C-MYC mRNA translation modulators and their use in treatment of cancer

Abstract

The present invention relates to novel c-MYC mRNA translation modulators, compositions and methods of preparation thereof, and their use in the treatment of cancer.

Description

Technical Field

[0001] The present invention relates to a novel c-MYC mRNA translation regulator, a composition and a preparation method thereof, and a use thereof in cancer treatment. Background Art

[0002] In the United States, cancer is the second most common cause of death, second only to heart disease. In the United States, cancer accounts for 1 in every 4 deaths. The 5-year relative survival rate for all cancer patients diagnosed in 1996-2003 was 66%, higher than 50% in 1975-1977 (Cancer Facts & Figures, American Cancer Society: Atlanta, GA (2008)). Between 2000 and 2009, the incidence of new cancers in men decreased by an average of 0.6% per year, and remained unchanged in women. From 2000 to 2009, the death rate from all cancers in men decreased by an average of 1.8% per year, and in women by an average of 1.4% per year. The improvement in survival reflects the improvement in early diagnosis and treatment. Discovering highly effective anticancer agents with low toxicity is a major goal of cancer research.

[0003] The Myc family includes three main members, namely the proto-oncogene c-Myc (myelocytomatosis, referred to as Myc), as well as L-myc and N-myc. These three Myc homologs are involved in the early carcinogenesis and metastatic spread of most human cancers. In most types of tumors, the Myc gene is not mutated or replicated, but its mRNA and / or protein levels increase, indicating that in cancer, Myc overexpression is induced at the transcription level, mRNA steady-state level and translation level. In fact, myc gene expression is usually dependent on growth factor signal transduction, and the half-life of both myc mRNA and Myc protein is very short (30 minutes and 20 minutes respectively) [Dang, CV (2012). MYC on the path to cancer. "Cell (Cell)" 149, 22-35]. However, in tumor cells, the cellular level of Myc becomes independent of such signal transduction and regulation, and the resulting aggravated Myc function drives intracellular and extracellular transcriptional programs, thereby allowing tumor growth and reproduction. However, Myc does not necessarily need to be overexpressed to make cancer highly dependent on its activity. A study by Soucek et al. (Nature (2008) 455 (7213): 679-83) showed that tumors expressing c-Myc at endogenous levels showed tumor regression after Myc was inhibited by a genetically engineered system. Therefore, treatment with Myc inhibitors is not necessarily limited to cancers that overexpress Myc. The compounds according to the present invention can also be used to regulate the translation of Myc mRNA, wherein the direct target of the compound is a protein or RNA that regulates the translation of Myc mRNA, and therefore any Myc-dependent tumor will benefit from the therapeutic utility of these compounds.

[0004] Due to its wide range of pathogenic significance, MYC is an important anti-cancer target. Deregulated Myc genes have been found in a wide range of human hematological malignancies and solid tumors, especially in breast cancer, ovarian cancer, acute myeloid leukemia, chronic myeloid leukemia, Hodgkin's and Burkitt's lymphoma, diffuse large B-cell lymphoma, prostate cancer, colon cancer, gastric cancer, primary central nervous system lymphoma, glioblastoma, medulloblastoma, melanoma, non-small cell lung cancer, germinal center-derived lymphoma, esophageal squamous cell carcinoma, osteosarcoma, bladder cancer, pancreatic cancer and lung adenocarcinoma. Recent studies have also shown that deregulation of c-MYC is associated with the occurrence of BRAF V600E thyroid cancer, choroid plexus carcinoma and colitis-related cancers. In addition, amplification of the MYC gene has been found in a large number of cases of epithelial ovarian cancer. In the TCGA dataset, Myc amplification occurs in several cancer types, including breast, colorectal, pancreatic, gastric, and uterine cancers.

[0005] Although the Myc gene is a very important oncogene and is considered a driver of carcinogenesis, and the MYC protein is a key transcription factor that is widely targeted for various genes, the rational design of direct Myc inhibitors remains challenging. This is mainly because the MYC protein lacks structural regions that are easily amenable to therapeutic inhibition by small molecules and is considered to be an undruggable target [BioDrugs (2019) 33:539–553].

[0006] Design and development of MYC regulators are challenging, mainly because MYC protein has a disordered structure that lacks pockets or grooves that can serve as binding sites for regulators. Interference with MYC transcription, blocking the protein-protein interaction (PPI) of MYC and its cofactors, and affecting the signal transduction pathways associated with MYC have been used as potential regulatory targets in the past, but have failed to be developed as drug candidates. Myc PPI inhibitors fail to show enough efficacy in cell-based assays and animal models because high target occupancy is required to drive efficacy. Regulators of myc upstream signal transduction pathways (e.g., mTOR regulators) fail due to lack of target specificity.

[0007] Despite this, therapeutic approaches targeting c-Myc remain elusive. The lack of a well-defined ligand-binding domain creates a formidable barrier to direct inhibition, a challenging feature shared by many compelling transcriptional targets in cancer. Therefore, alternative approaches to targeting Myc, namely compounds that modulate Myc mRNA translation, are needed, as outlined herein. Summary of the invention

[0008] The present invention provides a compound or a pharmaceutically acceptable salt thereof, a stereoisomer, a tautomer, a hydrate, an N-oxide, a reverse amide analog, a prodrug, an isotopic variant (e.g., a deuterated analog), a PROTAC, a pharmaceutical product, or any combination thereof, which is represented by the structure of Formula I and / or I(a)-I(n) as defined below and the structure listed in Table 1. In various embodiments, the compound is a c-MYC mRNA translation regulator. In various embodiments, the compound is a c-MYC mRNA transcription regulator. In various embodiments, the compound is a c-MYC inhibitor. In various embodiments, the compound is any combination of a c-MYC mRNA translation regulator, a c-MYC mRNA transcription regulator, and a c-MYC inhibitor.

[0009] The present invention further provides a pharmaceutical composition comprising: a compound or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, drug product or any combination thereof, which is represented by the structure of Formula I and / or I(a)-I(n) and the structures listed in Table 1 as defined below; and a pharmaceutically acceptable carrier.

[0010] The present invention further provides a method of treating cancer in a subject, suppressing cancer in a subject, reducing the severity of cancer in a subject, reducing the risk of developing cancer in a subject, or inhibiting cancer in a subject, the method comprising administering to a subject having cancer a compound represented by the structures of Formula I and / or I(a)-I(n) and the structures listed in Table 1 as defined below under conditions effective to treat the subject's cancer, suppress cancer in the subject, reduce the severity of cancer in the subject, reduce the risk of developing cancer in the subject, or inhibit cancer in the subject.

[0011] The present invention further provides a method for suppressing, reducing or inhibiting tumor growth in a subject, the method comprising administering to the subject a compound represented by the structures of Formula I and / or I(a)-I(n) and the structures listed in Table 1 as defined below under conditions effective to suppress, reduce or inhibit tumor growth in the subject. In some embodiments, the tumor is cancerous. In some embodiments, the subject has cancer.

[0012] The present invention further provides a method for regulating c-MYC mRNA translation in a cell, the method comprising contacting a compound represented by the structures of Formula I and / or I(a)-I(n) and the structures listed in Table 1 as defined below with a cell, thereby regulating c-MYC mRNA translation in the cell.

[0013] The present invention further provides a method for regulating c-MYC mRNA transcription in a cell, the method comprising contacting a compound represented by the structures of Formula I and / or I(a)-I(n) and the structures listed in Table 1 as defined below with a cell, thereby regulating c-MYC mRNA transcription in the cell. DETAILED DESCRIPTION

[0014] In various embodiments, the present invention relates to a compound represented by the structure of formula (I):

[0015]

[0016] in

[0017] X 2 , X3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0018] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0019] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0020] X 11 is N or C; if X 11 is N, then X 10 It is C=O;

[0021] X 12 Yes S, SO 2, O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0022] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0023] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH3 、CH(CH 3 )C(O)N(CH 3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0024] or R 6 and R 5 connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0025] or R 6 Represented by the structure of formula B or Bi:

[0026]

[0027] in

[0028] m is 0 or 1; and

[0029] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0030] R 12 and R 13 All are H;

[0031] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0032] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0033] R 12 and R 13 connected to form ring B; or

[0034] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0035] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0036] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0037] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0038] in

[0039] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine); C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine;

[0040] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0041] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0042] R 7 Is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, SR 10 , -R 8 -OR 10 , -R 8 -SR 10 , R 8 -(C 3 -C 8 Cycloalkyl), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 , C(O)NHR (e.g., C(O)NH(CH 3 ))、C(O)N(R 10 )(R 11 )(e.g., C(O)NH(CH 3 )、C(O)NH(CH 2 CH 2 OCH 3 )、C(O)NH(CH 2 CH 2 OH))、SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, ethoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkyl, C1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl), substituted or unsubstituted 4-7 membered heterocycle (e.g., morpholine (e.g., 2-morpholine or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, oxetane-3-ol, pyrrolidine, pyrrolidin-3-ol, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidinone, imidazole, pyrazole, piperazine, piperidine, piperidine-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2-oxopyrrolidine, pyridine, 1-methylpyridine), R 8 -(substituted or unsubstituted single, fused or spiro 3-8 membered heterocycle), substituted or unsubstituted aryl, substituted or unsubstituted benzyl;

[0043] or R 7 Represented by the structure of formula A:

[0044]

[0045] in

[0046] X 1 is N or O;

[0047] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0048] R 1 and R 2 Connect to form =O or C 3 -C 8 Carbocyclic or heterocyclic rings (e.g., cyclopropyl);

[0049] R 3 and R4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0050] R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0051] or R 2 and R 4 to form a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole), wherein if the ring is aromatic, then R 1 and / or R 3 does not exist;

[0052] If X 1 is O, then R 4 does not exist;

[0053] R 7 'is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0054] or R 7 and R 7 ' connected to form a 5- or 6-membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., piperidine, pyrrolidine, tetrahydrofuran, tetrahydropyran);

[0055] R 20 Represented by the following structure:

[0056]

[0057] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0058] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0059] Each R 8 Independently [CH 2 ] p

[0060] Where p is between 1 and 10 (e.g., 1, 2);

[0061] R 9 Yes [CH] q , [C] q

[0062] Where q is between 2 and 10;

[0063] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0064] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0065] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0066] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0067] In various embodiments, the invention relates to a compound represented by the structure of Formula I(a):

[0068]

[0069] in

[0070] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2-cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0071] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0072] If X 5 , X 6 , X 7 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 , R 7 ”' and R 7 ""Replacement does not exist;

[0073] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0074] X 11 is N or C; if X 11 is N, then X 10 It is C=O;

[0075] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0076] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0077] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH 3 ) 2), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0078] or R 6 and R 5 connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0079] or R 6 Represented by the structure of formula B or Bi:

[0080]

[0081] in

[0082] m is 0 or 1; and

[0083] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0084] R 12 and R 13 All are H;

[0085] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0086] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0087] R 12 and R 13 connected to form ring B; or

[0088] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0089] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0090] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0091] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0092] in

[0093] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0094] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0095] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0096] R 7 Is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, SR 10 , -R 8 -OR 10 , -R 8 -SR 10 , R 8 -(C 3 -C 8 Cycloalkyl), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 , C(O)NHR (e.g., C(O)NH(CH 3 ))、C(O)N(R 10 )(R 11 )(e.g., C(O)NH(CH 3 )、C(O)NH(CH 2 CH 2 OCH 3 )、C(O)NH(CH 2 CH 2 OH))、SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, ethoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkyl, C1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl), substituted or unsubstituted 4-7 membered heterocycle (e.g., morpholine (e.g., 2-morpholine or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, oxetane-3-ol, pyrrolidine, pyrrolidin-3-ol, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidinone, imidazole, pyrazole, piperazine, piperidine, piperidine-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2-oxopyrrolidine, pyridine, 1-methylpyridine), R 8 -(substituted or unsubstituted single, fused or spiro 3-8 membered heterocycle), substituted or unsubstituted aryl, substituted or unsubstituted benzyl;

[0097] or R 7 Represented by the structure of formula A:

[0098]

[0099] in

[0100] X 1 is N or O;

[0101] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0102] R 1 and R 2 Connect to form =O or C 3 -C 8 Carbocyclic or heterocyclic rings (e.g., cyclopropyl);

[0103] R 3 and R4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0104] R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0105] or R 2 and R 4 to form a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole), wherein if the ring is aromatic, then R 1 and / or R 3 does not exist;

[0106] If X 1 is O, then R 4 does not exist;

[0107] R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0108] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0109] or R 7 ” and R 7 connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0110] or R 7 and R 7 "' is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (eg, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0111] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0112] R 20 Represented by the following structure:

[0113]

[0114] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0115] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0116] Each R 8 Independently [CH 2 ] p

[0117] Where p is between 1 and 10 (e.g., 1, 2);

[0118] R 9 Yes [CH]q , [C] q

[0119] Where q is between 2 and 10;

[0120] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0121] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0122] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0123] In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0124] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0125] In various embodiments, the invention relates to a compound represented by the structure of Formula I(b):

[0126]

[0127] in

[0128] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0129] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0130] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0131] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0132] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0133] X 13 Yes CH 2 , CH(R) (e.g., CH-CH 3 )、C(R) 2 Or C=O;

[0134] Ring G is absent or is a substituted or unsubstituted 3-8 membered carbocyclic or heterocyclic ring (eg, cyclobutane, cyclopentane, cyclohexane);

[0135] R 7 Is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, SR 10 , -R 8 -OR 10 , -R 8 -SR 10 , R 8 -(C 3 -C 8 Cycloalkyl), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 , C(O)NHR (e.g., C(O)NH(CH 3 ))、C(O)N(R 10 )(R 11 )(e.g., C(O)NH(CH 3 )、C(O)NH(CH2 CH 2 OCH 3 )、C(O)NH(CH 2 CH 2 OH))、SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, ethoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkyl, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl), substituted or unsubstituted 4-7 membered heterocycle (e.g., morpholine (e.g., 2-morpholine or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, oxetane-3-ol, pyrrolidine, pyrrolidin-3-ol, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidinone, imidazole, pyrazole, piperazine, piperidine, piperidine-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2-oxopyrrolidine, pyridine, 1-methylpyridine), R 8 -(substituted or unsubstituted single, fused or spiro 3-8 membered heterocycle), substituted or unsubstituted aryl, substituted or unsubstituted benzyl;

[0136] or R 7Represented by the structure of formula A:

[0137]

[0138] in

[0139] X 1 is N or O;

[0140] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0141] R 1 and R 2 Connect to form =O or C 3 -C 8 Carbocyclic or heterocyclic rings (e.g., cyclopropyl);

[0142] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0143] R 3 and R 4connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0144] or R 2 and R 4 to form a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole), wherein if the ring is aromatic, then R 1 and / or R 3 does not exist;

[0145] If X 1 is O, then R 4 does not exist;

[0146] R 7 'is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0147] or R 7 and R 7 ' connected to form a 5- or 6-membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., piperidine, pyrrolidine, tetrahydrofuran, tetrahydropyran);

[0148] R 20 Represented by the following structure:

[0149]

[0150] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0151] R 50 It is H, R 20 ,F,Cl,Br,I,OH,SH,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkyl, -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0152] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0153] Each R 8 Independently [CH 2 ] p

[0154] Where p is between 1 and 10 (e.g., 1, 2);

[0155] R 9 Yes [CH] q , [C] q

[0156] Where q is between 2 and 10;

[0157] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0158] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0159] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0160] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0161] In various embodiments, the invention relates to a compound represented by the structure of Formula I(c):

[0162]

[0163] in

[0164] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0165] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0166] If X 5 , X 6 , X 7 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 , R 7 ”' and R 7 ""Replacement does not exist;

[0167] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0168] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0169] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0170] X 13 Yes CH 2 , CH(R) (e.g., CH-CH 3 )、C(R) 2 Or C=O;

[0171] Ring G is absent or is a substituted or unsubstituted 3-8 membered carbocyclic or heterocyclic ring (eg, cyclobutane, cyclopentane, cyclohexane);

[0172] R 7 Is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, SR 10 , -R 8 -OR 10 , -R 8 -SR 10 , R 8 -(C 3 -C 8 Cycloalkyl), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8-C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 , C(O)NHR (e.g., C(O)NH(CH 3 ))、C(O)N(R 10 )(R 11 )(e.g., C(O)NH(CH 3 )、C(O)NH(CH 2 CH 2 OCH 3 )、C(O)NH(CH 2 CH 2 OH))、SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, ethoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkyl, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl), substituted or unsubstituted 4-7 membered heterocycle (e.g., morpholine (e.g., 2-morpholine or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, oxetane-3-ol, pyrrolidine, pyrrolidin-3-ol, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidinone, imidazole, pyrazole, piperazine, piperidine, piperidine-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2-oxopyrrolidine, pyridine, 1-methylpyridine), R 8 -(substituted or unsubstituted single, fused or spiro 3-8 membered heterocycle), substituted or unsubstituted aryl, substituted or unsubstituted benzyl;

[0173] or R 7 Represented by the structure of formula A:

[0174]

[0175] in

[0176] X 1 is N or O;

[0177] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0178] R 1 and R 2 Connect to form =O or C 3 -C 8 Carbocyclic or heterocyclic rings (e.g., cyclopropyl);

[0179] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0180] R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0181] or R 2 and R 4 to form a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole), wherein if the ring is aromatic, then R 1 and / or R 3 does not exist;

[0182] If X 1 is O, then R 4 does not exist;

[0183] R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0184] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0185] or R 7 ” and R 7 connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0186] or R 7 and R 7 "' is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (eg, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0187] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0188] R 20 Represented by the following structure:

[0189]

[0190] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0191] R 50 It is H, R 20 ,F,Cl,Br,I,OH,SH,N(R) 2 NH(R 10 )、N(R 10 )(R11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkyl, -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0192] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2-O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2-OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0193] Each R 8 Independently [CH 2 ] p

[0194] Where p is between 1 and 10 (e.g., 1, 2);

[0195] R 9 Yes [CH] q , [C] q

[0196] Where q is between 2 and 10;

[0197] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0198] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0199] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0200] In some embodiments, R7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0201] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0202] In various embodiments, the invention relates to a compound represented by the structure of Formula I(d):

[0203]

[0204] in

[0205] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0206] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0207] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0208] X 11 is N or C; if X 11 is N, then X 10 It is C=O;

[0209] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2-COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0210] Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole);

[0211] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0212] or R 1 and R 2 Connected to form C=O or a 3-8 membered carbocyclic or heterocyclic ring (eg, cyclopropyl);

[0213] or R 2 and R 4 to form Ring F as defined above (e.g., pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R 1 and / or R 3 does not exist;

[0214] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2-O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0215] or R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0216] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0217] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11)(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH 3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0218] or R 6 and R 5connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0219] or R 6 Represented by the structure of formula B or Bi:

[0220]

[0221] in

[0222] m is 0 or 1; and

[0223] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0224] R 12 and R 13 All are H;

[0225] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0226] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0227] R 12 and R 13 connected to form ring B; or

[0228] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0229] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0230] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0231] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0232] in

[0233] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0234] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0235] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0236] R 7 'is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0237] R 20 Represented by the following structure:

[0238]

[0239] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3)-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0240] R30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 )2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0241] Each R 8 Independently [CH 2 ] p

[0242] Where p is between 1 and 10 (e.g., 1, 2);

[0243] R 9 Yes [CH] q , [C] q

[0244] Where q is between 2 and 10;

[0245] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0246] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0247] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0248] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 is not S. In some embodiments, R is not H. In some embodiments, if R 1 and R 2 Connect to form C=O, then X 2 , X 3 , X 4 and X 10 At least one of them is not CH;

[0249] In various embodiments, the invention relates to a compound represented by the structure of Formula I(e):

[0250]

[0251] in

[0252] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0253] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0254] If X 5 , X 6 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 ”' and R 7 ""Replacement does not exist;

[0255] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0256] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0257] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0258] Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole);

[0259] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0260] or R 1 and R 2 Connected to form C=O or a 3-8 membered carbocyclic or heterocyclic ring (eg, cyclopropyl);

[0261] or R 2 and R 4 to form Ring F as defined above (e.g., pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R 1 and / or R 3 does not exist;

[0262] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0263] or R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0264] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0265] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2-cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 )3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10)(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0266] or R 6 and R 5 connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0267] or R 6 Represented by the structure of formula B or Bi:

[0268]

[0269] in

[0270] m is 0 or 1; and

[0271] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0272] R 12 and R 13 All are H;

[0273] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0274] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0275] R 12 and R 13 connected to form ring B; or

[0276] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0277] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0278] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0279] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0280] in

[0281] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0282] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0283] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0284] R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0285] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0286] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0287] R 20 Represented by the following structure:

[0288]

[0289] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1-C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0290] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2-Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0291] Each R 8 Independently [CH 2 ] p

[0292] Where p is between 1 and 10 (e.g., 1, 2);

[0293] R 9 Yes [CH] q , [C] q

[0294] Where q is between 2 and 10;

[0295] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0296] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0297] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0298] In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0299] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 is not S. In some embodiments, R is not H. In some embodiments, if R 1 and R 2 Connect to form C=O, then X 2 , X 3 , X 4 and X 10 At least one of them is not CH;

[0300] In various embodiments, the invention relates to a compound represented by the structure of Formula I(f):

[0301]

[0302] in

[0303] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0304] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0305] If X 5 , X 6 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 ”' and R 7 ""Replacement does not exist;

[0306] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0307] X 11 is N or C; if X 11 is N, then X 10 It is C=O;

[0308] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0309] X 13 Yes CH 2 , CH(R) (e.g., CH-CH 3 )、C(R) 2 Or C=O;

[0310] Ring G is absent or is a substituted or unsubstituted 3-8 membered carbocyclic or heterocyclic ring (e.g., cyclobutane, cyclopentane, cyclohexane);

[0311] Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole);

[0312] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0313] or R 1 and R 2 Connected to form C=O or a 3-8 membered carbocyclic or heterocyclic ring (eg, cyclopropyl);

[0314] or R 2 and R 4 to form Ring F as defined above (e.g., pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R 1 and / or R 3 does not exist;

[0315] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0316] or R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0317] R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8-SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0318] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0319] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0320] R 20 Represented by the following structure:

[0321]

[0322] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0323] R 50 It is H, R 20 ,F,Cl,Br,I,OH,SH,N(R) 2 NH(R10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkyl, -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0324] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2)-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0325] Each R 8 Independently [CH 2 ] p

[0326] Where p is between 1 and 10 (e.g., 1, 2);

[0327] R 9 Yes [CH] q , [C] q

[0328] Where q is between 2 and 10;

[0329] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0330] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0331] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0332] In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H and are different from each other. In some embodiments, if R 1 and R 2 Connect to form C=O, then X 2 , X 3 , X 4 and X 10 At least one of is not CH;

[0333] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0334] In various embodiments, the invention relates to a compound represented by the structure of Formula I(g):

[0335]

[0336] in

[0337] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0338] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0339] If X 5 , X 6 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 ”' and R 7 ""Replacement does not exist;

[0340] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0341] X 11 is N or C; if X 11 is N, then X 10 It is C=O;

[0342] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0343] X 14 is S, O, N or CH, where if X 14 is CH, then ring F does not exist, and if X 14 is S or O, then R 3 does not exist;

[0344] Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole);

[0345] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0346] or R 1 and R 2 Connected to form C=O or a 3-8 membered carbocyclic or heterocyclic ring (eg, cyclopropyl);

[0347] or R 2 and R 4to form Ring F as defined above (e.g., pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R 1 and / or R 3 does not exist;

[0348] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0349] or R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0350] If X 14 is S or O, then R 3 does not exist;

[0351] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0352] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2-oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 )3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH 3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0353] or R 6 and R 5 connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0354] or R 6 Represented by the structure of formula B or Bi:

[0355]

[0356] in

[0357] m is 0 or 1; and

[0358] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0359] R 12 and R 13 All are H;

[0360] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0361] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0362] R 12 and R 13connected to form ring B; or

[0363] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0364] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0365] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0366] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0367] in

[0368] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0369] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0370] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0371] R 7 '、R 7 ”、R 7 ”' and R 7”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0372] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0373] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0374] R 20 Represented by the following structure:

[0375]

[0376] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3)-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0377] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0378] Each R 8 Independently [CH 2 ] p

[0379] Where p is between 1 and 10 (e.g., 1, 2);

[0380] R 9 Yes [CH] q , [C] q

[0381] Where q is between 2 and 10;

[0382] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0383] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0384] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0385] In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0386] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 is not S. In some embodiments, R is not H. In some embodiments, if R 1 and R 2 Connect to form C=O, then X 2 , X 3 , X 4 and X 10 At least one of them is not CH;

[0387] In various embodiments, the invention relates to a compound represented by the structure of Formula I(h):

[0388]

[0389] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0390] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0391] If X 5 , X 6 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 ”' and R 7 ""Replacement does not exist;

[0392] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0393] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0394] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0395] X 13 Yes CH 2 , CH(R) (e.g., CH-CH 3 )、C(R) 2 Or C=O;

[0396] X14 is S, O, N or CH, where if X 14 is CH, then ring F does not exist, and if X 14 is S or O, then R 3 does not exist;

[0397] Ring G is absent or is a substituted or unsubstituted 3-8 membered carbocyclic or heterocyclic ring (eg, cyclobutane, cyclopentane, cyclohexane);

[0398] Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole);

[0399] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0400] or R 1 and R 2 Connected to form C=O or a 3-8 membered carbocyclic or heterocyclic ring (eg, cyclopropyl);

[0401] or R 2 and R 4 to form Ring F as defined above (e.g., pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R 1 and / or R 3 does not exist;

[0402] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10(For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0403] or R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0404] R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0405] or R7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0406] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0407] R 20 Represented by the following structure:

[0408]

[0409] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 )2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0410] R 50 It is H, R 20 ,F,Cl,Br,I,OH,SH,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkyl, -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0411] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2-cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0412] Each R 8 Independently [CH 2 ] p

[0413] Where p is between 1 and 10 (e.g., 1, 2);

[0414] R 9 Yes [CH] q , [C] q

[0415] Where q is between 2 and 10;

[0416] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0417] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0418] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0419] In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0420] In some embodiments, X 2 , X 3 and X 4In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0421] In various embodiments, the invention relates to a compound represented by the structure of Formula I(i):

[0422]

[0423] in

[0424] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0425] X 5 , X 6 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0426] If X 5 , X 6 , X 8 and X9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 ”' and R 7 ""Replacement does not exist;

[0427] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0428] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0429] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0430] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0431] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 )3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH 3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0432] or R 6 and R 5 connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0433] or R 6 Represented by the structure of formula B or Bi:

[0434]

[0435] in

[0436] m is 0 or 1; and

[0437] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0438] R 12 and R 13 All are H;

[0439] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0440] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0441] R 12 and R 13 connected to form ring B; or

[0442] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0443] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0444] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0445] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0446] in

[0447] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0448] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0449] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0450] R 7 , R 7 '、R 7 ”、R 7 ”' and R 7”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0451] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0452] or R 7 ” and R 7 connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0453] or R 7 and R 7 "' is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (eg, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0454] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0455] R 20 Represented by the following structure:

[0456]

[0457] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0458] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0459] R50 It is H, R 20 ,F,Cl,Br,I,OH,SH,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkyl, -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0460] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2)-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0461] Each R 8 Independently [CH 2 ] p

[0462] Where p is between 1 and 10 (e.g., 1, 2);

[0463] R 9 Yes [CH] q , [C] q

[0464] Where q is between 2 and 10;

[0465] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0466] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0467] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0468] In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0469] In some embodiments, X 2 , X 3 and X 4 At least one of is C(R). In some embodiments, R is not H.

[0470] In various embodiments, the invention relates to a compound represented by the structure of Formula I(j):

[0471]

[0472] in

[0473] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2-cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0474] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0475] If X 5 , X 6 , X 7 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 , R 7 ”' and R 7 ""Replacement does not exist;

[0476] X 10 is nitrogen, carbon, CH or C(R) (e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0477] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0478] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0479] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0480] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2-Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 )3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1-C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH 3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0481] or R 6 and R 5 connected to form a substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0482] or R 6 Represented by the structure of formula B or Bi:

[0483]

[0484] in

[0485] m is 0 or 1; and

[0486] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0487] R 12 and R 13 All are H;

[0488] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0489] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0490] R 12 and R 13 connected to form ring B; or

[0491] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0492] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0493] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0494] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0495] in

[0496] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0497] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0498] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0499] R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0500] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0501] or R 7 ” and R 7 connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0502] or R 7 and R 7 "' is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (eg, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0503] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0504] R 20 Represented by the following structure:

[0505]

[0506] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 )2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0507] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0508] Each R 8 Independently [CH 2 ] p

[0509] Where p is between 1 and 10 (e.g., 1, 2);

[0510] R 9 Yes [CH] q , [C] q

[0511] Where q is between 2 and 10;

[0512] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0513] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0514] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0515] In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7At least two of the "" are not H and are different from each other.

[0516] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0517] In various embodiments, the invention relates to a compound represented by the structure of Formula I(k):

[0518]

[0519] in

[0520] Ring W may be an aromatic ring or a non-aromatic ring,

[0521] If ring W is aromatic, then

[0522] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0523] X 15 It is C;

[0524] If ring W is non-aromatic, then

[0525] X 2 , X 3 and X 4 Each is independently CH 2 、CH(R)、C(R) 2 , NH, N(R), O, S, S=O or SO 2 (For example, CH 2 );

[0526] X 15 is CH, C(R) or N (e.g., CH, N);

[0527] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0528] If X 5 , X 6 , X 7 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 , R 7 ”' and R 7 ""Replacement does not exist;

[0529] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0530] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0531] Ring W' may be an aromatic ring or a non-aromatic ring,

[0532] If ring W' is aromatic, then

[0533] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0534] If ring W' is non-aromatic, then

[0535] X 12 It is CH=CH, CH=CH(R), C(R)=CH, OCH 2 , CH 2 O. SCH 2 , CH 2 S, CH=N, C(R)=N, N=CH, N=C(R);

[0536] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0537] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 )2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH)2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 )2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH 3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0538] or R 6 and R 5 connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0539] or R 6 Represented by the structure of formula B or Bi:

[0540]

[0541]

[0542] in

[0543] m is 0 or 1; and

[0544] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0545] R 12 and R 13 All are H;

[0546] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0547] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0548] R 12 and R 13 connected to form ring B; or

[0549] R 12 and C1 to form ring C, and R 13 YesR 30;or

[0550] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0551] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0552] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0553] in

[0554] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0555] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0556] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0557] R 7 Is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, SR 10 , -R 8 -OR 10 , -R 8 -SR 10 , R8 -(C 3 -C 8 Cycloalkyl), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 , C(O)NHR (e.g., C(O)NH(CH 3 ))、C(O)N(R 10 )(R 11 )(e.g., C(O)NH(CH 3 )、C(O)NH(CH 2 CH 2 OCH 3 )、C(O)NH(CH 2 CH 2 OH))、SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5Straight or branched chain, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, ethoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkyl, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl), substituted or unsubstituted 4-7 membered heterocycle (e.g., morpholine (e.g., 2-morpholine or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, oxetane-3-ol, pyrrolidine, pyrrolidin-3-ol, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidinone, imidazole, pyrazole, piperazine, piperidine, piperidine-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2-oxopyrrolidine, pyridine, 1-methylpyridine), R 8 -(substituted or unsubstituted single, fused or spiro 3-8 membered heterocycle), substituted or unsubstituted aryl, substituted or unsubstituted benzyl;

[0558] or R 7 Represented by the structure of formula A:

[0559]

[0560] in

[0561] X 1 is N or O;

[0562] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3, substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0563] R 1 and R 2 Connect to form =O or C 3 -C 8 Carbocyclic or heterocyclic rings (e.g., cyclopropyl);

[0564] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0565] R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0566] or R 2 and R 4 to form a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole), wherein if the ring is aromatic, then R 1and / or R 3 does not exist;

[0567] If X 1 is O, then R 4 does not exist;

[0568] R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0569] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0570] or R 7 ” and R 7 connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0571] or R 7 and R 7"' is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (eg, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0572] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0573] R 20 Represented by the following structure:

[0574]

[0575] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0576] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0577] Each R 8 Independently [CH 2 ] p

[0578] Where p is between 1 and 10 (e.g., 1, 2);

[0579] R 9 Yes [CH] q , [C] q

[0580] Where q is between 2 and 10;

[0581] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0582] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0583] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0584] In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0585] In some embodiments, Ring W is aromatic and X 2 , X 3 and X 4 In some embodiments, ring W is aromatic, and X 11 is N. In some embodiments, Ring W is aromatic and X 12 is not S. In some embodiments, if Ring W is aromatic, then X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 is not S. In some embodiments, R is not H. In some embodiments, if both Ring W and Ring W' are aromatic, then X 2 , X 3 and X4 At least one of them is C(R); X 11 is N; or X 12 Not S.

[0586] In various embodiments, the present invention relates to a compound represented by the structure of Formula I(1):

[0587]

[0588] in

[0589] Ring W may be an aromatic ring or a non-aromatic ring,

[0590] If ring W is aromatic, then

[0591] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2 -O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0592] X 15 It is C;

[0593] If ring W is non-aromatic, then

[0594] X 2 , X 3 and X 4 Each is independently CH 2 、CH(R)、C(R) 2, NH, N(R), O, S, S=O or SO 2 (For example, CH 2 );

[0595] X 15 is CH, C(R) or N (e.g., CH, N);

[0596] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0597] If X 5 , X 6 , X 7 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 , R 7 ”' and R 7 ""Replacement does not exist;

[0598] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0599] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0600] Ring W' may be an aromatic ring or a non-aromatic ring,

[0601] If ring W' is aromatic, then

[0602] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0603] If ring W' is non-aromatic, then

[0604] X 12 It is CH=CH, CH=CH(R), C(R)=CH, OCH 2 , SCH 2 , CH=N, C(R)=N, N=CH, N=C(R);

[0605] X 14 is S, O, N or CH, where if X 14 is CH, then ring F does not exist, and if X 14 is S or O, then R 3 does not exist;

[0606] Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole);

[0607] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0608] or R 1 and R 2 Connected to form C=O or a 3-8 membered carbocyclic or heterocyclic ring (eg, cyclopropyl);

[0609] or R 2 and R 4to form Ring F as defined above (e.g., pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R 1 and / or R 3 does not exist;

[0610] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0611] or R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0612] If X 14 is S or O, then R 3 does not exist;

[0613] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0614] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2-oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 )3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH 3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0615] or R 6 and R 5 connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0616] or R 6 Represented by the structure of formula B or Bi:

[0617]

[0618] in

[0619] m is 0 or 1; and

[0620] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0621] R 12 and R 13 All are H;

[0622] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0623] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0624] R 12 and R 13connected to form ring B; or

[0625] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0626] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0627] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0628] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0629] in

[0630] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0631] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0632] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0633] R 7 '、R 7 ”、R 7 ”' and R 7”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0634] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0635] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0636] R 20 Represented by the following structure:

[0637]

[0638] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3)-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0639] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0640] Each R 8 Independently [CH 2 ] p

[0641] Where p is between 1 and 10 (e.g., 1, 2);

[0642] R 9 Yes [CH] q , [C] q

[0643] Where q is between 2 and 10;

[0644] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0645] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0646] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0647] In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0648] In some embodiments, Ring W is aromatic and X 2 , X 3 and X 4 In some embodiments, ring W is aromatic, and X 11 is N. In some embodiments, Ring W is aromatic and X 12 is not S. In some embodiments, if Ring W is aromatic, then X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 is not S. In some embodiments, if both ring W and ring W' are aromatic, then X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0649] In some embodiments, if R 1 and R 2 Connect to form C=O, then X 2 , X 3 , X 4 and X 10 At least one of is not CH;

[0650] In various embodiments, the present invention relates to a compound represented by the structure of Formula I(m):

[0651]

[0652] in

[0653] Ring W may be an aromatic ring or a non-aromatic ring,

[0654] If ring W is aromatic, then

[0655] X 2 , X 3 and X 4 are each independently CH, C(R) or N (e.g., C(CH 3 )、C(O-CH 2 -cyclopropyl), C(O-CH 2 -methylcyclobutyl), C(NH-CH 2 -cyclopropyl), C(isopropyloxy), C(O-CH(CH 3 )-CH 2-O-CH 3 )、C(CH 2 CH 3 )、C-iPr、C-CH 2 -cyclopropyl, C(OCH 3 ), C(OCH 2 CH 3 )、C(O-(CH 2 ) 2 -O-CH 3 , C(OCHF 2 ), C(Cl), C(C(O)CH3), C(O-CH 2 CH 2 -O-CH 3 ), C(OH));

[0656] X 15 It is C;

[0657] If ring W is non-aromatic, then

[0658] X 2 , X 3 and X 4 Each is independently CH 2 、CH(R)、C(R) 2 , NH, N(R), O, S, S=O or SO 2 (For example, CH 2 );

[0659] X 15 is CH, C(R) or N (e.g., CH, N);

[0660] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0661] If X 5 , X 6 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 ”' and R 7 ""Replacement does not exist;

[0662] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2-OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0663] X 11 is N or C; if X 11 is N, then X 10 is C=O;

[0664] Ring W' may be an aromatic ring or a non-aromatic ring,

[0665] If ring W' is aromatic, then

[0666] X 12 Yes S, SO 2 , O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0667] If ring W' is non-aromatic, then

[0668] X 12 It is CH=CH, CH=CH(R), C(R)=CH, OCH 2 , SCH 2 , CH=N, C(R)=N, N=CH, N=C(R);

[0669] X 13 Yes CH 2 , CH(R) (e.g., CH-CH 3 )、C(R) 2 Or C=O;

[0670] X 14 is S, O, N or CH, where if X 14 is CH, then ring F does not exist, and if X 14 is S or O, then R 3 does not exist;

[0671] Ring G is absent or is a substituted or unsubstituted 3-8 membered carbocyclic or heterocyclic ring (e.g., cyclobutane, cyclopentane, cyclohexane);

[0672] Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole);

[0673] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy;

[0674] or R 1 and R 2 Connected to form C=O or a 3-8 membered carbocyclic or heterocyclic ring (eg, cyclopropyl);

[0675] or R 2 and R 4 to form Ring F as defined above (e.g., pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine, pyridine, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R 1 and / or R 3 does not exist;

[0676] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ;

[0677] or R 3 and R 4 connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole);

[0678] R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0679] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0680] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0681] R 20 Represented by the following structure:

[0682]

[0683] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0684] R 50 It is H, R 20 ,F,Cl,Br,I,OH,SH,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkyl, -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0685] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0686] Each R 8 Independently [CH 2 ] p

[0687] Where p is between 1 and 10 (e.g., 1, 2);

[0688] R 9 Yes [CH] q , [C] q

[0689] Where q is between 2 and 10;

[0690] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C 3 -C 8Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0691] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0692] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0693] In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0694] In some embodiments, Ring W is aromatic and X 2 , X 3 and X 4 In some embodiments, ring W is aromatic, and X 11 is N. In some embodiments, Ring W is aromatic and X 12 is not S. In some embodiments, if Ring W is aromatic, then X 2 , X3 and X 4 At least one of them is C(R); X 11 is N; or X 12 is not S. In some embodiments, if both ring W and ring W' are aromatic, then X 2 , X 3 and X 4 At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0695] In various embodiments, the present invention relates to a compound represented by the structure of Formula I(n):

[0696]

[0697] in

[0698] X 5 , X 6 , X 7 , X 8 and X 9 are each independently a nitrogen or carbon atom;

[0699] If X 5 , X 6 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 ”' and R 7 ""Replacement does not exist;

[0700] X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N(e.g., C(CH 2 -OH), C(CH 2 -CH 2 -OH), C(NH-CH 2 -cyclopropyl), C(COOH), C(CH 3 ), C (cyclopropyl), C (isopropyloxy));

[0701] X 11 is N or C; if X 11 is N, then X 10 It is C=O;

[0702] X 12 Yes S, SO 2, O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (for example, N-CH 2 -COOH, N-CH 2 -CH 2 -OH、N-CH 3 、N-CH 2 CH 3 , N-iPr, N-cyclopropyl, N-CH 2 -cyclopropyl);

[0703] R 5 Is H or C 1 -C 5 Straight-chain or branched alkyl (e.g., methyl);

[0704] R 6 Is H, F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2) 2 -Cyclopentanol, CH 2 -cyclohexanol), R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic) (e.g., (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -azaspiroheptane), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ))、R 9 -R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -C(O)-piperidine), B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH3 、CH(CH 3 )C(O)N(CH 3 ) 2 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH 3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 - aryl (eg, benzyl), substituted or unsubstituted benzyl;

[0705] or R 6 and R 5 connected to form a substituted or unsubstituted 5-8 membered heterocycle (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);

[0706] or R 6 Represented by the structure of formula B or Bi:

[0707]

[0708]

[0709] in

[0710] m is 0 or 1; and

[0711] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0712] R 12 and R 13 All are H;

[0713] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl);

[0714] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0715] R 12 and R 13 connected to form ring B; or

[0716] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0717] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0718] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0719] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0720] in

[0721] Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine; C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine);

[0722] Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and

[0723] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutane, cyclohexane);

[0724] R 7 , R 7 '、R 7 ”、R 7 ”' and R 7 ”” are independently H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl (e.g., CHF 2 ), C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C8 Cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, tetrahydrofuran, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted benzyl;

[0725] or R 7 ' and R 7 " is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0726] or R 7 ” and R 7 connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0727] or R 7 and R 7 "' is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (eg, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0728] or R 7 ”' and R 7 "" is connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine);

[0729] R 20 Represented by the following structure:

[0730]

[0731] R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH2 -O-CH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched alkoxy, C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2 -Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , -R 8 -R 10 (For example, (CH 2 ) 2 -O-CH 3 ), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0732] R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )(e.g., C(O)CH 3 )、NH(R 10 ), NH-CH 2 -cyclopropyl, N(R 10 )(R 11 ), CF 3 、CN、NO 2 , C1 -C 5 Straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH 2 -Cyclopropyl, CH 2 -OH, CH 2 -CH 2 -OH, CH 2 -CH 2 -O-CH 2 -CH 2 -O-CH 3 , CH 2 -O-CH 2 -CH 2 -O-CH 3 ), C 3 -C 8 Substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C 1 -C 5 Straight-chain or branched alkoxy (e.g., methoxy, ethoxy, O-(CH 2 CH 3 ), OCHF 2 、O-(CH 2 ) 2 -O-CH 3 , isopropoxy, O-(CH 2 )-cyclopropyl, O-CH 2 -Methylcyclobutyl, O-CH 2 -3-Methyloxetane, O-CH(CH 3 )-CH 2 -O-CH 3 ), C 1 -C 5 Straight chain or branched haloalkyl (e.g., CHF 2 CF 3 CF 2 CH 3 , CH 2 CF 3 CF 2 CH 2 CH 3 , CH 2 CH 2 CF 3 CF 2 CH(CH 3 ) 2 CF(CH 3 )-CH(CH 3 ) 2 ), R 8 -aryl (e.g., CH 2-Ph), -R 8 -OR 8 -OR 10 (For example, (CH 2 ) 2 -O-(CH 2 ) 2 -O-CH 3 ),-R 8 -OR 10 , OR 8 -R 10 (For example, O-(CH 2 ) 2 -O-CH 3 、O-(CH 2 CH 3 )、O-(CH 2 )-cyclopropyl), -R 8 -R 10 (For example, (CH 2 )-cyclopropyl, (CH 2 ) 2 -O-CH 3 , (CH 2 )-OH, (CH 2 ) 2 -OH, (CH 2 )-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine));

[0733] Each R 8 Independently [CH 2 ] p

[0734] Where p is between 1 and 10 (e.g., 1, 2);

[0735] R 9 Yes [CH] q , [C] q

[0736] Where q is between 2 and 10;

[0737] R 10 and R 11 are independently H, OH, COOH, C 1 -C 5 Substituted or unsubstituted straight chain or branched alkyl (e.g., methyl, ethyl, CH 2 -Cyclopropyl, CH 2 -CH 2 -O-CH 3 ), C3 -C 8 Substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C 1 -C 5 Substituted or unsubstituted straight chain or branched chain haloalkyl (e.g., CH 2 CF 3 ), C 1 -C 5 Straight or branched alkoxy (e.g., O—CH 3 ), R 20 , C(O)R or S(O) 2 R;

[0738] or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2);

[0739] or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

[0740] In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” is not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are not H. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 ”” are different from each other. In some embodiments, R 7 '、R 7 ”、R 7 ”' and R 7 At least two of the "" are not H and are different from each other.

[0741] In some embodiments, X 2 , X 3 and X 4 In some embodiments, at least one of X is C(R). 11 is N. In some embodiments, X 12 is not S. In some embodiments, X 2 , X 3 and X 4At least one of them is C(R); X 11 is N; or X 12 In some embodiments, R is not H.

[0742] In some embodiments, X of Formula I and / or I(a)-I(j) 2 is N. In other embodiments, X 2 is CH. In other embodiments, X 2 is C(R). In other embodiments, X 2 It is C(CH 3 In other embodiments, X 2 It is C(CH 2 CH 3 ). In other embodiments, X 2 is C-iPr. In other embodiments, X 2 It is C-CH 2 -cyclopropyl. In other embodiments, X 2 is C(O-CH 2 -cyclopropyl). In other embodiments, X 2 is C(O-CH 2 -methylcyclobutyl). In other embodiments, X 2 is C(O-CH 2 -3-methyloxetane). In other embodiments, X 2 It is C(OCH 3 In other embodiments, X 2 It is C(OCH 2 CH 3 In other embodiments, X 2 It is C(O-(CH 2 ) 2 -O-CH 3 In other embodiments, X 2 is C(NH-CH 2 -cyclopropyl). In other embodiments, X 2 is C(isopropoxy). In other embodiments, X 2 is C(O-CH(CH 3 )-CH 2 -O-CH 3 In other embodiments, X 2 is C(OCHF 2 In other embodiments, X 2 is C(Cl). In other embodiments, X 2 is C(C(O)CH 3 In other embodiments, X 2 It is C(OH).

[0743] In some embodiments, ring W of Formula I(k)-I(m) is aromatic or non-aromatic. In some embodiments, if ring W is aromatic, then X 2 In other embodiments, if ring W is aromatic, then X 2 is C(R). In other embodiments, if ring W is aromatic, then X 2 It is C(CH 3 In other embodiments, if ring W is aromatic, then X 2 It is C(CH 2 CH 3 In other embodiments, if ring W is aromatic, then X 2 In other embodiments, if ring W is aromatic, then X 2 It is C-CH 2 -cyclopropyl. In other embodiments, if ring W is aromatic, then X 2 is C(O-CH 2 -cyclopropyl). In other embodiments, if ring W is aromatic, then X 2 is C(O-CH 2 -methylcyclobutyl). In other embodiments, if ring W is aromatic, then X 2 is C(O-CH 2 -3-methyloxetane). In other embodiments, if ring W is aromatic, then X 2 It is C(OCH 3 In other embodiments, if ring W is aromatic, then X 2 It is C(OCH 2 CH 3 In other embodiments, if ring W is aromatic, then X 2 It is C(O-(CH 2 ) 2 -O-CH 3 In other embodiments, if Ring W is aromatic, X 2 is C(NH-CH 2 -cyclopropyl). In other embodiments, if Ring W is aromatic, X 2 is C(isopropoxy). In other embodiments, if ring W is aromatic, X 2 is C(O-CH(CH 3 )-CH 2 -O-CH 3 In other embodiments, if ring W is aromatic, X 2 is C(OCHF 2In other embodiments, if ring W is aromatic, X 2 In other embodiments, if ring W is aromatic, X 2 is C(C(O)CH 3 In other embodiments, if ring W is aromatic, X 2 In some embodiments, if ring W is non-aromatic, then X 2 Yes CH 2 In some embodiments, if ring W is non-aromatic, then X 2 is CH(R). In some embodiments, if ring W is non-aromatic, then X 2 YesC(R) 2 In some embodiments, if ring W is non-aromatic, then X 2 In some embodiments, if ring W is non-aromatic, then X 2 is N(R). In some embodiments, if ring W is non-aromatic, then X 2 Is O. In some embodiments, if Ring W is non-aromatic, then X 2 is S. In some embodiments, if ring W is non-aromatic, then X 2 is S=O. In some embodiments, if ring W is non-aromatic, then X 2 Yes SO 2 .

[0744] In some embodiments, X of Formula I and / or I(a)-I(j) 3 is N. In other embodiments, X 3 is CH. In other embodiments, X 3 is CH. In other embodiments, X 3 is C(R). In other embodiments, X 3 It is C(CH 3 In other embodiments, X 3 It is C(CH 2 CH 3 In other embodiments, X 3 is C-iPr. In other embodiments, X 3 It is C-CH 2 -cyclopropyl. In other embodiments, X 3 is C(O-CH 2 -cyclopropyl). In other embodiments, X 3 is C(O-CH 2 -methylcyclobutyl). In other embodiments, X 3 is C(O-CH 2-3-methyloxetane). In other embodiments, X 3 It is C(OCH 3 In other embodiments, X 3 It is C(OCH 2 CH 3 In other embodiments, X 3 It is C(O-(CH 2 ) 2 -O-CH 3 In other embodiments, X 3 is C(NH-CH 2 -cyclopropyl). In other embodiments, X 3 is C(isopropoxy). In other embodiments, X 3 is C(O-CH(CH 3 )-CH 2 -O-CH 3 In other embodiments, X 3 is C(OCHF 2 In other embodiments, X 3 is C(Cl). In other embodiments, X 2 is C(C(O)CH 3 In other embodiments, X 3 It is C(OH).

[0745] In some embodiments, ring W of Formula I(k)-I(m) is aromatic or non-aromatic. In some embodiments, if ring W is aromatic, then X 3 In other embodiments, if ring W is aromatic, then X 3 is C(R). In other embodiments, if ring W is aromatic, then X 3 It is C(CH 3 In other embodiments, if ring W is aromatic, then X 3 It is C(CH 2 CH 3 In other embodiments, if ring W is aromatic, then X 3 In other embodiments, if ring W is aromatic, then X 3 It is C-CH 2 -cyclopropyl. In other embodiments, if ring W is aromatic, then X 3 is C(O-CH 2 -cyclopropyl). In other embodiments, if Ring W is aromatic, then X 3 is C(O-CH 2 -methylcyclobutyl). In other embodiments, if ring W is aromatic, then X3 is C(O-CH 2 -3-methyloxetane). In other embodiments, if ring W is aromatic, then X 3 It is C(OCH 3 In other embodiments, if ring W is aromatic, then X 3 It is C(OCH 2 CH 3 In other embodiments, if ring W is aromatic, then X 3 It is C(O-(CH 2 ) 2 -O-CH 3 In other embodiments, if Ring W is aromatic, X 3 is C(NH-CH 2 -cyclopropyl). In other embodiments, if Ring W is aromatic, X 3 is C(isopropoxy). In other embodiments, if ring W is aromatic, X 3 is C(O-CH(CH 3 )-CH 2 -O-CH 3 In other embodiments, if ring W is aromatic, X 3 is C(OCHF 2 In other embodiments, if ring W is aromatic, X 3 In other embodiments, if ring W is aromatic, X 3 is C(C(O)CH 3 In other embodiments, if ring W is aromatic, X 3 In some embodiments, if ring W is non-aromatic, then X 3 Yes CH 2 In some embodiments, if ring W is non-aromatic, then X 3 is CH(R). In some embodiments, if ring W is non-aromatic, then X 3 YesC(R) 2 In some embodiments, if ring W is non-aromatic, then X 3 In some embodiments, if ring W is non-aromatic, then X 3 is N(R). In some embodiments, if ring W is non-aromatic, then X 3 Is O. In some embodiments, if Ring W is non-aromatic, then X 3 is S. In some embodiments, if ring W is non-aromatic, then X 3is S=O. In some embodiments, if ring W is non-aromatic, then X 3 Yes SO 2 .

[0746] In some embodiments, X of Formula I and / or I(a)-I(j) 4 is N. In other embodiments, X 4 is CH. In other embodiments, X 4 is C(R). In other embodiments, X 4 It is C(CH 3 In other embodiments, X 4 It is C(CH 2 CH 3 In other embodiments, X 4 is C-iPr. In other embodiments, X 4 It is C-CH 2 -cyclopropyl. In other embodiments, X 4 is C(O-CH 2 -cyclopropyl). In other embodiments, X 4 is C(O-CH 2 -methylcyclobutyl). In other embodiments, X 4 is C(O-CH 2 -3-methyloxetane). In other embodiments, X 4 It is C(OCH 3 In other embodiments, X 4 It is C(OCH 2 CH 3 In other embodiments, X 4 It is C(O-(CH 2 ) 2 -O-CH 3 In other embodiments, X 4 is C(NH-CH 2 -cyclopropyl). In other embodiments, X 4 is C(isopropoxy). In other embodiments, X 4 is C(O-CH(CH 3 )-CH 2 -O-CH 3 In other embodiments, X 4 is C(OCHF 2 In other embodiments, X 4 is C(Cl). In other embodiments, X 4 is C(C(O)CH 3 In other embodiments, X 4 It is C(OH).

[0747] In some embodiments, ring W of Formula I(k)-I(m) is aromatic or non-aromatic. In some embodiments, if ring W is aromatic, then X 4 In other embodiments, if ring W is aromatic, then X 4 is C(R). In other embodiments, if ring W is aromatic, then X 4 It is C(CH 3 In other embodiments, if ring W is aromatic, then X 4 It is C(CH 2 CH 3 In other embodiments, if ring W is aromatic, then X 4 In other embodiments, if ring W is aromatic, then X 4 It is C-CH 2 -cyclopropyl. In other embodiments, if ring W is aromatic, then X 4 is C(O-CH 2 -cyclopropyl). In other embodiments, if Ring W is aromatic, then X 4 is C(O-CH 2 -methylcyclobutyl). In other embodiments, if ring W is aromatic, then X 4 is C(O-CH 2 -3-methyloxetane). In other embodiments, if ring W is aromatic, then X 4 It is C(OCH 3 In other embodiments, if ring W is aromatic, then X 4 It is C(OCH 2 CH 3 In other embodiments, if ring W is aromatic, then X 4 It is C(O-(CH 2 ) 2 -O-CH 3 In other embodiments, if Ring W is aromatic, X 4 is C(NH-CH 2 -cyclopropyl). In other embodiments, if Ring W is aromatic, X 4 is C(isopropoxy). In other embodiments, if ring W is aromatic, X 4 is C(O-CH(CH 3 )-CH 2 -O-CH 3 In other embodiments, if ring W is aromatic, X 4 is C(OCHF 2In other embodiments, if ring W is aromatic, X 4 In other embodiments, if ring W is aromatic, X 4 is C(C(O)CH 3 In other embodiments, if ring W is aromatic, X 4 In some embodiments, if ring W is non-aromatic, then X 4 Yes CH 2 In some embodiments, if ring W is non-aromatic, then X 4 is CH(R). In some embodiments, if ring W is non-aromatic, then X 4 YesC(R) 2 In some embodiments, if ring W is non-aromatic, then X 4 In some embodiments, if ring W is non-aromatic, then X 4 is N(R). In some embodiments, if ring W is non-aromatic, then X 4 Is O. In some embodiments, if Ring W is non-aromatic, then X 4 is S. In some embodiments, if ring W is non-aromatic, then X 4 is S=O. In some embodiments, if ring W is non-aromatic, then X 4 Yes SO 2 .

[0748] In some embodiments, X of Formula I and / or I(a)-I(n) 5 is a nitrogen atom. In other embodiments, X 5 is a carbon atom. In some embodiments, if X 5 is nitrogen, then the corresponding R 7 'Does not exist.

[0749] In some embodiments, X of Formula I and / or I(a)-I(n) 6 is a nitrogen atom. In other embodiments, X 6 is a carbon atom. In some embodiments, if X 6 is nitrogen, then the corresponding R 7 ” does not exist.

[0750] In some embodiments, X of Formula I and / or I(a)-I(k) and / or I(n) 7 is a nitrogen atom. In other embodiments, X 7 is a carbon atom. In some embodiments, if X 7 is nitrogen, then the corresponding R 7 Does not exist.

[0751] In some embodiments, X of Formula I and / or I(a)-I(n) 8 is a nitrogen atom. In other embodiments, X 8 is a carbon atom. In some embodiments, if X 8 is nitrogen, then the corresponding R 7 ”'Does not exist.

[0752] In some embodiments, X of Formula I and / or I(a)-I(n) 9 is a nitrogen atom. In other embodiments, X 9 is a carbon atom. In some embodiments, if X 9 is nitrogen, then the corresponding R 7 ”” does not exist.

[0753] In some embodiments, X of Formula I and / or I(a)-I(n) 10 is a nitrogen atom. In other embodiments, X 10 is carbon. In other embodiments, X 10 is N. In other embodiments, X 10 is CH. In other embodiments, X 10 is C(R), wherein R is as defined below. In other embodiments, X 10 is C(R), wherein R is alkyl. 10 is C(R), wherein R is methyl, substituted methyl, CH 2 -OH, ethyl, substituted ethyl, CH 2 -CH 2 -OH、NH(R 10 ), NH-CH 2 -cyclopropyl, COOH, cycloalkyl (such as cyclopropyl), alkoxy (such as isopropyl); each represents a separate embodiment according to the present invention. In other embodiments, X 10 is C(R), wherein R is a substituted alkyl. 10 is C(R), where R is CH 2 -OH. In other embodiments, X 10 is C(R), where R is CH 2 -CH 2 -OH. In other embodiments, X 10 is C(R), wherein R is cycloalkyl. 10 is C(R), wherein R is cyclopropyl. In other embodiments, X 10 is C(R), wherein R is not methyl. In other embodiments, X 10 is C(R), wherein R is not alkoxy. 10is C(R), wherein R is isopropoxy. In other embodiments, X 10 It is C(CH 2 -OH). In other embodiments, X 10 It is C(CH 2 -CH 2 -OH). In other embodiments, X 10 is C(R), where R is N(H)R 10 ; and R 10 is a substituted alkyl. In other embodiments, X 10 is C(NH-CH 2 -cyclopropyl). In other embodiments, X 10 is C(COOH). In other embodiments, X 10 It is C(CH 3 In other embodiments, X 10 is C(cyclopropyl). In other embodiments, X 10 is C(isopropoxy). In other embodiments, X 10 is C=O. In other embodiments, if X 10 If C=O, then X 11 It is N.

[0754] In some embodiments, X of Formula I and / or I(a)-I(n) 11 is a nitrogen atom. In other embodiments, X 11 is a carbon atom. In other embodiments, X 11 is N. In other embodiments, X 11 is C. In other embodiments, if X 11 is N, then X 10 is C=O. In other embodiments, if X 10 If C=O, then X 11 is N. In some embodiments, X of Formula I(j) 11 is CH. In some embodiments, X of Formula I(j) 11 It is C(R).

[0755] In some embodiments, X of Formula I and / or I(a)-I(j) 12 is S. In other embodiments, X 12 is not O. In other embodiments, X 12 Yes SO 2 In other embodiments, X 12 Is O. In other embodiments, X 12 is NH. In other embodiments, X 12 is N(R). In other embodiments, X 12 It is N-CH2 -COOH. In other embodiments, X 12 It is N-CH 2 -CH 2 -OH. In other embodiments, X 12 It is N-CH 3 In other embodiments, X 12 In other embodiments, X 12 is CH=CH. In other embodiments, X 12 is CH=CH(R). In other embodiments, X 12 is C(R)=CH. In other embodiments, X 12 is N=CH. In other embodiments, X 12 N = C (R). In other embodiments, X 12 is CH=N. In other embodiments, X 12 C(R)=N. In other embodiments, X 12 It is N-CH 2 CH 3 In other embodiments, X 12 In other embodiments, X 12 In other embodiments, X 12 It is N-CH 2 -cyclopropyl.

[0756] In some embodiments, ring W' of Formula I(k)-I(m) is aromatic or non-aromatic. In some embodiments, if ring W' is aromatic, then X 12 is S. In other embodiments, if ring W' is aromatic, then X 12 is not S. In other embodiments, if ring W' is aromatic, then X 12 Yes SO 2 In other embodiments, if ring W' is aromatic, then X 12 is O. In other embodiments, if ring W' is aromatic, then X 12 In other embodiments, if ring W' is aromatic, then X 12 is N(R). In other embodiments, if ring W' is aromatic, then X 12 It is N-CH 2 -COOH. In other embodiments, if ring W' is aromatic, then X 12 It is N-CH 2 -CH 2 -OH. In other embodiments, if ring W' is aromatic, then X 12 It is N-CH3 In other embodiments, if ring W' is aromatic, then X 12 In other embodiments, if ring W' is aromatic, then X 12 is CH=CH. In other embodiments, if ring W' is aromatic, then X 12 is CH=CH(R). In other embodiments, if ring W' is aromatic, then X 12 is C(R)=CH. In other embodiments, if ring W' is aromatic, then X 12 is N═CH. In other embodiments, if ring W′ is aromatic, then X 12 is N═C(R). In other embodiments, if ring W′ is aromatic, then X 12 is CH=N. In other embodiments, if ring W' is aromatic, then X 12 is C(R)=N. In other embodiments, if ring W' is aromatic, then X 12 It is N-CH 2 CH 3 In other embodiments, if ring W' is aromatic, then X 12 In other embodiments, if ring W' is aromatic, then X 12 In other embodiments, if ring W' is aromatic, then X 12 It is N-CH 2 -cyclopropyl. In other embodiments, if ring W' is non-aromatic, then X 12 is CH=CH. In other embodiments, if ring W' is non-aromatic, then X 12 is CH=CH(R). In other embodiments, if ring W' is non-aromatic, then X 12 is C(R)=CH. In other embodiments, if ring W' is non-aromatic, then X 12 OCH 2 In other embodiments, if ring W' is non-aromatic, then X 12 Yes CH 2 O. In other embodiments, if ring W' is non-aromatic, then X 12 It is SCH 2 In other embodiments, if ring W' is non-aromatic, then X 12 Yes CH 2 S. In other embodiments, if ring W' is non-aromatic, then X 12 is CH=N. In other embodiments, if ring W' is non-aromatic, then X 12is C(R)=N. In other embodiments, if ring W' is non-aromatic, then X 12 is N═CH. In other embodiments, if ring W′ is non-aromatic, then X 12 N=C(R).

[0757] In some embodiments, X of Formula I(b), I(c), I(f), I(h), and / or I(m) 13 Yes CH 2 In other embodiments, X 13 is CH(R). In other embodiments, X 13 It is CH-CH 3 In other embodiments, X 13 YesC(R) 2 In other embodiments, X 13 It is C=O.

[0758] In some embodiments, X of Formula I(g), I(h), I(l) and / or I(m) 14 is S. In other embodiments, X 14 Is O. In other embodiments, X 14 is N. In other embodiments, X 14 is CH. In other embodiments, if X 14 is CH, then ring F is not absent. In other embodiments, if X 14 If it is S, then R 3 In other embodiments, if X 14 is O, then R 3 Does not exist.

[0759] In some embodiments, X of Formula I, I(a)-I(c), and / or I(i)-I(k) 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 and X 9 In some embodiments, at least one of X in Formula I and / or I(a)-I(m) is a nitrogen atom. 2 , X 3 , X 4 , X 5 , X 6 , X 8 and X 9 In some embodiments, at least one of X in Formula I(d) is a nitrogen atom. 2 , X 3 , X 4 , X5 , X 6 , X 7 , X 8 and X 9 In some embodiments, at least one of X in Formula I(d) is a nitrogen atom. 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 and X 10 In some embodiments, if X 5 , X 6 , X 7 , X 8 and X 9 If any of is nitrogen, then the corresponding R 7 '、R 7 ”、R 7 , R 7 ”' and R 7 ””Replacement does not exist.

[0760] In some embodiments, if Ring W is aromatic, then X of Formula I(k)-I(m) 15 is C. In some embodiments, if ring W is non-aromatic, then X 15 is CH, C(R) or N; each represents a separate embodiment according to the present invention. In some embodiments, if ring W is non-aromatic, then X 15 In some embodiments, if ring W is non-aromatic, then X 15 In some embodiments, if ring W is non-aromatic, then X 15 It is N.

[0761] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), and / or I(i)-I(n) 5 is H. In other embodiments, R 5 It is C 1 -C 5 In other embodiments, R 5 In other embodiments, R 5 are methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, neopentyl; each representing a separate embodiment according to the invention.

[0762] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), and / or I(i)-I(n)5 and R 6 are connected to form a substituted or unsubstituted 5-8 membered heterocyclic ring. 5 and R 6 are connected to form a substituted 5-8 membered heterocyclic ring. 5 and R 6 to form an unsubstituted 5-8 membered heterocyclic ring. In some embodiments, the heterocyclic ring is azepane, piperazine, or 2-(piperazin-1-yl)acetamide; each represents a separate embodiment according to the present invention. In some embodiments, the heterocyclic ring is substituted with at least one substituent selected from the group consisting of F, Cl, Br, I, CF 3 , R 20 , C 1 -C 5 Straight or branched alkyl, C 1 -C 5 Straight-chain or branched halogenated alkyl, OH, alkoxy, R 8 -OH (e.g., CH 2 -OH), OMe, amide, C(O)N(R) 2 、C(O)N(R 10 )(R 11 ), R 8 -C(O)N(R 10 )(R 11 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2 NH(R 10 )、N(R 10 )(R 11 )、N(CH 3 ) 2 NH 2 CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, cyclobutanol, substituted or unsubstituted 3-8 membered heterocycle (which may be saturated, unsaturated, aromatic, single, fused or spiro), pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole, halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each is a separate embodiment according to the present invention.

[0763] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 is H. In other embodiments, R 6 Is H, F, Cl, Br, I, OH, SH, R 8-OH, R 8 -SH, -R 8 -OR 10 , CH 2 -O-CH 3 , (CH 2 ) 2 -O-CH 3 , (CH 2 ) 3 -O-CH 3 , (CH 2 ) 2 -O-CH(CH 3 ) 2 , R 8 -SR 10 , (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 , R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl), CH 2 -Cyclopropyl, CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol, R 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring), (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine, CH 2 -Azaspiroheptane, CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 )、(CH 2 ) 2 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -piperidin-2-one, (CH 2 ) 3 -4-cyano-piperidine, (CH 2 ) 3 -4-Trifluoromethyl-piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -NH 2 , (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ), R 8 -C(O)N(R 10 )(R 11 )、(CH 2 ) 2 -C(O)-piperidine, R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, CH(CH 3 )CH 2 OCH 3 、CH(CH3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 、CH(CH 3 )C(O)N(CH 3 ) 2 , C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8Cyclic alkoxymethoxy, optionally wherein at least one methylene group (CH 2 ) is replaced by an oxygen atom, O-(CH 2 ) 2 -O-CH 3 , C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, cyclopropyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol, R 8 -(substituted or unsubstituted C 3 -C 8 substituted or unsubstituted aryl, substituted or unsubstituted R 8 -aryl (e.g., benzyl) or substituted or unsubstituted benzyl; each represents a separate embodiment according to the present invention. In some embodiments, R 6 It may be further substituted by at least one substituted selected from the group consisting of F, Cl, Br, I, C 1 -C 5 Linear or branched alkyl, OH, alkoxy, OMe, amide, C(O)N(R) 2 , C(O)-alkyl, C(O)-pyrrolidine, C(O)-piperidine, N(R) 2 NH(R 10 )、N(R 10 )(R 11 )、N(CH 3 ) 2 NH 2 CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, cyclobutanol, substituted or unsubstituted 3-8 membered heterocyclic pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole, halophenyl, (benzyloxy)phenyl, CN and NO 2; Each represents a separate embodiment according to the present invention. In some embodiments, R 6 is H. In some embodiments, R 6 Yes-R 8 -OR 10 In some embodiments, R 6 Yes CH 2 -O-CH 3 In some embodiments, R 6 YesR 8 -SR 10 In some embodiments, R 6 Yes (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 In some embodiments, R 6 YesR 8 -NHC(O)-R 10 In some embodiments, R 6 Yes (CH 2 ) 3 -NHC(O)-R 10 In some embodiments, R 6 Yes (CH 2 )-NHC(O)-R 10 In some embodiments, R 6 YesR 8 -(substituted or unsubstituted C 3 -C 8 cycloalkyl). 8 -(substituted or unsubstituted C 3 -C 8 Examples of cycloalkyl groups include, but are not limited to: CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol and CH 2 -cyclohexanol; each represents a separate embodiment according to the present invention. In some embodiments, R 6 YesR 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-8 membered heterocyclic ring). In some embodiments, R 6 YesR 8 -(substituted or unsubstituted saturated single 3-8 membered heterocycle). In some embodiments, R 6 YesR8 -(substituted or unsubstituted unsaturated single 3-8 membered heterocyclic ring). In some embodiments, R 6 YesR 8 -(substituted or unsubstituted aromatic single 3-8 membered heterocycle). In some embodiments, R 6 YesR 8 -(substituted or unsubstituted saturated fused 3-8 membered heterocyclic ring). In some embodiments, R 6 YesR 8 -(substituted or unsubstituted unsaturated fused 3-8 membered heterocyclic ring). In some embodiments, R 6 YesR 8 -(substituted or unsubstituted aromatic fused 3-8 membered heterocyclic ring). In some embodiments, R 6 YesR 8 -(substituted or unsubstituted spiro 3-8 membered heterocycle) 8 Examples of -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-8 membered heterocyclic ring) include, but are not limited to: (CH 2 ) 3 -piperidine, (CH 2 ) 3 -4-Fluoro-piperidine, (CH 2 ) 3 -pyran, (CH 2 ) 2 -pyrazole, (CH 2 ) 2 -imidazole, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -Oxetane, CH 2 -piperidine, CH 2 -Triazole, CH 2 -1-oxa-8-azaspiro[4.5]decane, (CH 2 ) 3 -diazabicyclo[2.2.1]heptane, CH 2 -methyl-THF, CH 2 -ethyl-piperidine, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -2-Oxo-methylpyrrolidine, CH 2 -Methyl-azetidine and CH 2 -azaspiroheptane. In some embodiments, R 6 Yes NH 2 In some embodiments, R 6is NHR. In some embodiments, R 6 YesN(R) 2 In some embodiments, R 6 is NH(R 10 ). In some embodiments, R 6 is N(R 10 )(R 11 ). In some embodiments, R 6 YesR 8 -N(R 10 )(R 11 ). In some embodiments, R 8 -N(R 10 )(R 11 ) including but not limited to: (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 3 -N(CH(CH 3 ) 2 ) 2 , (CH 2 ) 3 -piperidine, (CH 2 ) 4 -NH(CH 3 )、(CH 2 ) 3 -NH-CH 3 , (CH 2 ) 3 -NH-CH 2 CH 3 , (CH 2 ) 3 -N(CH 2 CH 3 ) 2 , (CH 2 ) 2 -NH 2 , (CH 2 ) 3 -NH 2 and (CH 2 ) 3 -N(CH 2 CH 3 )(CH 2 CF 3 ). In some embodiments, R 6 YesR 8 -C(O)N(R 10 )(R 11 ), such as (CH 2 )2 -C(O)-piperidine. In some embodiments, R 6 It is C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl. 1 -C 5 Examples of straight or branched, substituted or unsubstituted alkyl groups include, but are not limited to: CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 )、CH(CH 3 )C(O)N(CH 3 ) 2 , benzyl, methyl, ethyl and CH 2 -OCH 2 -CH 2 -O-CH 3In some embodiments, R 6 In some embodiments, R 6 is substituted or unsubstituted C 3 -C 8 In some embodiments, the substituted or unsubstituted C 3 -C 8 Cycloalkyl includes: cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, cyclopropyl, aminomethyl-cyclobutyl, methoxycyclobutyl and 2,3-dihydro-1H-indeno. In some embodiments, R 6 YesR 8 -(substituted or unsubstituted C 3 -C 8 In some embodiments, R 6 is a substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring. In some embodiments, the substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring is piperidine, 1-methyl-piperidine, azetidine, pyrrolidine, pyrrolidone, quinuclidine, tetrahydropyran, azaspiro[3.3]heptane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofuran, azepan-2-one, azabicyclohexane; each represents a separate embodiment according to the present invention. In some embodiments, R 6 is piperidine. In some embodiments, R 6 is 1-methyl-piperidine. In some embodiments, R 6 is tetrahydropyran. In some embodiments, R 6 is substituted or unsubstituted R 8 -aryl, such as benzyl. In some embodiments, R 6 It may be further substituted by at least one substituted selected from the group consisting of F, Cl, Br, I, CF 3 , R 20 , C 1 -C 5 Straight or branched alkyl, C 1 -C 5 Straight-chain or branched halogenated alkyl, OH, alkoxy, R 8 -OH (e.g., CH 2 -OH), OMe, amide, C(O)N(R) 2 、C(O)N(R 10 )(R 11 ), R 8 -C(O)N(R 10 )(R 11 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2NH(R 10 )、N(R 10 )(R 11 )、N(CH 3 ) 2 NH 2 CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, cyclobutanol, substituted or unsubstituted 3-8 membered heterocycle (which may be saturated, unsaturated, aromatic, single, fused or spiro), pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole, halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each is a separate embodiment according to the present invention.

[0764] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 and R 5 connected to form a substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 5-8 membered heterocyclic ring. In some embodiments, the substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 5-8 membered heterocyclic ring is azepane, piperazine or 2-(piperazin-1-yl)acetamide; each represents a separate embodiment according to the present invention. In some embodiments, the ring can be further substituted with at least one substitution selected from the following: F, Cl, Br, I, C 1 -C 5 Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2 NH(R 10 )、N(R 10 )(R 11 )(For example, N(CH 3 ) 2 NH 2 ), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0765] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 Represented by the structure of formula B:

[0766]

[0767] in

[0768] m is 0 or 1; and

[0769] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0770] R 12 and R 13 All H; or

[0771] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl); or

[0772] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0773] R 12 and R 13 connected to form ring B; or

[0774] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0775] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0776] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0777] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0778] in

[0779] Ring A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring;

[0780] Ring B is a substituted or unsubstituted mono-, spiro- or fused 3-8 membered heterocyclic ring; and

[0781] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl;

[0782] In some embodiments, Formula B is represented by Formula Bi.

[0783] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 The structure of formula Bi is represented by:

[0784]

[0785] in

[0786] m is 0 or 1; and

[0787] R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 ;or

[0788] R 12 and R 13 All H; or

[0789] R 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 Alkyl (e.g., ethyl, trifluoroethyl); or

[0790] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0791] R 12 and R 13 connected to form ring B; or

[0792] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0793] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0794] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0795] R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D;

[0796] in

[0797] Ring A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring;

[0798] Ring B is a substituted or unsubstituted mono-, spiro- or fused 3-8 membered heterocyclic ring; and

[0799] Ring D is substituted or unsubstituted C 3 -C 8 Cycloalkyl;

[0800] In some embodiments, R of Formula B and / or Bi 12 is H. In some embodiments, R 12 YesR 20 In other embodiments, R 12 YesR 30 In some embodiments, R 12 It is C 1 -C 5 In some embodiments, R 12 is substituted or unsubstituted C 1 -C 5 In some embodiments, R 12 is unsubstituted C 1 -C 5 In some embodiments, the alkyl group is ethyl. In some embodiments, R 12 is substituted C 1 -C 5 In some embodiments, the alkyl group is trifluoroethyl.

[0801] In some embodiments, R of Formula B and / or Bi 13 is H. In other embodiments, R 13 YesR 30 In some embodiments, R 13 is substituted or unsubstituted C 1-C 5 In some embodiments, R 13 is unsubstituted C 1 -C 5 In some embodiments, the alkyl group is ethyl. In some embodiments, R 13 is substituted C 1 -C 5 In some embodiments, the alkyl group is trifluoroethyl.

[0802] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 Represented by formula B. In some embodiments, R of formula B 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 In some embodiments, R of Formula B 12 and R 13 All are H. In some embodiments, R of Formula B 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 In some embodiments, R of Formula B 12 and R 13 Each independently is H or trifluoroethyl. In some embodiments, R of Formula B 12 and C3 to form ring A, and R 13 YesR 30 In some embodiments, R of Formula B 12 and R 13 Connected to form Ring B. In some embodiments, R of Formula B 12 and C1 to form ring C, and R 13 YesR 30 In some embodiments, C1 and C3 of Formula B are linked to form Ring D, and R of Formula B 12 and R 13 Each is independently R 30 In some embodiments, R of Formula B 13 and C2 are connected to form ring E, m is 1, and R of formula B 12 YesR 30 In some embodiments, R of Formula B 12 and R 13 are connected to form ring B, and C1 and C3 of formula B are connected to form ring D.

[0803] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 Represented by the formula Bi. In some embodiments, R of the formula Bi 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R 13 YesR 30 In some embodiments, R of formula Bi 12 and R 13 All are H. In some embodiments, R of formula Bi 12 and R 13 are each independently H or substituted or unsubstituted C 1 -C 5 In some embodiments, R of formula Bi is 12 and R 13 Each independently is H or trifluoroethyl. In some embodiments, R 12 and C3 to form ring A, and R 13 YesR 30 In some embodiments, R of formula Bi 12 and R 13 Connected to form ring B. In some embodiments, R of formula Bi 12 and C1 to form ring C, and R 13 YesR 30 In some embodiments, C1 and C3 of formula Bi are linked to form ring D, and R of formula Bi 12 and R 13 Each is independently R 30 In some embodiments, R of formula Bi 13 and C2 are connected to form ring E, m is 1, and R of formula Bi 12 YesR 30 In some embodiments, R of formula Bi 12 and R 13 are connected to form ring B, and C1 and C3 of formula Bi are connected to form ring D.

[0804] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 represented by the formula Bi and / or B, and

[0805] Formula Bi and / or B R 12 YesR 20 or C 1 -C5 C(O)-alkyl, and R of formula Bi and / or B 13 YesR 30 ;or

[0806] R 12 and R 13 All H, or

[0807] R 12 and R 13 are each independently H or trifluoroethyl; or

[0808] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0809] R 12 and R 13 connected to form a substituted or unsubstituted pyrrolidine ring, piperazine, thiomorpholine 1,1-dioxide 2-oxa-6-azaspiro[3.3]heptane, pyrazole, imidazole, 2,5-diazabicyclo[2.2.1]heptane or diazabicyclo[2.2.1]heptane; or

[0810] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0811] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0812] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0813] R 12 and R 13 connect to form ring B, and C1 and C3 connect to form ring D.

[0814] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 represented by the formula Bi and / or B, and

[0815] Formula Bi and / or B R 12 YesR 20 or C 1 -C 5 C(O)-alkyl, and R of formula Bi and / or B 13 YesR30 ;or

[0816] R 12 and C3 to form ring A, and R 13 YesR 30 ;or

[0817] R 12 and R 13 connected to form a substituted or unsubstituted pyrrolidine ring, piperazine, thiomorpholine 1,1-dioxide 2-oxa-6-azaspiro[3.3]heptane, pyrazole, imidazole, 2,5-diazabicyclo[2.2.1]heptane or diazabicyclo[2.2.1]heptane; or

[0818] R 12 and C1 to form ring C, and R 13 YesR 30 ;or

[0819] C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or

[0820] R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or

[0821] R 12 and R 13 connect to form ring B, and C1 and C3 connect to form ring D.

[0822] In some embodiments, Ring A of Formula Bi is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle. In some embodiments, Ring A is an unsubstituted single 3-8 membered heterocycle. In some embodiments, Ring A is an unsubstituted spiro 3-8 membered heterocycle. In some embodiments, Ring A is an unsubstituted fused 3-8 membered heterocycle. In some embodiments, Ring A is a substituted single 3-8 membered heterocycle. In some embodiments, Ring A is a substituted spiro 3-8 membered heterocycle. In some embodiments, Ring A is a substituted fused 3-8 membered heterocycle. In some embodiments, Ring A is: pyrrolidine, methylpyrrolidine, ethylpyrrolidine, 2-oxopyrrolidine, piperidine, methylpiperidine, methyl-2-oxopyrrolidine, pyran-azetidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane or 2-azaspiro[3.3]heptane; each represents a separate embodiment according to the present invention. In some embodiments, Ring A is: pyrrolidine, methylpyrrolidine, or ethylpyrrolidine; each represents a separate embodiment according to the invention.

[0823] In some embodiments, Ring B of Formula Bi is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring. In some embodiments, Ring B is an unsubstituted single 3-8 membered heterocyclic ring. In some embodiments, Ring B is an unsubstituted spiro 3-8 membered heterocyclic ring. In some embodiments, Ring B is an unsubstituted fused 3-8 membered heterocyclic ring. In some embodiments, Ring B is a substituted single 3-8 membered heterocyclic ring. In some embodiments, Ring B is a substituted spiro 3-8 membered heterocyclic ring. In some embodiments, Ring B is a substituted fused 3-8 membered heterocyclic ring. In some embodiments, ring B is: pyrrolidine, methylpyrrolidine, ethylpyrrolidine, 2-oxopyrrolidine, hydroxymethyl-pyrrolidine, piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, methylpiperidine, fluoropiperidine, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, difluoropiperidine, piperazine, methyl-piperazine, dimethyl-pyrazole, methyl-2-oxopyrrolidine, pyran-, azetidine oxazolidinone, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane, diazabicyclo[2.2.1]heptane, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, thiomorpholine or 1,1-dioxa-2-oxa-6-azaspiro[3.3]heptane; each represents a separate embodiment according to the invention. In some embodiments, Ring B is: piperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine, methyl-piperazine, dimethyl-pyrazole, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, 1,1-dioxide-2-oxa-6-azaspiro[3.3]heptane, hydroxymethyl-pyrrolidine or diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane, each representing a separate embodiment according to the present invention. In some embodiments, Ring B is 4-fluoropiperidine.

[0824] In some embodiments, ring C of formula Bi is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle. In some embodiments, ring C is an unsubstituted single 3-8 membered heterocycle. In some embodiments, ring C is an unsubstituted spiro 3-8 membered heterocycle. In some embodiments, ring C is an unsubstituted fused 3-8 membered heterocycle. In some embodiments, ring C is a substituted single 3-8 membered heterocycle. In some embodiments, ring C is a substituted spiro 3-8 membered heterocycle. In some embodiments, ring C is a substituted fused 3-8 membered heterocycle. In some embodiments, ring C is: pyrrolidine, methylpyrrolidine, ethylpyrrolidine, 2-oxopyrrolidine, piperidine, methylpiperidine, methyl-2-oxopyrrolidine, pyran-azetidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane or 2-azaspiro[3.3]heptane; each represents a separate embodiment according to the present invention. In some embodiments, Ring C is: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, or 2-azaspiro[3.3]heptane; each represents a separate embodiment according to the invention.

[0825] In some embodiments, Ring D of Formula Bi is substituted or unsubstituted C 3 -C 8 In some embodiments, ring D is substituted C 3 -C 8 In some embodiments, ring D is an unsubstituted C 3 -C 8 Cycloalkyl. In some embodiments, ring D is cyclopropane, cyclobutane, cyclopentane, cyclohexane, or cycloheptane; each represents a separate embodiment according to the invention.

[0826] In some embodiments, ring E of formula Bi is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle. In some embodiments, ring E is an unsubstituted single 3-8 membered heterocycle. In some embodiments, ring E is an unsubstituted spiro 3-8 membered heterocycle. In some embodiments, ring E is an unsubstituted fused 3-8 membered heterocycle. In some embodiments, ring E is a substituted single 3-8 membered heterocycle. In some embodiments, ring E is a substituted spiro 3-8 membered heterocycle. In some embodiments, ring E is a substituted fused 3-8 membered heterocycle. In some embodiments, ring E is: pyrrolidine, methylpyrrolidine, ethylpyrrolidine, 2-oxopyrrolidine, piperidine, methylpiperidine, methyl-2-oxopyrrolidine, pyran-azetidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane or 2-azaspiro[3.3]heptane; each represents a separate embodiment according to the present invention. In some embodiments, Ring E is: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, or methylpiperidine; each represents a separate embodiment according to the invention.

[0827] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 Is F, Cl, Br, I, OH, SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 (For example, CH 2 -O-CH 3 ), R 8 -SR 10 (For example, (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 ), R 8 -NHC(O)-R 10 、-OR 8 -R 10 , R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) (e.g., CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol), (CH 2 )3 -Pyran, CH 2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -methyl-THF, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -Methyl-azetidine, CH 2 -Azaspiroheptane, CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH 3 ), C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl (e.g., CH(CH 3 )CH 2 OCH3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH 3 ) 2 )(CH 2 CH 3 ), benzyl, methyl, ethyl, CH 2 -OCH 2 -CH 2 -O-CH 3 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy (e.g., methoxy, O-(CH 2 ) 2 -O-CH3 ), optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl (e.g., methoxycyclopropyl, methylcyclobutyl, cyclopropyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., trifluoromethyl-oxetane, hydroxy-tetrahydrofuran, 1-methylazepan-2-one, 3-azabicyclo[3.1.0]hexane), substituted or unsubstituted aryl, or substituted or unsubstituted benzyl; each represents a separate embodiment according to the present invention. In some embodiments, R 6 It may be further substituted by at least one substituted selected from the group consisting of F, Cl, Br, I, C 1 -C 5 Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 ), C(O)-alkyl, C(O)-pyrrolidine, C(O)-piperidine, N(R) 2 (For example, N(CH 3 ) 2 NH 2 )、NH(R 10 )、N(R 10 )(R 11 ), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0828] In some embodiments, R of Formula I, I(a), I(d), I(e), I(g), I(i), I(j)-I(l), and / or I(n) 6 Yes-R 8 -OR 10 In some embodiments, -R 8 -OR10 Yes CH 2 -O-CH 3 In some embodiments, R 6 YesR 8 -SR 10 In some embodiments, R 8 -SR 10 Yes (CH 2 ) 3 -S-(CH 2 ) 2 CH 3 In some embodiments, R 6 YesR 8 -NHC(O)-R 10 In some embodiments, R 6 YesR 8 -(substituted or unsubstituted C 3 -C 8 In some embodiments, R 8 -(substituted or unsubstituted C 3 -C 8 Cycloalkyl) is CH 2 -Cyclobutanol, CH 2 -Difluorocyclopropyl, CH 2 -Methylcyclopropyl, CH 2 -dimethylamino-cyclohexyl, (CH 2 ) 2 -Cyclopentanol, CH 2 -cyclohexanol; each represents a separate embodiment according to the present invention. In some embodiments, R 6 YesR 8 -(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring). In some embodiments, R 6 Yes (CH 2 ) 3 -piperidine. In some embodiments, R 6 Yes (CH 2 ) 2 -NH 2 In some embodiments, R 6 Yes (CH 2 ) 3 -NH 2 In some embodiments, R 6 Yes (CH 2 ) 3 -4-fluoro-piperidine. In some embodiments, R 6 Yes (CH 2 ) 3 -Pyran, CH2 -Tetrahydrofuran, CH 2 -Dioxane, CH 2 -methyl-THF, CH 2 -oxa-azaspirodecane, (CH 2 ) 3 -Dimethylpyrazole, CH 2 -methyl-azetidine or CH 2 -azaspiroheptane; each represents a separate embodiment according to the present invention. In some embodiments, R 6 It is C 1 -C 5 In some embodiments, R 6 It is C 1 -C 5 In some embodiments, the substituted alkyl group is CH(CH 3 )CH 2 OCH 3 、CH(CH 3 )CH 2 NH 2 、CH(CH 3 )C(O)N(CH 3 ) 2 , CH 2 -CH(OH)Ph, (CH 2 ) 3 N(H)CH 2 CH 3 、CH(CH 3 )(CH 2 ) 2 OH, CH(CH 2 OH)(CH 2 CH 3 )、(CH 2 ) 3 -OCH 3 , (CH 2 ) 2 -OCH 3 , (CH 2 ) 2 -OCH(CH 3 ) 2 、CH(CH 2 OH)(CH 2 CH(CH 3 ) 2 ), CH 2 CH(CH 3 )(OCH 3 ), CH 2 CH(N(CH3 ) 2 )(CH 2 CH 3 ), CH 2 -OCH 2 -CH 2 -O-CH 3 or benzyl; each represents a separate embodiment according to the present invention. In some embodiments, R 6 It is C 1 -C 5 In some embodiments, the unsubstituted alkyl group is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, or neopentyl; each of which represents a separate embodiment according to the present invention. In some embodiments, R 6 is substituted or unsubstituted C 3 -C 8 In some embodiments, R 6 is substituted C 3 -C 8 Cycloalkyl. In some embodiments, the substituted cycloalkyl is methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl or methoxycyclobutyl, 2,3-dihydro-1H-indanol; each represents a separate embodiment according to the present invention. In some embodiments, R 6 is unsubstituted C 3 -C 8 In some embodiments, the unsubstituted cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; each of which represents a separate embodiment according to the present invention. In some embodiments, R 6 is a substituted or unsubstituted 3-8 membered heterocycle. In some embodiments, the substituted heterocycle is piperidine, 1-methyl-piperidine, tetrahydropyran, trifluoromethyl-oxetane, hydroxy-tetrahydrofuran, 1-methylazepan-2-one, or 3-azabicyclo[3.1.0]hexane; each represents a separate embodiment according to the present invention. In some embodiments, R 6 is piperidine. In some embodiments, R 6 is 1-methyl-piperidine. In some embodiments, R 6 It is tetrahydropyran.

[0829] In some embodiments, R of Formula I, I(a)-I(c(, I(i(, I(j(, I(k(, and / or I(n) 7 Is H, F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, SR 10 , -R8 -OR 10 , -R 8 -SR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 )、C(O)NH(CH 3 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, methyl, C 1 -C 5Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkyl, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted 3-8 membered heterocycle, substituted or unsubstituted aryl, or substituted or unsubstituted benzyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 Further substituted with at least one substituted selected from the group consisting of F, Cl, Br, I, C 1 -C 5 Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 ), C(O)-alkyl, C(O)-pyrrolidine, C(O)-piperidine, N(R) 2 NH(R 10 )、N(R 10 )(R 11 )(For example, N(CH 3 ) 2 NH 2 ), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0830] In some embodiments, R of Formula I, I(a)-I(c(, I(i(, I(j(, I(k(, and / or I(n)7 is H. In some embodiments, R 7 is F. In some embodiments, R 7 is Cl. In some embodiments, R 7 is Br. In some embodiments, R 7 is 1. In some embodiments, R 7 is OH. In some embodiments, R 7 Yes OR 20 In some embodiments, R 7 It is CF 3 In some embodiments, R 7 is CN. In some embodiments, R 7 Yes NH 2 In some embodiments, R 7 is NHR. In some embodiments, R 7 YesN(R) 2 In some embodiments, R 7 is NH(R 10 ). In some embodiments, R 7 is N(R 10 )(R 11 ). In some embodiments, R 7 NHC(O)-R 10 In some embodiments, R 7 is COOH. In some embodiments, R 7 is -C(O)Ph. In some embodiments, R 7 It is C(O)OR 10 In some embodiments, R 7 is C(O)H. In some embodiments, R 7 It is C(O)-R 10 In some embodiments, R 7 It is C 1 -C 5 In some embodiments, R 7 Yes -C(O)NH 2 In some embodiments, R 7 is C(O)NHR. In some embodiments, C(O)NHR is C(O)NH(CH 3 ). In some embodiments, R 7 is C(O)N(R 10 )(R 11 In some embodiments, C(O)N(R 10 )(R 11 ) is C(O)NH(CH 3 )、C(O)NH(CH2 CH 2 OCH 3 ) or C(O)NH(CH 2 CH 2 OH); each represents a separate embodiment according to the present invention. In some embodiments, R 7 Yes SO 2 R. In some embodiments, R 7 It is C 1 -C 5 A linear or branched, substituted or unsubstituted alkyl group. In some embodiments, the alkyl group is methylimidazole, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, or hexyl; each of which represents a separate embodiment according to the present invention. In some embodiments, R 7 It is C 1 -C 5 Straight chain or branched chain or C 3 -C 8 In some embodiments, R 7 It is C 1 -C 5 In some embodiments, the haloalkyl group is CHF 2 In some embodiments, R 7 It is C 1 -C 5 In some embodiments, R 7 It is C 3 -C 8 In some embodiments, R 7 It is C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, optionally wherein at least one methylene group (CH 2 ) is replaced by an oxygen atom. In some embodiments, R 7 It is C 1 -C 5 In some embodiments, the alkoxy group is a methoxy group. In some embodiments, the alkoxy group is an ethoxy group. In some embodiments, R 7 It is C 1 -C 5 In some embodiments, R 7 It is C 3 -C 8 In some embodiments, R 7 It is C 1 -C 5 In some embodiments, R7 It is C 1 -C 5 In some embodiments, R 7 It is C 1 -C 5 In some embodiments, R 7 It is C 1 -C 5 In some embodiments, R 7 It is C 1 -C 5 In some embodiments, R 7 is substituted or unsubstituted C 3 -C 8 In some embodiments, the cycloalkyl group is cyclopropyl, cyclopropanol, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; each of which represents a separate embodiment according to the present invention. In some embodiments, R 7 is a substituted or unsubstituted 3-8 membered heterocyclic ring. 7 is an unsubstituted 3-8 membered heterocyclic ring. 7 is a substituted 3-8 membered heterocyclic ring. 7 is a substituted or unsubstituted 4-7 membered heterocyclic ring. 7 is an unsubstituted 4-7 membered heterocyclic ring. 7 is a substituted 4-7 membered heterocycle. In some embodiments, the heterocycle is morpholine (e.g., 2-morpholine or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, oxetane-3-ol, pyrrolidine, pyrrolidin-3-ol, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidone, imidazole, pyrazole, piperazine, piperidine, piperidine-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2-oxopyrrolidine, pyridine, or 1-methylpyridine; each represents a separate embodiment according to the present invention. In some embodiments, R 7 YesR 8 -(substituted or unsubstituted single, fused or spiro 3-8 membered heterocyclic ring). In some embodiments, R 7 YesR 8 -(unsubstituted single 3-8 membered heterocycle). In some embodiments, R 7 YesR 8 -(unsubstituted fused 3-8 membered heterocyclic ring). In some embodiments, R 7 is R8-(unsubstituted spiro 3-8 membered heterocycle). In some embodiments, R 7 YesR 8-(substituted single 3-8 membered heterocycle). In some embodiments, R 7 YesR 8 -(substituted fused 3-8 membered heterocyclic ring). In some embodiments, R 7 YesR 8 -(Substituted spiro 3-8 membered heterocycle). In some embodiments, the heterocycle may be saturated. In some embodiments, the heterocycle may be unsaturated. In some embodiments, the heterocycle may be aromatic. In some embodiments, R 7 is a substituted or unsubstituted aryl group. In some embodiments, R 7 In some embodiments, R 7 It may be further substituted by at least one substituted selected from the group consisting of F, Cl, Br, I, C 1 -C 5 Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2 NH(R 10 )、N(R 10 )(R 11 )(For example, N(CH 3 ) 2 NH 2 ), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0831] In some embodiments, R of Formula I, I(a)-I(c(, I(i(, I(j(, I(k(, and / or I(n) 7 Yes OR 20 In some embodiments, R 7 is a substituted or unsubstituted 4-7 membered heterocyclic ring. 7 is an unsubstituted 4-7 membered heterocyclic ring. 7is a substituted 4-7 membered heterocycle. In some embodiments, the heterocycle is morpholine (e.g., 2-morpholine or 3-morpholine), pyran, oxetane, pyrrolidine, pyrrolidin-3-ol, tetrahydrofuran, imidazole, piperazine, piperidine, piperidin-4-ol, dioxazole, triazole, pyridine, 1-methylpyridine, or 2-oxopyrrolidine; each represents a separate embodiment according to the present invention. In some embodiments, R 7 is a substituted or unsubstituted aryl group. In some embodiments, R 7 In some embodiments, R 7 It may be further substituted by at least one substituted selected from the group consisting of F, Cl, Br, I, C 1 -C 5 Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2 NH(R 10 )、N(R 10 )(R 11 )(For example, N(CH 3 ) 2 NH 2 ), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0832] In some embodiments, R of Formula I, I(a)-I(c(, I(i(, I(j(, I(k(, and / or I(n) 7 Not H, F, Cl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy or C 1 -C 5 Straight-chain or branched, substituted or unsubstituted alkyl.

[0833] In some embodiments, R of Formula I, I(a)-I(c(, I(i(, I(j(, I(k(, and / or I(n) 7 Represented by the structure of formula A:

[0834]

[0835] in

[0836] X 1 is N or O;

[0837] R 1 and R 2 are each independently H, F, Cl, Br, I, OH, SH or CF 3 , substituted or unsubstituted C 1 -C 5 Alkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, substituted or unsubstituted C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy; or R 1 and R 2 Connect to form =O or C 3 -C 8 carbocyclic or heterocyclic (eg, cyclopropyl); each is a separate embodiment according to the invention;

[0838] R 3 and R 4 are each independently H, Me, substituted or unsubstituted C 1 -C 5 Alkyl (e.g., methoxyethyl, methylaminoethyl, aminoethyl), -R 8 -OR 10 (For example, (CH 2 ) 2 -O-CH 3 ), R 8 -N(R 10 )(R 11 )(For example, (CH 2 ) 2 -NH(CH 3 )), substituted or unsubstituted C 3 -C 8 Cycloalkyl (eg, cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (eg, pyrrolidine, methylpyrrolidine, piperidine), or R 20 ; each is a separate embodiment according to the present invention;

[0839] or R 3 and R 4connected to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); each is a separate embodiment according to the invention;

[0840] or R 2 and R 4 to form a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyridine, piperidine, tetrahydrofuran, tetrahydrothiophene, cyclopropyl, oxetane, imidazole, pyrimidine, triazole, oxadiazole, pyrazole; each of which is a separate embodiment according to the present invention), wherein if the ring is aromatic, then R 1 and / or R 3 does not exist;

[0841] If X 1 is O, then R 4 does not exist;

[0842] In some embodiments, X of Formula A 1 is N. In other embodiments, X 1 It's O.

[0843] In some embodiments, R of Formula A 1 is H. In other embodiments, R 1 is F. In other embodiments, R 1 It is CF 3 .

[0844] In some embodiments, R of Formula A 2 is H. In other embodiments, R 2 is F. In other embodiments, R 2 It is CF 3 .

[0845] In some embodiments, R of Formula A 1 and R 2 Connect to form =0. In other embodiments, R 1 and R 2 Connect to form C 3 -C 8 In other embodiments, R 1 and R 2 Connect to form C 3 -C 8 In some embodiments, the carbocyclic ring is cyclopropyl. In other embodiments, R 1 and R 2 Connected to form a 3-8 membered heterocyclic ring.

[0846] In some embodiments, R of Formula A of Formula I, I(a)-I(c), I(i), and / or I(k)-I(n) 1 and R 2 Not connected to form =0.

[0847] In some embodiments, R of Formula A 3 is H. In some embodiments, R 3 In some embodiments, R 3 is substituted or unsubstituted C 1 -C 5 In some embodiments, alkyl is methoxyethylene, methylaminoethylene, aminoethylene; each represents a separate embodiment according to the present invention. In some embodiments, R 3 is substituted or unsubstituted C 3 -C 8 In some embodiments, the cycloalkyl group is cyclopropyl. In some embodiments, R 3 is a substituted or unsubstituted 5-7 membered heterocycle. In some embodiments, the heterocycle is pyrrolidine, methylpyrrolidine, or piperidine; each represents a separate embodiment according to the present invention. In some embodiments, R 3 is defined as follows 20 .

[0848] In some embodiments, R of Formula A 4 is H. In some embodiments, R 4 In some embodiments, R 4 is substituted or unsubstituted C 1 -C 5 In some embodiments, alkyl is methoxyethylene, methylaminoethylene, aminoethylene; each represents a separate embodiment according to the present invention. In some embodiments, R 4 is substituted or unsubstituted C 3 -C 8 In some embodiments, the cycloalkyl group is cyclopropyl. In some embodiments, R 4 is a substituted or unsubstituted 5-7 membered heterocycle. In some embodiments, the heterocycle is pyrrolidine, methylpyrrolidine, or piperidine; each represents a separate embodiment according to the present invention. In some embodiments, R 4 is defined as follows: 20 .

[0849] In some embodiments, R of Formula A 3 and R 4Connected to form a 3-8 membered heterocyclic ring. In some embodiments, the heterocyclic ring is imidazole, pyrrolidine, 2-oxopyrrolidine, piperidine, morpholine, or piperazine; each represents a separate embodiment according to the invention.

[0850] In some embodiments, if X of Formula A 1 is O, then R 4 Does not exist.

[0851] In some embodiments, R of Formula I, I(a)-I(c(, I(i(, I(j(, I(k(, and / or I(n) 7 is O-R20, a substituted or unsubstituted 4-7 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, imidazole, piperazine, piperidine, dioxazole, triazole, 2-oxopyrrolidine), or a substituted or unsubstituted aryl. In some embodiments, R of Formula I, I(a)-I(c(, I(i(, I(j(, I(k(, and / or I(n) 7 Represented by formula A, where X 1 , R 1 , R 2 , R 3 and R 4 As defined above, only R 1 and R 2 Cannot connect to form =0.

[0852] In some embodiments, R of Formula I and / or I(a)-I(n) 7 'Not H.

[0853] In some embodiments, R of Formula I and / or I(a)-I(n) 7 ' is H. In some embodiments, R of Formula I and / or I(a)-I(n) 7 ' is F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10)、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, isopropyl, methyl, ethyl, C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, cyclopropyl, cyclohexyl, substituted or unsubstituted 3-8 membered heterocycle, substituted or unsubstituted aryl, phenyl or substituted or unsubstituted benzyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 ' is further substituted by at least one selected from the group consisting of: F, Cl, Br, I, C 1 -C 5 Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2 NH(R 10 )、N(R 10 )(R 11 )(For example, N(CH 3 ) 2 NH 2 ), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0854] In some embodiments, R of Formula I and / or I(a)-I(n) 7 ' is H. In some embodiments, R 7 ' is F. In some embodiments, R 7 ' is Cl. In some embodiments, R 7 ' is Br. In some embodiments, R 7 ' is 1. In some embodiments, R 7 'It's CF 3 In some embodiments, R 7 'It's C 1 -C 5 In some embodiments, R 7 'It's C 1 -C 5 In some embodiments, alkyl is isopropyl, methyl, ethyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 'It's C1 -C 5 In some embodiments, R 7 ' is isopropyl. In some embodiments, R 7 ' is methyl. In some embodiments, R 7 ' is ethyl. In some embodiments, R 7 'It's C 1 -C 5 Straight chain or branched chain or C 3 -C 8 In some embodiments, R 7 'It's C 1 -C 5 Straight or branched haloalkyl. In some embodiments, the haloalkyl is CHF 2 In some embodiments, R 7 'It's C 3 -C 8 In some embodiments, R 7 ' is substituted or unsubstituted C 3 -C 8 In some embodiments, the cycloalkyl group is cyclopropyl. In some embodiments, the cycloalkyl group is cyclohexyl. In some embodiments, R 7 ' is a substituted or unsubstituted aryl group. In some embodiments, R 7 ' is phenyl. In some embodiments, R 7 'It's C 1 -C 5 Straight chain or branched chain or C 3 -C 8 In some embodiments, R 7 ' is a methoxy group.

[0855] In some embodiments, R of Formula I, I(a)-I(c), and / or I(i)-I(n) 7 and R 7 ' are connected to form a 5- or 6-membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring. In some embodiments, R 7 and R 7 ' is connected to form a 5-membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 and R 7 ' is connected to form a 6-membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 and R 7 ' is connected to form a 5-membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 and R 7' is connected to form a 6-membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 and R 7 ' are connected to form a 6-membered substituted or unsubstituted, aromatic carbocyclic ring. In some embodiments, R 7 and R 7 ' are connected to form a 5 or 6-membered substituted or unsubstituted, aromatic heterocyclic ring. In some embodiments, R 7 and R 7 ' are connected to form a 5- or 6-membered substituted or unsubstituted heterocyclic ring. In some embodiments, R 7 and R 7 ' is connected to form a 6-membered substituted or unsubstituted heterocyclic ring. In some embodiments, R 7 and R 7 ' is connected to form piperidine. In some embodiments, R 7 and R 7 ' is connected to form tetrahydropyran. In some embodiments, R 7 and R 7 ' is connected to form a 5-membered substituted or unsubstituted heterocyclic ring. In some embodiments, R 7 and R 7 ' is connected to form pyrrolidine. In some embodiments, R 7 and R 7 'Connect to form tetrahydrofuran.

[0856] In some embodiments, R of Formula I, I(a)-I(c), I(i)-I(k), and / or I(n) 7 and R 7 In some embodiments, R of Formula I, I(a)-I(c), I(i)-I(k) and / or I(n) 7 and R 7 'Not H, F, Cl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy or C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to the present invention.

[0857] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 "Not H.

[0858] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ” is H. In some embodiments, R of Formula I(a), I(c), I(e) and / or I(f)-I(n) 7 ” is F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3)(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, cyclopropyl, cyclohexyl, substituted or unsubstituted 3-8 membered heterocycle, substituted or unsubstituted aryl, phenyl or substituted or unsubstituted benzyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 " is further substituted by at least one substituted selected from the group consisting of F, Cl, Br, I, C 1 -C 5 Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2 NH(R 10 )、N(R 10 )(R 11 )(For example, N(CH 3 ) 2 NH 2 ), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0859] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ” is H. In some embodiments, R 7 " is F. In some embodiments, R 7 " is Cl. In some embodiments, R 7 " is Br. In some embodiments, R 7 " is 1. In some embodiments, R 7 "It is CF 3 In some embodiments, R 7 "It is C 1 -C 5 In some embodiments, R 7 "It is C 1 -C 5 In some embodiments, alkyl is isopropyl, methyl, ethyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 "It is C 1 -C 5 In some embodiments, R 7 " is isopropyl. In some embodiments, R 7 " is methyl. In some embodiments, R 7 " is ethyl. In some embodiments, R 7 "It is C 1 -C 5 Straight chain or branched chain or C 3 -C 8 In some embodiments, R 7 "It is C 1 -C 5 Straight or branched haloalkyl. In some embodiments, the haloalkyl is CHF 2 In some embodiments, R 7 "It is C 3 -C 8 In some embodiments, R 7 " is substituted or unsubstituted C 3 -C 8 In some embodiments, the cycloalkyl group is cyclopropyl. In some embodiments, the cycloalkyl group is cyclohexyl. In some embodiments, R 7 " is a substituted or unsubstituted aryl group. In some embodiments, R 7 " is phenyl. In some embodiments, R 7 "It is C 1 -C 5Straight chain or branched chain or C 3 -C 8 In some embodiments, R 7 ” is a methoxy group.

[0860] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ”'Not H.

[0861] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ” ' is H. In some embodiments, R of Formula I(i) 7 "'is F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3 、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight-chain or branched thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, cyclopropyl, cyclohexyl, substituted or unsubstituted 3-8 membered heterocycle, substituted or unsubstituted aryl, phenyl or substituted or unsubstituted benzyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 "' is cyclopropyl. In some embodiments, R 7 "' is further substituted by at least one substituted selected from the group consisting of F, Cl, Br, I, C 1 -C 5 Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2 NH(R 10 )、N(R 10 )(R 11 )(For example, N(CH 3 ) 2 NH 2), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0862] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ” ' is H. In some embodiments, R 7 ” ' is F. In some embodiments, R 7 ”' is Cl. In some embodiments, R 7 ” is Br. In some embodiments, R 7 ” ' is 1. In some embodiments, R 7 ”'It's CF 3 In some embodiments, R 7 ”' is C 1 -C 5 In some embodiments, R 7 ”' is C 1 -C 5 In some embodiments, alkyl is isopropyl, methyl, ethyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 ”' is C 1 -C 5 In some embodiments, R 7 "' is isopropyl. In some embodiments, R 7 "' is methyl. In some embodiments, R 7 ' is ethyl. In some embodiments, R 7 ”' is C 1 -C 5 Straight chain or branched chain or C 3 -C 8 In some embodiments, R 7 ”' is C 1 -C 5 Straight or branched haloalkyl. In some embodiments, the haloalkyl is CHF 2 In some embodiments, R 7 ”' is C 3 -C 8 In some embodiments, R7 ” is substituted or unsubstituted C 3 -C 8 In some embodiments, the cycloalkyl group is cyclopropyl. In some embodiments, the cycloalkyl group is cyclohexyl. In some embodiments, R 7 "' is a substituted or unsubstituted aryl group. In some embodiments, R 7 "' is phenyl. In some embodiments, R 7 ”' is C 1 -C 5 Straight chain or branched chain or C 3 -C 8 In some embodiments, R 7 ”' is a methoxy group.

[0863] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ”” is not H.

[0864] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ” ” is H. In some embodiments, R of Formula I(i) 7 "" is F, Cl, Br, I, OH, OR 20 SH, R 8 -OH, R 8 -SH, -R 8 -OR 10 , R 8 -(C 3 -C 8 Cycloalkyl), R 8 -(3-8 membered heterocyclic ring), CF 3 , CD 3 , OCD 3 、CN、NO 2 、-CH 2 CN, -R 8 CN、NH 2 、NHR、N(R) 2 NH(R 10 )、N(R 10 )(R 11 ), R 8 -N(R 10 )(R 11 ), R 9 -R 8 -N(R 10 )(R 11 )、B(OH) 2 、-OC(O)CF 3、-OCH 2 Ph、NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 , R 8 -C(O)-R 10 、C(O)H、C(O)-R 10 , C 1 -C 5 Straight chain or branched C(O)-haloalkyl, -C(O)NH 2 、C(O)NHR、C(O)N(R 10 )(R 11 ), SO 2 R, SO 2 N(R 10 )(R 11 )、CH(CF 3 )(NH-R 10 ), C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkyl, C 1 -C 5 Straight or branched chain, substituted or unsubstituted alkenyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic haloalkyl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, optionally wherein at least one methylene group (CH 2 ) is replaced by oxygen atoms, C 1 -C 5 Straight chain or branched chain thioalkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy, C 1 -C 5 Straight-chain or branched alkoxyalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, cyclopropyl, cyclohexyl, substituted or unsubstituted 3-8 membered heterocycle, substituted or unsubstituted aryl, phenyl or substituted or unsubstituted benzyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 "" is further substituted by at least one substituted selected from the group consisting of F, Cl, Br, I, C 1 -C 5Straight or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R) 2 )、C(O)-pyrrolidine、C(O)-piperidine、N(R) 2 NH(R 10 )、N(R 10 )(R 11 )(For example, N(CH 3 ) 2 NH 2 ), CF 3 , aryl, phenyl, heteroaryl, substituted or unsubstituted C 3 -C 8 Cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocycle (e.g., pyran, oxetane, piperidine, pyrazole, methyl-pyrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO 2 ; each represents a separate embodiment according to the present invention.

[0865] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ”” is H. In some embodiments, R 7 ”” is F. In some embodiments, R 7 "" is Cl. In some embodiments, R 7 "" is Br. In some embodiments, R 7 "" is I. In some embodiments, R 7 "" is CF 3 In some embodiments, R 7 "" is C 1 -C 5 In some embodiments, R 7 "" is C 1 -C 5 In some embodiments, alkyl is isopropyl, methyl, ethyl; each represents a separate embodiment according to the present invention. In some embodiments, R 7 "" is C 1 -C 5 In some embodiments, R 7 "" is isopropyl. In some embodiments, R 7 "" is methyl. In some embodiments, R 7 "" is ethyl. In some embodiments, R 7 "" is C 1 -C 5 Straight chain or branched chain or C3 -C 8 In some embodiments, R 7 "" is C 1 -C 5 Straight or branched haloalkyl. In some embodiments, the haloalkyl is CHF 2 In some embodiments, R 7 "" is C 3 -C 8 In some embodiments, R 7 "" is substituted or unsubstituted C 3 -C 8 In some embodiments, the cycloalkyl group is cyclopropyl. In some embodiments, the cycloalkyl group is cyclohexyl. In some embodiments, R 7 "" is a substituted or unsubstituted aryl group. In some embodiments, R 7 "" is phenyl. In some embodiments, R 7 "" is C 1 -C 5 Straight chain or branched chain or C 3 -C 8 In some embodiments, R 7 "" is a methoxy group.

[0866] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ' and R 7 " are connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring. In some embodiments, R 7 ' and R 7 " is connected to form a 5-membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 ' and R 7 " is connected to form cyclopentane. In some embodiments, R 7 ' and R 7 " is connected to form a 6-membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 ' and R 7 " is connected to form cyclohexane. In some embodiments, R 7 ' and R 7 " is connected to form a 5-membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 ' and R 7 " is connected to form a 6-membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 ' and R 7" are connected to form a 6-membered substituted or unsubstituted, aromatic carbocyclic ring. In some embodiments, R 7 ' and R 7 " are connected to form a 5- or 6-membered substituted or unsubstituted, aromatic heterocyclic ring. In some embodiments, R 7 ' and R 7 " are connected to form a 5- or 6-membered substituted or unsubstituted heterocyclic ring. In some embodiments, R 7 ' and R 7 " is connected to form a 6-membered substituted or unsubstituted heterocyclic ring. In some embodiments, R 7 ' and R 7 " is connected to form piperidine. In some embodiments, R 7 ' and R 7 " is connected to form tetrahydropyran. In some embodiments, R 7 ' and R 7 " are connected to form a 5-membered substituted or unsubstituted heterocyclic ring. In some embodiments, R 7 ' and R 7 " to form tetrahydrofuran. In some embodiments, R 7 ' and R 7 " connection to form a pyrrolidine.

[0867] In some embodiments, R of Formula I(a), I(c), I(e), and / or I(f)-I(n) 7 ' and R 7 " is different. In some embodiments, R of Formula I(a), I(c), I(e) and / or I(f)-I(n) 7 ' and R 7 "Not H, F, Cl, C 1 -C 5 Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy or C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to the present invention.

[0868] In some embodiments, R of Formula I(a), I(c), I(i), I(j)-I(k), and / or I(n) 7 ” and R 7 are connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring. 7 ” and R 7are connected to form a 5-membered unsubstituted saturated or unsaturated carbocyclic ring. 7 ” and R 7 In some embodiments, R 7 ” and R 7 are connected to form a 6-membered unsubstituted saturated or unsaturated carbocyclic ring. 7 ” and R 7 In some embodiments, R 7 ” and R 7 are connected to form a 5-membered substituted saturated or unsaturated carbocyclic ring. 7 ” and R 7 are connected to form a 6-membered substituted saturated or unsaturated carbocyclic ring. 7 ' and R 7 " are connected to form a 6-membered substituted or unsubstituted, aromatic carbocyclic ring. In some embodiments, R 7 ” and R 7 are connected to form a 5- or 6-membered substituted or unsubstituted aromatic heterocyclic ring. 7 ” and R 7 are connected to form a 5- or 6-membered substituted or unsubstituted heterocyclic ring. 7 ” and R 7 are connected to form a 6-membered substituted or unsubstituted heterocyclic ring. 7 ” and R 7 In some embodiments, R 7 ” and R 7 In some embodiments, R 7 ” and R 7 are connected to form a 5-membered substituted or unsubstituted heterocyclic ring. 7 ” and R 7 In some embodiments, R 7 ” and R 7 Connect to form the pyrrolidine.

[0869] In some embodiments, R of Formula I(a), I(c), I(i), I(j)-I(k), and / or I(n) 7 ” and R 7 In some embodiments, R of I(a), I(c), I(i), I(j)-I(k) and / or I(n) is 7 ” and R 7 Not H, F, Cl, C 1 -C 5Straight chain or branched chain or C 3 -C 8 Cyclic alkoxy, C 1 -C 5 Straight chain or branched chain halogenated alkoxy or C 1 -C 5 Straight or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to the present invention.

[0870] In some embodiments, R of Formula I(a), I(c), I(i), I(j)-I(k), and / or I(n) 7 and R 7 "' is connected to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring. In some embodiments, R 7 and R 7 "' is connected to form a 5-membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 and R 7 "' is connected to form a 6-membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 and R 7 "' is connected to form a 5-membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 and R 7 "' is connected to form a 6-membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R 7 and R 7 "' is connected to form a 6-membered substituted or unsubstituted, aromatic carbocyclic ring. In some embodiments, R 7 and R 7 "' is connected to form a 5- or 6-membered substituted or unsubstituted aromatic heterocyclic ring. In some embodiments, R 7 and R 7 "' is connected to form a 5- or 6-membered substituted or unsubstituted heterocyclic ring. In some embodiments, R 7 and R 7 "' is connected to form a 6-membered substituted or unsubstituted...

Claims

1. A compound represented by the structure of Formula I(k): in Ring W may be an aromatic ring or a non-aromatic ring, If ring W is aromatic, then X2, X3 and X4 are each independently CH, C(R) or N (e.g., C(CH3), C(O-CH2-cyclopropyl), C(O-CH2-methylcyclobutyl), C(O-CH2-3-methyloxetane), C(NH-CH2-cyclopropyl), C(isopropoxy), C(O-CH(CH3)-CH2-O-CH3), C(CH2CH3), C-iPr, C-CH2-cyclopropyl, C(OCH3), C(OCH2CH3), C(O-(CH2)2-O-CH3, C(OCHF2), C(Cl), C(C(O)CH3), C(O-CH2CH2-O-CH3), C(OH)); X 15 is C; and If ring W is non-aromatic, then X2, X3 and X4 are each independently CH2, CH(R), C(R)2, NH, N(R), O, S, S=O or SO2 (e.g., CH2); X 15 is CH, C(R) or N (e.g., CH, N); X5, X6, X7, X8 and X9 are each independently a nitrogen or carbon atom; wherein if any of X5, X6, X7, X8 and X9 is nitrogen, then the corresponding R7′, R7″, R7, R7″′ and R7″″ substitutions are absent; X 10 is N, CH, C(R) or C=O; wherein if X 10 If C=O, then X 11 is N (e.g., C(CH2-OH), C(CH2-CH2-OH), C(NH-CH2-cyclopropyl), C(COOH), C(CH3), C(cyclopropyl), C(isopropoxy)); X 11 is N or C; if X 11 is N, then X 10 is C=O; Ring W' may be an aromatic ring or a non-aromatic ring, If ring W' is aromatic, then X 12 is S, SO2, O, NH, N(R), N-OH, CH=CH, CH=CH(R), C(R)=CH, N=CH, N=C(R), CH=N or C(R)=N (e.g., N-CH2-COOH, N-CH2-CH2-OH, N-CH3, N-CH2CH3, N-iPr, N-cyclopropyl, N-CH2-cyclopropyl); If ring W' is non-aromatic, then X 12 is CH=CH, CH=CH(R), C(R)=CH, OCH2, SCH2, CH=N, C(R)=N, N=CH, N = C (R); Wherein if both ring W and ring W' are aromatic, then at least one of X2, X3 and X4 is C(R); X 11 is N; or X 12 Not S; R5 is H or C1-C5 straight or branched chain alkyl (e.g., methyl); R6 is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-OR 10 (e.g., CH2-O-CH3, (CH2)2-O-CH3, (CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-SR 10 (e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R 10 、-O-R8-R 10 , R8-(substituted or unsubstituted C3-C8 cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2-difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanol, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocycle) (e.g., (CH2)3-piperidine, (CH2)3-4-fluoro-piperidine, (CH2)3-pyran, (CH2)2-pyrazole, (CH2)2-imidazole, CH2-tetrahydrofuran, CH 2-dioxane, CH2-oxetane, CH2-piperidine, CH2-triazole, CH2-1-oxa-8-azaspiro[4.5]decane, (CH2)3-diazabicyclo[2.2.1]heptane, CH2-methyl-THF, CH2-ethyl-piperidine, CH2-oxa-azaspirodecane, (CH2)3-dimethylpyrazole, CH2-2-oxo-methylpyrrolidine, CH2-methyl-azetidine, CH2-azaspiroheptane), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R 10 )、N(R 10 )(R 11 )、R8-N(R 10 )(R 11 )(e.g., (CH2)2-NH2, (CH2)3-N(CH2CH3)2, (CH2)3-N(CH(CH3)2)2, (CH2)3-piperidine, (CH2)3-4-fluoro-piperidine, (CH2)3-4-cyano-piperidine, (CH2)4-NH(CH3), (CH2)3-NH-CH3, (CH2)3-NH-CH2CH3, (CH2)3-N(CH2CH3)2, (CH2)3-NH2, (CH2)3-N(CH2CH3)(CH2CF3)), R9-R8-N(R 10 )(R 11 )(e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 、R8-C(O)-R 10 、C(O)H、C(O)-R 10 (e.g., C(O)CH3), C1-C5 straight or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R 10 )(R 11 )、SO2R、SO2N(R 10 )(R 11 )、CH(CF3)(NH-R 10 ), C1-C5 linear or branched, substituted or unsubstituted alkyl (e.g., CH(CH3)CH2OCH3, CH(CH3)CH2NH2, CH(CH3)C(O)N(CH3)2, CH2-CH(OH)Ph, (CH2)3N(H)CH2CH3, CH(CH3)(CH2)2OH, CH(CH2OH)(CH2CH3), (CH2)3-OCH3, (CH2)2-OCH3, (CH2)2-OCH(CH3)2, CH(CH2OH)(CH2CH(CH3)2), CH2CH(CH3)(OCH3), CH2CH(N(CH3)2)(CH2CH3), benzyl, methyl, ethyl, CH2-OCH2-CH2-O-CH3, CH(CH3)C(O)N(CH3)2), C1-C5 straight or branched, substituted or unsubstituted alkenyl, C1-C5 straight or branched or C3-C8 cyclic haloalkyl, substituted or unsubstituted C1-C5 straight or branched or C3-C8 cyclic haloalkyl, C8 cyclic alkoxy (e.g., methoxy, O—(CH2)2—O—CH3), optionally wherein at least one methylene (CH2) in the alkoxy is replaced by an oxygen atom, C1-C5 straight or branched chain thioalkoxy, C1-C5 straight or branched chain haloalkoxy, C1-C5 straight or branched chain alkoxyalkyl, substituted or unsubstituted C3-C8 cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indene), R8-(substituted or unsubstituted C3-C8 cycloalkyl), substituted or unsubstituted 3-8 membered heterocycle (e.g., piperidine, 1-methyl-piperidine, azetidine, pyrrolidine, pyrrolidone, quinuclidine, tetrahydropyran, azaspiro[3.3]heptane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofuran, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6 and R5 are linked to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide; Or R6 is represented by the structure of formula B or Bi: in m is 0 or 1; and R 12 YesR 20 or C1-C5 C(O)-alkyl, and R 13 YesR 30 ;or R 12 and R 13 All are H; R 12 and R 13 Each is independently H or substituted or unsubstituted C1-C5 alkyl (e.g., ethyl, trifluoroethyl); R 12 and C3 to form ring A, and R 13 YesR 30 ;or R 12 and R 13 connected to form ring B; or R 12 and C1 to form ring C, and R 13 YesR 30 ;or C1 and C3 are connected to form ring D, and R 12 and R 13 Each is independently R 30 ;or R 13 and C2 are connected to form ring E, m is 1, and R 12 YesR 30 ;or R 12 and R 13 connected to form ring B, and C1 and C3 connected to form ring D; in Rings A, C and E are each independently a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring (e.g., A: pyrrolidine, methylpyrrolidine, ethylpyrrolidine); C: piperidine, pyrrolidine, methyl-2-oxopyrrolidine, pyran-pyrrolidine, methyl-azetidine, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, 2-azaspiro[3.3]heptane; E: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, methylpiperidine; Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocycle (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidine, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrrolidine, imidazole, 2-methyl-2,5-diazabicyclo[2.2.1]heptane, hydroxymethyl-pyrrolidine, diazabicyclo[2.2.1]heptane, 6-fluoro-3-azabicyclo[3.1.1]heptane; and Ring D is a substituted or unsubstituted C3-C8 cycloalkyl group (eg, cyclobutane, cyclohexane); R7 is H, F, Cl, Br, I, OH, OR 20 ,SH,R8-OH,R8-SH,SR 10 、-R8-OR 10 、-R8-SR 10 、R8-(C3-C8 cycloalkyl)、CF3、CD3、OCD3、CN、NO2、-CH2CN、-R8CN、NH2、NHR、N(R)2、NH(R 10 )、N(R 10 )(R 11 )、R8-N(R 10 )(R 11 )、R9-R8-N(R 10 )(R 11 ), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 、R8-C(O)-R 10 、C(O)H、C(O)-R 10 , C1-C5 straight or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR (e.g., C(O)NH(CH3)), C(O)N(R 10 )(R 11 )(e.g., C(O)NH(CH3), C(O)NH(CH2CH2OCH3), C(O)NH(CH2CH2OH)), SO2R, SO2N(R 10 )(R 11 )、CH(CF3)(NH-R 10 ), C1-C5 straight chain or branched, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C1-C5 straight chain or branched, substituted or unsubstituted alkenyl, C1-C5 straight chain or branched or C3-C8 cyclic haloalkyl (e.g., CHF2), C1-C5 straight chain or branched or C3-C8 cyclic alkoxy (e.g., methoxy, ethoxy), optionally wherein at least one methylene (CH2) in the alkoxy is replaced by an oxygen atom, C1-C5 straight chain or branched thioalkyl, C1-C5 straight chain or branched thioalkoxy, C1-C5 straight chain or branched haloalkoxy, C1-C5 straight chain or branched alkoxyalkyl, substituted or unsubstituted C3-C8 cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl), substituted or unsubstituted 4-7 membered heterocycle (e.g., morpholine (e.g., 2-morpholine or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-3-ol, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidone, imidazole, pyrazole, piperazine, piperidine, piperidine-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2-oxopyrrolidine, pyridine, 1-methylpyridine), R8- (substituted or unsubstituted single, fused or spiro 3-8 membered heterocycle), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; R7', R7", R7'" and R7"" are each independently H, F, Cl, Br, I, OH, OR 20 ,SH,R8-OH,R8-SH,-R8-OR 10 、R8-(C3-C8 cycloalkyl), R8-(3-8 membered heterocycle), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R 10 )、N(R 10 )(R 11 )、R8-N(R 10 )(R 11 )、R9-R8-N(R 10 )(R 11 ), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R 10 、NHCO-N(R 10 )(R 11 )、COOH、-C(O)Ph、C(O)OR 10 、R8-C(O)-R 10 、C(O)H、C(O)-R 10 、C1-C5 straight chain or branched C(O)-haloalkyl、-C(O)NH2、C(O)NHR、C(O)N(R 10 )(R 11 )、SO2R、SO2N(R 10 )(R 11 )、CH(CF3)(NH-R 10 ), C1-C5 straight chain or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5 straight chain or branched, substituted or unsubstituted alkenyl, C1-C5 straight chain or branched or C3-C8 cyclic haloalkyl (e.g., CHF2), C1-C5 straight chain or branched or C3-C8 cyclic alkoxy (e.g., methoxy), optionally wherein at least one methylene (CH2) in the alkoxy is replaced by an oxygen atom, C1-C5 straight chain or branched, substituted or unsubstituted alkenyl, C1-C5 straight chain or branched or C3-C8 cyclic haloalkyl (e.g., CHF2), C1-C5 straight chain or branched or C3-C8 cyclic alkoxy (e.g., methoxy), a C1-C5 straight chain or branched chain thioalkoxy group, a C1-C5 straight chain or branched chain haloalkoxy group, a C1-C5 straight chain or branched chain alkoxyalkyl group, a substituted or unsubstituted C3-C8 cycloalkyl group (e.g., cyclopropyl, cyclohexyl group), a substituted or unsubstituted 3-8 membered heterocycle (e.g., morpholine, pyran, oxetane, pyrrolidine, imidazole, piperazine, piperidine, dioxazole, 2-oxopyrrolidine), a substituted or unsubstituted aryl group (e.g., phenyl), a substituted or unsubstituted benzyl group; or R7′ and R7″ are linked to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine); or R7″ and R7 are connected to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine); or R7 and R7″′ are linked to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (eg, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine); or R7'" and R7"" are linked to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (eg, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine); R 20 Represented by the following structure: R 30 It is H, R 20 ,F,Cl,Br,I,OH,SH,alkoxy,N(R)2,NH(R 10 )、N(R 10 )(R 11 ), CF3, CN, NO2, C1-C5 straight chain or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5 straight chain or branched alkoxy, C1-C5 straight chain or branched haloalkyl (e.g., CHF2, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)-CH(CH3)2), R8-aryl (e.g., CH2-Ph), -R8-O-R8-OR 10 (e.g., (CH2)2-O-(CH2)2-O-CH3), -R8-OR 10 、-R8-R 10 (e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine)); R is H, F, Cl, Br, I, OH, SH, COOH, CO(R 10 )、C(O)CH3、NH(R 10 ), NH-CH2-cyclopropyl, N(R 10 )(R 11 ), CF3, CN, NO2, C1-C5 straight or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, iPr, CH2-cyclopropyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8 substituted or unsubstituted cycloalkyl, cyclopropyl, substituted or unsubstituted C1-C5 straight or branched alkoxy (e.g., methoxy, ethoxy, O-(CH2CH3), OCHF2, O- (CH2)2-O-CH3, isopropoxy, O-(CH2)-cyclopropyl, O-CH2-methylcyclobutyl, O-CH2-3-methyloxetane, O-CH(CH3)-CH2-O-CH3), C1-C5 straight or branched chain halogenated alkyl (e.g., CHF2, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)-CH(CH3)2), R8-aryl (e.g., CH2-Ph), -R8-O-R8-OR 10 (e.g., (CH2)2-O-(CH2)2-O-CH3), -R8-OR 10 、O-R8-R 10 (e.g., O-(CH2)2-O-CH3, O-(CH2CH3), O-(CH2)-cyclopropyl), -R8-R 10 (e.g., (CH2)-cyclopropyl, (CH2)2-O-CH3, (CH2)-OH, (CH2)2-OH, (CH2)-COOH), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine)); Each R8 is independently [CH2] p Where p is between 1 and 10 (e.g., 1, 2); R9 is [CH] q , [C] q Where q is between 2 and 10; R 10 and R 11 are each independently H, OH, COOH, C1-C5 substituted or unsubstituted straight or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C3-C8 substituted or unsubstituted cycloalkyl (e.g., cyclopropyl), C1-C5 substituted or unsubstituted straight or branched haloalkyl (e.g., CH2CF3), C1-C5 straight or branched alkoxy (e.g., O-CH3), R 20 , C(O)R or S(O)2R; or R 10 and R 11 connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperazine, piperidine), n is an integer between 0 and 4 (eg, 1, 2); or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., a deuterated analog), PROTAC, drug product, or any combination thereof.

2. The compound according to claim 1, wherein R5 is H or CH3.

3. The compound according to claim 1 or 2, wherein R6 is H, C1-C5 straight or branched chain, substituted or unsubstituted alkyl (preferably methyl), substituted or unsubstituted 3-8 membered heterocycle (preferably substituted or unsubstituted piperidine or tetrahydropyran), R8-N (R 10 )(R 11 )(preferably, (CH2)2-NH2, (CH2)3-NH2, (CH2)3-piperidine or (CH2)3-4-fluoro-piperidine), or R6 is represented by a structure of formula Bi.

4. The compound according to claim 3, wherein R 12 and R 13 connected to form a substituted or unsubstituted piperidine ring, or wherein R 10 and R 11 Connected to form a substituted or unsubstituted 3-8 membered heterocyclic ring (eg, piperidine or 4-fluoro-piperidine).

5. A compound according to any one of the preceding claims, wherein R7 is H, C(O)N(R 10 )(R 11 )(preferably, C(O)NH(CH3)), C1-C5 linear or branched, substituted or unsubstituted alkyl (preferably, methyl), substituted or unsubstituted C3-C8 cycloalkyl (preferably, cyclopropanol), substituted or unsubstituted 4-7 membered heterocycle (preferably, morpholine, pyrrolidine, pyrrolidin-3-ol, piperidine, piperidine-4-ol, tetrahydrofuran, oxetane, oxetane-3-ol, pyridine or 1-methylpyridine) or substituted or unsubstituted aryl.

6. A compound according to any one of the preceding claims, wherein R7' is H or F.

7. A compound according to any one of the preceding claims, wherein ring W is aromatic and one of X2, X3 and X4 is C(R); preferably, wherein R is alkoxy, more preferably methoxy.

8. A compound according to any one of the preceding claims, wherein X 12 is O, NH, N(R), CH=N, N=CH, CH=CH, OCH2 or N-OH; preferably, wherein R is C1-C5 straight chain or branched, substituted or unsubstituted alkyl, substituted or unsubstituted C1-C5 straight chain or branched alkoxy, O-R8-R 10 OH, NH(R 10 ), haloalkoxy or cycloalkyl.

9. A compound according to any one of the preceding claims, wherein R is CH2-COOH, CH2-CH2-OH, CH3, CH2CH3, iPr, cyclopropyl or CH2-cyclopropyl.

10. A compound according to any one of the preceding claims, wherein X4 is C(R), and R is alkoxy, preferably methoxy.

11. A compound according to any one of the preceding claims, selected from the following:

12. The compound according to claim 1, which is represented by the structure of Formula I(1): in Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated 3-8 membered heterocyclic or carbocyclic ring (e.g., pyrrolidine, 1-methylpyrrolidine, pyrrolidin-3-ol, pyrrolidin-2-one, pyridine, piperidine, piperidin-4-ol, tetrahydrofuran, morpholine, tetrahydrothiophene, cyclopropyl, oxetane, oxetane-3-ol, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); R1 and R2 are each independently H, F, Cl, Br, I, OH, SH or CF3, substituted or unsubstituted C1-C5 alkyl, C1-C5 linear or branched or C3-C8 cyclic haloalkyl, substituted or unsubstituted C1-C5 linear or branched or C3-C8 cyclic alkoxy; or R1 and R2 are linked to form a 3-8 membered carbocyclic or heterocyclic ring (e.g., cyclopropyl, oxetane); or R2 and R4 are linked to form Ring F as defined above (e.g., pyrrolidine, pyrrolidin-2-one, piperidine, morpholine, pyridine, pyrimidine, triazole, oxadiazole, pyrazole, tetrahydrofuran), wherein if Ring F is aromatic, then R1 and / or R3 are absent; R3 and R4 are each independently H, Me, substituted or unsubstituted C1-C5 alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R8-OR 10 (e.g., (CH2)2-O-CH3), R8-N(R 10 )(R 11 ) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8 cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocycle (e.g., pyrrolidine, methylpyrrolidine, piperidine) or R 20 ; or R3 and R4 are linked to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); and X 14 is S, O, N or CH, where if X 14 is CH, then ring F does not exist, and if X 14 is S or O, then R3 does not exist.

13. The compound according to claim 1 or 12, which is represented by the structure of formula I(m): in X 13 is CH2, CH(R) (e.g., CH-CH3), C(R)2 or C=O; Ring G is absent or is a substituted or unsubstituted 3-8 membered carbocyclic or heterocyclic ring (e.g., cyclobutane, cyclopentane, cyclohexane); R 50 is H, R 20 , F, Cl, Br, I, OH, SH, N(R)2, NH(R 10 ), N(R 10 )(R 11 ), CF3, CN, NO2, C1-C5 straight chain or branched, substituted or unsubstituted alkyl, C1-C5 straight chain or branched alkoxy, C1-C5 straight chain or branched haloalkyl, -R8-R 10 (e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2-pyridine, 3-pyridine and 4-pyridine)).

14. A compound according to any one of claims 12 or 13, wherein X 14 Is O or N.

15. A compound according to any one of claims 12 to 14, wherein R1 is H, or wherein R1 and R2 are linked to form a 3-8 membered carbocyclic or heterocyclic ring (eg, cyclopropyl, oxetane, pyrrolidine).

16. A compound according to any one of claims 12 to 15, wherein R3 is H, substituted or unsubstituted C1-C5 alkyl or absent.

17. A compound according to any one of claims 12 to 16, wherein R2 and R4 are linked to form ring F (preferably, pyrrolidine, piperidine, tetrahydrofuran, pyrrolidin-2-one, pyrrolidin-3-ol, morpholine).

18. A compound represented by any of the following structures:

19. The compound according to any one of the preceding claims, wherein the compound is a substantially pure single stereoisomer.

20. The compound of any one of the preceding claims, wherein the compound is a c-MYC mRNA translation regulator, a c-MYC mRNA transcription regulator, a c-MYC inhibitor, or any combination thereof.

21. A pharmaceutical composition comprising a compound according to any one of the preceding claims and a pharmaceutically acceptable carrier.

22. A compound according to any one of claims 1 to 21 for use in treating, suppressing, reducing the severity of, reducing the risk of developing, or inhibiting cancer in a subject.

23. The compound according to claim 22, wherein the cancer is selected from the following list: breast cancer, ovarian cancer, acute myeloid leukemia, chronic myeloid leukemia, Hodgkin's and Burkitt's lymphoma, diffuse large B-cell lymphoma, prostate cancer, colon cancer, gastric cancer, primary central nervous system lymphoma, glioblastoma, medulloblastoma, melanoma, non-small cell lung cancer, germinal center-derived lymphoma, esophageal squamous cell carcinoma, osteosarcoma, bladder cancer, pancreatic cancer, lung adenocarcinoma, BRAF V600E thyroid cancer, choroid plexus carcinoma, colitis-associated cancer, epithelial ovarian cancer, colorectal cancer, pancreatic cancer, and uterine cancer; wherein the cancer is an early stage cancer, an advanced stage cancer, an invasive cancer, a metastatic cancer, a drug-resistant cancer, or any combination thereof; wherein the subject has been previously treated with chemotherapy, immunotherapy, radiation therapy, biological therapy, surgical intervention, or any combination thereof; wherein the compound is administered in combination with an anti-cancer therapy; or any combination thereof.

24. The compound of claim 23, wherein the anti-cancer therapy is chemotherapy, immunotherapy, radiotherapy, biological therapy, surgical intervention, or any combination thereof.

25. A compound according to any one of claims 1 to 21 for use in suppressing, reducing or inhibiting tumor growth in a subject.

26. A method of regulating c-MYC mRNA translation in a cell or regulating c-MYC mRNA transcription in a cell, the method comprising contacting a compound according to any one of claims 1 to 22 with a cell, thereby regulating c-MYC mRNA translation in the cell or regulating c-MYC mRNA transcription in the cell.

27. The method according to claim 26, wherein the method is carried out as follows: (a) by regulating c-MYC mRNA splicing (inclusion or exclusion of untranslated regions or alternative usage of exons); (b) by regulating c-MYC mRNA modification; (c) by modulating the interaction of RNA binding proteins with c-MYC mRNA, thereby altering mRNA localization; (d) by regulating c-MYC mRNA localization in the cytoplasm; (e) by regulating ribosomes or ribosomal cofactors of c-MYC mRNA; (f) by reducing the amount of c-MYC protein in the cell; or any combination thereof.

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