbenzoate (400 mg, 1.299 mmol), 3-aminopiperidine-2,6-dione hydrochloride (257 mg, 1.559 mmol), triethylamine (263 mg, 1.559 mmol) and acetonitrile (10 mL) was placed in a 100 mL single-necked flask, heated in an oil bath at 80° C., and allowed to react overnight. After the temperature was lowered to room temperature, it was allowed to stand and filtered to obtain a crude product. After adding 10 mL DMSO and heating to dissolve, separate on a reverse-phase C18 column (eluent (v / v): acetonitrile / (water + 0.05% TFA) = 10%-100%), remove the solvent under reduced pressure. was removed to give compound 3-(4-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione SIAIS1213029 (light purple solid, 357 mg, 85% yield). 1 H NMR (500 MHz, MeOD) δ 7.81 (dd, J = 7.7, 3.7 Hz, 2H), 7.49 (t, J = 7.8 Hz, 1H), 5.18 (dd, J = 13.4, 5.2 Hz, 1H), 4.48 (d, J = 17.4 Hz, 1H), 4.41 (d, J = 17.4 Hz, 1H), 2.96 - 2.86 (m, 1H), 2.58 - 2.47 (m, 1H), 2.34 - 2.27 (m, 1H), 2.22 - 2.15 (m, 1H). HRMS (ESI) m / z: calculated value C 13 H. 12 BrN 2 O 3 + [M+H] + , 323.0026, 325.0005; found 322.9970, 324.9954. Step 3:

[0307] 3-(4-Bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione (32.3 mg, 0.100 mmol), potassium carbonate (27.6 mg, 0.200 mmol) and NMP (5 mL) in 25 mL Place in a two-neck flask, replace with argon gas and protect, add palladium acetate (2.2 mg, 0.010 mmol) and dppf (11.1 mg, 0.020 mmol), replace with argon gas and protect, tert-butylthiol. (10.8 mg, 0.120 mmol) was added, heated to 110° C. and allowed to react for 3 h. After filtration through a membrane to remove insolubles, separation by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10%-100%), acetonitrile was rotary evaporated. After lyophilization, compound SIAIS1213167 (gray solid, 10 mg, 30% yield) was obtained. 1 H NMR (500 MHz, CDCl 3 ) δ 8.00 (s, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 5.17 (dd, J = 13.4, 5.1 Hz, 1H), 4.46 (d, J = 16.8 Hz, 1H), 4.33 (d, J = 16.8 Hz, 1H), 2.90 - 2.83 (m, 1H), 2.82 - 2.73 (m, 1H) , 2.40 - 2.29 (m, 1H), 2.20 - 2.13 (m, 1H), 1.27 (s, 9H). HRMS (ESI) m / z: calculated value C 17 H. 21 N. 2 O 3 S. + [M+H] +, 333.1267; found 333.1264. Example 45: Preparation of 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-4-sulfonamide (SIAIS164074) JPEG2022521746000153.jpg57164

[0308] Compound SIAIS151014 (500 mg, 1.72 mmol) was placed in a 100 mL single-necked flask, then 10 mL MeCN was added, and while stirring at room temperature, aqueous ammonia (1.206 g, 8.6 mmol, 25% in water), iodine (87.3 mg, 0.344 mmol, TBHP (1.107 g, 8.6 mmol) were added in this order, and after the addition was completed, 100 o Refluxed at C for 3 h. Quenched with water, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (eluent (v / v):dichloromethane / methanol = 20:1) and rotary dried to give the desired product SIAIS164074 (yellow solid, 140mg, Yield 24%) was obtained. 1 H NMR (500 MHz, DMSO) δ 12.08 (s, 1H), 11.80 (s, 1H), 11.17 (s, 1H), 8.23 ​​(d, J = 7.1 Hz, 1H), 8.07-8.00 (m, 1H) , 7.41 (d, J = 7.1 Hz, 1H), 5.21 (dd, J = 12.9, 5.4 Hz, 1H), 2.91-2.88 (m, 1H), 2.73-2.61 (m, 2H), 2.17-2.11 (m , 1H). HRMS (ESI) m / z: calculated value C 13 H. 12 N. 3 O 6 S. + [M+H] + , 338.0441; found 338.0546.

[0309] Example 46: Preparation of N-(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)acetamide (SIAIS1216095) JPEG2022521746000154.jpg39170

[0310] 3-(4-((5-amino)thio)-1-oxo-2-isoindoline)piperidine-2,6-dione SIAIS171132 (14.5 mg, 0.04 mmol), triethylamine (12.1 mg, 0.12 mmol) and DCM ( 2 mL) was placed in a 15 mL sample bottle, acetyl chloride (3.8 mg, 0.048 mmol) was added with stirring, and the mixture was allowed to react for 0.5 h with stirring at room temperature. After quenching dropwise with a drop of water and filtering through a membrane, separate by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), acetonitrile After rotary evaporation and lyophilization, compound SIAIS1216095 (pale yellow solid, 6 mg, 38% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.81 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.58 - 7.51 (m, 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.07 (t, J = 7.3 Hz, 2H), 3.03 - 2.97 ( m, 2H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 18.0 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H), 1.77 (s, 3H) , 1.63 - 1.56 (m, 2H), 1.42 - 1.37 (m, 4H). HRMS (ESI) m / z: calculated value C 20 H. 26 N. 3 O 4 S. + [M+H] + , 404.1639; found 404.1689.

[0311] Example 47: Preparation of 3-(4-((8-(diisopropylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220021) JPEG2022521746000155.jpg39170

[0312] A 15 mL sample of 3-(4-((8-bromooctyl)thio)-1-oxo-2-isoindoline)piperidine-2,6-dione SIAIS1216137 (23.4 mg, 0.05 mmol) and DMF (2 mL) It was placed in a bottle, and diisopropylamine (10.1 mg, 0.10 mmol) was added with stirring and heated at 90° C. to react for 3 h. After membrane filtration, it was separated by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), acetonitrile was rotary evaporated, and freeze-dried. , to obtain the hydrochloride salt of compound SIAIS1220021 (white solid, 6 mg, 25% yield). 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 8.70 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.60 - 7.51 (m, 2H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.20 (d, J = 17.4 Hz, 1H), 3.62 - 3.55 (m, 2H), 3.09 (t, J = 7.2 Hz, 2H), 3.02 - 2.95 (m, 2H), 2.94 - 2.86 (m, 1H), 2.63 - 2.56 (m, 1H), 2.49 - 2.40 (m, 1H), 2.04 - 1.97 (m, 1H), 1.67 - 1.56 (m, 4H), 1.45 - 1.35 (m, 2H), 1.33 - 1.26 (m, 12H), 1.24 (d, J = 6.4 Hz, 6H). HRMS (ESI) m / z: calculated value C 27 H. 42 N. 3 O 3 S. + [M+H] + , 488.2941; found 488.2930.

[0313] Example 48: 3,3'-((octane-1,8-diyldi(sulfanediyl))di(1-oxoisoindoline-4,2-diyl))di(piperidine-2,6-dione)( Manufacture of SIAIS1216137B)

[0314] The method of Scheme 9 prepared compound SIAIS1216137B under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,8-dibromooctane. The target compound SIAIS1216137B (white solid, 10 mg, 12% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 2H), 7.62 (dd, J = 7.5, 0.9 Hz, 2H), 7.58 - 7.50 (m, 4H), 5.13 (dd, J = 13.3, 5.1 Hz, 2H), 4.35 (d, J = 17.4 Hz, 2H), 4.20 (d, J = 17.4 Hz, 2H), 3.07 (t, J = 7.2 Hz, 4H), 2.95 - 2.86 (m, 2H), 2.62 - 2.55 (m, 2H), 2.48 - 2.40 (m, 2H), 2.04 - 1.96 (m, 2H), 1.61 - 1.53 (m, 4H), 1.42 - 1.34 (m, 4H), 1.25 (s, 4H). HRMS (ESI) m / z: calculated value C 34 H. 39 N. 4 O 6 S. 2 + [M+H] + , 663.2306; found 663.2303.

[0315] Example 49: 3,3'-((nonane-1,9-diyldi(sulfanediyl))di(1-oxoisoindoline-4,2-diyl))bis(piperidine-2,6-dione)( Manufacture of SIAIS1220059B)

[0316] The method of Scheme 9 above prepared compound SIAIS1220059B under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,9-dibromononane. The target compound SIAIS1220059B (white solid, 12 mg, 13% yield) was obtained. 1H NMR (500 MHz, DMSO) δ 10.98 (s, 2H), 7.61 (dd, J = 7.5, 1.1 Hz, 2H), 7.59 - 7.49 (m, 4H), 5.12 (dd, J = 13.3, 5.1 Hz, 2H), 4.35 (d, J = 17.4 Hz, 2H), 4.21 (d, J = 17.4 Hz, 2H), 3.06 (t, J = 7.2 Hz, 4H), 2.95 - 2.86 (m, 2H), 2.59 ( d, J = 17.0 Hz, 2H), 2.49 - 2.41 (m, 2H), 2.04 - 1.96 (m, 3.1 Hz, 2H), 1.61 - 1.53 (m, 4H), 1.42 - 1.34 (m, 4H), 1.29 - 1.20 (m, 6H). HRMS (ESI) m / z: calculated value C 35 H. 41 N. 4 O 6 S. 2 + [M+H] + , 677.2462; found 677.2468. Example 50: Preparation of 3-(5-Mercapto-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1213175) JPEG2022521746000156.jpg36170 Step 1: Preparation of 3-(5-(benzylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1213173)

[0317] 3-(5-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione (64.6 mg, 0.200 mmol), potassium carbonate (55.2 mg, 0.400 mmol) and NMP (5 mL) were mixed in 25 mL of 2 Place in a necked flask, replace with argon gas for protection, add palladium acetate (4.4 mg, 0.02 mmol) and dppf (22.2 mg, 0.04 mmol), replace with argon gas for protection, and benzyl mercaptan (29 mg, 0.24 mmol) was added, heated to 110° C. and reacted for 3 h. After filtration through a membrane to remove insolubles, separation was performed by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), and acetonitrile was rotary evaporated. After lyophilization, compound SIAIS1213173 (grey solid, 50 mg, 68% yield) was obtained. 1 H NMR (500 MHz, CDCl 3 ) δ 7.95 (s, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.39 - 7.31 (m, 5H), 7.31 - 7.29 (m, 1H) , 5.22 (dd, J = 13.2, 4.9 Hz, 1H), 4.46 (d, J = 15.9 Hz, 1H), 4.30 (d, J = 15.9 Hz, 1H), 4.24 (s, 2H), 2.95 (d, J = 16.7 Hz, 1H), 2.89 - 2.81 (m, 1H), 2.40 - 2.31 (m, 1H), 2.27 - 2.20 (m, 1H). Calculated value C 20 H. 19 N. 2 O 3 S. + [M+H] + , 367.1111; found 367.1124. Step 2: Preparation of 3-(5-mercapto-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1213175)

[0318] 3-(5-Benzylthio-1-oxo-2-isoindoline)piperidine-2,6-dione (50 mg, 0.136 mmol) and toluene (3 mL) were placed in a 15 mL sample bottle, and another sample bottle was added. Take aluminum chloride (36.3 mg, 0.272 mmol) and toluene (2 mL) and add the above 3-(5-benzylthio-1-oxo-2-isoindoline group) piperidine-2,6-dione under ice bath. A toluene suspension was added, and after the addition was completed, the mixture was cooled to room temperature and reacted for 10 hours. After adding ice water, the mixture was allowed to react for 0.5 hours while continuously stirring, then diluted hydrochloric acid was added to adjust the acidity, allowed to stand, and filtered. The filter cake was dissolved by adding 3 mL DMSO, filtered through a membrane, and separated by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%). After rotary evaporation of acetonitrile and lyophilization, compound SIAIS1216175 (pale yellow solid, 4 mg, 11% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.98 (s, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 0.8 Hz, 1H), 7.37 (dd, J = 8.1, 1.6 Hz , 1H), 5.73 (s, 1H), 5.10 (dd, J = 13.3, 5.1 Hz, 1H), 4.42 (d, J = 17.3 Hz, 1H), 4.31 (d, J = 17.3 Hz, 1H), 2.95 - 2.86 (m, 1H), 2.64 - 2.57 (m, 1H), 2.45 - 2.33 (m, 1H), 2.05 - 1.96 (m, 1H). 13 H. 13 N. 2 O 3 S. + [M+H] + , 277.0641; found 277.0633. Example 51: Preparation of 3-(5-(methylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1213111)

[0319] The method of Scheme 9 above prepared compound SIAIS1213111 under suitable conditions understood in the art, the difference being that the substrate used was 3-(5-mercapto-1-oxoisoindolin-2-yl)piperidine- 2,6-dione (SIAIS1213175) and methyl iodide. The target compound SIAIS1213111 (gray solid, 7 mg, 12% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.98 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 0.8 Hz, 1H), 7.37 (dd, J = 8.1, 1.6 Hz , 1H), 5.09 (dd, J = 13.3, 5.1 Hz, 1H), 4.42 (d, J = 17.3 Hz, 1H), 4.30 (d, J = 17.3 Hz, 1H), 2.95 - 2.86 (m, 1H) , 2.64 - 2.57 (m, 1H), 2.55 (s, 3H), 2.44 - 2.33 (m, 1H), 2.04 - 1.96 (m, 1H). 14 H. 15 N. 2 O 3 S. + [M+H] + , 291.0798; found 291.0752. Example 52: Preparation of 3-(5-(tert-butylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1213163)

[0320] Compound SIAIS1213163 was prepared by referring to the method of Example 49, the difference being that the substrates used were 3-(5-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione and tert -Butylthiol. The target compound SIAIS1213163 (yellow solid, 19 mg, 56% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.75 (d, J = 0.6 Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.63 (dd, J = 7.8, 1.4 Hz , 1H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.50 (d, J = 17.5 Hz, 1H), 4.37 (d, J = 17.5 Hz, 1H), 2.95 - 2.87 (m, 1H) , 2.61 (d, J = 16.7 Hz, 1H), 2.45 - 2.35 (m, 1H), 2.06 - 1.99 (m, 1H), 1.29 (s, 9H). 17 H. 21 N. 2 O 3 S. + [M+H] + , 333.1267; found 333.1263. Example 53: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-mercaptoisoindoline-1,3-dione (SIAIS1216131) JPEG2022521746000157.jpg46170 Step 1:

[0321] 5-Fluorophthalic anhydride (996.7 mg, 6 mmol) and acetic acid (15 mL) were placed in a 100 mL single-neck flask and stirred while 3-aminopiperidine-2,6-dione (1086.3 mg, 6.6 mmol) and sodium acetate were added. (1476.5 mg, 18.0 mmol) was added and allowed to react at 90° C. overnight. Add water to dilute, stir under ice bath, filter to obtain a black solid, then add 10 mL DMSO, heat to dissolve, then separate on a reverse-phase C18 column (eluent: 10% - 100% (v1:v2) acetonitrile:water), evaporate the solvent under reduced pressure and give the compound 2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1, 3-dione (SIAIS1216157) (light purple solid, 950 mg, 57% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.14 (s, 1H), 8.01 (dd, J = 8.3, 4.5 Hz, 1H), 7.85 (dd, J = 7.4, 2.3 Hz, 1H), 7.75 - 7.70 (m, 1H), 5.17 (dd, J = 12.9, 5.4 Hz, 1H), 2.94 - 2.85 (m, 1H), 2.64 - 2.58 (m, 1H), 2.58 - 2.52 (m, 1H), 2.10 - 2.04 (m, 1H). HRMS (ESI) m / z: calculated value C 13 H. 10 FN 2 O 4 + [M+H] + , 277.0619; found 277.0621. Step 2:

[0322] 3-(5-Fluoro-1,3-dioxo-2-isoindoline group)piperidine-2,6-dione (165.7 mg, 0.6 mmol) and DMF (5 mL) were placed in a 15 mL sample bottle and stirred. Sodium sulfide nonahydrate (216.2 mg, 0.9 mmol) was added and then reacted for 2 h with stirring at room temperature. After the reaction was completed, it was extracted three times with EA, and diluted hydrochloric acid was added dropwise to the aqueous phase in an ice bath to adjust the acidity. %). 1 H NMR (500 MHz, DMSO) δ 11.12 (s, 1H), 8.00 - 7.70 (m, 3H), 6.47 (s, 1H), 5.12 (dd, J = 12.9, 5.3 Hz, 1H), 2.93 - 2.83 ( m, 1H), 2.59 (d, J = 17.7 Hz, 1H), 2.56 - 2.51 (m, 1H), 2.08 - 2.01 (m, 1H). HRMS (ESI) m / z: calculated value C 13 H. 11 N. 2 O 4 S. + [M+H] + , 291.0434; found 291.0410.

[0323] Intermediate Example 12: Preparation of 3-(4-((4-(bromomethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220141)

[0324] The method of Scheme 9 prepared compound SIAIS1220141 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 1,4-di(bromomethyl)benzene. The target compound SIAIS1220141 (pale yellow solid, 247 mg, 27% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.00 (s, 1H), 7.67 (dd, J = 7.7, 0.7 Hz, 1H), 7.58 (d, J = 6.9 Hz, 1H), 7.50 (t, J = 7.6 Hz , 1H), 7.43 - 7.31 (m, 4H), 5.10 (dd, J = 13.3, 5.1 Hz, 1H), 4.67 (s, 2H), 4.34 (s, 2H), 4.24 (d, J = 17.4 Hz, 1H), 4.13 (d, J = 17.4 Hz, 1H), 2.95 - 2.86 (m, 1H), 2.58 (d, J = 16.6 Hz, 1H), 2.45 - 2.35 (m, 1H), 2.00 - 1.94 (m , 1H). HRMS (ESI) m / z: calculated value C 21 H. 20 BrN 2 O 3 S. + [M+H] + , 459.0373; found 459.0370.

[0325] Example 54: Preparation of 3-(4-((4-(morpholinomethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220167)

[0326] The method of Scheme 11 prepared compound SIAIS1220167 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((4-(bromomethyl)benzyl)thio)-1-oxo It is isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220141) and morpholine. The hydrochloride salt of the target compound SIAIS1220167 (white solid, 10 mg, 45% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 10.71 (s, 1H), 7.69 (dd, J = 7.7, 0.7 Hz, 1H), 7.59 (d, J = 6.9 Hz, 1H), 7.51 (t, J = 6.7 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.37 (s, 2H), 4.30 - 4.24 (m, 3H), 4.12 (d, J = 17.4 Hz, 1H), 3.93 (d, J = 12.3 Hz, 2H), 3.71 (t, J = 13.0 Hz, 2H) , 3.20 - 3.13 (m, 2H), 3.10 - 3.00 (m, 2H), 2.95 - 2.86 (m, 1H), 2.59 (d, J = 17.3 Hz, 1H), 2.46 - 2.36 (m, 1H), 2.01 - 1.94 (m, 1H). HRMS (ESI) m / z: calculated value C 25 H. 28 N. 3 O 4 S. + [M+H] + ,466.1795; found 466.1802.

[0327] Example 55: Preparation of 3-(1-oxo-4-((4-(piperidin-1-ylmethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220165)

[0328] The method of Scheme 11 prepared compound SIAIS1220165 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((4-(bromomethyl)benzyl)thio)-1-oxo It is isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220141) and piperidine. The hydrochloride salt of the target compound SIAIS1220165 (white solid, 12 mg, yield 52%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 9.78 (s, 1H), 7.68 (dd, J = 7.7, 0.7 Hz, 1H), 7.59 (d, J = 6.9 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.45 (d, J = 8.3 Hz, 2H), 7.42 (d, J = 8.3 Hz, 2H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.37 (s, 2H), 4.27 (d, J = 17.4 Hz, 1H), 4.20 (d, J = 5.3 Hz, 2H), 4.13 (d, J = 17.4 Hz, 1H), 3.23 (d, J = 11.8 Hz , 2H), 2.96 - 2.86 (m, 1H), 2.85 - 2.75 (m, 2H), 2.59 (d, J = 16.8 Hz, 1H), 2.43 - 2.35 (m, 1H), 2.00 - 1.94 (m, 1H) ), 1.78 (d, J = 13.6 Hz, 2H), 1.65 - 1.60 (m, 3H), 1.38 - 1.29 (m, 1H). HRMS (ESI) m / z: calculated value C 26 H. 30 N. 3 O 3 S. + [M+H] + , 464.2002; observed 464.2004.

[0329] Example 56: Preparation of 3-(1-oxo-4-((7-(pyrrolidin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220161)

[0330] The method of Scheme 11 prepared compound SIAIS1220161 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135) and tetrahydropyrrole. The hydrochloride salt of the target compound SIAIS1220161 (pale yellow solid, 14 mg, 45% yield) was obtained.1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 10.38 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.5, 1.1 Hz, 1H) , 7.56 - 7.52 (m, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.48 - 3.44 (m, 2H), 3.11 - 3.01 (m, 5H), 2.95 - 2.90 (m, 2H), 2.59 (d, J = 17.9 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.00 - 1.95 ( m, 3H), 1.88 - 1.82 (m, 2H), 1.64 - 1.58 (m, 4H), 1.43 - 1.38 (m, 2H), 1.33 - 1.24 (m, 4H). HRMS (ESI) m / z: calculated value C 24 H. 34 N. 3 O 3 S. + [M+H] + , 444.2315; found 444.2321.

[0331] Example 57: Preparation of 3-(1-oxo-4-((7-(piperidin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220105)

[0332] The method of Scheme 11 prepared the compound SIAIS1220105 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135) and piperidine. The hydrochloride salt of the target compound SIAIS1220105 (pale yellow solid, 14 mg, 63% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.93 (s, 1H), 7.63 (dd, J = 7.6, 1.1 Hz, 1H), 7.58 (dd, J = 7.4, 0.9 Hz, 1H) , 7.53 (t, J = 7.5 Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.40 (d, J = 11.2 Hz, 2H), 3.09 (td, J = 7.1, 2.6 Hz, 2H), 3.01 - 2.90 (m, 3H), 2.86 - 2.78 (m, 2H), 2.59 (d, J = 17.5 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.04 - 1.98 (m, 1H), 1.80 (d, J = 14.0 Hz, 2H), 1.68 - 1.54 (m, 8H), 1.44 - 1.39 ( m, 2H), 1.33 - 1.23 (m, 4H). HRMS (ESI) m / z: calculated value C 25 H. 36 N. 3 O 3 S. + [M+H] + , 458.2472; found 458.2473.

[0333] Example 58: Preparation of 3-(4-((7-(azepan-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220163)

[0334] The method of Scheme 11 prepared compound SIAIS1220163 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135) and azacycloheptane. The hydrochloride salt of the target compound SIAIS1220163 (pale yellow solid, 14 mg, 67% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 10.22 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.57 (dd, J = 7.5, 1.1 Hz, 1H) , 7.54 (t, J = 7.5 Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.34 - 3.27 (m, 2H), 3.09 (td, J = 7.0, 1.3 Hz, 2H), 3.06 - 2.96 (m, 4H), 2.96 - 2.87 (m, 1H), 2.59 (d, J = 17.5 Hz , 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.98 (m, 1H), 1.83 - 1.75 (m, 4H), 1.69 - 1.54 (m, 8H), 1.44 - 1.38 (m, 2H), 1.33 - 1.22 (m, 4H). HRMS (ESI) m / z: calculated value C 26 H. 38 N. 3 O 3 S. + [M+H] + , 472.2628; found 472.2632.

[0335] Example 59: Preparation of 3-(4-((7-(diisopropylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220107)

[0336] The method of Scheme 11 prepared compound SIAIS1220107 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135) and diisopropylamine. The hydrochloride salt of the target compound SIAIS1220107 (white solid, 2 mg, yield 8%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 8.59 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.5, 1.0 Hz, 1H) , 7.53 (t, J = 7.5 Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.20 (d, J = 17.4 Hz, 1H) , 3.62 - 3.54 (m, 2H), 3.12 - 3.07 (m, 2H), 3.03 - 2.96 (m, 2H), 2.96 - 2.88 (m, 1H), 2.59 (d, J = 16.7 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.04 - 1.98 (m, 1H), 1.65 - 1.58 (m, 4H), 1.45 - 1.38 (m, 2H), 1.35 - 1.28 (m, 4H), 1.25 (dd, J = 13.1, 6.5Hz, 12H). HRMS (ESI) m / z: calculated value C 26 H. 40 N. 3 O 3 S. + [M+H] + , 474.2785; found 474.2783.

[0337] Example 60: Preparation of 3-(4-((7-((adamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220155)

[0338] The method of Scheme 11 prepared compound SIAIS1220155 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135) and adamantane-1-amine. The hydrochloride salt of the target compound SIAIS1220155 (white solid, 6 mg, yield 22%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 8.42 (s, 2H), 7.63 (d, J = 7.3 Hz, 1H), 7.57 (d, J = 7.3 Hz, 1H), 7.56 - 7.51 (m, 1H), 5.14 (dd, J = 13.1, 4.9 Hz, 1H), 4.35 (d, J = 17.3 Hz, 1H), 4.21 (d, J = 17.3 Hz, 1H), 3.09 (t, J = 6.8 Hz, 2H), 2.96 - 2.87 (m, 1H), 2.81 (s, 2H), 2.59 (d, J = 17.5 Hz, 1H), 2.48 - 2.40 (m, 1H), 2.11 (s, 3H), 2.04 - 1.97 (m, 1H), 1.83 (s, 6H), 1.70 - 1.52 (m, 10H), 1.41 (s, 2H), 1.31 (s, 4H). HRMS (ESI) m / z: calculated value C 30 H. 42 N. 3 O 3 S. + [M+H] + , 524.2941; found 524.2946.

[0339] Example 61: 3-(4-((7-((3,5-dimethyladamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione Manufacture of (SIAIS1220157)

[0340] The method of Scheme 11 prepared compound SIAIS1220157 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135) and 3,5-dimethyladamantan-1-amine. The hydrochloride salt of the target compound SIAIS1220157 (white solid, 10 mg, 34% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 8.49 (s, 2H), 7.63 (d, J = 7.1 Hz, 1H), 7.59 - 7.51 (m, 2H), 5.14 (dd, J = 13.1, 4.8 Hz, 1H), 4.35 (d, J = 17.3 Hz, 1H), 4.21 (d, J = 17.5 Hz, 1H), 3.09 (d, J = 6.3 Hz, 2H), 2.96 - 2.88 (m, 1H), 2.81 (s, 2H), 2.59 (d, J = 17.0 Hz, 1H), 2.47 - 2.40 (m, 1H), 2.18 (s, 1H), 2.04 - 2.1.97 (m, 1H), 1.68 (s, 2H), 1.64 - 1.54 (m, 4H), 1.54 - 1.44 (m, 4H), 1.41 (s, 2H), 1.30 (s, 8H), 1.13 (dd, J = 30.6, 12.4 Hz, 2H ), 0.86 (s, 6H). HRMS (ESI) m / z: calculated value C 32 H. 46 N. 3 O 3 S. + [M+H] + , 552.3254; found 552.3239.

[0341] Example 62: Preparation of 3-(4-((7-((adamantan-2-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220159)

[0342] The method of Scheme 11 prepared compound SIAIS1220159 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216135) and adamantane-2-amine. The hydrochloride salt of the target compound SIAIS1220159 (white solid, 7 mg, 25% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 8.36 (s, 2H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.4, 1.0 Hz, 1H) , 7.54 (t, J = 7.5 Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.20 (d, J = 17.4 Hz, 1H) , 3.26 (s, 1H), 3.12 - 3.07 (m, 2H), 2.96 - 2.85 (m, 3H), 2.59 (d, J = 17.2 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.12 (s , 2H), 2.04 - 1.97 (m, 3H), 1.84 (d, J = 12.5 Hz, 4H), 1.72 (d, J = 17.0 Hz, 4H), 1.68 - 1.52 (m, 6H), 1.45 - 1.38 ( m, 2H), 1.33 - 1.26 (m, 4H). HRMS (ESI) m / z: calculated value C 30 H. 42 N. 3 O 3 S. + [M+H] + , 524.2941; found 524.2957.

[0343] Example 63: Preparation of 3-(4-((8-((adamantan-1-yl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220087)

[0344] The method of Scheme 11 prepared compound SIAIS1220087 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidin-2,6-dione (SIAIS1216137) and adamantane-1-amine. The hydrochloride salt of the target compound SIAIS1220087 (white solid, 9 mg, 33% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.35 (s, 2H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.57 (d, J = 6.5 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.33 - 3.28 (m, 1H), 3.08 (t, J = 7.0 Hz, 2H), 2.96 - 2.88 (m, 1H), 2.84 - 2.78 (m, 2H), 2.59 (d, J = 17.4 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.18 (t, J = 8.1 Hz, 1H), 2.11 (s, 2H), 2.04 - 1.97 (m, 1H), 1.93 - 1.86 (m, 1H), 1.82 (s, 4H), 1.70 - 1.54 (m, 10H), 1.45 - 1.37 (m, 2H), 1.28 (s, 6H). HRMS (ESI) m / z: calculated value C 30 H. 44 N. 3 O 3 S. + [M+H] + , 538.3098; found 538.3091.

[0345] Example 64: Preparation of 3-(4-((8-((adamantan-2-yl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220089)

[0346] The method of Scheme 11 prepared compound SIAIS1220089 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidin-2,6-dione (SIAIS1216137) and adamantane-2-amine. The hydrochloride salt of the target compound SIAIS1220089 (white solid, 14 mg, yield 50%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.02 (s, 1H), 8.49 (s, 2H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (dd, J = 7.4, 1.0 Hz, 1H) , 7.53 (t, J = 7.5 Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.26 (s, 1H), 3.09 (t, J = 6.9 Hz, 2H), 2.96 - 2.84 (m, 3H), 2.59 (d, J = 17.2 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.13 (s, 2H), 2.07 - 1.97 (m, 3H), 1.83 (d, J = 12.9 Hz, 4H), 1.75 - 1.65 (m, 6H), 1.62 - 1.58 (m, 2H), 1.54 (d, J = 13.1 Hz, 2H), 1.45 - 1.37 (m, 2H), 1.28 (s, 6H). HRMS (ESI) m / z: calculated value C 30 H. 44 N. 3 O 3 S. + [M+H] + ,538.3098; found 538.3088.

[0347] Example 65: 3,3'-(((piperazine-1,4-diylbis(octane-8,1-diyl))bis(sulfanediyl))bis(1-oxoisoindoline-4,2-diyl) ) bis(piperidine-2,6-dione) (SIAIS1220061)

[0348] The method of Scheme 11 prepared compound SIAIS1220061 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((8-bromooctyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216137) and piperazine (0.5 equivalents). The target compound SIAIS1220061 (white solid, 30 mg, yield 70%) was obtained. 1H NMR (500 MHz, DMSO) δ 10.99 (s, 2H), 7.63 (dd, J = 7.5, 1.0 Hz, 2H), 7.57 (d, J = 6.7 Hz, 2H), 7.53 (t, J = 7.5 Hz , 2H), 5.13 (dd, J = 13.3, 5.1 Hz, 2H), 4.35 (d, J = 17.4 Hz, 2H), 4.21 (d, J = 17.4 Hz, 2H), 3.60 - 3.30 (m, 12H) , 3.10 - 3.06 (m, 4H), 2.96 - 2.87 (m, 2H), 2.59 (d, J = 17.2 Hz, 2H), 2.49 - 2.41 (m, 2H), 2.04 - 1.98 (m, 2H), 1.72 - 1.55 (m, 8H), 1.44 - 1.37 (m, 4H), 1.27 (s, 12H). HRMS (ESI) m / z: calculated value C 46 H. 63 N. 6 O 6 S. 2 + [M+H] + , 859.4245; found 859.4260.

[0349] Example 66: Preparation of 3-(1-oxo-4-((4,4,5,5,5-pentafluoropentyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220133)

[0350] Compound SIAIS1220133 was prepared by referring to the method of step 3 of Example 44, the difference being that 4,4,5,5,5-pentafluoropentane-1-thiol was used instead of tert-butylthiol. That's what it is. The target compound SIAIS1220133 (brown solid, 4 mg, yield 8%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.68 (s, 1H), 7.62 - 7.52 (m, 2H), 5.14 (s, 1H), 4.38 (d, J = 17.3 Hz, 1H) , 4.23 (d, J = 17.3 Hz, 1H), 3.20 (s, 2H), 2.91 (s, 1H), 2.60 - 2.57(m, 1H), 2.42 - 2.30 (m, 3H), 2.00 (s, 1H ), 1.82 (s, 2H). HRMS (ESI) m / z: calculated value C 18 H. 18 F. 5 N. 2 O 3 S. + [M+H] + , 437.0953; found 437.0951.

[0351] Example 67: 3-(1-oxo-4-((9-((4,4,5,5,5-pentafluoropentyl)thio)nonyl)thio)isoindolin-2-yl)piperidine-2, Production of 6-dione (SIAIS1220131)

[0352] Referring to the synthetic method of Scheme 11, the compound SIAIS1220131 was prepared under suitable conditions understood in the art, the difference being that 3-(4-((8-bromooctyl)thio)-1-oxo Isoindolin-2-yl)piperidine-2,6-dione (SIAIS1216137) and 4,4,5,5,5-pentafluoropentane-1-thiol were used. The target compound SIAIS1220131 (white solid, 8 mg, 27% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.00 (s, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.58 - 7.50 (m, 2H), 5.13 (d, J = 13.0, 4.5 Hz, 1H) , 4.35 (d, J = 17.3 Hz, 1H), 4.21 (d, J = 17.2 Hz, 1H), 3.10 - 3.04 (m, 2H), 2.96 - 2.85 (m, 1H), 2.63 - 2.54 (m, 3H ), 2.48 - 2.42 (m, 3H), 2.37 - 2.23 (m, 2H), 2.04 - 1.97 (m, 1H), 1.80 - 1.70 (m, 2H), 1.63 - 1.55 (m, 2H), 1.53 - 1.45 (m, 2H), 1.43 - 1.26 (m, 2H), 1.35 - 1.26 (m, 2H), 1.24 (s, 6H). HRMS (ESI) m / z: calculated value C 27 H. 36 F. 5 N. 2 O 3 S. 2 + [M+H] + , 595.2082; found 595.2082.

[0353] Example 68: 3-(1-oxo-4-((9-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonyl)thio)isoindolin-2-yl)piperidine-2, Production of 6-dione (SIAIS1220145) JPEG2022521746000158.jpg63170 Steps 1 and 2:

[0354] 4,4,5,5,5-Pentafluoropentyl-1-thiol (194.2 mg, 1 mmol), potassium carbonate (414.6 mg, 3 mmol) and DMF (5 mL) were placed in a 100 mL one-necked flask and stirred for 1 ,9-Dibromononane (582.5 mg, 3 mmol) was added and reacted at 50° C. for 3 h. After that, meta-chloroperbenzoic acid was added, reacted at room temperature for 1 h, separated on a reversed-phase C18 column (eluent: 10%-100% (v1:v2) acetonitrile:water), and the solvent was removed to give the compound 9-((4,4,5,5,5-pentafluoropentyl)sulfoxide group)1-bromononane (SIAIS1220139, white solid, 120 mg, yield 29%) and 9-((4,4,5,5, 5-Pentafluoropentyl)sulfonyl)1-bromononane (SIAIS1220140, white solid, 84 mg, 19% yield) was obtained. Step 3:

[0355] The method of Scheme 9 prepared compound SIAIS1220145 under suitable conditions understood in the art, the difference being that the halogenated substrate used was 9-((4,4,5,5,5-pentafluoropentyl) sulfoxide group) 1-bromononane (SIAIS1220139). The target compound SIAIS1220145 (white solid, 17 mg, 50% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.63 (dd, J = 7.5, 1.2 Hz, 1H), 7.56 (dd, J = 7.5, 1.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.08 (t, J = 7.2Hz, 2H), 2.96 - 2.87 (m, 1H), 2.88 - 2.80 (m, 1H), 2.77 - 2.69 (m, 2H), 2.68 - 2.62 (m, 1H), 2.59 (d, J = 17.3Hz , 1H), 2.49 - 2.43 (m, 1H), 2.43 - 2.31 (m, 2H), 2.03 - 1.97 (m, 1H), 1.94 - 1.87 (m, 2H), 1.65 - 1.55 (m, 4H), 1.43 - 1.33 (m, 4H), 1.30 - 1.22 (m, 6H). HRMS (ESI) m / z: calculated value C 27 H. 36 F. 5 N. 2 O 4 S. 2 + [M+H] + , 611.2031; observed 611.2032.

[0356] Example 69: 3-(1-oxo-4-((9-((4,4,5,5,5-pentafluoropentyl)sulfonyl)nonyl)thio)isoindolin-2-yl)piperidine-2, Production of 6-dione (SIAIS1220147)

[0357] Compound SIAIS1220147 was prepared by referring to the method of Example 68, the difference being that the halogenated substrate used in step 3 was 9-((4,4,5,5,5-pentafluoropentyl)sulfonyl)1- It is bromononane (SIAIS1220140) (white solid, 8 mg, yield 20%). 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.62 (dd, J = 7.5, 1.1 Hz, 1H), 7.56 (dd, J = 7.4, 1.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.24 - 3.19 (m, 2H), 3.14 - 3.04 (m, 4H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 16.8 Hz, 1H), 2.48 - 2.34 (m, 3H), 2.04 - 1.97 (m, 1H) , 1.97 - 1.89 (m, 2H), 1.68 - 1.55 (m, 4H), 1.43 - 1.32 (m, 4H), 1.30 - 1.22 (s, 6H). HRMS (ESI) m / z: calculated value C27 H. 36 F. 5 N. 2 O 5 S. 2 + [M+H] + , 627.1980; observed 627.1979.

[0358] Example 70: Preparation of 3-(4-((8-mercaptooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220143) JPEG2022521746000159.jpg42170

[0359] 3-(4-((8-bromooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216137) (28 mg, 0.06 mmol) was placed in a 15 mL sample bottle, After that, DMF (2 mL) was added to dissolve, sodium hydrogen sulfide (6.7 mg, 0.12 mmol) was added with stirring and reacted at room temperature for 10 min. After membrane filtration and separation by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), acetonitrile was rotary evaporated and lyophilized after , to give compound SIAIS1220143 (white solid, 10 mg, 39% yield). 1 H NMR (500 MHz, DMSO) δ 11.01 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.56 (dd, J = 7.5, 1.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.08 (t, J = 7.2 Hz, 2H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 17.4 Hz, 1H), 2.45 (dd, J = 14.6, 7.4 Hz, 3H), 2.22 (t, J = 7.7 Hz, 1H), 2.03 - 1.96 (m, 1H), 1.62 - 1.55 (m, 2H), 1.55 - 1.48 (m, 2H), 1.43 - 1.36 (m, 2H), 1.33 - 1.22 (m, 6H). HRMS (ESI) m / z: calculated value C 21 H. 29 N. 2 O 3 S. 2 + [M+H] + , 421.1614; found 421.1611.

[0360] Example 71: 3-(1-oxo-4-((7-oxo-7-(piperidin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220115) manufacturing JPEG2022521746000160.jpg37170

[0361] 7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanoic acid (SIAIS171092) (20.2 mg, 0.05 mmol), piperidine (4.3 mg, 0.05 mmol) and HATU (38.0 mg, 0.1 mmol) were placed in this order in a 15 mL sample bottle, then DMF (2 mL) was added to dissolve, and N,N-diisopropylethylamine (12.9 mg, 0.1 mmol) was stirred with stirring. ) was added and allowed to react at room temperature for 12 h. After membrane filtration and separation by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), acetonitrile was rotary evaporated and lyophilized after , to give compound SIAIS1220115 (white solid, 23 mg, 97% yield). 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.63 (dd, J = 7.5, 1.1 Hz, 1H), 7.56 (dd, J = 7.5, 1.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.40 - 3.37 (m, 2H), 3.37 - 3.33 (m, 2H), 3.07 (t, J = 7.2 Hz, 2H), 2.95 - 2.86 (m, 1H), 2.59 (d, J = 16.7 Hz, 1H), 2.49 - 2.41 (m , 1H), 2.25 (t, J = 7.4 Hz, 2H), 2.04 - 1.97 (m, 1H), 1.61 - 1.53 (m, 4H), 1.47 - 1.37 (m, 8H), 1.31 - 1.25 (m, 2H) ). HRMS (ESI) m / z: C 25 H. 34 N. 3 O 4 S. + [M+H] + , 472.2265; found 472.2262.

[0362] Example 72: Preparation of 7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-N,N-diisopropylheptanamide (SIAIS1220117)

[0363] Compound SIAIS1220117 was prepared by referring to the method of Example 71, the difference being that instead of piperidine, diisopropylamine was used. The target compound SIAIS1220117 (white solid, 13 mg, 8% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.56 (d, J = 7.4, 1.0 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.99 - 3.91 (m, 1H), 3.44 (s, 1H), 3.08 (t, J = 7.3 Hz, 2H), 2.96 - 2.86 (m, 1H), 2.59 (d, J = 17.2 Hz, 1H), 2.48 - 2.41 (m, 1H) ), 2.21 (t, J = 7.4 Hz, 2H), 2.04 - 1.97 (m, 1H), 1.63 - 1.56 (m, 2H), 1.47 - 1.38 (m, 4H), 1.32 - 1.27 (m, 2H), 1.26 (d, J = 6.7 Hz, 6H), 1.11 (d, J = 6.5 Hz, 6H). HRMS (ESI) m / z: C 26 H. 38 N. 3 O 4 S. + [M+H] + , 488.2578; found 488.2573.

[0364] Example 73: 8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-N,N,N-triethyloctane-1-ammonium chloride Manufacture of (SIAIS1220093) JPEG2022521746000161.jpg35170

[0365] 3-(4-((8-bromooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1216137) (23.4 mg, 0.05 mmol) was placed in a 15 mL sample bottle, After that, acetonitrile (2 mL) was added to dissolve, triethylamine (6.1 mg, 0.06 mmol) was added with stirring, and reacted under reflux for 12 h. After membrane filtration, separation by preparative HPLC (eluent (v / v): acetonitrile / (water + 0.05% HCl) = 10% -100%), acetonitrile was rotary evaporated and lyophilized after , to give compound SIAIS1220093 (white solid, 8 mg, 31% yield). 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.63 (dd, J = 7.6, 1.1 Hz, 1H), 7.57 (d, J = 7.2 Hz, 1H), 7.53 (t, J = 7.5 Hz , 1H), 5.13 (dd, J = 13.3, 5.2 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.21 (q, J = 7.2 Hz , 6H), 3.10 - 3.05 (m, 4H), 2.96 - 2.87 (m, 1H), 2.59 (d, J = 17.7 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.04 - 1.97 (m, 1H) ), 1.63 - 1.58 (m, 2H), 1.57 - 1.50 (m, 2H), 1.44 - 1.32 (m, 2H), 1.28 (s, 6H), 1.15 (t, J = 7.2 Hz, 9H). HRMS (ESI) m / z: calculated value C 27 H. 42 N. 3 O 3 S. + [M+H] + , 488.2941; found 488.2944.

[0366] Example 74: Preparation of 3-(1-oxo-4-((8-(quinazolin-4-ylamino)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS264011) JPEG2022521746000162.jpg32170

[0367] 25 mg (0.15 mmol) of 4-chloroquinazoline and 61 mg (0.15 mmol) of 3-(4-((8-aminooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione Dissolve in 2 mL absolute ethanol, add 41 μL triethylamine, reflux overnight, detect completion of reaction by TLC, evaporate solvent under reduced pressure, dissolve in DMF, separate on preparative column. Compound SIAIS264011 (white solid 31 mg, yield 39%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.44 (s, 1H), 8.26 (s, 1H), 8.23 ​​(d, J = 7.6 Hz, 1H), 7.77 - 7.72 (m, 1H) , 7.67 - 7.64 (m, 1H), 7.61 (dd, J = 7.5, 1.1 Hz, 1H), 7.56 (dd, J = 7.5, 1.1 Hz, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.50 - 7.47 (m, 1H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.52 (dd , J = 13.0, 6.9 Hz, 2H), 3.06 (t, J = 7.3 Hz, 2H), 2.95 - 2.86 (m, 1H), 2.59 (d, J = 17.6 Hz, 1H), 2.49 - 2.40 (m, 1H), 2.03 - 1.96 (m, 1H), 1.65 - 1.55 (m, 4H), 1.42 - 1.27 (m, 8H). HRMS (ESI) m / z: calculated value C 29 H. 34 N. 5 O 3 S. + [M+H] + , 532.2377; found 532.2374.

[0368] Example 75: 1-(3-Chloro-4-methylphenyl)-3-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl) Production of thio)ethyl)urea (SIAIS269012) JPEG2022521746000163.jpg41170

[0369] 3-Chloro-4-methylaniline (10 mg, 1 equiv), THF (2 mL), DIEA (36.5 mg, 4.0 equiv) were placed in that order in a 10 mL two-necked flask and triphosgene (25.1 mg, 1.2 equiv) was added at 0°C. of THF (1 mL) solution was added. After completion of dropping, gas replacement was performed three times, and reaction was carried out at 0°C for 30 minutes under the protection of argon gas. After that, the temperature was raised to room temperature and the reaction was performed for 30 minutes. was added and allowed to react overnight. Preparative HPLC (mobile phase is water / acetonitrile) gave 11.2 mg of white solid product (SIAIS269012). Yield was 33%. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.71 (s, 1H), 7.74 (dd, J = 7.6, 1.0 Hz, 1H), 7.63 (d, J = 2.1 Hz, 1H), 7.58 (dd, J = 7.5, 1.0 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.17 (d, J = 8.5 Hz, 1H), 7.11 (dd, J = 8.3, 2.2 Hz, 1H) , 6.43 (t, J = 5.1 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.39 (d, J = 17.4 Hz, 1H), 4.24 (d, J = 17.3 Hz, 1H) , 3.30 (d, J = 7.2 Hz, 2H), 3.18 (t, J = 6.9 Hz, 2H), 2.95 - 2.86 (m, 1H), 2.58 (d, J = 17.5 Hz, 1H), 2.48 - 2.38 ( m, 1H), 2.23 (s, 3H), 2.03 - 1.96 (m, 1H). HRMS (ESI) m / z: calculated value C 23 H. 24 ClN 4 O 4 S. + [M+H] + , 487.1201; found 487.1198.

[0370] Example 76: Preparation of 3-(1-oxo-4-((8-(2-oxopiperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS264019) JPEG2022521746000164.jpg76170

[0371] 0.27 mg (4 mmol) of sodium hydride was placed in 1.5 mL of DMF, piperidone (2 mmol) dissolved in THF was added under ice bath and stirred for 0.5 h. After that, 1,8-dibromooctane was added, reacted at room temperature for 4 h, column chromatography was performed, and was directly subjected to the next step. The above intermediate (0.17 mmol) and 47 mg (0.17 mmol) of thiolenalidomide SIAIS171095 were placed in 2 mL of DMF, 28 mg of potassium carbonate was added, allowed to stand at room temperature overnight, and the completion of the reaction was detected by TLC. A white solid (SIAIS264019) 31 mg was obtained by separation with a take-up column. The total yield for the two steps was 39%. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.62 (dd, J = 7.5, 1.1 Hz, 1H), 7.56 (dd, J = 7.4, 1.0 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.23 - 3.18 (m, 4H), 3.07 (t, J = 7.2 Hz, 2H), 2.96 - 2.87 (m, 1H), 2.59 (d, J = 17.4 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.17 (t, J = 6.3 Hz, 2H), 2.04 - 1.97(m, 1H), 1.73 - 1.63 (m, 4H), 1.63 - 1.55 (m, 2H), 1.45 - 1.36 (m, 4H), 1.28 - 1.16 (m, 6H ). HRMS (ESI) m / z: C 26 H. 36 N. 3 O 4 S. + [M+H] + , calculated 486.2421; found 486.2425.

[0372] Example 77: 3-(4-((6-((adamantan-1-yl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220177)

[0373] The method of Scheme 11 prepared compound SIAIS1220177 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((6-bromohexyl)thio)-1-oxoiso Indolin-2-yl)piperidin-2,6-dione (SIAIS1216133) and adamantane-1-amine. The hydrochloride salt of the target compound SIAIS1220177 (pale yellow solid, 7 mg, 28% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.55 (s, 2H), 7.64 (dd, J = 7.5, 1.1 Hz, 1H), 7.57 (d, J = 7.2 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.36 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.10 (t, J = 6.9 Hz, 2H), 2.96 - 2.87 (m, 1H), 2.80 (s, 2H), 2.59 (d, J = 17.1 Hz, 1H), 2.49 - 2.40 (m, 1H), 2.11 ( s, 3H), 2.04 - 1.98 (m, 1H), 1.83 (s, 6H), 1.70 - 155 (m, 10H), 1.47 - 1.40 (m, 2H), 1.38 - 1.31 (m, 2H). HRMS (ESI) m / z: calculated value C 29 H. 40 N. 3 O 3 S. + [M+H] + , 510.2785; found 510.2780.

[0374] Example 78: 3-(4-((6-((adamantan-2-yl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220179)

[0375] The method of Scheme 11 prepared compound SIAIS1220179 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((6-bromohexyl)thio)-1-oxoiso Indolin-2-yl)piperidin-2,6-dione (SIAIS1216133) and adamantane-2-amine. The hydrochloride salt of the target compound SIAIS1220179 (pale yellow solid, 22 mg, 87% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.42 (s, 2H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.57 (dd, J = 7.4, 0.9 Hz, 1H) , 7.54 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.26 (s, 1H), 3.12 - 3.07 (m, 2H), 2.96 - 2.84 (m, 3H), 2.59 (d, J = 16.6 Hz, 1H), 2.48 - 2.40 (m, 1H), 2.12 (s , 2H), 2.05 - 1.99 (m, 3H), 1.84 (d, J = 12.6 Hz, 4H), 1.76 - 1.57 (m, 9H), 1.55 (d, J = 13.0 Hz, 2H), 1.47 - 1.40 ( m, 2H), 1.36 - 1.30 (m, 2H). HRMS (ESI) m / z: calculated value C 29 H. 40 N. 3 O 3 S. + [M+H] + , 510.2785; found 510.2783.

[0376] Example 79: 3-(4-((4-(((adamantan-1-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1221003 )

[0377] The method of Scheme 11 prepared compound SIAIS1221003 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((4-(bromomethyl)benzyl)thio)-1-oxo isoindolin-2-yl)piperidin-2,6-dione (SIAIS1220141) and adamantane-1-amine. The hydrochloride salt of the target compound SIAIS1221003 (white solid, 14 mg, yield 54%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.86 (s, 2H), 7.70 (d, J = 7.7 Hz, 1H), 7.57 (d, J = 7.5 Hz, 1H), 7.49 (dd , J = 15.6, 7.9 Hz, 3H), 7.43 (d, J = 8.1 Hz, 2H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.42 - 4.35 (m, 2H), 4.29 (d, J = 17.4 Hz, 1H), 4.16 (d, J = 17.4 Hz, 1H), 4.05 (s, 2H), 2.95 - 2.86 (m, 1H), 2.59 (d, J = 16.8 Hz, 1H), 2.48- 2.37 (m, 1H), 2.14 (s, 3H), 2.02 - 1.96 (m, 1H), 1.94 (s, 6H), 1.68 (d, J = 12.3Hz, 3H), 1.60 (d, J = 12.0Hz , 3H). HRMS (ESI) m / z: calculated value C 31 H. 36 N. 3 O 3 S. + [M+H] + , 530.2472; found 530.2460.

[0378] Example 80: 3-(4-((4-((adamantan-2-ylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1221005)

[0379] Scheme 11 prepared the compound under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((4-(bromomethyl)benzyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1220141) and adamantane-2-amine. The hydrochloride salt of the target compound SIAIS1221005 (white solid, 20 mg, yield 77%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 9.07 (s, 2H), 7.67 (d, J = 7.7 Hz, 1H), 7.58 - 7.52 (m, 3H), 7.49 (t, J = 7.6 Hz, 1H), 7.43 - 7.39 (m, 2H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.41 - 4.34 (m, 2H), 4.29 (d, J = 17.4 Hz, 1H), 4.17 (d, J = 17.7 Hz, 1H), 4.13 (s, 2H), 3.12 (s, 1H), 2.96 - 2.86 (m, 1H), 2.59 (d, J = 17.4 Hz, 1H), 2.48 - 2.38 (m, 1H), 2.17 - 2.07 (m, 4H), 2.02 - 1.94 (m, 1H), 1.81 (s, 4H), 1.68 (s, 2H), 1.61 - 1.49 (m, 4H). HRMS (ESI) m / z: calculated value C 31 H. 36 N. 3 O 3 S. + [M+H] + , 530.2472; found 530.2465.

[0380] Example 81: 3-(4-((6-((adamantan-1-ylmethyl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1221013)

[0381] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((6-bromohexyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216133) and 1-adamantanamine. The hydrochloride salt of the target compound SIAIS1221013 (white solid, 23 mg, yield 88%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.06 (s, 2H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.58 (d, J = 6.6 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 5.14 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.09 (t, J = 7.6, 2H), 2.96 - 2.88 (m, 1H), 2.87 - 2.80 (m, 2H), 2.63 - 2.57 (m, 3H), 2.48 - 2.40 (m, 1H), 2.05 - 1.98 ( m, 1H), 1.97 (s, 3H), 1.70 - 1.57 (m, 10H), 1.54 (d, J = 2.0Hz, 6H), 1.46 - 1.39 (m, 2H), 1.34 - 1.27 (m, 2H) . HRMS (ESI) m / z: calculated value C 30 H. 42 N. 3 O 3 S. + [M+H] + , 524.2941; found 524.2945.

[0382] Example 82: 3-(4-((7-(adamantan-1-ylthio)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1221025)

[0383] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1216135) and adamantane-1-thiol. The target compound SIAIS1221025 (white solid, 10 mg, 37% yield) was obtained. 1H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.62 (dd, J = 7.5, 1.1 Hz, 1H), 7.56 (dd, J = 7.4, 1.0 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.08 (t, J = 7.2 Hz, 2H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 17.0 Hz, 1H), 2.48 - 2.41 (m, 3H), 2.04 - 1.99 (m, 1H), 1.97 (s, 3H) ), 1.77 (d, J = 2.8 Hz, 6H), 1.64 (d, J = 13.4 Hz, 6H), 1.62 - 1.55 (m, 2H), 1.48 - 1.36 (m, 4H), 1.35 - 1.25 (m, 4H). HRMS (ESI) m / z: calculated value C 30 H. 41 N. 2 O 3 S. 2 + [M+H] + , 541.2553; found 541.2553.

[0384] Example 83: 3-(4-((7-(((adamantan-1-yl)methyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220171 )

[0385] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1216135) and 1-adamantanamine. The hydrochloride salt of the target compound SIAIS1220171 (white solid, 16 mg, yield 59%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.21 (s, 2H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.57 (d, J = 6.5 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.09 (t, J = 6.8 Hz, 2H), 2.96 - 2.87 (m, 1H), 2.87 - 2.79 (m, 2H), 2.63 - 2.56 (m, 3H), 2.49 - 2.40 (m, 1H), 2.05 - 1.99 (m, 1H), 1.97 (s, 3H), 1.70 - 1.55 (m, 16H), 1.45 - 1.37 (m, 2H), 1.32 - 1.24 (m, 4H). HRMS (ESI) m / z: calculated value C 31 H. 44 N. 3 O 3 S. + [M+H] + , 538.3098; found 538.3094.

[0386] Example 84: N-(Adamantan-1-yl)-7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanamide (SIAIS1220195 )

[0387] Compound SIAIS1220195 was prepared by referring to the method of Example 71, the difference being that adamantane-1-amine was used in place of piperidine. The target compound SIAIS1220195 (white solid, 18 mg, 67% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.62 (dd, J = 7.5, 1.0 Hz, 1H), 7.56 (dd, J = 7.4, 1.0 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 7.18 (s, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.07 (t, J = 7.2 Hz, 2H), 2.96 - 2.86 (m, 1H), 2.59 (d, J = 17.2 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.04 - 1.95 (m, 6H ), 1.89 (d, J = 2.6 Hz, 6H), 1.63 - 1.55 (m, 8H), 1.47 - 1.35 (m, 4H), 1.27 - 1.20 (m, 2H). HRMS (ESI) m / z: calculated value C 30 H. 40 N. 3 O 4 S. + [M+H] + , 538.2734; found 538.2736.

[0388] Example 85: N-(3,5-dimethyladamantan-1-yl)-7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio )Heptanamide (SIAIS1220197)

[0389] Compound SIAIS1220197 was prepared by referring to the method of Example 71, the difference being that 3,5-dimethyladamantan-1-amine was used in place of piperidine. The target compound SIAIS1220197 (white solid, 21 mg, 75% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.62 (dd, J = 7.5, 1.2 Hz, 1H), 7.56 (dd, J = 7.5, 1.1 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 7.21 (s, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.07 (t, J = 7.2 Hz, 2H), 2.96 - 2.87 (m, 1H), 2.59 (d, J = 17.6 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.06 - 1.94 (m, 4H ), 1.72 (d, J = 2.5 Hz, 2H), 1.62 - 1.50 (m, 6H), 1.46 - 1.35 (m, 4H), 1.31 - 1.20 (m, 6H), 1.07 (s, 2H), 0.79 ( s, 6H). HRMS (ESI) m / z: calculated value C 32 H. 44 N. 3 O 4 S. + [M+H] + , 566.3047; found 566.3040.

[0390] Example 86: N-(Adamantan-2-yl)-7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanamide (SIAIS1220199 )

[0391] Compound SIAIS1220199 was prepared by the method of Example 71, the difference being that adamantane-2-amine was used in place of piperidine. The target compound SIAIS1220199 (white solid, 21 mg, yield 78%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 7.61 (dd, J = 7.4, 0.8 Hz, 1H), 7.59 (s, 1H), 7.56 (d, J = 6.5 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.81 (d, J = 7.3 Hz, 1H), 3.06 (t, J = 7.2 Hz, 2H), 2.95 - 2.87 (m, 1H), 2.59 (d, J = 18.0 Hz, 1H), 2.49 - 2.39 (m, 1H), 2.12 (t, J = 7.3 Hz, 2H), 2.03 - 1.98 (m, 1H), 1.95 (d, J = 12.6 Hz, 2H), 1.80 - 1.66 (m, 10H), 1.62 - 1.55 (m , 2H), 1.51 - 1.37 (m, 6H), 1.28 - 1.22 (m, 2H). HRMS (ESI) m / z: calculated value C 30 H. 40 N. 3 O 4 S. + [M+H] + , 538.2734; found 538.2718.

[0392] Example 87: 3-(4-((6-(Cyclohexylamino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220183)

[0393] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((6-bromohexyl)thio)-1-oxoisoindoline -2-yl)piperidine-2,6-dione (SIAIS1216133) and cyclohexane. The hydrochloride salt of the target compound SIAIS1220183 (white solid, 18 mg, yield 78%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.40 (s, 2H), 7.63 (dd, J = 7.5, 0.9 Hz, 1H), 7.58 (d, J = 6.6 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.12 - 3.06 (m, 2H), 2.96 - 2.83 (m, 4H), 2.60 (d, J = 17.2 Hz, 1H), 2.48 - 2.40 (m, 1H), 2.04 - 1.96 (m, 3H), 1.78 - 1.96 (m, 2H), 1.64 - 1.53 (m, 5H), 1.46 - 1.39 (m, 2H), 1.37 - 1.30 (m, 2H), 1.27 - 1.18 (m, 4H), 1.14 - 1.05 (m, 1H) . HRMS (ESI) m / z: calculated value C 25 H. 36 N. 3 O 3 S. + [M+H] + , 458.2472; found 458.2580.

[0394] Example 88: 3-(4-((7-(Cyclohexylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220185)

[0395] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1216135) and cyclohexane. The hydrochloride salt of the target compound SIAIS1220185 (white solid, 7 mg, yield 29%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.29 (s, 2H), 7.63 (d, J = 7.5 Hz, 1H), 7.57 (d, J = 7.2 Hz, 1H), 7.53 (t , J = 7.5 Hz, 1H), 5.14 (dd, J = 13.0, 4.8 Hz, 1H), 4.35 (d, J = 17.2 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H), 3.09 (t , J = 7.0 Hz, 2H), 2.99 - 2.82 (m, 4H), 2.60 (d, J = 18.2 Hz, 1H), 2.48 - 2.40 (m, 1H), 1.99 (s, 3H), 1.76 (s, 2H), 1.64 - 1.52 (m, 5H), 1.41 (s, 2H), 1.30 (s, 4H), 1.23 (t, J = 9.6 Hz, 4H), 1.10 (s, 1H). HRMS (ESI) m / z: calculated value C 26 H. 38 N. 3 O 3 S. + [M+H] + , 472.2628; found 472.2625.

[0396] Example 89: 3-(1-oxo-4-((7-(phenylamino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1220187)

[0397] Scheme 11 prepared the compound under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline-2- yl)piperidine-2,6-dione (SIAIS1216135) and aniline. The target compound SIAIS1220187 (white solid, 8 mg, 35% yield) was obtained. 1 H NMR (500 MHz, CDCl 3 ) δ 8.69 (s, 1H), 7.75 (d, J = 6.7 Hz, 1H), 7.59 (d, J = 6.9 Hz, 2H), 7.53 (d, J = 6.9 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.44 - 7.36 (m, 3H), 5.26 (dd, J = 13.3, 5.0 Hz, 1H), 4.43 (d, J = 16.5 Hz, 1H), 4.32 (d, J = 16.5 Hz , 1H), 3.30 - 3.22 (m, 2H), 2.97 - 2.92 (m, 2H), 2.90 - 2.81 (m, 1H), 2.48 - 2.38 (m, 1H), 2.28 - 2.21 (m, 1H), 1.88 - 1.80 (m, 2H), 1.65 - 1.56 (m, 6H), 1.38 - 1.25 (m, 4H). HRMS (ESI) m / z: calculated value C 26 H. 32 N. 3 O 3 S. + [M+H] + , 466.2159; found 466.2159.

[0398] Example 90: 3-(4-((7-(methyl(phenyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220189)

[0399] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1216135) and N-methylaniline. The target compound SIAIS1220189 (white solid, 13 mg, 54% yield) was obtained. 1 H NMR (500 MHz, CDCl 3 ) δ 8.70 (s, 1H), 7.85 - 7.68 (m, 3H), 7.62 - 7.43 (m, 5H), 5.25 (dd, J = 13.3, 4.9 Hz, 1H), 4.43 (d, J = 16.5 Hz, 1H), 4.32 (d, J = 16.5 Hz, 1H), 3.61 - 3.38 (m, 1H), 3.27 (s, 1H), 3.00 - 2.90 (m, 3H), 2.90 - 2.81 (m, 1H), 2.50 - 2.38 (m, 1H), 2.29 - 2.22 (m, 1H), 1.95 (s, 1H), 1.69 (s, 3H), 1.65 - 1.53 (m, 2H), 1.50 - 1.34 (m, 3H), 1.27 (s, 4H). HRMS (ESI) m / z: calculated value C 27 H. 34 N. 3 O 3 S. + [M+H] + , 480.2315; found 480.2313.

[0400] Example 91: 3-(4-((7-(Azocan-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1220193)

[0401] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1216135) and azacyclooctane. The hydrochloride salt of the target compound SIAIS1220193 (pale yellow solid, 22 mg, 92% yield) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 9.39 (s, 1H), 7.63 (dd, J = 7.5, 1.0 Hz, 1H), 7.57 (dd, J = 7.4, 0.9 Hz, 1H) , 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 5.1 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H) , 3.36 - 3.29 (m, 2H), 3.12 - 3.05 (m, 4H), 3.04 - 2.99 (m, 2H), 2.97 - 2.87 (m, 1H), 2.59 (d, J = 17.6 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.05 - 1.98 (m, 1H), 1.92 - 1.82 (m, 2H), 1.74 - 1.58 (m, 9H), 1.55 - 1.47 (m, 3H), 1.45 - 1.38 (m, 2H), 1.33 - 1.23 (m, 4H). HRMS (ESI) m / z: calculated value C 27 H. 40 N. 3 O 3 S. + [M+H] + , 486.2785; found 486.2784.

[0402] Example 92: 3-(1-oxo-4-((7-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)heptyl) Thio)isoindolin-2-yl)piperidine-2,6-dione (SIAIS1221019)

[0403] Scheme 11 prepared the compound under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline-2- yl)piperidine-2,6-dione (SIAIS1216135) and norcamphanylamine. The hydrochloride salt of the target compound SIAIS1221019 (white solid, 14 mg, yield 54%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.64 (s, 1H), 8.22 (s, 1H), 7.63 (d, J = 7.5 Hz, 1H), 7.57 (d, J = 7.3 Hz , 1H), 7.53 (t, J = 7.5 Hz, 1H), 5.13 (dd, J = 13.2, 4.9 Hz, 1H), 4.35 (d, J = 17.3 Hz, 1H), 4.21 (d, J = 17.3 Hz , 1H), 3.20 (s, 1H), 3.09 (t, J = 7.1 Hz, 2H), 2.96 - 2.83 (m, 3H), 2.59 (d, J = 17.7 Hz, 1H), 2.49 - 2.41 (m, 1H), 2.15 (t, J = 11.9 Hz, 1H), 2.04 - 1.98 (m, 1H), 1.71 - 1.65 (m, 4H), 1.63 - 1.58 (m, 2H), 1.47 - 1.35 (m, 4H) , 1.35 - 1.17 (m, 6H), 0.96 (s, 3H), 0.83 (s, 6H). HRMS (ESI) m / z: calculated value C 30 H. 44 N. 3 O 3 S. + [M+H] + , 526.3098; found 526.3094.

[0404] Example 93: 3-(4-((7-(3-Azaspiro[5.5]undecane-3-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1221015 )

[0405] Scheme 11 prepared the compound under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline-2- yl)piperidine-2,6-dione (SIAIS1216135) and 3-azaspiro[5.5]undecane. The hydrochloride salt of the target compound SIAIS1221015 (white solid, 24 mg, yield 92%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.00 (d, J = 11.1 Hz, 1H), 9.47 (s, 1H), 7.63 (d, J = 7.5 Hz, 1H), 7.57 (d, J = 7.4 Hz, 1H ), 7.53 (t, J = 7.4 Hz, 1H), 5.13 (dd, J = 13.2, 5.0 Hz, 1H), 4.35 (d, J = 17.4 Hz, 1H), 4.21 (d, J = 17.4 Hz, 1H ), 3.25 (d, J = 11.9 Hz, 2H), 3.08 (t, J = 7.1 Hz, 2H), 3.02 - 2.97 (m, 2H), 2.95 - 2.88 (m, 3H), 2.59 (d, J = 17.1 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.04 - 1.98 (m, 1H), 1.73 (d, J = 14.1 Hz, 2H), 1.65 - 156 (m, 4H), 1.53 - 1.45 (m , 4H), 1.42 - 1.35 (m, 8H), 1.31 - 1.22 (m, 6H). HRMS (ESI) m / z: calculated value C 30 H. 44 N. 3 O 3 S. + [M+H] + , 526.3098; found 526.3094.

[0406] Example 94: 3-(4-((7-(3,5-dimethylpiperidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1221021)

[0407] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1216135) and 3,5-dimethylpiperidine. The hydrochloride salt of the target compound SIAIS1221021 (white solid, 16 mg, yield 67%) was obtained. 1 H NMR (500 MHz, DMSO) δ 11.00 (s, 1H), 10.55 (s, 1H), 7.63 (d, J = 7.4 Hz, 1H), 7.57 (d, J = 7.3 Hz, 1H), 7.56 - 7.52 (m, 1H), 5.13 (dd, J = 13.2, 4.9 Hz, 1H), 4.36 (d, J = 17.4 Hz, 1H), 4.22 (d, J = 17.4 Hz, 1H), 3.29 (d, J = 11.1 Hz, 2H), 3.08 (t, J = 7.1 Hz, 2H), 2.97 - 2.87 (m, 3H), 2.60 (d, J = 17.1 Hz, 1H), 2.49 - 2.42 (m, 1H), 2.37 ( dd, J = 21.0, 11.2 Hz, 2H), 2.07 - 1.97 (m, 3H), 1.75 - 1.66 (m, 3H), 1.64 - 1.56 (m, 2H), 1.45 - 1.38 (m, 2H), 1.33 - 1.23 (m, 4H), 0.87 (d, J = 6.5 Hz, 6H), 0.76 (q, J = 12.3 Hz, 1H). HRMS (ESI) m / z: calculated value C 27 H. 40 N. 3 O 3 S. + [M+H] + , 486.2785; found 486.2784.

[0408] Example 95: 3-(4-((7-(4,4-dimethylpiperidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1221027)

[0409] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1216135) and 4,4-dimethylpiperidine. The hydrochloride salt of the target compound SIAIS1221027 (white solid, 12 mg, yield 50%) was obtained. 1 H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 9.78 (s, 1H), 7.63 (d, J = 7.4 Hz, 1H), 7.57 (d, J = 7.4 Hz, 1H), 7.53 (t , J = 7.4 Hz, 1H), 5.13 (dd, J = 13.2, 5.1 Hz, 1H), 4.35 (d, J = 17.3 Hz, 1H), 4.21 (d, J = 17.3 Hz, 1H), 3.26 (d , J = 12.1 Hz, 2H), 3.08 (t, J = 7.0 Hz, 2H), 3.00 - 2.87 (m, 5H), 2.59 (d, J = 17.5 Hz, 1H), 2.48 - 2.41 (m, 1H) , 2.04 - 1.98 (m, 1H), 1.72-1.57 (m, 6H), 1.49 - 1.38 (m, 4H), 1.33 - 1.23 (m, 4H), 0.99 (s, 3H), 0.95 (s, 3H) . HRMS (ESI) m / z: calculated value C 27 H. 40 N. 3 O 3 S. + [M+H] + , 486.2785; found 486.2784.

[0410] Example 96: 3-(4-((7-((4,4-dimethylcyclohexyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SIAIS1221029)

[0411] The compound was prepared by the method of Scheme 11 under suitable conditions understood in the art, the difference being that the substrate used was 3-(4-((7-bromoheptyl)thio)-1-oxoisoindoline- 2-yl)piperidine-2,6-dione (SIAIS1216135) and 4,4-dimethylcyclohexane. The hydrochloride salt of the target compound SIAIS1221029 (white solid, 12 mg, 50% yield) was obtained. 1H NMR (500 MHz, DMSO) δ 10.99 (s, 1H), 8.33 (s, 2H), 7.63 (d, J = 7.5 Hz, 1H), 7.57 (d, J = 7.3 Hz, 1H), 7.53 (t , J = 7.5 Hz, 1H), 5.13 (dd, J = 13.3, 4.9 Hz, 1H), 4.35 (d, J = 17.5 Hz, 1H), 4.21 (d, J = 17.5 Hz, 1H), 3.09 (t , J = 7.1 Hz, 2H), 2.96 - 2.84 (m, 4H), 2.59 (d, J = 19.2 Hz,, 1H), 2.48 - 2.40 (m, 1H), 2.05 - 1.97 (m, 1H), 1.81 (d, J = 10.9 Hz, 2H), 1.64 - 1.38 (m, 10H), 1.30 (s, 4H), 1.25 - 1.14 (m, 2H), 0.89 (d, J = 5.5 Hz, 6H). HRMS (ESI) m / z: calculated value C 28 H. 42 N. 3 O 3 S. + [M+H] + , 500.2941; found 500.2945.

[0412] Example 97: 3-(4-((7-((adamantan-1-yl)(methyl)amino)he...

Claims

1. A compound of formula (I) or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, In formula (I), A is CH ２ or C(O), B, U, V, and W each independently represent CH or C; Y represents O, and (i) R is S, S(O) or S(O) ２ represents, and L is halogen, cyano, C １－３ Alkyl, C １－３ a straight-chain or branched C alkyl group optionally substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof; １－４０ represents alkylene, The linear or branched C １－４０ Alkylene is O, C(O), S, S(O), S(O) ２ , C(O)N(R １ ), N(R ２ ) C(O), N(R ３ ), N(R ４ )C(O)N(R ５ ), optionally substituted C ３－１２ Cycloalkylene, optionally substituted C ５－１４ optionally interrupted one or more times by one or more selected from the group consisting of arylene, optionally substituted 3- to 12-membered heterocyclylene, optionally substituted 5- to 10-membered heteroarylene, or any combination thereof, wherein R １ , R ２ , R ３ , R ４ and R ５ are each independently H or C １－３ represents alkyl, The optionally substituted C ３－１２ Cycloalkylene is substituted with halogen, cyano, C １－５ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with alkyl, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo, or any combination thereof; The optionally substituted C ５－１４ Arylene is C １－５ Alkyl, halogenated C １－３ Alkoxy, cyano, C １－３ Alkoxy, halogenated C １－３ optionally substituted with a substituent selected from alkyl, halogen, amino, hydroxyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; The optionally substituted 3- to 12-membered heterocyclylene is １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, and oxo; The optionally substituted 5- to 10-membered heteroarylene is C １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; and X １ is NR ６ R ７ , C(O)NR ｅ R ｆ , NHC(O)R ８ , NHC(O)NR ９ R １０ , OR ｈ , or SH, Here, R ６ , R ７ , R ｅ , R ｆ , R ｈ , R ９ , and R １０ are each independently, H: halogen, cyano, C １－３ Alkyl, C １－３ a straight or branched C alkyl group optionally substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof; １－１０ Alkyl; Halogen, cyano, C １－３ Alkyl, C １－３ Alkoxy, halogenated C １－３ C optionally substituted with a substituent selected from alkyl, amino, hydroxyl, or any combination thereof ３－１２ cycloalkyl; C １－５ Alkyl, halogenated C １－３ Alkoxy, cyano, C １－３ Alkoxy, halogenated C １－３ C optionally substituted with a substituent selected from alkyl, halogen, amino, and hydroxyl groups ５－１４ aryl; C １－６ Alkyl, C １－３ a 3- to 12-membered heterocyclyl optionally substituted by a substituent selected from alkoxy, cyano, trifluoromethyl, a halogen atom, amino, and hydroxy; or C １－３ Alkyl, C １－３ 5-10 membered heteroaryl optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, and hydroxy; and R ６ and R ７ is not H and R ８ is a linear or branched C １－6 Alkyl, C ５ -C １４ aryl, 5-10 membered heteroaryl, or 3-12 membered heterocyclyl; or R ｅ and R ｆ is joined to the nitrogen atom to form a 5-8 membered heterocyclyl; or R ６ is H and R ７ is ethyl substituted with 2,6-dichloro-3-fluorophenyl; or R ６ is H and R ７ is the formula C(O)NHR ｄ and R is a thiazolyl substituted with a group ｄ is C １－５ alkyl or 2-chloro-6-methylphenyl; or R ６ represents H or methyl, R ７ is an optionally substituted C ３－１２ Cycloalkyl, optionally substituted C ５－１４ aryl, an optionally substituted 3- to 12-membered heterocyclyl group, or an optionally substituted 5- to 10-membered heteroaryl group; R ７ The group represented by is a halogen atom; １－５ Alkyl; Bis(C １－６ alkyl)phosphono group; C １－６ Alkylsulfonyl group; oxo group; cyano; C １－６ Alkyl, halogen, and halogenated C １－３ a 6-membered aryl optionally substituted with a substituent selected from alkyl; １－６ a 5- or 6-membered heterocyclyl optionally substituted with a substituent selected from alkyl and halogen; or C １－６ a 5- or 6-membered heteroaryl optionally substituted with a substituent selected from alkyl and halogen; Or X １ represents a quaternary ammonium base, The quaternary ammonium base is represented by the formula N ＋ R ａ R ｂ R ｃ X － Of these, R ａ , R ｂ , R ｃ are each independently C １－２０ represents alkyl, and X － is F － , Cl － ,Br － , or I － or among them, R ａ and R ｂ together with the N atom to which they are attached form a 5-8 membered heterocyclyl, the ring atoms of which optionally further include a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur; R ｃ is C １－２０ represents alkyl, and X － is F － , Cl － ,Br － , or I － represents Or X １ is a linear or branched C substituted with one or more fluorines １－１０ represents alkyl, Or X １ is an optionally substituted C ３ -C １２ represents cycloalkyl, The optionally substituted C ３－１２ Cycloalkyl includes halogen, oxo, cyano, trifluoromethyl, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C １－６ Alkyl, C １－３ alkoxycarbonyl, or any combination thereof; Or X １ represents an optionally substituted 5-10 membered heteroaryl; The optionally substituted 5-10 membered heteroaryl may be selected from the group consisting of halogen, cyano, amino, hydroxy, and C. １－３ Alkoxy; halogenated C １－３ Alkoxy; halogenated C １－３ Alkyl; Bis(C １－６ alkyl)phosphono; １－６ Alkyl sulfonyl; methanesulfonyloxy; trifluoromethanesulfonyloxy; p-toluenesulfonyloxy; C １－６ optionally substituted with substituents selected from alkyl; optionally substituted phenyl; optionally substituted 5- or 6-membered heterocyclyl; optionally substituted 5- or 6-membered heteroaryl, or any combination thereof; The optionally substituted phenyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; and The optionally substituted 5- or 6-membered heterocyclyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; and The optionally substituted 5- or 6-membered heteroaryl is C １－６ Alkyl, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; Or X １ is the formula (G １ ) group, Formula (G １ ) In A １ is CH ２ or C(O), B １ , U １ , V １ , W １ each independently represents CH or C; Y １ represents O, and Z is S, S(O) or S(O) ２ represents Or, in formula (I), A is CH ２ or C(O), B, U, V, and W each independently represent CH or C; Y represents O, and (ii) R represents S, and L is Halogen, cyano, C １－３ Alkyl, C １－３ a straight-chain or branched C alkyl group optionally substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof; １－４０ represents an alkylene group, The linear or branched C １－４０ The alkylene group is O; C(O); S; S(O); S(O) ２ ;C(O)N(R １ ); N(R ２ )C(O);N(R ３ ); N(R ４ )C(O)N(R ５ ); optionally substituted C ３ - １２ Cycloalkylene; optionally substituted C ５－１４ optionally substituted 3- to 12-membered heterocyclylene; optionally substituted 5- to 10-membered heteroarylene, or any combination thereof, wherein R １ , R ２ , R ３ , R ４ and R ５ are each independently H or C １－３ represents alkyl, The optionally substituted C ３－１２ Cycloalkylene is substituted with halogen, cyano, C １－５ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with alkyl, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo, or any combination thereof; The optionally substituted C ５－１４ Arylene is C １－５ Alkyl, halogenated C １－３ Alkoxy, cyano, C １－３ Alkoxy, halogenated C １－３ optionally substituted with a substituent selected from alkyl, halogen, amino, hydroxyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; The optionally substituted 3- to 12-membered heterocyclylene is １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, and oxo; The optionally substituted 5- to 10-membered heteroarylene is C １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; and X １ teeth, Halogen, cyano, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, halogenated C １－３ Alkyl, C １－６ Alkyl sulfonyl, bis(C １－６ alkyl)phosphono, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo, optionally substituted 5- or 6-membered heterocyclyl, optionally substituted 5- or 6-membered heteroaryl, C １－６ alkyl, or a 3- to 12-membered heterocyclyl optionally substituted with substituents selected from any combination thereof; The optionally substituted 5- or 6-membered heterocyclyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heteroaryl is C １－６ Alkyl, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; 1. A compound of formula (I) or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, characterized in that:

2. In formula (I), (i) R is S, S(O) or S(O) ２ represents, and L is Halogen, cyano, C １－３ Alkyl, C １－３ a straight-chain or branched C alkyl group optionally substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof; １－３０ represents an alkylene group, The linear or branched C １－３０ The alkylene group is O; C(O); S; S(O); S(O) ２ ;C(O)N(R １ ); N(R ２ )C(O);N(R ３ ); N(R ４ )C(O)N(R ５ ); optionally substituted C ３－１２ Cycloalkylene; optionally substituted C ５－１４ optionally substituted 3- to 12-membered heterocyclylene; optionally substituted 5- to 10-membered heteroarylene, or any combination thereof, wherein R １ , R ２ , R ３ , R ４ and R ５ are each independently H or C １－３ represents alkyl, The optionally substituted C ３－１２ Cycloalkylene is substituted with halogen, cyano, C １－５ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with alkyl, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo, or any combination thereof; The optionally substituted C ５－１４ Arylene is C １－５ Alkyl, halogenated C １－３ Alkoxy, cyano, C １－３ Alkoxy, halogenated C １－３ optionally substituted with a substituent selected from alkyl, halogen, amino, hydroxyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; The optionally substituted 3- to 12-membered heterocyclylene is １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, and oxo; The optionally substituted 5- to 10-membered heteroarylene is C １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; and X １ is NR ６ R ７ , C(O)NR ｅ R ｆ , NHC(O)R ８ , NHC(O)NR ９ R １０ , OR ｈ , or SH, Here, R ６ , R ７ , R ｅ , R ｆ , R ｈ , R ９ , and R １０ are each independently, H; Halogen, cyano, C １－３ Alkyl, C １－３ a straight or branched C alkyl group optionally substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof; １－１０ Alkyl; Halogen, cyano, C １－３ Alkyl, C １－３ Alkoxy, halogenated C １－３ C optionally substituted with a substituent selected from alkyl, amino, hydroxyl, or any combination thereof ３－１２ cycloalkyl; C １－５ Alkyl, halogenated C １－３ Alkoxy, cyano, C １－３ Alkoxy, halogenated C １－３ C optionally substituted with a substituent selected from alkyl, halogen, amino, and hydroxyl groups ５－１４ aryl; C １－６ Alkyl, C １－３ a 3- to 12-membered heterocyclyl optionally substituted by a substituent selected from alkoxy, cyano, trifluoromethyl, a halogen atom, amino, and hydroxy; or C １－3 Alkyl, C １－３ 5-10 membered heteroaryl optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, and hydroxy; and R ６ and R ７ is not H and R ８ is a linear or branched C １－6 Alkyl, C ５ -C １４ aryl, 5-10 membered heteroaryl, or 3-12 membered heterocyclyl; or R ｅ and R ｆ is joined to the nitrogen atom to form a 5-8 membered heterocyclyl; or R ６ is H and R ７ is ethyl substituted with 2,6-dichloro-3-fluorophenyl; or R ６ is H and R ７ is the formula C(O)NHR ｄ and R is a thiazolyl substituted with a group ｄ is C １－５ alkyl or 2-chloro-6-methylphenyl; or R ６ represents H or methyl, R ７ is an optionally substituted C ３－１２ Cycloalkyl, optionally substituted C ５－１４ aryl, an optionally substituted 3- to 12-membered heterocyclyl group, or an optionally substituted 5- to 10-membered heteroaryl group; R ７ The group represented by is a halogen atom; １－５ Alkyl; Bis(C １－６ alkyl)phosphono group; C １－６ Alkylsulfonyl group; oxo group; cyano; C １－６ Alkyl, halogen and halogenated C １－３ a 6-membered aryl optionally substituted with a substituent selected from alkyl; １－６ a 5- or 6-membered heterocyclyl optionally substituted with a substituent selected from alkyl and halogen; or C １－６ a 5- or 6-membered heteroaryl optionally substituted with a substituent selected from alkyl and halogen; Or X １ represents a quaternary ammonium base, The quaternary ammonium base is represented by the formula N ＋ R ａ R ｂ R ｃ X － It is expressed as, among which, R ａ , R ｂ , R ｃ are each independently C １－1０ represents alkyl, and X － is F － , Cl － ,Br － , or I － or R therein ａ and R ｂ together with the N atom to which they are attached form a 5- to 8-membered heterocyclyl, the ring atoms of which optionally further include a heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur; R ｃ is C １－２０ represents alkyl, and X － is F － , Cl － ,Br － , or I － represents Or X １ is a straight or branched chain C substituted with one or more fluorines １－１０ represents alkyl, Or X １ is an optionally substituted C ３ -C １２ represents cycloalkyl, The optionally substituted C ３－１２ Cycloalkyl includes halogen, oxo, cyano, trifluoromethyl, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C １－６ Alkyl, C １－３ alkoxycarbonyl, or any combination thereof, Or X １ represents an optionally substituted 5-10 membered heteroaryl; The optionally substituted 5-10 membered heteroaryl may be selected from the group consisting of halogen, cyano, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, halogenated C １－３ Alkyl, bis(C １－６ alkyl)phosphono, C １－６ Alkyl sulfonyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C １－６ optionally substituted with substituents selected from alkyl, optionally substituted phenyl, optionally substituted 5- or 6-membered heterocyclyl, optionally substituted 5- or 6-membered heteroaryl, or any combination thereof; The optionally substituted phenyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heterocyclyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heteroaryl is C １－６ Alkyl, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; Or X １ is the formula (G １ ) group, Formula (G １ ) In A １ is CH ２ or C(O), B １ , U １ , V １ , W １ each independently represents CH; Y １ represents O, and Z is S, S(O) or S(O) ２ represents Or, in formula (I), (ii) R represents S, and L is halogen, cyano, C １－３ Alkyl, C １－３ a straight-chain or branched C alkyl group optionally substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof; １－３０ represents alkylene, The linear or branched C １－３０ The alkylene group is O; C(O); S; S(O); S(O) ２ ;C(O)N(R １ ); N(R ２ )C(O);N(R ３ ); N(R ４ )C(O)N(R ５ ); optionally substituted C ３ -C １２ Cycloalkylene; optionally substituted C ５ -C １４ optionally substituted 3- to 12-membered heterocyclylene; optionally substituted 5- to 10-membered heteroarylene, or any combination thereof, wherein R １ , R ２ , R ３ , R ４ and R ５ are each independently H or C １－３ represents alkyl, The optionally substituted C ３－１２ Cycloalkylene is substituted with halogen, cyano, C １－５ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with alkyl, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo, or any combination thereof; The optionally substituted C ５ -C １４ Arylene is C １－５ Alkyl, halogenated C １－３ Alkoxy, cyano, C １－３ Alkoxy, halogenated C １－３ optionally substituted with a substituent selected from alkyl, halogen, amino, hydroxyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; The optionally substituted 3- to 12-membered heterocyclylene is １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, and oxo; The optionally substituted 5- to 10-membered heteroarylene is C １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; and X １ teeth, Halogen, cyano, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, halogenated C １－３ Alkyl, C １－６ Alkyl sulfonyl, bis(C １－６ alkyl)phosphono, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo, optionally substituted 5- or 6-membered heterocyclyl, optionally substituted 5- or 6-membered heteroaryl, C １－６ alkyl, or a 3- to 12-membered heterocyclyl optionally substituted with substituents selected from any combination thereof; The optionally substituted 5- or 6-membered heterocyclyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heteroaryl is C １－６ Alkyl, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; 2. A compound of formula (I) according to claim 1, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

3. A compound of formula (Ia), a compound of formula (Ib), or a compound of formula (Ic), where the groups A, R, L, and X １ , Y is as defined in claim 1; 2. A compound of formula (I) according to claim 1, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

4. L is a halogen atom, C １－３ The compound of formula (I) according to claim 1, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, which represents the following group optionally substituted with a substituent selected from alkyl, methanesulfonyloxy group, trifluoromethanesulfonyloxy group, p-toluenesulfonyloxy group, or any combination thereof: (i) Linear or branched C １ -C ４０ Alkylene; *-((CH ２ ) ｎ１ O) ｍ１ - (CH ２ ) ｎ２ -; *-((CH ２ ) ｎ１ O) ｍ１ - (CH ２ ) ｎ２ -O-(CH ２ ) ｎ３ -; *-(CH ２ ) ｎ１ -O-(CH ２ ) ｎ２ -; *-((CR １１ R １２ ) ｎ１ O) ｍ１ - (CR １３ R １４ ) ｎ２ -; *-((CR １５ R １６ ) ｎ１ O) ｍ１ - (CR １７ R １８ ) ｎ２ -O-(CR １９ R ２０ ) ｎ３ -; *-(CH ２ ) ｎ１ -S-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -S(O)-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -S(O) ２ - (CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -N(R ２１ )-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -N(R ２２ )C(O)—(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -C(O)N(R ２３ )-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -N(R ２４ )C(O)N(R ２５ )-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -(N(R ２６ )C(O)—(CH ２ ) ｎ２ ) ｍ１ -; *-(CH ２ ) ｎ１ -piperazinylene-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -phenylene-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -phenylene-(CH ２ ) ｎ２ -N(R ２１ )-(CH ２ ) ｎ３ -; *-(CH ２ ) ｎ１ -Furanylene-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -Furanylene-(CH ２ ) ｎ２ -N(R ２１ )-(CH ２ ) ｎ３ -; *-(CH ２ ) ｎ１ -thiazolylene-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -thiazolylene-C(O)N(R ２３ )-(CH ２ ) ｎ２ -; *-(CH ２ ) ｎ１ -thiazolylene-(CH ２ ) ｎ２ -N(R ２１ )-(CH ２ ) ｎ３ - or (ii) C(O), N(R ２１ ), C(O)N(R ２３ ), N(R ２２ ) C(O), optionally substituted C ３－１２ Cycloalkylene, optionally substituted C ５－１４ a straight or branched C alkyl group optionally interrupted one or more times by one or more substituents selected from the group consisting of arylene, optionally substituted 3- to 12-membered heterocyclylene, optionally substituted 5- to 10-membered heteroarylene, or any combination thereof; １－４０ is an alkylene group, The optionally substituted C ３－１２ Cycloalkylene is substituted with halogen, cyano, C １－５ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with a substituent selected from alkyl, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo, or any combination thereof; The optionally substituted C ５－１４ Arylene is C １－５ Alkyl, halogenated C １－３ Alkoxy, cyano, C １－３ Alkoxy, halogenated C １－３ optionally substituted with substituents selected from alkyl, halogen, amino, hydroxyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy; The optionally substituted 3- to 12-membered heterocyclylene is １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, and oxo; The optionally substituted 5- to 10-membered heteroarylene is C １－５ Alkyl, C １－３ It may be substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; or (iii) the carbon chain is C(O), optionally substituted C ３－１２ Cycloalkylene, optionally substituted C ５ -C １４ *-((CH) interrupted one or more times by one or more substituents selected from the group consisting of arylene, optionally substituted 3-12 membered heterocyclylene, optionally substituted 5-10 membered heteroarylene, or any combination thereof ２ ) ｎ１ O) ｍ１ - (CH ２ ) ｎ２ - and The optionally substituted C ３－１２ Cycloalkylene is substituted with halogen, cyano, C １－５ Alkyl, C １－３ Alkoxy, halogenated C １－３ optionally substituted with alkyl, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, oxo, or any combination thereof; The optionally substituted C ５－１４ Arylene is C １－５ Alkyl, halogenated C １－３ Alkoxy, cyano, C １－３ Alkoxy, halogenated C １－３ optionally substituted with a substituent selected from alkyl, halogen, amino, hydroxyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; The optionally substituted 3- to 12-membered heterocyclylene is １－５ Alkyl, C １－３ optionally substituted with a substituent selected from alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, and oxo; The optionally substituted 5- to 10-membered heteroarylene is C １－５ Alkyl, C １－３ optionally substituted with alkoxy, cyano, trifluoromethyl, halogen, amino, hydroxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; where * is the point of attachment to the group R, R ２１ , R ２２ , R ２３ , R ２４ , R ２５ and R ２６ are independently H and C １－３ alkyl, R １１ , R １２ , R １３ , R １４ , R １５ , R １６ , R １７ , R １８ , R １９ and R ２０ are each independently H, straight-chain or branched-chain C １ -C １０ Alkyl or C ３ -C １０ cycloalkyl, in which, when in the same group L, R １１ , R １２ , R １３ , R １４ or R １５ , R １６ , R １７ , R １８ , R １９ , R ２０ is not H at the same time, and n1, n2, n3, and m1 each independently represent an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

5. L is a halogen atom, C １－３ represents a group described in any one of the following (a) to (e), which may be substituted with a substituent selected from alkyl, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a p-toluenesulfonyloxy group, or any combination thereof: (a): -CH ２ -; -(CH ２ ) ２ -; -(CH ２ ) ３ -; -(CH ２ ) ４ -; -(CH ２ ) ５ -; -(CH ２ ) ６ -; -(CH ２ ) ７ -; -(CH ２ ) ８ -; -(CH ２ ) ９ -; -(CH ２ ) １０ -; -(CH ２ ) １１ -; -(CH ２ ) １２ -; -(CH ２ ) １３ -; -(CH ２ ) １４ -; -(CH ２ ) １５ -; -(CH ２ ) １６ -; -(CH ２ ) １７ -; -(CH ２ ) １８ -; -(CH ２ ) １９ -; or -(CH ２ ) ２０ -; (b): *-CH ２ CH ２ O(CH) ２ ) ２ -;*-(CH ２ CH ２ O) ２ -(CH) ２ ) ２ -;*-(CH ２ CH ２ O) ３ -(CH) ２ ) ２ -;*-(CH ２ CH ２ O) ４ -(CH) ２ ) ２ -;*-(CH ２ CH ２ O) ５ -(CH) ２ ) ２ -;*-(CH ２ CH ２ O) ６ -(CH) ２ ) ２ -;*-(CH ２ CH ２ O) ７ -(CH) ２ ) ２ -;*-(CH ２ CH ２ O) ８ -(CH) ２ ) ２ -;*-(CH ２ CH ２ O) ９ (CH) ２ ) ２ -;*-(CH ２ CH ２ O) １０ (CH) ２ ) ２ -;*-CH ２ CH ２ OCH ２ -;*-(CH ２ CH ２ O) ２ -CH ２ -;*-(CH ２ CH ２ O) ３ -CH ２ -;*-(CH ２ CH ２ O) ４ -CH ２ -;*-(CH ２ CH ２ O) ５ -CH ２ -;*-(CH ２ CH ２ O) ６ -CH ２ -;*-(CH ２ CH ２ O) ７ -CH ２ -;*-(CH ２ CH ２ O) ８ -CH ２ -;*-(CH ２ CH ２ O) ９ -CH ２ -;*-(CH ２ CH ２ O) １０ -CH ２ -;*-CH ２ CH ２ O(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ２ -(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ３ -(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ４ -(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ５ -(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ６ -(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ７ -(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ８ -(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ９ (CH) ２ ) ３ -;*-(CH ２ CH ２ O) １０ (CH) ２ ) ３ -;*-CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ -;*-CH ２ CH ２ OCH ２ CH ２ CH ２ O-(CH) ２ ) ２ -;*-CH ２ CH ２ OCH ２ CH ２ CH ２ O-(CH) ２ ) ３ -;*-(CH ２ CH ２ O) ２ (CH) ２ CH ２ CH ２ O) (CH ２ ) ３ -;*-(CH ２ CH ２ O) ２ (CH) ２ CH ２ CH ２ O) ２ (CH) ２ ) ３ -;*-(CH ２ ) １ O(CH) ２ ) １ -;*-(CH ２ ) １ O(CH) ２ ) ２ -;*-(CH ２ ) ２ O(CH) ２ ) ４ -; *-(CH ２ ) ２ O(CH ２ ) ５ -; *-(CH ２ ) ２ O(CH ２ ) ６ -; *-(CH ２ ) ３ O(CH ２ ) １ -; *-(CH ２ ) ３ O(CH [[ID=3I]] ２ ) ２ -; *-(CH ２ ) ３ O(CH ２ ) [[ID=A]] ３ -; *-(CH ２ ) ４ O(CH ２ ) １ -; *-(CH ２ ) ４ O(CH ２ ) <0CO0832> -; *-(CH <000083J> ) ４ O(CH ２ ) ３ -; *-(CH ２ ) ５ O(CH ２ ) １ -= *-(CH ２ ) ５ O(CH ２ ) ２ -; *-(CH ２ ​​​​​​​​​​​​​​​​​​​​​​​ (c): *-(CH) ２ ) １ -NHH-(CH ２ ) １ -、*-(CH ２ ) ２ -NHH-(CH ２ ) １ -、*-(CH ２ ) ２ -NHH-(CH ２ ) ２ -、*-(CH ２ ) ２ -NHH-(CH ２ ) ３ -、*-(CH ２ ) ２ -NHH-(CH ２ ) ４ -、*-(CH ２ ) ２ -NHH-(CH ２ ) ５ -、*-(CH ２ ) ２ -NHH-(CH ２ ) ６ -、*-(CH ２ ) ２ -NHH-(CH ２ ) ７ -、*-(CH ２ ) ２ -NHH-(CH ２ ) ８ -、*-(CH ２ ) ２ -NHH-(CH ２ ) ９ -、*-(CH ２ ) ２ -NHH-(CH ２ ) １０ -、*-(CH ２ ) ２ -NHH-(CH ２ ) １１ -、*-(CH ２ ) ２ -NHH-(CH ２ ) １２ -、*-(CH ２ ) ３ -NHH-(CH ２ ) １ -、*-(CH ２ ) ３ -NHH-(CH ２ ) ２ -、*-(CH ２ ) ３ -NHH-(CH ２ ) ３ -、*-(CH ２ ) ４ -NHH-(CH ２ ) １ -、*-(CH ２ ) ４ -NHH-(CH ２ ) ２ -、*-(CH ２ ) ５ -NHH-(CH ２ ) ３ -、*-(CH ２ ) ５ -NHH-(CH ２ ) １ -、*-(CH ２ ) ５ -NHH-(CH ２ ) ２ -、*-(CH ２ ) ８ -NHH-(CH ２ ) ２ -、*-(CH ２ ) ５ -NHH-(CH ２ ) ３ -、*-(CH ２ ) ５ -NHH-(CH ２ ) ４ -、*-(CH ２ ) ５ -NHH-(CH ２ ) ５ -、*-(CH ２ ) １ -N(CH) ３ ()-(CH ２ ) ８ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) １ -、*-(CH ２ ) ３ -N(CH) ３ ()-(CH ２ ) １ -、*-(CH ２ ) ４ -N(CH) ３ ()-(CH ２ ) １ -、*-(CH ２ ) ５ -N(CH) ３ ()-(CH ２ ) １ -、*-(CH ２ ) ６ -N(CH) ３ ()-(CH ２ ) １ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) ２ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) ３ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) ４ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) ５ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) ６ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) ７ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) ８ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) ９ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) １０ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) １１ -、*-(CH ２ ) ２ -N(CH) ３ ()-(CH ２ ) １２ -、*-(CH ２ ) ２ -NHC(O)-CH ２ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) ２ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) ３ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) ４ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) ５ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) ６ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) ７ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) ８ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) ９ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) １０ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) １１ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) １２ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) １３ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) １４ -、*-(CH ２ ) ２ -NHC(O)-(CH ２ ) １５ -、*-(CH ２ ) ３ -NHC(O)-CH ２ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) ２ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) ３ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) ４ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) ５ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) ６ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) ７ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) ８ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) ９ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) １０ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) １１ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) １２ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) １３ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) １４ -、*-(CH ２ ) ３ -NHC(O)-(CH ２ ) １５ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) １ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) ２ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) ３ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) ４ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) ５ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) ６ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) ７ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) ８ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) ９ -、*-(CH ２ ) ４ NHC(O)(CH ２ ) １０ -、*-(CH ２ ) ５ NHC(O)(CH ２ ) １ -、*-(CH ２ ) ８ NHC(O)(CH ２ ) ２ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-CH ２ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) ２ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) ３ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) ４ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) ５ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) ６ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) ７ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) ８ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) ９ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) １０ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) １１ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) １２ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) １３ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) １４ -、*-(CH ２ ) ２ -N(CH) ３ )C(O)-(CH ２ ) １５ -、*-(CH ２ ) ２ -C(O)NH-CH ２ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) ２ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) ３ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) ４ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) ５ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) ６ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) ７ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) ８ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) ９ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) １０ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) １１ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) １２ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) １３ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) １４ -、*-(CH ２ ) ２ -C(O)NH-(CH ２ ) １５ -、*-(CH ２ ) ３ -C(O)NH-CH ２ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) ２ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) ３ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) ４ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) ５ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) ６ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) ７ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) ８ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) ９ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) １０ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) １１ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) １２ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) １３ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) １４ -、*-(CH ２ ) ３ -C(O)NH-(CH ２ ) １５ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) １ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) ２ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) ３ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) ４ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) ５ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) ６ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) ７ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) ８ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) ９ -、*-(CH ２ ) ４ C(O)NH(CH ２ ) １０ -、*-(CH ２ ) ２ -C(O)N(CH) ３ )-CH ２ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) ２ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) ３ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) ４ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) ５ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) ６ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) ７ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) ８ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) ９ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) １０ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) １１ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) １２ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) １３ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) １４ -、*-(CH ２ ) ２ -C(O)N(CH) ３ ()-(CH ２ ) １５ -、*-(CH ２ ) ２ -NHC(O)NH--(CH ２ ) ４ -、*-(CH ２ ) ４ -NHC(O)NH--(CH ２ ) ２ -、*-CH ２ -NHC(O)NH--(CH ２ ) ２ -、*-(CH ２ ) ２ -NHC(O)NH-CH ２ -、*-(CH ２ ) ２ -NHC(O)NH--(CH ２ ) ２ -、*-(CH ２ ) ２ -NHC(O)NH--(CH ２ ) ３ -、*-(CH ２ ) ３ -NHC(O)NH--(CH ２ ) ２ -、*-CH ２ -ピペラジニレン-CH ２ -、*-(CH ２ ) ２ -piperazinylene-(CH ２ ) ２ -, *-(CH ２ ) ２ -piperazinylene-(CH ２ ) ３ -, *-(CH ２ ) ２ -piperazinylene-(CH ２ ) ４ -, *-(CH ２ ) ２ -piperazinylene-(CH ２ ) ５ -, *-(CH ２ ) ３ -piperazinylene-CH ２ -, *-(CH ２ ) ３ -piperazinylene-(CH ２ ) ２ -, *-(CH ２ ) ３ -piperazinylene-(CH ２ ) ３ -, *-(CH ２ ) ４ -piperazinylene-CH ２ -, *-(CH ２ ) ４ -piperazinylene-(CH ２ ) ２ -, *-(CH ２ ) ４ -piperazinylene-(CH ２ ) ３ -, *-(CH ２ ) ８ -piperazinylene-CH ２ -, *-(CH ２ ) ８ -piperazinylene-(CH ２ ) ２ -, *-(CH ２ ) ８ -piperazinylene-(CH ２ ) ３ -, *-(CH ２ ) ８ -piperazinylene-(CH ２ ) ４ -, *-(CH ２ ) ８ -piperazinylene-(CH ２ ) ５ -, *-(CH ２ ) ８ -piperazinylene-(CH ２ ) ６ -, *-(CH ２ ) ８ -piperazinylene-(CH ２ ) ７ -, *-(CH ２ ) ８ -piperazinylene-(CH ２ ) ８ -, *-CH ２ -piperazinylene-(CH ２ ) ８ -, *-(CH ２ ) ２ -piperazinylene-(CH ２ ) ８ -, *-(CH ２ ) ３ -piperazinylene-(CH ２ ) ８ -, *-(CH ２ ) ４ -piperazinylene-(CH ２ ) ８ -, *-(CH ２ ) ５ -piperazinylene-(CH ２ ) ８ -, *-(CH ２ ) ６ -piperazinylene-(CH ２ ) ８ -, *-(CH ２ ) ７ -piperazinylene-(CH ２ ) ８ -, *-CH ２ -phenylene-CH ２ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ４ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ５ -, *-(CH ２ ) ３ -phenylene-CH ２ -, *-(CH ２ ) ３ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) ３ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ４ -phenylene-CH ２ -, *-(CH ２ ) ４ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) ４ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ５ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ６ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ７ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ８ -phenylene-CH ２ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ４ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ５ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ６ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ７ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ８ -, *-CH ２ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ３ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ４ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ５ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ６ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ７ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) １ S (CH ２ ) １ -, *-(CH ２ ) ２ S (CH ２ ) ２ -, *-(CH ２ ) ２ S (CH ２ ) １ -, *-(CH ２ ) １ S (CH ２ ) ２ -, *-(CH ２ ) １ S(CH ２ ) ３ -、*-(CH ２ ) １ S(CH ２ ) ４ -、*-(CH ２ ) ２ S(CH ２ ) ３ -、*-(CH ２ ) ２ S(CH ２ ) ４ -、*-(CH ２ ) ２ S(CH ２ ) ５ -、*-(CH ２ ) ３ S(CH ２ ) １ -、*-(CH ２ ) ３ S(CH ２ ) ２ -、*-(CH ２ ) ３ S(CH ２ ) ３ -、*-(CH ２ ) ４ S(CH ２ ) １ -、*-(CH ２ ) ４ S(CH ２ ) ２ -、*-(CH ２ ) ４ S(CH ２ ) ３ -、*-(CH ２ ) ５ S(CH ２ ) １ -、*-(CH ２ ) ５ S(CH ２ ) ２ -、*-(CH ２ ) ５ S(CH ２ ) ３ -、*-(CH ２ ) ６ S(CH ２ ) １ -、*-(CH ２ ) ６ S(CH ２ ) ２ -、*-(CH ２ ) ６ S(CH ２ ) ３ -、*-(CH ２ ) ７ S(CH ２ ) １ -、*-(CH ２ ) ７ S(CH ２ ) ２ -、*-(CH ２ ) ７ S(CH ２ ) ３ -、*-(CH ２ ) ８ S(CH ２ ) １ -、*-(CH ２ ) ８ S(CH ２ ) ２ -、*-(CH ２ ) ８ S(CH ２ ) ３ -、*-(CH ２ ) ９ S(CH ２ ) １ -、*-(CH ２ ) ９ S(CH ２ ) ２ -、*-(CH ２ ) ９ S(CH ２ ) ３ -、*-(CH ２ ) １ S(O) (CH ２ ) １ -、*-(CH ２ ) ２ S(O)(CH ２ ) ２ -、*-(CH ２ ) ２ S(O)(CH ２ ) １ -、*-(CH ２ ) １ S(O)(CH ２ ) ２ -、*-(CH ２ ) １ S(O)(CH ２ ) ３ -、*-(CH ２ ) １ S(O)(CH ２ ) ４ -、*-(CH ２ ) ２ S(O)(CH ２ ) ３ -、*-(CH ２ ) ２ S(O)(CH ２ ) ４ -、*-(CH ２ ) ２ S(O)(CH ２ ) ５ -、*-(CH ２ ) ３ S(O)(CH ２ ) １ -、*-(CH ２ ) ３ S(O)(CH ２ ) ２ -、*-(CH ２ ) ３ S(O)(CH ２ ) ３ -、*-(CH ２ ) ４ S(O)(CH ２ ) １ -、*-(CH ２ ) ４ S(O)(CH ２ ) ２ -、*-(CH ２ ) ４ S(O)(CH ２ ) ３ -、*-(CH ２ ) ５ S(O)(CH ２ ) １ -、*-(CH ２ ) ５ S(O)(CH ２ ) ２ -、*-(CH ２ ) ５ S(O)(CH ２ ) ３ -、*-(CH ２ ) ６ S(O)(CH ２ ) １ -、*-(CH ２ ) ６ S(O)(CH ２ ) ２ -、*-(CH ２ ) ６ S(O)(CH ２ ) ３ -、*-(CH ２ ) ７ S(O)(CH ２ ) １ -、*-(CH ２ ) ７ S(O)(CH ２ ) ２ -、*-(CH ２ ) ７ S(O)(CH ２ ) ３ -、*-(CH ２ ) ８ S(O)(CH ２ ) １ -、*-(CH ２ ) ８ S(O)(CH ２ ) ２ -、*-(CH ２ ) ８ S(O)(CH ２ ) ３ -、*-(CH ２ ) ９ S(O)(CH ２ ) １ -、*-(CH ２ ) ９ S(O)(CH ２ ) ２ -、*-(CH ２ ) ９ S(O)(CH ２ ) ３ -、*-(CH ２ ) １ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) ２ S(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ２ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) １ S(O) ２ (CH ２ ) ２ -、*-(CH ２ ) １ S(O) ２ (CH ２ ) ３ -、*-(CH ２ ) １ S(O) ２ (CH ２ ) ４ -、*-(CH ２ ) ２ S(O) ２ (CH ２ ) ３ -、*-(CH ２ ) ２ S(O) ２ (CH ２ ) ４ -、*-(CH ２ ) ２ S(O) ２ (CH ２ ) ５ -、*-(CH ２ ) ３ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) ３ S(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ３ S(O) ２ (CH ２ ) ３ -、*-(CH ２ ) ４ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) ４ S(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ４ S(O) ２ (CH ２ ) ３ -、*-(CH ２ ) ５ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) ５ S(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ５ S(O)(CH ２ ) ３ -、*-(CH ２ ) ６ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) ６ S(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ６ S(O) ２ (CH ２ ) ３ -、*-(CH ２ ) ７ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) ７ S(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ７ S(O) ２ (CH ２ ) ３ -、*-(CH ２ ) ８ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) ８ S(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ８ S(O) ２ (CH ２ ) ３ -、*-(CH ２ ) ９ S(O) ２ (CH ２ ) １ -、*-(CH ２ ) ９ S(O) ２ (CH ２ ) ２ - or *- (CH ２ ) ９ S (O) ２ (CH ２ ) ３ -, The piperazinylene and the phenylene may each independently be substituted with a substituent selected from halogen, alkyl having 1 to 5 carbon atoms, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; (d): *-(CH) ２ ) ６ -NHH-(CH ２ ) １ -、*-(CH ２ ) ６ -NHH-(CH ２ ) ３ -、*-(CH ２ ) ６ -NHH-(CH ２ ) ４ -、*-(CH ２ ) ６ -NHH-(CH ２ ) ５ -、*-(CH ２ ) ７ -NHH-(CH ２ ) １ -、*-(CH ２ ) ７ -NHH-(CH ２ ) ２ -、*-(CH ２ ) ７ -NHH-(CH ２ ) ３ -、*-(CH ２ ) ７ -NHH-(CH ２ ) ４ -、*-(CH ２ ) ６ -NH-CH(CH) ３ )-、*-(CH ２ ) ５ -NH-CH(CH) ３ )-、*-(CH ２ ) ４ -NH-CH(CH) ３ )-、*-(CH ２ ) ３ -NH-CH(CH) ３ )-、*-(CH ２ ) ２ -NH-CH(CH) ３ )-、*-(CH ２ ) ７ -NH-CH(CH) ３ )-、*-(CH ２ ) ８ -NH-CH(CH) ３ )-、*-(CH ２ ) ７ -NH-CH(CF) ３ ) -, *-(CH ２ ) ６ -NH-CH(CF ３ ) -, *-(CH ２ ) ５ -NH-CH(CF ３ ) -, *-(CH ２ ) ４ -NH-CH(CF ３ ) -, *-(CH ２ ) ３ -NH-CH(CF ３ ) -, *-(CH ２ ) ２ -NH-CH(CF ３ ) -, *-(CH ２ ) ８ -NH-CH(CF ３ )-, *-CH ２ -C(O)NH-(CH ２ ) ４ -, *-CH ２ -C(O)NH-(CH ２ ) ２ -, *-CH ２ -C(O)NH-(CH ２ ) ３ -, *-CH ２ -C(O)NH-(CH ２ ) ５ -, *-(CH ２ ) １ -phenylene-(CH ２ ) １ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) １ -, *-(CH ２ ) １ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) １ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ３ -phenylene-(CH ２ ) １ -, *-(CH ２ ) ４ -phenylene-(CH ２ ) １ -, *-(CH ２ ) １ -phenylene-(CH ２ ) ４ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ２ -, *-CH ２ -phenylene-CH ２ -NH-CH(CH ３ )-, *-CH ２ -phenylene-(CH ２ ) ２ -NH-CH(CH ３ )-, *-CH ２ -phenylene-CH ２ -NH-CH ２ -, *-CH ２ -phenylene-(CH ２ ) ２ -NH-CH ２ -, *-(CH ２ ) １ -C(O)NH-(CH ２ ) ４ -, *-(CH ２ ) １ -Furanylene-(CH ２ ) １ -, *-(CH ２ ) １ -Furanylene-(CH ２ ) ２ -, *-(CH ２ ) １ -Furanylene-(CH ２ ) ３ -, *-(CH ２ ) ２ -Furanylene-(CH ２ ) １ -, *-(CH ２ ) ２ -Furanylene-(CH ２ ) ２ -, *-(CH ２ ) ３ -Furanylene-(CH ２ ) １ -, *-(CH ２ ) ３ -Furanylene-(CH ２ ) ２ -, *-(CH ２ ) １ -thiazolylene-(CH ２ ) １ -, *-(CH ２ ) １ -thiazolylene-(CH ２ ) ２ -, *-(CH ２ ) １ -thiazolylene-(CH ２ ) ３ -, *-(CH ２ ) ２ -thiazolylene-(CH ２ ) １ -, *-(CH ２ ) ２ -thiazolylene-(CH ２ ) ２ -, *-(CH ２ ) ３ -thiazolylene-(CH ２ ) １ -, *-(CH ２ ) ３ -thiazolylene-(CH ２ ) ２ - or *-CH ２ -thiazolylene-CH ２ -NH-CH ２ ; (e): In the formula, * represents the connection point with the group R.

5. A compound of formula (I) according to claim 4, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

6. X １ is C(O)NH ２ , piperidine-1-carbonyl, N,N-diisopropylcarbamoyl, NHC(O)CH ３ , OH, adamantyl-O-, norcamphanyl-O-, 1,7,7-trimethylbiscyclo[2.2.1]heptanyl-O-, or SH, or X １ is 2-isopropyl-5-methylcyclohexyl-O-, adamantan-1-yl-O-, adamantan-2-yl-O-, adamantyl-NHC(O)-, 3,5-dimethyladamantan-1-yl-NHC(O)-, adamantan-2-yl-NHC(O)-, or NHC(O)CH ３ Represents, 6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

7. X １ is a straight-chain or branched C optionally substituted with one or more fluorines １－１０ represents alkyl, 6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

8. X １ is CF ２ CF ３ or CF ３ Represents, 8. A compound of formula (I) according to claim 7, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

9. X １ is halogen, oxo, cyano, C １－３ Alkoxy, trifluoromethyl, amino, hydroxy, halogenated C １－３ Alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, C １－５ C optionally substituted with a substituent selected from the group consisting of alkyl, ３－１２ represents cycloalkyl, 6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

10. X １ teeth, cyclobutyl, 3,3-difluorocyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.2.1]heptan-2-yl, adamantyl, cyclopropyl, 2,3-dihydro-1H-indenyl, or 4-cyano-2,3-dihydro-1H-indenyl, adamantan-1-yl, adamantan-2-yl, 3,5-dimethyladamantan-1-yl, or (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 10. A compound of formula (I) according to claim 9, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

11. R ａ , R ｂ , R ｃ are each independently C １－１０ represents alkyl, or R ａ , R ｂ each independently represents methyl, ethyl, propyl, isopropyl, or butyl; R ｃ represents ethyl, and X － is Cl － represents or R ａ , R ｂ , R ｃ Each of the groups represents ethyl, and X － is Cl － or where R ａ , R ｂ , R ｃ Each of the groups represents methyl, and X － is Cl － represents or X １ teeth Represents 2. A compound of formula (I) according to claim 1, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

12. X １ represents an optionally substituted 3-12 membered heterocyclyl or an optionally substituted 5-10 membered heteroaryl; wherein the substituents of the optionally substituted 3-12 membered heterocyclyl are C １－６ Alkyl, halogen, oxo group, cyano, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, halogenated C １－３ Alkyl, di(C １－６ alkyl)phosphoryl, C １－６ selected from the group consisting of alkylsulfonyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl, or any combination thereof; The optionally substituted 5- or 6-membered heterocyclyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with a substituent selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heteroaryl is C １－６ Alkyl, halogenated C １－３ optionally substituted with a substituent selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; and The substituents of the optionally substituted 5-10 membered heteroaryl are C １－６ Alkyl, halogen, cyano, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, halogenated C １－３ Alkyl, di(C １－６ alkyl)phosphoryl, C １－６ selected from the group consisting of alkylsulfonyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, optionally substituted phenyl, optionally substituted 5- or 6-membered heterocyclyl, or optionally substituted 5- or 6-membered heteroaryl, or any combination thereof; The optionally substituted phenyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with a substituent selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heterocyclyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with a substituent selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heteroaryl is C １－６ Alkyl, halogenated C １－３ Optionally substituted with a substituent selected from alkyl, amino, hydroxyl, halogen, or any combination thereof.

6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

13. X １ represents the following group: (i) optionally substituted morpholinyl, optionally substituted piperidinyl, optionally substituted piperazinyl, optionally substituted 1,4-diazacycloheptan-1-yl, optionally substituted 3,8-diazabicyclo[3.2.1]octan-3-yl, optionally substituted 2-azabicyclo[3.2.1]octanyl, optionally substituted 1,4-diazacyclobicyclo[3.2.1]octanyl, optionally substituted 2,5-diazabicyclo[2.2.2]octan-2-yl, optionally substituted pyrrolidinyl, optionally substituted tetrahydro-2H-pyranyl, optionally substituted azacycloheptyl, optionally substituted azacyclooctyl, optionally substituted thiomorpholino, optionally substituted 5-aza spiro[2.4]heptyl, optionally substituted 6-azaspiro[2.5]octyl, optionally substituted 2-oxa-7-azaspiro[3.5]nonyl, optionally substituted 3-azabicyclo[3.1.0]hexyl, optionally substituted 3-azabicyclo[4.1.0]heptyl, optionally substituted 3-azaspiro[5.5]undecan-3-yl, optionally substituted hexahydro-1H-isoindol-2(3H)-yl, optionally substituted (3aR,7aS)-hexahydro-1H-isoindol-2(3H)-yl, optionally substituted (3aR,7aS)-octahydro-2H-isoindol-2-yl, optionally substituted azacyclobutyl, or [1,4'-dipiperidin]-1'-yl; The group is C １－６ Alkyl, halogen, cyano, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, halogenated C １－３ Alkyl, di(C １－６ alkyl)phosphono, C １－６ optionally substituted with substituents selected from alkylsulfonyl, optionally substituted 5- or 6-membered heterocyclyl, optionally substituted 5- or 6-membered heteroaryl groups, or any combination thereof; The optionally substituted 5- or 6-membered heterocyclyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heteroaryl is C １－６ Alkyl, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; (ii) optionally substituted quinazolinyl, optionally substituted pyridyl, optionally substituted pyrimidyl, optionally substituted thiazolyl, optionally substituted quinolyl, optionally substituted indolyl, optionally substituted benzothienyl, optionally substituted isoindolyl, optionally substituted 5,7-dihydro-6H-pyrrolo[3,4-b]pyridyl, or optionally substituted benzofuranyl; The group is C １－６ Alkyl, halogen, cyano, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, halogenated C １－３ Alkyl, di(C １－６ alkyl)phosphono, C １－６ optionally substituted with substituents selected from alkylsulfonyl, optionally substituted phenyl, optionally substituted 5- or 6-membered heterocyclyl, optionally substituted 5- or 6-membered heteroaryl groups, or any combination thereof; The optionally substituted phenyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heterocyclyl is C １－６ Alkyl, cyano, halogenated C １－３ optionally substituted with substituents selected from alkyl, amino, hydroxyl, halogen, or any combination thereof; The optionally substituted 5- or 6-membered heteroaryl is C １－６ Alkyl, halogenated C １－３ Optionally substituted with a substituent selected from alkyl, amino, hydroxyl, halogen, or any combination thereof.

13. A compound of formula (I) according to claim 12, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

14. X １ is morpholinyl, piperidinyl, 2-oxopiperidin-1-yl, piperazinyl, N-methylpiperazinyl, 4-(methylsulfonyl)piperazin-1-yl, 4-(ethylsulfonyl)piperazin-1-yl, (N-methylpiperazinyl)piperidinyl, 3,5-dimethylpiperazinyl, 1,4-diazacycloheptan-1-yl, 4-methyl-1,4-diazacycloheptan-1-yl, 1-methyl-1,4-diazacycloheptan-1-yl, 8-methyl-3,8-diazabicyclo[3.2.1]octyl 1,4-diazacyclobicyclo[3.2.1]octan-4-yl, 5-methyl-2,5-diazabicyclo[2.2.2]octan-2-yl, 8,8-difluoro-2-azabicyclo[3.2.1]octan-2-yl, 4-(3,4-difluorophenyl)piperazin-1-yl, 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 3-fluoro-4-hydroxypyrrolidin-1-yl, 3-methyl-4-(trifluoromethyl)pyrrolidin-1-yl, 2,6-dioxo Piperidin-3-yl, 4,4-dimethylpiperidin-1-yl, 3,5-dimethylpiperidin-1-yl, 4,4-difluoropiperidin-1-yl, 4-methylpiperazin-1-yl, tetrahydro-2H-pyran-2-yl, pyridyl, pyrimidyl, thiazolyl, quinolyl, 6,7-difluoroquinazolin-4-yl, 3-cyano-quinolyl, indolyl, 1-methyl-1H-indol-7-yl, benzothienyl, benzofuranyl, quinazolinyl, 6,7-difluoroquinazolin-4-yl, pyrrolidinyl yl, pyrrolidin-1-yl, 4-(pyridin-3-yl)pyrimidin-2-yl, 3-cyanoazacyclobutyl, 3-hydroxyazacyclobutyl, 3-hydroxy-3-methylazacyclobutyl, 3-hydroxy-2-methylazetidin-1-yl, 3-(trifluoromethoxy)azetidin-1-yl, azacycloheptan-1-yl, azacyclooctan-1-yl, 7-fluoro-5-azaspiro[2.4]heptan-5-yl, 1,1-difluoro-5-azaspiro[2.4]heptan-5-yl, 1,1-difluoro-6-azaspiro[2.5]octan-6-yl, 6-azaspiro[2.5]octan-6-yl, 2-oxa-7-azaspiro[3.5]nonan-7-yl, 3-azabicyclo[3.1.0]hexan-3-yl, 6-(difluoromethyl)-3-azabicyclo[4.1.0]heptan-3-yl, 3-fluoro-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, 3-(trifluoromethyl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, isoindole-2-yl, thiomorpholino, [1,4'-dipiperidin]-1'-yl, 4,4-difluoropiperidinyl, or Represents, 14. A compound of formula (I) according to claim 13, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

15. X １ is an optionally substituted C ３－１２ represents cycloalkyl, wherein the optionally substituted C ３－１２ The cycloalkyl substituents are C １－６ Alkyl, halogen, C １－３ alkoxycarbonyl, or any combination thereof; 6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

16. X １ teeth, Represents, 16. A compound of formula (I) according to claim 15, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

17. X １ is NR ６ R ７ represents Among them, R ６ and R ７ are each independently H or an optionally substituted straight or branched chain C １－１０ Represents alkyl, and the condition is R ６ , R ７ is not H at the same time, The optionally substituted straight or branched chain C １－１０ The alkyl substituents are halogen, cyano, C １－３ Alkyl, C １－３ selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof; Or, R ６ represents H, methyl, ethyl, isopropyl or cyclohexyl, and R ７ is one of the following groups: adamantyl, noradamantyl, norcamphanyl, cyclohexyl, cyclopentyl, cyclopropyl, cyclobutyl, ethyl, isopropyl, tert-butyl, methyl, 2,4-dimethylpentan-3-yl, bicyclopropylmethyl, spiro[3.3]heptyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, 4,4-dimethylcyclohexyl, oxacyclobutyl, oxazolyl, 2,3-dihydro-1H-indenyl, quinuclidine group, 1,7,7-trimethylbicyclo[2.2.1]heptyl, 7,7-dimethylbicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptyl, or 1-cyclopropylethyl; Or, R ６ represents H, and R ７ represents pyrimidin-4-yl, pyridin-4-yl or quinazolin-4-yl; Or, R ６ and R ７ represents phenyl, 6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

18. X １ is NHCH ３ , N(CH ３ ) ２ , N(CH ２ CH ３ ) ２ , or N(CH(CH ３ ) ２ ) ２ Represents, 18. A compound of formula (I) according to claim 17, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

19. X １ is NR ６ R ７ where R ６ represents H or methyl, and R ７ are pyrimidyl, pyridyl, quinazolinyl, 6,7-difluoroquinazolin-4-yl, phenyl, 3-chloro-4-methylphenyl, 4-fluorophenyl, 3,5-difluorophenyl, 3,4,5-trifluorophenyl, 2-(dimethylphosphoryl)phenyl, 2-(isopropylsulfonyl)phenyl, 4-(pyridin-3-yl)pyrimidin-2-yl, indolyl, 1-methyl-1H-indol-7-yl, benzothienyl, benzo[b]thiophen-7-yl, benzofuran-7-yl, benzofuranyl, 3-cyano-quinolin-4-yl, quinolyl, thiazolyl, adamantyl , adamantan-1-yl, adamantan-2-yl, 3,5-dimethyladamantan-1-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 4-(4-methylpiperazin-1-yl)piperidin-1-yl, cyclohexyl, dimethylcyclohexyl, 4,4-dimethylcyclohexyl, spirocycloalkyl, spiro[5.5]undecan-3-yl, spiro[3.3]heptyl, spiro[3.3]heptan-2-yl, pyrrolidinyl, azacycloheptanyl, azacyclooctanyl, piperidinyl, dimethylpiperidinyl, or azaspirocycloalkyl, 18. A compound of formula (I) according to claim 17, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

20. R ６ represents H, methyl, ethyl, isopropyl or cyclohexyl, R ７ Examples include bicyclo[1.1.1]pentan-1-yl, 4,4-dimethylcyclohexyl, 2-methoxycyclopropyl, 3-fluorocyclobutyl, 3,3-difluorocyclobutyl, 3,3-difluoro-1-(2-(trifluoromethyl)phenyl)cyclobutyl, 3-(2-(trifluoromethyl)phenyl)oxacyclobutan-3-yl, 3,3-difluorocyclopentyl, 3-hydroxycyclohexyl, (1S,3S)-3-hydroxycyclohexyl, 3-cyano-bicyclo[1.1.1]pentan-1-yl, bicyclo[2.2.2]octan-1-yl, 4-hydroxybicyclo[2.2.2]octan-1-yl, 2-isopropyl-5-methylcyclohexyl, 5-methyloxazol-2-yl, 4-cyano-2,3-dihydro-1H-inden-1-yl, 2,4-dimethylpentan-3-yl, bicyclo Chloropropylmethyl, quinuclidin-3-yl, (S)-quinuclidin-3-yl, (R)-quinuclidin-3-yl, adamantan-1-yl, 3-hydroxyadamantyl, 3-hydroxyadamantan-1-yl, 3-chloroadamantan-1-yl, 4-chloroadamantan-1-yl, 2-chloroadamantan-1-yl, adamantan-2-yl, 1,7,7-trimethylbicyclo[2.2.1]hepta hexahydro-2,5-methanopentalen-3a(1H)-yl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptan-2-yl, 1-cyclopropylethyl, or Represents, 18. A compound of formula (I) according to claim 17, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

21. X １ is NHC(O)NR ９ R １０ where R ９ represents H, and R １０ represents adamantyl, adamantan-1-yl, adamantan-2-yl, 3,5-dimethyladamantan-1-yl, phenyl, or 3-chloro-4-methylphenyl; 6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

22. X １ is the formula (G ２ ) group, Formula (G ２ ) and A １ is CH ２ or C(O), and Y １ represents O, and Z is S, S(O) or S(O) ２ Represents, 6. A compound of formula (I) according to any one of claims 1 to 5, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

23. Formula (G ２ ) and A １ is CH ２ or C(O), and Y １ represents O and Z represents S; 23. A compound of formula (I) according to claim 22, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

24. 4-((6-(diethylamino)hexyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((6-(dimethylamino)hexyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((6-(methylamino)hexyl)thio)isoindoline-1,3-dione; 3-(4-((3-hydroxypropyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-hydroxypentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-hydroxyoctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)acetamide; 3-(1-oxo-4-((9-((4,4,5,5,5-pentafluoropentyl)thio)nonyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((9-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((9-((4,4,5,5,5-pentafluoropentyl)sulfonyl)nonyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((9,9,10,10,10-pentafluorodecyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-morpholinoethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((2-(piperazin-1-yl)ethyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((2-(piperidin-1-yl)ethyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(diethylamino)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(diisopropylamino)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-morpholinopropyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-(piperazin-1-yl)propyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-(piperidin-1-yl)propyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(diethylamino)propyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(diisopropylamino)propyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-morpholinobutyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(piperazin-1-yl)butyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(piperidin-1-yl)butyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(diethylamino)butyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(diisopropylamino)butyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-morpholinopentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((5-(piperazin-1-yl)pentyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((5-(piperidin-1-yl)pentyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-(diethylamino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-(diisopropylamino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-(dimethylamino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-(methylamino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)acetamide; 3-(4-((6-morpholinohexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((6-(piperazin-1-yl)hexyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((6-(piperidin-1-yl)hexyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-(diethylamino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-(diisopropylamino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-(dimethylamino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-(methylamino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-morpholinoheptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(piperazin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(piperidin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(diethylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(diisopropylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-morpholinooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-(piperazin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(4-methylpiperazin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(3,5-dimethylpiperazin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-(piperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(4,4-difluoropiperidin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(1,4-diazacycloheptan-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(4-methyl-1,4-diazacycloheptan-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-(4-(piperazin-1-yl)piperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(diisopropylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-((2-(diethylamino)ethyl)amino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-N-(2-morpholinoethyl)pentanamide; N-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)-3-morpholinopropanamide; 3-(4-((8-(diethylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(dimethylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(methylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((9-morpholinononyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((9-(piperazin-1-yl)nonyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((9-(piperidin-1-yl)nonyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((9-(diethylamino)nonyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((9-(diisopropylamino)nonyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((10-morpholinodecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((10-(piperazin-1-yl)decyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((10-(piperidin-1-yl)decyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((10-(diethylamino)decyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((10-(diisopropylamino)decyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((11-morpholinoundecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((11-(piperazin-1-yl)undecyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((11-(piperidin-1-yl)undecyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((11-(diethylamino)undecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((11-(diisopropylamino)undecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((2-(diethylamino)ethyl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((12-morpholinododecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((12-(piperazin-1-yl)dodecyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((12-(piperidin-1-yl)dodecyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((12-(diethylamino)dodecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((12-(diisopropylamino)dodecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)-3-morpholinopropanamide; 3-(4-((15-morpholinopentadecyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((15-(piperidin-1-yl)pentadecyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(5-methyl-2,5-diazabicyclo[2.2.2]octan-2-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(4-(2-morpholinoethyl)phenyl)butyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(4-((3,3-difluorocyclobutyl)methyl)piperazin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-((2-hydroxyethyl)amino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-(2-oxopiperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-(2-oxopyrrolidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 1-(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)piperidine-2,6-dione; 3-(1-oxo-4-((8-(pyrimidin-4-ylamino)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-(pyridin-4-ylamino)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-(quinazolin-4-ylamino)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((6,7-difluoroquinazolin-4-yl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((4-fluorophenyl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((3,5-difluorophenyl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-((3,4,5-trifluorophenyl)amino)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((2-(dimethylphosphoryl)phenyl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((2-(isopropylsulfonyl)phenyl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((8-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; N-(2-chloro-6-methylphenyl)-2-((8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)amino)thiazole-5-carboxamide; 3-(4-((8-((1-(2,6-dichloro-3-fluorophenyl)ethyl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((1-methyl-1H-indol-7-yl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(benzo[b]thiophen-7-ylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(benzofuran-7-ylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 4-((8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)amino)quinoline-3-carbonitrile; 8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-N-ethyl-N,N-diisopropyloctane-1-ammonium chloride; 8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-N,N,N-triethyloctane-1-ammonium chloride; 8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-N,N,N-trimethyloctane-1-ammonium chloride; 4-(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)-4-methylmorpholin-4-ium chloride; 1-(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)-1-methylpiperidin-1-ium chloride; 3-(4-((4-((adamantan-1-yl)amino)butyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-((adamantan-1-yl)amino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((adamantan-1-yl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((adamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((adamantan-1-yl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((adamantan-2-yl)amino)butyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-((adamantan-2-yl)amino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-((adamantan-2-yl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((adamantan-2-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-((adamantan-2-yl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-((adamantan-2-yl)amino)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-(2-((adamantan-2-yl)amino)ethoxy)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 1-(adamantan-1-yl)-3-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)urea; 1-(4-(adamantan-1-yl)butyl)-3-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)urea; 3-(4-((8-((adamantan-1-yl)(methyl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((8-(((3,5-dimethyladamantan-1-yl)amino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((9-(adamantan-1-yl)nonyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2-((adamantan-1-yl)amino)-N-(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)acetamide; 3-(1-oxo-4-((8-(((1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-morpholinoethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((2-(2-(piperazin-1-yl)ethoxy)ethyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-(diethylamino)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-(dimethylamino)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-(methylamino)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(3-morpholinopropoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((2-(3-(piperazin-1-yl)propoxy)ethyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-(2-morpholinoethoxy)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((2-(2-(2-(piperazin-1-yl)ethoxy)ethoxy)ethyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-(2-(diethylamino)ethoxy)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-(2-(dimethylamino)ethoxy)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(2-(2-(methylamino)ethoxy)ethoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(3-(3-morpholinopropoxy)propoxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((2-(3-(3-(piperazin-1-yl)propoxy)propoxy)ethyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-(2-morpholinoethoxy)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-((5-morpholinopentyl)oxy)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 1-(3-chloro-4-methylphenyl)-3-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)urea; 1-(3-chloro-4-methylphenyl)-3-(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)propyl)urea; 1-(3-chloro-4-methylphenyl)-3-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)butyl)urea; 1-(3-chloro-4-methylphenyl)-3-(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)pentyl)urea; 1-(3-chloro-4-methylphenyl)-3-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)urea; 1-(3-chloro-4-methylphenyl)-3-(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptyl)urea; 1-(3-chloro-4-methylphenyl)-3-(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)octyl)urea; 1-(3-chloro-4-methylphenyl)-3-(9-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)nonyl)urea; 1-(3-chloro-4-methylphenyl)-3-(10-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)decyl)urea; 1-(3-chloro-4-methylphenyl)-3-(11-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)undecyl)urea; 3,3'-((octane-1,8-diylbis(sulfanediyl))bis(1-oxoisoindoline-4,2-diyl))bis(piperidine-2,6-dione); 3,3'-((nonane-1,9-diylbis(sulfanediyl))bis(1-oxoisoindoline-4,2-diyl))bis(piperidine-2,6-dione); 3,3'-(((piperazine-1,4-diylbis(octane-8,1-diyl))bis(sulfanediyl))bis(1-oxoisoindoline-4,2-diyl))bis(piperidine-2,6-dione); 3-(5-((5-morpholinopentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((6-morpholinohexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-morpholinoheptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-morpholinooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((8-(piperazin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(4-methylpiperazin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((8-(piperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(diethylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(diisopropylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(dimethylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((8-(methylamino)octyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 1-(3-chloro-4-methylphenyl)-3-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)ethyl)urea; 1-(3-chloro-4-methylphenyl)-3-(3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)propyl)urea; 1-(3-chloro-4-methylphenyl)-3-(4-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)butyl)urea; 1-(3-chloro-4-methylphenyl)-3-(5-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)pentyl)urea; 1-(3-chloro-4-methylphenyl)-3-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)hexyl)urea; 1-(3-chloro-4-methylphenyl)-3-(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)heptyl)urea; 3-(4-((8-mercaptooctyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4,4,5,5,5-pentafluoropentyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-(cyclohexylamino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-((4,4-dimethylcyclohexyl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((6-(spiro[5.5]undecan-3-ylamino)hexyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((6-(spiro[3.3]heptan-2-ylamino)hexyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(pyrrolidin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(azacycloheptan-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(azacyclooctan-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(4,4-dimethylpiperidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(3,5-dimethylpiperidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(3-azaspiro[5.5]undecan-3-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(cyclohexylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((4,4-dimethylcyclohexyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(spiro[3.3]heptan-2-ylamino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-oxo-7-(piperidin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-N,N-diisopropylheptanamide; 3-(1-oxo-4-((7-(phenylamino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(methyl(phenyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(diphenylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-(benzyl(methyl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)ethyl)-5-(piperidin-1-yl)pentanamide; 3-(1-oxo-4-((8-oxo-8-(piperidin-1-yl)octyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)-N,N-diisopropyloctanamide; 3-(4-((7-((3,5-dimethyladamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((adamantan-1-yl)oxy)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((adamantan-2-yl)oxy)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(((1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(morpholinomethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(piperidin-1-ylmethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((diisopropylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4,4,5,5,5-pentafluoropentyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 1-(3-chloro-4-methylphenyl)-3-(8-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)octyl); 2-(2,6-dioxopiperidin-3-yl)-4-((7-(piperidin-1-yl)heptyl)thio)isoindoline-1,3-dione; 4-((5-((adamantan-1-yl)amino)pentyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((6-((adamantan-1-yl)amino)hexyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((7-((adamantan-1-yl)amino)heptyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((7-((adamantan-1-yl)(methyl)amino)heptyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((6-(((adamantan-1-yl)methyl)amino)hexyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((4-(((adamantan-1-yl)amino)methyl)benzyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((7-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)heptyl)thio)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-((((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)methyl)benzyl)thio)isoindoline-1,3-dione; 4-((7-(cyclohexylamino)heptyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((7-(spiro[3.3]heptan-2-ylamino)heptyl)thio)isoindoline-1,3-dione; 4-((4-(((adamantan-1-yl)amino)methyl)phenethyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(piperidin-1-ylmethyl)phenethyl)thio)isoindoline-1,3-dione; 4-((4-((cyclohexylamino)methyl)phenethyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(3-(piperidin-1-yl)propyl)benzyl)thio)isoindoline-1,3-dione; 4-((4-(3-(cyclohexylamino)propyl)benzyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((4-(3-morpholinopropyl)benzyl)thio)isoindoline-1,3-dione; 2-(2,6-dioxopiperidin-3-yl)-4-((3-(4-(piperidin-1-ylmethyl)phenyl)propyl)thio)isoindoline-1,3-dione; 4-((3-(4-((cyclohexylamino)methyl)phenyl)propyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((3-(4-(((adamantan-1-yl)amino)methyl)phenyl)propyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 4-((8-((adamantan-1-yl)amino)octyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(4-((5-(3-azaspiro[5.5]undecan-3-yl)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-(3-azaspiro[5.5]undecan-3-yl)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((cyclohexylmethyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(cyclopropylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(cyclopropyl(methyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(cyclobutylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(bicyclo[1.1.1]pentan-1-ylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(cyclopentylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((4,4-dimethylcyclohexyl)(methyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-((cyclohexylmethyl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3aR,7aS)-hexahydro-1H-isoindol-2(3H)-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(tert-butylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(((1R,2R)-2-methoxycyclopropyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((1-cyclopropyl-2,2,2-trifluoroethyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 1-(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptyl)azetidine-3-carbonitrile; 3-(4-((7-(3-hydroxyazetidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(3-hydroxy-3-methylazetidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(oxetan-3-ylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3-fluorocyclobutyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3,3-difluorocyclobutyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((2S,3R)-3-hydroxy-2-methylazetidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(3-(trifluoromethoxy)azetidin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3,3-difluoro-1-(2-(trifluoromethyl)phenyl)cyclobutyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-((3-(2-(trifluoromethyl)phenyl)oxetan-3-yl)amino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3,3-difluorocyclopentyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3R,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3S,4S)-3-methyl-4-(trifluoromethyl)pyrrolidin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(7-fluoro-5-azaspiro[2.4]heptan-5-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3-hydroxycyclohexyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; Methyl 5-((7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptyl)amino)-3,3-difluorocyclohexane-1-carboxylate; 3-(4-((7-(3-azabicyclo[3.1.0]hexan-3-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(6-(difluoromethyl)-3-azabicyclo[4.1.0]heptan-3-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(3-fluoro-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(3-(trifluoromethyl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(1,1-difluoro-5-azaspiro[2.4]heptan-5-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(1,1-difluoro-6-azaspiro[2.5]octan-6-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(2-oxa-7-azaspiro[3.5]nonan-7-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-((7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptyl)amino)bicyclo[1.1.1]pentane-1-carbonitrile; 3-(4-((7-(bicyclo[2.2.2]octan-1-ylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((4-hydroxybicyclo[2.2.2]octan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(((1S,2R,5S)-2-isopropyl-5-methylcyclohexyl)oxy)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(((1S,2R,5S)-2-isopropyl-5-methylcyclohexyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(8,8-difluoro-2-azabicyclo[3.2.1]octan-2-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(1,4-diazabicyclo[3.2.1]octan-4-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(((5-methyloxazol-2-yl)methyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (1R)-1-((7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptyl)amino)-2,3-dihydro-1H-indene-4-carbonitrile; 3-(4-((7-((2,4-dimethylpentan-3-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((bicyclopropylmethyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(((R)-1-cyclopropylethyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(6-azaspiro[2.5]octan-6-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(isoindolin-2-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(((S)-quinuclidin-3-yl)amino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(((R)-quinuclidin-3-yl)amino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-thiomorpholinoheptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(4-(methylsulfonyl)piperazin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(4-(ethylsulfonyl)piperazin-1-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(2-oxopiperidin-1-yl)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(adamantan-1-yl)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-(adamantan-1-ylamino)ethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(adamantan-1-ylamino)propyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (3S)-3-(4-((7-((adamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; (3R)-3-(4-((7-((adamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((adamantan-1-yl)(methyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(adamantan-1-yl(methyl)amino)ethoxy)butyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((3-hydroxyadamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-((adamantan-1-ylmethyl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-((adamantan-1-ylmethyl)(methyl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((6-((1-(adamantan-1-yl)ethyl)amino)hexyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((5-((2-(adamantan-1-yl)ethyl)amino)pentyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(((adamantan-1-yl)methyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(adamantan-1-yl)-7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanamide; N-(3,5-dimethyladamantan-1-yl)-7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanamide; N-(adamantan-2-yl)-7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptanamide; 3-(4-((7-((3-chloroadamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((4-chloroadamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-((2-chloroadamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(adamantan-1-yloxy)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(adamantan-2-yloxy)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((adamantan-2-ylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((1-(adamantan-1-yl)ethyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-ylmethyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(adamantan-1-ylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(4-(adamantan-1-yl(methyl)amino)butyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)acetamide; 3-(1-oxo-4-((5-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)pentyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((6-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)hexyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((7-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(methyl((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-((((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)methyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; (S)-3-(1-oxo-4-((4-(piperidin-1-ylmethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; (R)-3-(1-oxo-4-((4-(piperidin-1-ylmethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-(piperidin-1-ylmethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-((cyclohexylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(((adamantan-1-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(morpholinomethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2,5-dibromo-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2,5-dibromo-4-((cyclohexylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)-2,5-dibromobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(azacyclooctan-1-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(4,4-difluoropiperidin-1-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(6-azaspiro[2.5]octan-6-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(3,5-dimethylpiperidin-1-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4,4-difluoropiperidin-1-yl)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4-methylpiperazin-1-yl)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((3aR,7aS)-octahydro-2H-isoindol-2-yl)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((((R)-1-cyclopropylethyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-fluoro-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3,5-difluoro-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-fluoro-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2,6-difluoro-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2,3-difluoro-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((2,3,5-trifluoro-4-(piperidin-1-ylmethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((2,3,5,6-tetrafluoro-4-(piperidin-1-ylmethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-chloro-2-fluoro-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-chloro-6-fluoro-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-chloro-5-fluoro-4-(piperidin-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((cyclohexylamino)methyl)-2-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)-2-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-fluoro-4-(morpholinomethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((bicyclopropylmethyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((cyclopropylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((bicyclo[1.1.1]pentan-1-ylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-((spiro[3.3]heptan-2-ylamino)methyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((cyclohexylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((cyclohexylmethyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-((((tetrahydro-2H-pyran-2-yl)methyl)amino)methyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(thiomorpholinomethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((diethylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((bicyclohexylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((3-hydroxyadamantan-1-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((4,4-dimethylcyclohexyl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((4,4-dimethylcyclohexyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((4,4-dimethylpiperidin-1-yl)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((6-azaspiro[2.5]octan-6-yl)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((3,5-dimethylpiperidin-1-yl)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((3-azaspiro[5.5]undecan-3-yl)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((tert-butylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(azacyclooctan-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(2-(piperidin-1-yl)ethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(cyclohexylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-morpholinoethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(diethylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(4-methylpiperazin-1-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(2-thiomorpholinoethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)phenethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(piperidin-1-ylmethyl)phenethyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((cyclohexylamino)methyl)phenethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(3-(piperidin-1-yl)propyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(3-(cyclohexylamino)propyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(3-((adamantan-1-yl)amino)propyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(3-morpholinopropyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(2-(piperidin-1-yl)ethyl)phenethyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((adamantan-1-yl)amino)ethyl)phenethyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-(4-(piperidin-1-ylmethyl)phenyl)propyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(4-((cyclohexylamino)methyl)phenyl)propyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(4-(((adamantan-1-yl)amino)methyl)phenyl)propyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(4-(morpholinomethyl)phenyl)propyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(diisopropylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((2,4-dimethylpentan-3-yl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(dimethylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(methylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(tert-butylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)methyl)phenethyl)acetamide; 3-(1-oxo-4-((4-(2-(pyrrolidin-1-yl)ethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(azepan-1-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(4,4-dimethylpiperidin-1-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(3-azaspiro[5.5]undecan-3-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((3aR,7aS)-octahydro-2H-isoindol-2-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(4-(methylsulfonyl)piperazin-1-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-([1,4'-dipiperidine]-1'-yl)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(cyclopropylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(cyclobutylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(cyclopentylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((bicyclopropylmethyl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(((R)-1-cyclopropylethyl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(bicyclo[1.1.1]pentan-1-ylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(2-(spiro[3.3]heptan-2-ylamino)ethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((cyclohexylmethyl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(bicyclohexylamino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((hexahydro-2,5-methanopentalen-3a(1H)-yl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((adamantan-2-yl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((3,5-dimethyladamantan-1-yl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((3-hydroxyadamantan-1-yl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(((adamantan-1-yl)methyl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-((1-(adamantan-1-yl)ethyl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(2-(((1R,2S,4S)-bicyclo[2.2.1]heptan-2-yl)amino)ethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((4-(2-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)ethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(azacyclooctan-1-ylmethyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-((bicyclohexylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(((2,4-dimethylpentan-3-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(((4,4-dimethylcyclohexyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-((spiro[3.3]heptan-2-ylamino)methyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-(((3,5-dimethyladamantan-1-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-((((adamantan-1-yl)methyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-((3-((((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)methyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((diisopropylamino)methyl)-2-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((diisopropylamino)methyl)-3-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(azacyclooctan-1-ylmethyl)-2-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(azacyclooctan-1-ylmethyl)-3-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((4,4-dimethylcyclohexyl)amino)methyl)-2-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((4,4-dimethylcyclohexyl)amino)methyl)-3-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-fluoro-4-((spiro[3.3]heptan-2-ylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-fluoro-4-((spiro[3.3]heptan-2-ylamino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((3,5-dimethyladamantan-1-yl)amino)methyl)-2-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((3,5-dimethyladamantan-1-yl)amino)methyl)-3-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((((adamantan-1-yl)methyl)amino)methyl)-2-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-((((adamantan-1-yl)methyl)amino)methyl)-3-fluorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((2-fluoro-4-((((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((3-fluoro-4-((((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)-2-chlorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)-3-chlorobenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)-2-methylbenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)-3-methylbenzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((7-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((7-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)oxy)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((4-((((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)methyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((adamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((adamantan-1-yl)(methyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((3-hydroxyadamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((adamantan-2-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((adamantan-2-yl)(methyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((1-(adamantan-1-yl)ethyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(4-((adamantan-1-yl)(methyl)amino)butyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)acetamide; 3-(5-((4-(((adamantan-1-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((4-(((adamantan-1-yl)(methyl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 1-(((adamantan-1-yl)amino)methyl)-3-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)thio)ethyl)urea; 3-(5-((7-(cyclopropylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-(cyclobutylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-((7-(spiro[3.3]heptan-2-ylamino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-(cyclopentylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-(cyclohexylamino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-(3-azaspiro[5.5]undecan-3-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((4,4-dimethylcyclohexyl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-((3aR,7aS)-octahydro-2H-isoindol-2-yl)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 5-((7-((adamantan-1-yl)amino)heptyl)thio)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione; 3-(5-((7-((adamantan-1-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-(((5-(piperidin-1-ylmethyl)furan-2-yl)methyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((5-(morpholinomethyl)furan-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((5-(((((S)-1-cyclopropylethyl)amino)methyl)furan-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((5-(azepan-1-ylmethyl)furan-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((5-((cyclopentylamino)methyl)furan-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-(((5-((((tetrahydro-2H-pyran-2-yl)methyl)amino)methyl)furan-2-yl)methyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((5-(((bicyclopropylmethyl)amino)methyl)furan-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((2-(morpholinomethyl)thiazol-4-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-(((2-(piperidin-1-ylmethyl)thiazol-4-yl)methyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((2-(azepan-1-ylmethyl)thiazol-4-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((2-((cyclopentylamino)methyl)thiazol-4-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((4-(morpholinomethyl)thiazol-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-(((4-(piperidin-1-ylmethyl)thiazol-2-yl)methyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((4-(azepan-1-ylmethyl)thiazol-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((4-((3,5-dimethylpiperidin-1-yl)methyl)thiazol-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((4-((hexahydro-1H-isoindol-2(3H)-yl)methyl)thiazol-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-4-(((4-(thiomorpholinomethyl)thiazol-2-yl)methyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((4-((diethylamino)methyl)thiazol-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((4-((cyclohexylamino)methyl)thiazol-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(((4-(((cyclohexylmethyl)amino)methyl)thiazol-2-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; N-(cyclohexylmethyl)-4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)methyl)thiazole-2-carboxamide; 3-(4-((7-((hexahydro-2,5-methanopentalen-3a(1H)-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((hexahydro-2,5-methanopentalen-3a(1H)-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 3-(4-((7-(((1R,2S,4S)-bicyclo[2.2.1]heptan-2-yl)amino)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione selected from the group consisting of 2. A compound of formula (I) according to claim 1, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

25. A compound of formula (I') or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, In formula (I'), A, B, U, V, W, and Y are as defined in claim 1; R is S, S(O) or S(O) ２ represents L is halogen, cyano, C １－３ Alkyl, C １－３ a straight-chain or branched C alkyl group optionally substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof; １－４０ represents alkylene, wherein the linear or branched C １－４０ Alkylene is O, C(O), S, S(O), S(O) ２ , S(O) ２ N (R １ ), N(R ２ ) S (O) ２ , C(O)N(R １ ), N(R ２ ) C(O), N(R ３ ), N(R ４ )C(O)N(R ５ ), optionally substituted C ３ - １２ Cycloalkylene, optionally substituted C ５ - １４ optionally interrupted one or more times by one or more selected from the group consisting of arylene, optionally substituted 3- to 12-membered heterocyclylene, optionally substituted 5- to 10-membered heteroarylene, or any combination thereof; R １ , R ２ , R ３ , R ４ and R ５ are each independently H or C １－３ represents alkyl, The optionally substituted C ３ - １２ Cycloalkylene is a group containing halogen, C １－５ optionally substituted with a substituent selected from alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, and oxo; The optionally substituted C ５ - １４ The arylene may be selected from halogen, C １－５ optionally substituted with a substituent selected from alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy; The optionally substituted 3- to 12-membered heterocyclylene may be selected from the group consisting of halogen, C １－５ optionally substituted with a substituent selected from alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, and oxo; The optionally substituted 5-10 membered heteroarylene may be selected from the group consisting of halogen, C １－５ may be substituted with a substituent selected from alkyl, methanesulfonyloxy, trifluoromethanesulfonyloxy, and p-toluenesulfonyloxy, and L １ is H or C １－３ represents alkyl, L １ If represents H, X １ is NHC(O)R ｉ or SR ｊ where R ｉ and R ｊ are each independently １－６ Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ C optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof ３ - １２ represents cycloalkyl, or X １ is C １－６ Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ C optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof ３ - １２ represents cycloalkyl; or L １ is C １－３ When representing alkyl, X １ teeth, NR ６ R ７ represents R ６ is H or C １－６ represents alkyl, and R ７ is C １－６ Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ C optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof ３ - １２ represents cycloalkyl; or X １ teeth, C １－６ Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ represents a 3- to 12-membered heterocyclyl optionally substituted with a substituent selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; 1. A compound of formula (I') or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof, characterized in that:

26. L is halogen, cyano, C １－３ Alkyl, C １－３ represents the following group, which may be substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof: Linear or branched C １－４０ Alkylene, *-(CH ２ ) ｎ１ -N(R ２２ ) S (O) ２ - (CH ２ ) ｎ２ -, *-(CH ２ ) ｎ１ -S(O) ２ N (R ２３ )-(CH ２ ) ｎ２ - or *- (CH ２ ) ｎ１ -phenylene-(CH ２ ) ｎ２ -, in which * represents the connection point with the group R, and R ２２ , R ２３ are independently H and C １－３ alkyl, and n1 and n2 each independently represent an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; 26. A compound of formula (I') according to claim 25, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

27. L is halogen, cyano, C １－３ Alkyl, C １－３ represents the following group, which may be substituted with one or more substituents selected from alkoxy, trifluoromethyl, 3- to 12-membered heterocyclyl, or any combination thereof: -CH ２ -、-(CH ２ ) ２ -、-(CH ２ ) ３ -、-(CH ２ ) ４ -、-(CH ２ ) ５ -、-(CH ２ ) ６ -、-(CH ２ ) ７ -、-(CH ２ ) ８ -、-(CH ２ ) ９ -、-(CH ２ ) １０ -、-(CH ２ ) １１ -、-(CH ２ ) １２ -、-(CH ２ ) １３ -、-(CH ２ ) １４ -、-(CH ２ ) １５ -、-(CH ２ ) １６ -、-(CH ２ ) １７ -、-(CH ２ ) １８ -、-(CH ２ ) １９ -、-(CH ２ ) ２０ -、*-(CH ２ ) ２ -NHS(O) ２ -CH ２ -、*-(CH ２ ) ２ -NHS(O) ２ -(CH ２ ) ２ -、*-(CH ２ ) ２ -NHS(O) ２ -(CH ２ ) ３ -、*-(CH ２ ) ２ -NHS(O) ２ -(CH ２ ) ４ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) ５ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) ６ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) ７ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) ８ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) ９ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) １０ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) １１ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) １２ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) １３ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) １４ -、*-(CH ２ ) ２ - NHS(O) ２ -(CH ２ ) １５ -、*-(CH ２ ) ３ - NHS(O) ２ -CH ２ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) ２ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) ３ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) ４ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) ５ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) ６ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) ７ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) ８ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) ９ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) １０ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) １１ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) １２ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) １３ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) １４ -、*-(CH ２ ) ３ - NHS(O) ２ -(CH ２ ) １５ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) １ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) ３ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) ４ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) ５ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) ６ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) ７ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) ８ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) ９ -、*-(CH ２ ) ４ NHS(O) ２ (CH ２ ) １０ -、*-(CH ２ ) ５ NHS(O) ２ (CH ２ ) １ -、*-(CH ２ ) ６ NHS(O) ２ (CH ２ ) １ -、*-(CH ２ ) ７ NHS(O) ２ (CH ２ ) １ -、*-(CH ２ ) ８ NHS(O) ２ (CH ２ ) １ -、*-(CH ２ ) ８ NHS(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ９ NHS(O) ２ (CH ２ ) １ -、*-(CH ２ ) １０ NHS(O) ２ (CH ２ ) １ -、*-(CH ２ ) ５ NHS(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ６ NHS(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ７ NHS(O) ２ (CH ２ ) ２ -、*-(CH ２ ) ８ NHS(O) ２ (CH ２ ) ３ -、*-(CH ２ ) ９ NHS (O) ２ (CH ２ ) ２ -, *-(CH ２ ) １０ NHS (O) ２ (CH ２ ) ２ -, *-CH ２ -phenylene-CH ２ -, *-(CH ２ ) １ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) １ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) １ -phenylene-(CH ２ ) ４ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) １ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ４ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ５ -, *-(CH ２ ) ３ -phenylene-(CH ２ ) １ -, *-(CH ２ ) ３ -phenylene-CH ２ -, *-(CH ２ ) ３ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) ３ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ４ -phenylene-CH ２ -, *-(CH ２ ) ４ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) ４ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ５ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ６ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ７ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ８ -phenylene-CH ２ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ２ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ３ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ４ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ５ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ６ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ７ -, *-(CH ２ ) ８ -phenylene-(CH ２ ) ８ -, *-CH ２ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ２ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ３ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ４ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ５ -phenylene-(CH ２ ) ８ -, *-(CH ２ ) ６ -phenylene-(CH ２ ) ８ - or *- (CH ２ ) ７ -phenylene-(CH ２ ) ８ - or In the formula, * represents the connection point with the group R.

26. A compound of formula (I') according to claim 25, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

28. L １ represents H, and X １ is an optionally substituted group: adamantyl-C(O)NH-, adamantyl-S-, or norcamphanyl, wherein the substituents of said group are C １－６ Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; 28. A compound of formula (I') according to any one of claims 25 to 27, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

29. X １ are adamantan-1-yl-C(O)NH-, 3-hydroxyadamantyl-C(O)NH-, 3-hydroxyadamantan-1-yl-C(O)NH-, 3-chloroadamantan-1-yl-C(O)NH-, 4-chloroadamantan-1-yl-C(O)NH-, 2-chloroadamantan-1-yl-C(O)NH-, adamantan-2-yl-C(O)NH-, adamantan-1-yl-S-, 3-hydroxyadamantyl-S-, 3-hydroxyadamantan adamantan-1-yl-S-, 3-chloroadamantan-1-yl-S-, 4-chloroadamantan-1-yl-S-, 2-chloroadamantan-1-yl-S-, adamantan-2-yl-S-, bicyclo[2.2.1]heptan-2-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 7,7-dimethylbicyclo[2.2.1]heptan-1-yl, or 7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl, 29. A compound of formula (I') according to claim 28, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

30. L １ is C １－３ When representing alkyl, X １ teeth NR ６ R ７ represents R ６ is H or C １－３ represents alkyl, and R ７ represents an optionally substituted group: adamantyl, cyclohexyl, spirocycloalkyl or norcamphanyl, wherein the substituent of the group is C １－６ Alkyl, oxo group, halogen, cyano, trifluoromethyl, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ selected from the group consisting of alkoxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or any combination thereof; 28. A compound of formula (I') according to any one of claims 25 to 27, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

31. R ７ represents adamantan-1-yl, 3-hydroxyadamantyl, 3-hydroxyadamantan-1-yl, 3-chloroadamantan-1-yl, 4-chloroadamantan-1-yl, 2-chloroadamantan-1-yl, adamantan-2-yl, bicyclo[2.2.1]heptan-2-yl, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl, 7,7-dimethylbicyclo[2.2.1]heptan-1-yl, or 7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl, 31. The compound of formula (I') of claim 30, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

32. L １ is C １－３ When it represents alkyl, X １ represents optionally substituted piperidinyl, in which The substituents of the optionally substituted piperidinyl are C １－６ Alkyl, halogen, oxo group, cyano, amino, hydroxy, C １－３ Alkoxy, halogenated C １－３ Alkoxy, halogenated C １－３ Alkyl, di(C １－６ alkyl)phosphoryl, C １－６ alkylsulfonyl, or any combination thereof; 28. A compound of formula (I') according to any one of claims 25 to 27, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

33. N-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)adamantane-1-carboxamide; 3-chloro-N-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)adamantane-1-carboxamide; 3-(4-((7-(adamantan-1-ylthio)heptyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 1-((1R,4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)-N-(6-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)hexyl)methanesulfonamide; 1-((1R,4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)-N-(7-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)thio)heptyl)methanesulfonamide; 3-(4-((7-(adamantan-1-ylamino)heptyl)thio)-1-oxoisoindolin-2-yl)-1-methylpiperidine-2,6-dione; 1-methyl-3-(1-oxo-4-((7-(((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 1-methyl-3-(1-oxo-4-((4-((((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)amino)methyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((7-(cyclohexylamino)heptyl)thio)-1-oxoisoindolin-2-yl)-1-methylpiperidine-2,6-dione; 1-methyl-3-(1-oxo-4-((4-(piperidin-1-ylmethyl)benzyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 3-(4-((4-(((adamantan-1-yl)amino)methyl)benzyl)thio)-1-oxoisoindolin-2-yl)-1-methylpiperidine-2,6-dione; or 1-methyl-3-(1-oxo-4-((7-(spiro[3.3]heptan-2-ylamino)heptyl)thio)isoindolin-2-yl)piperidine-2,6-dione; 26. A compound of formula (I') according to claim 25, or a salt, solvate, tautomer, polymorph, stereoisomer, or mixture of stereoisomers thereof.

34. A compound of formula (I) according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof, or a compound of formula (I') according to any one of claims 25 to 33 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. A pharmaceutical composition comprising:

35. 35. The pharmaceutical composition of claim 34, further comprising at least one additional therapeutic agent.

36. 36. The pharmaceutical composition of claim 35, wherein the at least one additional therapeutic agent is used to treat or prevent cancer.

37. A pharmaceutical composition for treating or preventing cancer, comprising, as an active ingredient, a compound of formula (I) according to any one of claims 1 to 24 or a pharmaceutically acceptable salt thereof, or a compound of formula (I') according to any one of claims 25 to 33 or a pharmaceutically acceptable salt thereof, and the pharmaceutical composition is used in a subject.

38. The cancers include multiple myeloma, myelodysplastic syndromes (MDS), previously treated myelodysplastic syndromes, plasma cell myeloma, transplant-related cancers, myelofibrosis, bone marrow disease, neutropenia, leukemia, acute myeloid cell leukemia, anemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, acute myeloid leukemia (AML), CD20 positive, primary lymphoma, B-cell lymphoma, relapsed B-cell non-Hodgkin's lymphoma, relapsed the disease is selected from the group consisting of recurrent diffuse large B-cell lymphoma, recurrent primary mediastinal (thymic) large B-cell, recurrent transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell, refractory transformed non-Hodgkin's lymphoma, smoldering myeloma, smoldering multiple myeloma, or Richter's syndrome, 38. The pharmaceutical composition of claim 37.

39. The subject is administered at least one dosage form selected from the group consisting of nasal administration, inhalation administration, topical administration, oral administration, oral mucosal administration, rectal administration, pleural administration, peritoneal administration, vaginal administration, intramuscular administration, subcutaneous administration, transdermal administration, epidural administration, intrathecal administration, and intravenous administration.

38. The pharmaceutical composition of claim 37.

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