C-myc mRNA translation modulators and uses thereof in the treatment of cancer

Abstract

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

Description

c-MYC mRNA TRANSLATION MODULATORS AND USES THEREOF IN THE TREATMENT OF CANCER FIELD OF THE INVENTION

[0001] The present invention relates to novel c-MYC mRNA translation modulators, composition and methods of preparation thereof, and uses thereof in the treatment of cancer. BACKGROUND OF THE INVENTION

[0002] Cancer is the second most common cause of death in the United States, exceeded only by heart disease. In the United States, cancer accounts for 1 of every 4 deaths. The 5-year relative survival rate for all cancer patients diagnosed in 1996-2003 is 66%, up from 50% in 1975-1977 (Cancer Facts & Figures American Cancer Society: Atlanta, GA (2008)). The rate of new cancer cases decreased by an average 0.6% per year among men between 2000 and 2009 and stayed the same for women. From 2000 through 2009, death rates from all cancers combined decreased on average 1.8% per year among men and 1.4% per year among women. This improvement in survival reflects progress in diagnosing at an earlier stage and improvements in treatment. Discovering highly effective anticancer agents with low toxicity is a primary goal of cancer research.

[0003] The Myc family includes three major members, the proto-oncogene c-Myc (cellular Myelocytomatosis, short Myc), as well as L-myc and N-myc. These three Myc homologs are involved in the early stages of carcinogenesis and metastatic spread in most human cancers. In most types of tumors Myc gene is not mutated or duplicated, but its mRNA and / or protein levels are increased, indicating that in cancer Myc overexpression is induced at the level of transcription, mRNA steady state levels and translation. Indeed, myc gene expression normally depends on growth factor signaling and both myc mRNA and Myc protein have very short half-lives (of 30 and 20 min respectively) [Dang, C. V. (2012). MYC on the path to cancer. Cell 149, 22–35]. In tumor cells however, the cellular levels of Myc become independent from such signaling and regulation, and the resulting exacerbated Myc function drives intracellular and extracellular transcription programs that allow tumors to grow and thrive. However, Myc does not necessarily need to be overexpressed in order for a cancer to be highly dependent upon its activity. A study from Soucek et al. (Nature (2008) 455(7213):679-83) shows that tumors that express c-Myc at endogenous levels exhibit tumor regression upon Myc inhibition via a genetically engineered system. Therefore, treatment with a Myc inhibitor is not necessarily limited to cancers that overexpress Myc. Compounds according to this invention may also be used to regulate the translation of Myc mRNA, wherein the direct target for the compounds is a protein or RNA which regulate Myc mRNA translation, and as such any tumor which is Myc dependent will benefit from the therapeutic utility of these compounds.

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

[0005] Although Myc gene is a very important oncogene and considered as a driver in carcinogenesis and MYC protein is a key transcription factor broadly targeting various genes, rational designing a direct Myc inhibitor is still challenging. This is mainly because MYC protein lacks structural regions amenable to therapeutic inhibition by small molecules and is considered an undruggable target [BioDrugs (2019) 33:539–553].

[0006] Designing and developing MYC modulators is challenging, primarily because the MYC protein has a disordered structure which lacks a pocket or groove that can act as a binding site for modulators. Interfering with the MYC transcription, blocking the protein–protein interaction (PPI) of MYC and its cofactors, and influencing on signaling pathways related to MYC were used in the past as potential modulatory targets, but failed to be developed as drug candidates. Myc PPI inhibitors failed to show sufficinet efficacy in cell-based assays and animal models due to the requirement of high target occupancy to drive efficacy. Modulators of signaling pathways upstream to myc, for example mTOR modulators, failed due to lack of target specificity.

[0007] Nevertheless, a therapeutic approach to target c-Myc has remained elusive. The absence of a clear ligand-binding domain establishes a formidable obstacle toward direct inhibition, which is a challenging feature shared among many compelling transcriptional targets in cancer. Thus, alternative modalities that target Myc are required, as outlined herein, namely compounds which regulate Myc mRNA translation. SUMMARY OF THE INVENTION

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

[0009] This invention further provides a pharmaceutical composition comprising a compound or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, prodrug, isotopic variants (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof, represented by the structure of formula I(j), I(n) and / or I(o), and by the structures listed in Table 1, as defined herein below, and a pharmaceutically acceptable carrier.

[0010] This invention further provides a method of treating, suppressing, reducing the severity, reducing the risk of developing or inhibiting cancer in a subject, comprising administering a compound represented by the structure of formula I(j), I(n) and / or I(o), and by the structures listed in Table 1, as defined herein below, to a subject suffering from cancer under conditions effective to treat, suppress, reduce the severity, reduce the risk of developing, or inhibit cancer in said subject.

[0011] This invention further provides a method for suppressing, reducing or inhibiting tumor growth in a subject, comprising administering a compound represented by the structure of formula I(j), I(n) and / or I(o), and by the structures listed in Table 1, as defined herein below, to a subject, under conditions effective to suppress, reduce or inhibit tumor growth in said subject. In some embodiment, the tumor is cancerous. In some embodiment, the subject suffers from cancer.

[0012] This invention further provides a method of modulating c-MYC mRNA translation in a cell, comprising contacting a compound represented by the structure of formula I(j), I(n) and / or I(o)and by the structures listed in Table 1, as defined herein below, with a cell, thereby modulating c-MYC mRNA translation in said cell.

[0013] This invention further provides a method of regulating c-MYC mRNA transcription in a cell, comprising contacting a compound represented by the structure of formula I(j), I(n) and / or I(o) and by the structures listed in Table 1, as defined herein below, with a cell, thereby regulating c-MYC mRNA transcription in said cell. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the office upon request and payment of the necessary fee.

[0015] Figure 1 demonstrates how Protein Synthesis Monitoring (PSM) specifically monitors c-Myc synthesis. The assay system comprises human non-small cell lung carcinoma cell line A549, which is expressing high level of c-Myc. Two tRNAs (di-tRNA) which decode one specific glutamine codon and one specific serine codon were transfected with control RNAi or an RNAi directed to c-Myc. The FRET signal specifically monitors c-Myc translation, as the FRET signal in c-Myc siRNA treated cells was inhibited. In blue, cell nuclei stained with DAPI; in yellow, FRET signals from tRNA pair which decodes glutamine-serine di-codons.

[0016] Figure 2 depicts selective regulation of c-Myc translation. The panel demonstrates metabolic labeling in A549 cells, treated with vehicle, general translation inhibitor cycloheximide or anti-c-Myc compound. Treatment with cycloheximide resulted in total inhibition of global protein synthesis, while treatment with tested compound showed no significant effect. In gray, cell nuclei stained with DAPI; in yellow, L-Azidohomoalanine (AHA) metabolic labeling.

[0017] Figure 3 demonstrates that compounds act at the level of mRNA processing / stability. A549 cells were exposed to vehicle, general transcription inhibitor actinomycin D or anti-c-Myc compound. In the upper panel, significant decrease in c-Myc protein level was observed after treatment with either actinomycin D or tested compound. Lower panel shows complete reduction in c-Myc mRNA level as well as transcription sites after treatment with actinomycin D. Treatment with tested compound although reduced c-Myc mRNA levels by 30% without affecting transcription sites. In gray, cell nuclei stained with DAPI; in red, c-Myc protein; in purple, c-Myc mRNA; in yellow, c-Myc transcription sites.

[0018] Figure 4 demonstrates the efficacy of compounds according to this invention in A549 cells.

[0019] Figure 5 demonstrates the in vivo data measured for compound 332. Compound 332 inhibited c-Myc-dependent tumor growth in-vivo. Relative tumor volumes of A549 xenografts in NMRI female nude mice after treatment with compound 3 mg / kg twice a week for 49 days. Error bars represent median ± SEM, n = 10 mice at each time point and analyzed by one-tailed T-TEST in Prism for *p < 0.05 DETAILED DESCRIPTION OF THE INVENTION

[0020] In various embodiments, this invention is directed to a compound represented by the structure of formula (I):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH));R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted, saturated or unsaturated, single fused, bridged or spiro 3-10 membered heterocyclic ring (e.g., piperidine, 1- methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8- azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy- tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide);or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine,thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8- N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10(COO-CH3), R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR (e.g., C(O)NH(CH3)), C(O)N(R10)(R11) (e.g., C(O)NH(CH3), C(O)NH(CH2CH3), C(O)NH(CH2CH2OCH3), C(O)NH(CH2CH2OH)), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, ethoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkyl, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl, bicyclo[1.1.1]pentane), substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 1-methylpyrrolidine, pyrrolidin-2- one, pyrrolidin-3-one, 3-cyanopyrrolidine, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4- fluoropiperidine, oxadiazole, triazole, pyrazole, 2-oxopyrrolidine, 4,7-diazaspiro[2.5]octane, 2,5- diazabicyclo[2.2.1]heptane, piperazine-2-one), R8-(substituted or unsubstituted single, fused or spiro 3- 8 membered heterocyclic ring), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7is represented by the structure of formula A:wherein X1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched or C3-C8cyclic alkoxy;or R1and R2are joined to form =O or a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethylene, aminoethylene), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); wherein if X1is O then R4is absent; R7’ is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3- 8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)- R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3- difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4- ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7and R7’ are joined 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); R20is represented by the following structure:R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3,CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0021] In various embodiments, this invention is directed to a compound represented by the structure of formula I(a):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched or C3-C8cyclic haloalkyl, substituted or unsubstitutedC1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1- methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; orC1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7is O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), CD3, OCD3, NO2, -CH2CN, -R8CN, R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHCO- N(R10)(R11), R8-C(O)-R10, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched thioalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3- methoxypyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, pyrrolidine-3- carbonitrile, 3-cyanopyrrolidine, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4- fluoropiperidine, oxadiazole, triazole, pyrazole, 2-oxopyrrolidine, 4,7-diazaspiro[2.5]octane, 2,5- diazabicyclo[2.2.1]heptane, piperazine-2-one), R8-(substituted or unsubstituted single, fused or spiro 3- 8 membered heterocyclic ring), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7is represented by the structure of formula A:A wherein X1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; or R1and R2are joined to form a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); wherein if X1is O then R4is absent; R7’ is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3- 8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)- R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3- difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4- ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl;or R7and R7’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0022] In various embodiments, this invention is directed to a compound represented by the structure of formula I(b):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R6is F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3), R8-S-R10(e.g., (CH2)3- S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8-R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclobutanol, CH2-difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), (CH2)3-pyran, CH2-tetrahydrofurane, CH2-dioxane, CH2- methyl-THF, CH2-oxa-azaspirodecane, (CH2)3-dimethylpyrazole, CH2-methyl-azetidine, CH2- azaspiroheptane, CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, - C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, - C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., methoxycyclopropyl, methylcyclobutyl, cyclopropyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indenol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine,morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; or R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined 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 a diazabicyclo[2.2.1]heptane; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8- N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10(COO-CH3), R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR (e.g., C(O)NH(CH3)), C(O)N(R10)(R11) (e.g., C(O)NH(CH3), C(O)NH(CH2CH2OCH3), C(O)NH(CH2CH2OH)), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, ethoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkyl, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl, bicyclo[1.1.1]pentane), substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, pyrrolidine-3-carbonitrile, 3-cyanopyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4- carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2-oxopyrrolidine, 4,7-diazaspiro[2.5]octane, 2,5- diazabicyclo[2.2.1]heptane, piperazine-2-one), R8-(substituted or unsubstituted single, fused or spiro 3- 8 membered heterocyclic ring), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7is represented by the structure of formula A:whereinX1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; or R1and R2are joined to form =O or a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethylene, aminoethylene), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); wherein if X1is O then R4is absent; R7’ is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3- 8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)- R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3- difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4- ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7and R7’ are joined 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); R20is represented by the following structure:R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0023] In various embodiments, this invention is directed to a compound represented by the structure of formula I(c):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched or C3-C8cyclic haloalkyl, substituted or unsubstitutedC1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1- methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; orC1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7is Br, I, OH, O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8- N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10(COO-CH3), R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR (e.g., C(O)NH(CH3)), C(O)N(R10)(R11) (e.g., C(O)NH(CH3), C(O)NH(CH2CH2OCH3), C(O)NH(CH2CH2OH)), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched thioalkyl, C1-C5linear or branched thioalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl bicyclo[1.1.1]pentane), substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, 3- cyanopyrrolidine, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3- ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, pyrazole, 2-oxopyrrolidine, 4,7-diazaspiro[2.5]octane, 2,5-diazabicyclo[2.2.1]heptane, piperazine-2-one), R8-(substituted or unsubstituted single, fused or spiro 3-8 membered heterocyclic ring), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7is represented by the structure of formula A:wherein X1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; or R1and R2are joined to form =O or a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethylene, aminoethylene), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); wherein if X1is O then R4is absent; R7’ is F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, - OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein atleast one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; wherein R7’ is different than R7; or R7and R7’ are joined 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); R20is represented by the following structure:R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R;or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 1 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0024] In various embodiments, this invention is directed to a compound represented by the structure of formula I(d):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); wherein at least one of X2, X3, X4, X5, X6, X7, X8, X9or X10is N; R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro- 1H-indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8- N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10(COO-CH3), R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR (e.g., C(O)NH(CH3)), C(O)N(R10)(R11) (e.g., C(O)NH(CH3), C(O)NH(CH2CH2OCH3), C(O)NH(CH2CH2OH)), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl(e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, ethoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkyl, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl bicyclo[1.1.1]pentane), substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, 3-cyanopyrrolidine, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4- fluoropiperidine, oxadiazole, triazole, pyrazole, 2-oxopyrrolidine, 4,7-diazaspiro[2.5]octane, 2,5- diazabicyclo[2.2.1]heptane, piperazine-2-one), R8-(substituted or unsubstituted single, fused or spiro 3- 8 membered heterocyclic ring), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7is represented by the structure of formula A:wherein X1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; or R1and R2are joined to form =O or a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethylene, aminoethylene), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole pyrazole);wherein if X1is O then R4is absent; R7’ is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, - OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7and R7’ are joined 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); R20is represented by the following structure:R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0025] In various embodiments, this invention is directed to a compound represented by the structure of formula I(e):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); R7is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10(COO-CH3), R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR (e.g., C(O)NH(CH3)), C(O)N(R10)(R11) (e.g., C(O)NH(CH3), C(O)NH(CH2CH2OCH3), C(O)NH(CH2CH2OH)), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, ethoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkyl, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl, bicyclo[1.1.1]pentane), substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, 3-cyanopyrrolidine, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4- fluoropiperidine, oxadiazole, triazole, pyrazole, 2-oxopyrrolidine, 4,7-diazaspiro[2.5]octane, 2,5- diazabicyclo[2.2.1]heptane, piperazine-2-one), R8-(substituted or unsubstituted single, fused or spiro 3- 8 membered heterocyclic ring), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7is represented by the structure of formula A:wherein X1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; or R1and R2are joined to form =O or a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethylene, aminoethylene), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20;or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); wherein if X1is O then R4is absent; R7’ is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, - OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7and R7’ are joined 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); R20is represented by the following structure:R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0026] In various embodiments, this invention is directed to a compound represented by the structure of formula I(f):whereinA’ is a 3-8 membered single or fused, saturated, unsaturated or aromatic carbocyclic or heterocyclic ring (e.g., pyrrolidine, piperidine, piperazine, isochroman, 1,2,3,4-tetrahydroisoquinoline, indoline, isoindoline, 1,3-dihydroisobenzofuran, 2,3-dihydro-1H-indene, 1,2,3,4- tetrahydronaphthalene); X2, X3, and X4, are each independently nitrogen or CH; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide; or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8- N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10(COO-CH3), R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR (e.g., C(O)NH(CH3)), C(O)N(R10)(R11) (e.g., C(O)NH(CH3), C(O)NH(CH2CH2OCH3), C(O)NH(CH2CH2OH)), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, ethoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkyl, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl, bicyclo[1.1.1]pentane), substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, 3-cyanopyrrolidine, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4- fluoropiperidine, oxadiazole, triazole, pyrazole, 2-oxopyrrolidine, 4,7-diazaspiro[2.5]octane, 2,5- diazabicyclo[2.2.1]heptane, piperazine-2-one), R8-(substituted or unsubstituted single, fused or spiro 3- 8 membered heterocyclic ring), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7is represented by the structure of formula A:wherein X1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; or R1and R2are joined to form =O or a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethylene, aminoethylene), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); wherein if X1is O then R4is absent; R7’ is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3- 8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)- R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4- ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7and R7’ are joined 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); R20is represented by the following structure:R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0027] In various embodiments, this invention is directed to a compound represented by the structure of formula I(g):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R100is a C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl), R8- OH (e.g., (CH2)2-OH), -R8-O-R10(e.g., (CH2)2-O-CH3), R8-N(R10)(R11) (e.g., (e.g., (CH2)2-NH(CH3), (CH2)2-NH2), R20, or a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., pyrrolidine, piperidine); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph,NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1- methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); or R6is represented by the structure of formula C:wherein k is between 1 and 4; R12and R13are each independedntly H, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., ethyl, isopropyl), R20, or R12and R13are joined to form a substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., piperidine, piperazine, pyrrolidine, oxa-6-azaspiro[3.3]heptane); or R6is represented by the structure of formula Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane);R7’ is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3- 8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)- R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3- difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4- ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; R20is represented by the following structure:R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10;R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0028] In some embodiments, if R100is methyl and R5is H, then R12and R13are not both alkyls. In some embodiments, if R100is methyl and R5is H, then R12and R13cannot be joined to form piperidine.

[0029] In various embodiments, this invention is directed to a compound represented by the structure of formula I(h):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3- one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3-(difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole);R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; or R1and R2are joined to form a 3-8 membered carbocyclic or heterocyclic ring (e.g., cyclopropyl); or R2and R4are joined to form Ring F as defined above (e.g., pyrrolidine, morpholine,1- methylpyrrolidine, pyrrolidine-2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3- methoxypyrrolidine, 3-(difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R1and / or R3are absent; R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R8-O-R10(e.g., (CH2)2-O-CH3), R8-N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, , pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-dioxane, CH2-oxetane, (CH2)3-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1- methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl);R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7’ and R7’’ are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine,piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7' and R7’' are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0030] In various embodiments, this invention is directed to a compound represented by the structure of formula I(i):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-dioxane, CH2-oxetane, (CH2)3-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1- methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H;R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine, dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7, R7’, R7’’, R7’’’ and R7’’’’ are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8- C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g.,morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; with the proviso that at least two of R7, R7’, R7’’, R7’’’ and R7’’’’ are not H; or R7’ and R7’’ are joined 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 R7are joined to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine); or R7and R7’’’ are joined 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 joined to form a 3-8 membered substituted or unsubstituted carbocyclic or heterocyclic ring (e.g., cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0031] In various embodiments, this invention is directed to a compound represented by the structure of formula I(j):wherein X2, X3, and X4, are each independently nitrogen or CH; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); Ring W is a 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3- ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 3-cyanopyrrolidine, 1- methylpyrrolidine, 3-(difluoromethyl)pyrrolidine, 3,3-difluoropyrrolidine, pyrrolidin-2-one, pyrrolidin- 3-one, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2- oxopyrrolidine, cyclopropyl, 2,2-dimethylpyrrolidine, 4-azaspiro[2.4]heptane, pyrrolidin-3-one O- methyl oxime, 2-oxa-5-azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane, 3,3-dimethylmorpholine, 1-methylpiperazine, 4,7-diazaspiro[2.5]octane, bicyclo[1.1.1]pentane, 2,5-diazabicyclo[2.2.1]heptane, piperazine, piperazine-2-one);W1is CH2, C=O or CH(R10) (e.g., CHCH3); R7' and R7’' are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7’ and R7’’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine);R200is H, R20, F, Cl, Br, I, OH, SH, alkoxy, NH2, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2- O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy (e.g., methoxy), C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); or R200and the carbon atom to which it is connected are C=O or CF2; each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0032] In various embodiments, the compound is not (R)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3- (4-fluoropiperidin-1-yl)propyl) benzo[d]imidazo [2,1-b] thiazole-7-carboxamide. In various embodiments, the compound is not (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3-(4-fluoropiperidin- 1-yl)propyl)benzo[d]imidazo[2,1-b]thiazole-7-carboxamide. In various embodiments, the compound is not 2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3-(4-fluoropiperidin-1-yl)propyl) benzo[d]imidazo[2,1- b]thiazole-7-carboxamide.

[0033] In various embodiments, this invention is directed to a compound represented by the structure of formula I(k):wherein X2, X3, and X4, are each independently nitrogen or CH; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); Q1is O, NH or CH2; Q2is C=O, NH or CH2; R7and R7’ are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7and R7’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R200is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy (e.g., methoxy), C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); or R200and the carbon atom to which it is connected are C=O or CF2; each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); t is an integer between 0 and 4 (e.g., 1, 2);or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0034] In various embodiments, the compound is not (R)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3- (4-fluoropiperidin-1-yl)propyl) benzo[d]imidazo [2,1-b] thiazole-7-carboxamide. In various embodiments, the compound is not (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3-(4-fluoropiperidin- 1-yl)propyl)benzo[d]imidazo[2,1-b]thiazole-7-carboxamide. In various embodiments, the compound is not 2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3-(4-fluoropiperidin-1-yl)propyl) benzo[d]imidazo[2,1- b]thiazole-7-carboxamide.

[0035] In various embodiments, this invention is directed to a compound represented by the structure of formula I(l):wherein X2, X3, and X4, are each independently nitrogen or CH; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3-N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted, saturated or unsaturated, single fused, bridged or spiro 3-10 membered heterocyclic ring (e.g., piperidine, 1- methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8- azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy- tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); R7’ and R7'' are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N®2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran,oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7' and R7’' are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R200is H, R20, F, Cl, Br, I, OH, SH, alkoxy, NH2, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2- O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy (e.g., methoxy), C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); or R200and the carbon atom to which it is connected are C=O or CF2; each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10;R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0036] In various embodiments, R6of compound of formula I(l) is H, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane; each represents a separate embodiment according to this invention). In various embodiments, R6is H. . In various embodiments, R6is C1-C5linear or branched, substituted or unsubstituted alkyl. In various embodiments, R6is methyl. In various embodiments, R6is substituted or unsubstituted 3-8 membered heterocyclic ring. In various embodiments, R6is piperidine. In various embodiments, R6is 1- methylpiperidine. In various embodiments, R6is 3-fluoro-1-methylpiperidine. In various embodiments, R6is azetidine. In various embodiments, R6is 1-methyl-azetidine. In various embodiments, R6is morpholine. In various embodiments, R6is tetrahydropyran. In various embodiments, R6is tetrahydrofurane. In various embodiments, R6is 8-methyl-8-azabicyclo[3.2.1]octane. In various embodiments, R6is dioxane. In various embodiments, R6is 1,3-dioxane.

[0037] In various embodiments, this invention is directed to a compound represented by the structure of formula I(m):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); W1is CH2, C=O or CH(R10) (e.g., CHCH3); Ring F is absent or is a substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3- one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3-(difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; or R1and R2are joined to form a 3-8 membered carbocyclic or heterocyclic ring (e.g., cyclopropyl); or R2and R4are joined to form Ring F as defined above (e.g., pyrrolidine, morpholine,1- methylpyrrolidine, pyrrolidine-2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3- methoxypyrrolidine, 3-(difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole), wherein if Ring F is aromatic, then R1and / or R3are absent; R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R8-O-R10(e.g., (CH2)2-O-CH3), R8-N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20;orR3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, , pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); R7’ and R7’’ are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7’ and R7’’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0038] In various embodiments, this invention is directed to a compound represented by the structure of formula I(n):wherein X2, X3, and X4, are each independently nitrogen or CH; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); Ring W is a 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3- ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 3-cyanopyrrolidine, 1-methylpyrrolidine, 3-(difluoromethyl)pyrrolidine, 3,3-difluoropyrrolidine, pyrrolidin-2-one, pyrrolidin- 3-one, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2- oxopyrrolidine, cyclopropyl, 2,2-dimethylpyrrolidine, 4-azaspiro[2.4]heptane, pyrrolidin-3-one O- methyl oxime, 2-oxa-5-azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane, 3,3-dimethylmorpholine, 1-methylpiperazine, 4,7-diazaspiro[2.5]octane, bicyclo[1.1.1]pentane, 2,5-diazabicyclo[2.2.1]heptane, piperazine, piperazine-2-one); W1is CH2, C=O or CH(R10) (e.g., CHCH3); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted, saturated orunsaturated, single fused, bridged or spiro 3-10 membered heterocyclic ring (e.g., piperidine, 1- methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8- azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy- tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); R7' and R7’' are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7’ and R7’’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine);R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R200is H, R20, F, Cl, Br, I, OH, SH, alkoxy, NH2, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2- O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy (e.g., methoxy), C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); or R200and the carbon atom to which it is connected are C=O or CF2; each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0039] In various embodiments, the compound is not (R)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3- (4-fluoropiperidin-1-yl)propyl) benzo[d]imidazo [2,1-b] thiazole-7-carboxamide. In various embodiments, the compound is not (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3-(4-fluoropiperidin- 1-yl)propyl)benzo[d]imidazo[2,1-b]thiazole-7-carboxamide. In various embodiments, the compound is not 2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3-(4-fluoropiperidin-1-yl)propyl) benzo[d]imidazo[2,1- b]thiazole-7-carboxamide.

[0040] In various embodiments, this invention is directed to a compound represented by the structure of formula I(o):wherein X2, X3, and X4are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R1is H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; R2is substituted or unsubstituted C1-C5alkyl (e.g., CH2OH, CH2OCH3), 3-8 membered carbocyclic or heterocyclic ring (e.g., oxetane); or R1and R2are joined to form a 3-8 membered carbocyclic or heterocyclic ring (e.g., cyclopropyl, oxetane); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R8-O-R10(e.g., (CH2)2-O-CH3), R8-N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, , pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran (CH2)2-pyrrazole, (CH2)2-imidazole, CH2-tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted, saturated or unsaturated, single fused, bridged or spiro 3-10 membered heterocyclic ring (e.g., piperidine, 1- methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8- azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy- tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); R7' and R7’' are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7’ and R7’’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R;or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0041] In various embodiments, R7' is F. In various embodiments, R7'' is H. In various embodiments, R1is H. In various embodiments, R2is a substituted C1-C5alkyl. In various embodiments, R2is CH2OH. In various embodiments, R2is CH2OCH3. In various embodiments, R2is 3-8 membered heterocyclic ring. In various embodiments, R2is oxetane. In various embodiments, R2is 3-oxetane or 2-oxetane; each represents a separate embodiment. In various embodiments, R6is H. In various embodiments, R6is C1-C5linear or branched, substituted or unsubstituted alkyl. In various embodiments, R6is methyl. In various embodiments, R6is substituted or unsubstituted, saturated or unsaturated, single fused, bridged or spiro 3-10 membered heterocyclic ring. In various embodiments, R6is substituted or unsubstituted, saturated single 3-8 membered heterocyclic ring. In various embodiments, the heterocyclic ring is tetrahydropyrane. In various embodiments, R7' is F, R1is H and R6is unsubstituted C1-C5linear or branched, alkyl or substituted or unsubstituted, saturated single 3-8 membered heterocyclic ring. In various embodiments, R7' is F, R1is H and R6is methyl.

[0042] In various embodiments, this invention is directed to a compound represented by the structure of formula (II):wherein X2, X3, and X4, are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R5is H or C1-C5linear or branched alkyl (e.g. methyl);R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10(e.g., CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2), R8-S-R10(e.g., (CH2)3-S-(CH2)2CH3), R8-NHC(O)-R10, -O-R8- R10, R8-(substituted or unsubstituted C3-C8cycloalkyl) (e.g., CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring) (e.g., (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11) (e.g., (CH2)3-4-fluoro-piperidine, (CH2)3-N(CH2CH3)2, (CH2)3- N(CH(CH3)2)2, (CH2)3-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)), R8-C(O)N(R10)(R11) (e.g., (CH2)2-C(O)- piperidine), R9-R8-N(R10)(R11) (e.g., (CH2)2-C(O)-piperidine), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear 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-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, O-(CH2)2-O-CH3), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H- indenol), R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1- methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane), substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), substituted or unsubstituted benzyl; or R6and R5are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring (e.g., azepane, piperazine, 2-(piperazin-1-yl)acetamide); or R6is represented by the structure of formula B or Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring 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 heterocyclic ring (B: piperidine, piperidin-2-one, 4-fluoropiperidin-2-one, piperidine- 4-carbonitrile, 4-fluoropiperidine, 4-fluoro-2-methylpiperidine, methyl-piperidin, fluoropiperidine, difluoropiperidine, pyrrolidine, piperazine, methylpyrrolidine, thiomorpholine 1,1-dioxide, 2-oxa-6-azaspiro[3.3]heptane, methyl-piperazine,dimethyl-pyrazole, 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-C8cycloalkyl (e.g., cyclobutane, cyclohexane); R7is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8- N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10(COO-CH3), R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR (e.g., C(O)NH(CH3)), C(O)N(R10)(R11) (e.g., C(O)NH(CH3), C(O)NH(CH2CH3), C(O)NH(CH2CH2OCH3), C(O)NH(CH2CH2OH)), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methylimidazole, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy, ethoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkyl, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclopropanol, cyclohexyl, bicyclo[1.1.1]pentane), substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 1-methylpyrrolidine, pyrrolidin-2- one, pyrrolidin-3-one, 3-cyanopyrrolidine, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4- fluoropiperidine, oxadiazole, triazole, pyrazole, 2-oxopyrrolidine, 4,7-diazaspiro[2.5]octane, 2,5- diazabicyclo[2.2.1]heptane, piperazine-2-one), R8-(substituted or unsubstituted single, fused or spiro 3- 8 membered heterocyclic ring), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7is represented by the structure of formula A:wherein X1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy;or R1and R2are joined to form =O or a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethylene, aminoethylene), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); wherein if X1is O then R4is absent; R7’ is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3- 8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)- R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3- difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4- ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7and R7’ are joined 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); R20is represented by the following structure:R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3,CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

[0043] In some embodiments, X2of formula I, II and / or I(a)-I(o) is a nitrogen atom. In other embodiments, X2is a CH.

[0044] In some embodiments, X3of formula I, II and / or I(a)-I(o) is a nitrogen atom. In other embodiments, X3is a CH.

[0045] In some embodiments, X4of formula I, II and / or I(a)-I(o) is a nitrogen atom. In other embodiments, X4is a CH.

[0046] In some embodiments, X5of formula I, II, I(a)-I(i), I(m) and / or I(o) is a nitrogen atom. In other embodiments, X5is a carbon atom.

[0047] In some embodiments, X6of formula I, II, I(a)-I(i), I(m) and / or I(o) is a nitrogen atom. In other embodiments, X6is a carbon atom.

[0048] In some embodiments, X7of formula I, II and / or I(a)-I(e) is a nitrogen atom. In other embodiments, X7is a carbon atom.

[0049] In some embodiments, X8of formula I, II, I(a)-I(i), I(m) and / or I(o) is a nitrogen atom. In other embodiments, X8is a carbon atom.

[0050] In some embodiments, X9of formula I, II, I(a)-I(i), I(m) and / or I(o) is a nitrogen atom. In other embodiments, X9is a carbon atom.

[0051] In some embodiments, X10of formula I, II and / or I(a)-I(o) is a nitrogen atom. In other embodiments, X10is N. In other embodiments, X10is CH. In other embodiments, X10is C(R), wherein R is as defined below. In other embodiments, X10is C(R), wherein R is an alkyl. In other embodiments, X10is C(R), wherein R is a methyl. In other embodiments, X10is C(R), wherein R is a cycloalkyl. In other embodiments, X10is C(R), wherein R is a cyclopropyl. In other embodiments, X10is C(R), wherein R is a COOH. In other embodiments, X10is C(R), wherein R is N(H)R10; and R10is a substituted alkyl. In other embodiments, X10is C(N(H)(CH2-cyclopropyl)). In other embodiments, X10is C(R), wherein R is a substituted alkyl. In other embodiments, X10is C(R), wherein R is CH2-OH. In other embodiments, X10is C(R), wherein R is CH2-CH2-OH. In other embodiments, X10is C(R), wherein R is an alkoxy. In other embodiments, X10is C(R), wherein R is a isopropoxy.

[0052] In some embodiments, at least one of X2, X3, X4, X5, X6, X7, X8and X9of formula I, II, I(a)-I(e) is a nitrogen atom. In some embodiments, at least one of X2, X3, X4, X5, X6, X8and X9of formula I, II, I(a)-I(e), I(g)-I(i), I(m) and / or I(o) is a nitrogen atom. In some embodiments, at least one of X2, X3, X4, X5, X6, X7, X8and X9of formula I(d) is a nitrogen atom. In some embodiments, at least one of X2, X3, X4, X5, X6, X7, X8, X9and X10of formula I(d) is a nitrogen atom.

[0053] In some embodiments, at least one of X2, X3, X4, and X10of formula I, II and / or I(a)-I(o) is a nitrogen atom. In some embodiments, at least one of X2, X3, X4and X10of formula I(d) is a nitrogen atom. In some embodiments, at least one of X5, X6, X8and X9of formula I, II and / or I(a)-I(o) is a nitrogen atom.

[0054] In some embodiments, R5of formula I, II, I(a)-I(d), I(f)-I(i), I(l), I(n) and / or I(o) is H. In other embodiments, R5is C1-C5linear or branched alkyl. In other embodiments, R5is methyl. In other embodiments, R5is methyl, ethyl, propyl, isopropyl, butyl, t-butyl, iso-butyl, pentyl, neopentyl; each represents a separate embodiment according to this invention.

[0055] In some embodiments, R5and R6of formula I, II, I(a)-I(i) and / or I(l) are joined to form a substituted or unsubstituted 5-8 membered heterocyclic ring. In some embodiments, R5and R6are joined to form a substituted 5-8 membered heterocyclic ring. In some embodiments, R5and R6are joined 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 this invention. In some embodiments, the heterocyclic ring is substituted with at least one substitutionselected from: F, Cl, Br, I, CF3, R20, C1-C5linear or branched alkyl, C1-C5linear or branched haloalkyl, OH, alkoxy , R8-OH (e.g., CH2-OH), OMe, amide , C(O)N(R)2, C(O)N(R10)(R11), R8-C(O)N(R10)(R11), C(O)-pyrrolidine, C(O)-piperidine, N(R)2, NH(R10), N(R10)(R11), N(CH3)2, NH2, CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl , cyclobutanol, substituted or unsubstituted 3- 8 membered heterocyclic ring, which may be saturated, unsaturated, aromatice, single fused or spiral, pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole, halophenyl, (benzyloxy)phenyl, CN, and NO2; each is a separate embodiment according to this invention. In some embodiments, the heterocyclic ring of formula I(e) is not substituted with CO2-R.

[0056] In some embodiments, R6of formula I, II, I(a)-I(d), I(f)-I(i), I(l), I(n), and / or I(o) is H. In other embodiments, R6is H, F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10, CH2-O-CH3, (CH2)2-O-CH3(CH2)3-O-CH3, (CH2)2-O-CH(CH3)2, R8-S-R10, (CH2)3-S-(CH2)2CH3, R8-NHC(O)-R10, -O-R8-R10, R8- (substituted or unsubstituted C3-C8cycloalkyl), CH2-cyclopropyl, CH2-cyclobutanol, CH2- difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), R8-(substituted or unsubstituted, saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring), (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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(R10), N(R10)(R11), R8-N(R10)(R11), (CH2)3-N(CH2CH3)2, (CH2)3-N(CH(CH3)2)2, (CH2)3-piperidine, (CH2)3-4- fluoro-piperidine, (CH2)3-piperidine-2-one, (CH2)3-4-cyano-piperidine, (CH2)3-4-trifluoromethyl- 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), R8-C(O)N(R10)(R11), (CH2)2-C(O)-piperidine, R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8- C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl, 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, propyl, iso-propyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, CH2-OCH2-CH2-O-CH3, CH(CH3)C(O)N(CH3)2, C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy methoxy, optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, O-(CH2)2-O-CH3, C1-C5linear or branched thioalkoxy, C1- C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3- C8cycloalkyl, cyclopropyl, cyclobutyl, cyclohexyl, 4,4-difluorocyclohexane, methoxycyclopropyl, methylcyclobutyl, cyclopropyl, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3-dihydro-1H-indenol,R8-(substituted or unsubstituted C3-C8cycloalkyl), substituted or unsubstituted saturated or unsaturated, single fused, bridged or spiro 3-10 membered carbocyclic or heterocyclic ring, piperidine (2, 3, or 4- piperidine), 1-methylpiperidine (e.g., 1-methyl-3-piperidine, 1-methyl-4-piperidine), 3-fluoro-1- methylpiperidine, 1-(2,2,2-trifluoroethyl)piperidine, azetidine, 1-methyl-azetidine (e.g., 1-methyl-3- azetidine), morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran (e.g., 4 or 3- tetrahydropyrane), tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane, 4,4-difluorocyclohexane, substituted or unsubstituted aryl, substituted or unsubstituted R8-aryl (e.g., benzyl), or substituted or unsubstituted benzyl; each represents a separate embodiment according to this invention. In some embodiments, R6may be further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear 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(R10), N(R10)(R11), N(CH3)2, NH2, CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl , cyclobutanol, substituted or unsubstituted 3-8 membered heterocyclic ring pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole, C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), halophenyl, (benzyloxy)phenyl, CN, and NO2; each represents a separate embodiment according to this invention. In some embodiments, R6is H. In some embodiments, R6is -R8-O-R10. In some embodiments, R6is CH2-O-CH3. In some embodiments, R6is R8-S-R10. In some embodiments, R6is (CH2)3-S-(CH2)2CH3. In some embodiments, R6is R8-NHC(O)-R10. In some embodiments, R6is (CH2)3- NHC(O)-R10. In some embodiments, R6is (CH2)-NHC(O)-R10. In some embodiments, R6is R8- (substituted or unsubstituted C3-C8cycloalkyl). Examples of R8-(substituted or unsubstituted C3-C8cycloalkyl) include but not limited to: CH2-cyclobutanol, CH2-difluorocyclopropyl, CH2- methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, and CH2-cyclohexanol; each represents a separate embodiment according to this invention. In some embodiments, R6is R8- (substituted or unsubstituted saturated, unsaturated or aromatic, single, fused or spiro 3-8 membered heterocyclic ring). In some embodiments, R6is R8-(substituted or unsubstituted saturated, single 3-8 membered heterocyclic ring). In some embodiments, R6is R8-(substituted or unsubstituted unsaturated, single 3-8 membered heterocyclic ring). In some embodiments, R6is (CH2)3-4-fluoro-piperidine. In some embodiments, R6is R8-(substituted or unsubstituted aromatic, single 3-8 membered heterocyclic ring). In some embodiments, R6is R8-(substituted or unsubstituted saturated, fused 3-8 membered heterocyclic ring). In some embodiments, R6is R8-(substituted or unsubstituted unsaturated, fused 3-8 membered heterocyclic ring). In some embodiments, R6is R8-(substituted or unsubstituted aromatic, fused 3-8 membered heterocyclic ring). In some embodiments, R6is R8-(substituted or unsubstituted spiro 3-8 membered heterocyclic ring). Examples of R8-(substituted or unsubstituted saturated, unsaturated or aromatic, single, fused or spiro 3-8 membered heterocyclic ring) include but not limited to: (CH2)3-4-fluoro-piperidine, (CH2)3-pyran, (CH2)2-pyrrazole, (CH2)2-imidazole, CH2- tetrahydrofurane, CH2-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, and CH2-azaspiroheptane. In some embodiments, R6is NH2. In some embodiments, R6is NHR. In some embodiments, R6is N(R)2. In some embodiments, R6is NH(R10). In some embodiments, R6is N(R10)(R11). In some embodiments, R6is R8-N(R10)(R11). In some embodiments, R8-N(R10)(R11) includes but not limited to: (CH2)3-N(CH2CH3)2, (CH2)3-N(CH(CH3)2)2, (CH2)3-piperidine, (CH2)4- NH(CH3), (CH2)3-NH-CH3, (CH2)3-NH-CH2CH3, (CH2)3-N(CH2CH3)2, (CH2)3-NH2, and (CH2)3- N(CH2CH3)(CH2CF3). In some embodiments, R6is R8-C(O)N(R10)(R11) such as (CH2)2-C(O)- piperidine. In some embodiments, R6is C1-C5linear or branched, substituted or unsubstituted alkyl. Examples of C1-C5linear or branched, substituted or unsubstituted alkyl include but not limited to: 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), CH(CH3)C(O)N(CH3)2, benzyl, methyl, ethyl, and CH2-OCH2-CH2-O-CH3. In some embodiments, R6is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, substituted or unsubstituted C3- C8 cycloalkyl include: cyclopropyl, cyclobutyl, cyclohexyl, methoxycyclopropyl, methylcyclobutyl, aminomethyl-cyclobutyl, methoxycyclobutyl and 2,3-dihydro-1H-indeno. In some embodiments, R6is R8-(substituted or unsubstituted C3-C8cycloalkyl). In some embodiments, R6is substituted or unsubstituted saturated or unsaturated, single fused, bridged or spiro 3-10 membered carbocyclic or heterocyclic ring. In some embodiments, the ring may be further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear 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(R10), N(R10)(R11), N(CH3)2, NH2, CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl , cyclobutanol, substituted or unsubstituted 3-8 membered heterocyclic ring pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole, C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), halophenyl, (benzyloxy)phenyl, CN, and NO2; each represents a separate embodiment according to this invention. In some embodiments, R6is substituted or unsubstituted saturated or unsaturated, single fused, bridged or spiro 3-10 membered heterocyclic ring. In some embodiments, R6is substituted or unsubstituted saturated, unsaturated or aromatic, single, fused or spiro 3-10 membered heterocyclic ring. In some embodiments, R6is substituted or unsubstituted saturated, unsaturated or aromatic, single 3-10 membered heterocyclic ring. In some embodiments, R6is substituted or unsubstituted saturated single 3-10 membered heterocyclic ring. In some embodiments, the ring is piperidine, 1-methylpiperidine, 3- fluoro-1-methylpiperidine, 1-(2,2,2-trifluoroethyl)piperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy-tetrahydrofurane, azepan-2-one, azabicyclohexane; each represents a separate embodiment according to this invention. In some embodiments, R6is substituted orunsubstituted saturated or unsaturated, single fused, bridged or spiro 3-10 membered carbocyclic ring. In some embodiments, R6is 4,4-difluorocyclohexane. In some embodiments, R6is substituted or unsubstituted R8-aryl, such as benzyl. In some embodiments, R6may be further substituted by at least one substitution selected from: F, Cl, Br, I, CF3, R20, C1-C5linear or branched alkyl, C1-C5linear or branched haloalkyl, OH, alkoxy , R8-OH (e.g., CH2-OH), OMe, amide , C(O)N(R)2, C(O)N(R10)(R11), R8-C(O)N(R10)(R11), C(O)-pyrrolidine, C(O)-piperidine, N(R)2, NH(R10), N(R10)(R11), N(CH3)2, NH2, CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl , cyclobutanol, substituted or unsubstituted 3-8 membered heterocyclic ring, which may be saturated, unsaturated, aromatice, single fused or spiral, pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole, C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), halophenyl, (benzyloxy)phenyl, CN, and NO2; each is a separate embodiment according to this invention.

[0057] In some embodiments, R6of formula I(n) and / or I(o) is H. In some embodiments, R6is CD3. In some embodiments, R6is C1-C5linear or branched alkyl. In some embodiments, R6is methyl. In some embodiments, R6is ethyl. In some embodiments, R6is iso-propyl. In some embodiments, R6is substituted or unsubstituted, saturated or unsaturated, single fused, bridged or spiro 3-10 membered heterocyclic ring. In some embodiments, R6is unsubstituted single 3-8 membered heterocyclic ring. In some embodiments, R6is piperidine. In some embodiments, R6is 4-piperidine. In some embodiments, R6is azetidine. In some embodiments, R6is morpholine. In some embodiments, R6is tetrahydropyran. In some embodiments, R6is tetrahydrofurane. In some embodiments, R6is dioxane. In some embodiments, R6is 1,3-dioxane. In some embodiments, R6is pyrrolidine. In some embodiments, R6is substituted single 3-8 membered heterocyclic ring. In some embodiments, R6is 1-methylpiperidine. In some embodiments, R6is 3-fluoro-1-methylpiperidine. In some embodiments, R6is 1-methyl-azetidine. In some embodiments, R6is trifluoromethyl-oxetane. In some embodiments, R6is hydroxy- tetrahydrofurane. In some embodiments, R6is 1-(2,2,2-trifluoroethyl)piperidine. In some embodiments, R6is substituted or unsubstituted, unsaturated, single 3-8 membered heterocyclic ring. In some embodiments, R6is pyrrolidinone. In some embodiments, R6is imidazole. In some embodiments, R6is azepan-2-one. In some embodiments, R6is substituted or unsubstituted, saturated bridged 3-10 membered heterocyclic ring. In some embodiments, R6is quinuclidine. In some embodiments, R6is 8- methyl-8-azabicyclo[3.2.1]octane. In some embodiments, R6is azabicyclohexane. In some embodiments, R6is substituted or unsubstituted, saturated spiro 3-10 membered heterocyclic ring. In some embodiments, R6is azaspiro[3.3]heptane. In some embodiments, R6is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, R6is cyclopropyl In some embodiments, R6is 4,4- difluorocyclohexane.

[0058] In some embodiments, R6and R5of formula I, II, I(a)-I(i), I(l), I(n) and / or I(o) are joined 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 this invention. In some embodiments, the ring may be further substituted by at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0059] In some embodiments, R6of formula I, II and / or I(a)-I(i) is represented by the structure of formula B:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; or R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); or R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring A, C and E are each independently a substituted or unsubstituted single spiro or fused 3-8 membered heterocyclic rings; Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring; and Ring D is a substituted or unsubstituted C3-C8cycloalkyl;

[0060] In some embodiments, formula B is represented by formula Bi.

[0061] In some embodiments, R6of formula I, II and / or I(a)-I(i) is represented by the structure of formula Bi:wherein m is 0 or 1; and R12is R20or C1-C5C(O)-alkyl, and R13is R30; or R12and R13are both H; or R12and R13are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl); or R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined to form ring B; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D; wherein Ring A, C and E are each independently a substituted or unsubstituted single spiro or fused 3-8 membered heterocyclic rings; Ring B is a substituted or unsubstituted single, spiro or fused 3-8 membered heterocyclic ring; and Ring D is a substituted or unsubstituted C3-C8cycloalkyl;

[0062] In some embodiments, R12of formula B and / or Bi is H. In some embodiments, R12is R20. In other embodiments, R12is R30. In some embodiments, R12is C1-C5C(O)-alkyl. In some embodiments, R12is substituted or unsubstituted C1-C5alkyl. In some embodiments, R12is unsubstituted C1-C5alkyl. In some embodiments, the alkyl is ethyl. In some embodiments, R12is substituted C1-C5alkyl. In some embodiments,the alkyl is trifluoroethyl.

[0063] In some embodiments, R13of formula B and / or Bi is H. In other embodiments, R13is R30. In some embodiments, R13is substituted or unsubstituted C1-C5alkyl. In some embodiments, R13is unsubstituted C1-C5alkyl. In some embodiments, the alkyl is ethyl. In some embodiments, R13is substituted C1-C5alkyl. In some embodiments,the alkyl is trifluoroethyl.

[0064] In some embodiments, R6of formula I, II and / or I(a)-I(i) is represented by formula B. In some embodiments, R12of formula B is R20or C1-C5C(O)-alkyl, and R13is R30. In some embodiments, R12and R13of formula B are both H. In some embodiments R and R of formula B are each independentlyH or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl). In some embodiments, R12and R13of formula B are each independently H or trifluoroethyl. In some embodiments, R12and C3 of formula B are joined to form ring A and R13is R30. In some embodiments, R12and R13of formula B are joined to form ring B. In some embodiments, R12and C1 of formula B are joined to form ring C and R13is R30. In some embodiments, C1 and C3 of formula B are joined to form ring D and R12and R13of formula B are each independently R30. In some embodiments, R13and C2 of formula B are joined to form ring E, m is 1, and R12of formula B is R30. In some embodiments, R12and R13of formula B are joined to form ring B and C1 and C3 of formula B are joined to form ring D.

[0065] In some embodiments, R6of formula I, II and / or I(a)-I(h) is represented by formula Bi. in some embodiments, R12of formula Bi is R20or C1-C5C(O)-alkyl, and R13is R30. In some embodiments, R12and R13of formula Bi are both H. In some embodiments, R12and R13of formula Bi are each independently H or substituted or unsubstituted C1-C5alkyl (e.g., ethyl, trifluoroethyl). In some embodiments, R12and R13of formula Bi are each independently H or trifluoroethyl. In some embodiments, R12and C3 of formula Bi are joined to form ring A and R13is R30. In some embodiments, R12and R13of formula Bi are joined to form ring B. In some embodiments, R12and C1 of formula Bi are joined to form ring C and R13is R30. In some embodiments, C1 and C3 of formula Bi are joined to form ring D and R12and R13of formula Bi are each independently R30. In some embodiments, R13and C2 of formula Bi are joined to form ring E, m is 1, and R12of formula Bi is R30. In some embodiments, R12and R13of formula Bi are joined to form ring B and C1 and C3 of formula Bi are joined to form ring D.

[0066] In some embodiments, R6of formula I(g) is represented by the structure of formula C:wherein k is an integer number between 1 and 4; R12and R13are each independedntly H, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., ethyl, isopropyl), R20, or R12and R13are joined to form a substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., piperidine, piperazine, pyrrolidine, oxa-6-azaspiro[3.3]heptane).

[0067] In some embodiments, k of formula C is 1. In some embodiments, k is 2. In some embodiments, k is 3. In some embodiments, k is 4.

[0068] In some embodiments, R12and R13of formula C are each independently H, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., ethyl, isopropyl) or R20; each represents a separate embodiment according to this invention. In some embodiments, R12and R13of formula C are bothethyls. In some embodiments, R12and R13of formula C are both isopropyls. In some embodiments, R12and R13of formula C are both alkyls.

[0069] In some embodiments, R12and R13of formula C are joined to form a substituted or unsubstituted 4-7 membered heterocyclic ring. In some embodiments, R12and R13of formula C are joined to form a piperidine, piperazine, pyrrolidine, oxa-6-azaspiro[3.3]heptane; each represents a separate embodiment according to this invention. in some embodiments the heterocyclic ring maybe further substituted with at least one substitution as defined herein for heterocyclic rings.

[0070] In some embodiments, R6of formula I(b) is represented by formula Bi and / or B and R12of formula Bi and / or B is R20or C1-C5C(O)-alkyl, and R13of formula Bi and / or B is R30; or R12and R13are both H, or R12and R13are each independently H or trifluoroethyl; or R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined 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 a diazabicyclo[2.2.1]heptane; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D.

[0071] In some embodiments, R6of formula I(b) is represented by formula Bi and / or B and R12of formula Bi and / or B is R20or C1-C5C(O)-alkyl, and R13of formula Bi and / or B is R30; or R12and C3 are joined to form ring A and R13is R30; or R12and R13are joined 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 a diazabicyclo[2.2.1]heptane; or R12and C1 are joined to form ring C and R13is R30; or C1 and C3 are joined to form ring D and R12and R13are each independently R30; or R13and C2 are joined to form ring E, m is 1, and R12is R30; or R12and R13are joined to form ring B and C1 and C3 are joined to form ring D.

[0072] In some embodiments, ring A of formula Bi, is a substituted or unsubstituted single spiro or fused 3-8 membered heterocyclic ring. In some embodiments, ring A, is an unsubstituted single 3-8 membered heterocyclic ring. In some embodiments, ring A, is an unsubstituted spiro 3-8 membered heterocyclic ring. In some embodiments, ring A, is an unsubstituted fused 3-8 membered heterocyclic ring. In some embodiments, ring A, is a substituted single 3-8 membered heterocyclic ring. In some embodiments, ring A, is a substituted spiro 3-8 membered heterocyclic ring. In some embodiments, ringA, is a substituted fused 3-8 membered heterocyclic ring. 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 this invention. In some embodiments, ring A is: pyrrolidine, methylpyrrolidine, or ethylpyrrolidine; each represents a separate embodiment according to this invention.

[0073] 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, methyl-azetidine, imidazole, azabicyclooctane, 2-azabicyclo[2.1.1]hexane, or 2-azaspiro[3.3]heptane, diazabicyclo[2.2.1]heptane, 2- methyl-2,5-diazabicyclo[2.2.1]heptane, thiomorpholine, or 1,1-dioxide-2-oxa-6-azaspiro[3.3]heptane; each represents a separate embodiment according to this invention. In some embodiments, ring B is: piperidine, methyl-piperidin, 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 represents a separate embodiment according to this invention.

[0074] In some embodiments, ring C of formula Bi, is a substituted or unsubstituted single spiro or fused 3-8 membered heterocyclic ring. In some embodiments, ring C, is an unsubstituted single 3-8 membered heterocyclic ring. In some embodiments, ring C, is an unsubstituted spiro 3-8 membered heterocyclic ring. In some embodiments, ring C, is an unsubstituted fused 3-8 membered heterocyclic ring. In some embodiments, ring C, is a substituted single 3-8 membered heterocyclic ring. In some embodiments, ring C, is a substituted spiro 3-8 membered heterocyclic ring. In some embodiments, ring C, is a substituted fused 3-8 membered heterocyclic ring. 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 this 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 this invention.

[0075] In some embodiments, ring D of formula Bi, is a substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, ring D, is a substituted C3-C8cycloalkyl. In some embodiments, ring D, is an unsubstituted C3-C8cycloalkyl. In some embodiments, ring D is cyclopropane, cyclobutane, cyclopentane, cyclohexane or cycloheptane; each represents a separate embodiment according to this invention.

[0076] In some embodiments, ring E of formula Bi, is a substituted or unsubstituted single spiro or fused 3-8 membered heterocyclic ring. In some embodiments, ring E, is an unsubstituted single 3-8 membered heterocyclic ring. In some embodiments, ring E, is an unsubstituted spiro 3-8 membered heterocyclic ring. In some embodiments, ring E, is an unsubstituted fused 3-8 membered heterocyclic ring. In some embodiments, ring E, is a substituted single 3-8 membered heterocyclic ring. In some embodiments, ring E, is a substituted spiro 3-8 membered heterocyclic ring. In some embodiments, ring E, is a substituted fused 3-8 membered heterocyclic ring. 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 this invention. In some embodiments, ring E is: pyrrolidine, azetidine, ethylpyrrolidine, oxopyrrolidine, or methylpiperidine; each represents a separate embodiment according to this invention.

[0077] In some embodiments, R6of formula I(b) is F, Cl, Br, I, OH, SH, R8-OH, R8-SH, -R8-O-R10, CH2-O-CH3, R8-S-R10, (CH2)3-S-(CH2)2CH3, R8-NHC(O)-R10, -O-R8-R10, R8-(substituted or unsubstituted C3-C8cycloalkyl), CH2-cyclobutanol, CH2-difluorocyclopropyl, CH2-methylcyclopropyl, CH2-dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol, (CH2)3-pyran, CH2- tetrahydrofurane, CH2-dioxane, CH2-methyl-THF, CH2-oxa-azaspirodecane, CH2-azaspiroheptane, (CH2)3-dimethylpyrazole, CH2-methyl-azetidine, CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl, 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, iso-propyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, CH2-OCH2-CH2-O-CH3, C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy, methoxy, O- (CH2)2-O-CH3), substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear orbranched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl, methoxycyclopropyl, methylcyclobutyl, cyclopropyl, cyclobutyl, cyclohexyl, 4,4-difluorocyclohexane, aminomethyl-cyclobutyl, methoxycyclobutyl, 2,3- dihydro-1H-indenol, substituted or unsubstituted saturated or unsaturated, single fused, bridged or spiro 3-10 membered carbocyclic or heterocyclic ring , piperidine, 1-methylpiperidine, 3-fluoro-1- methylpiperidine, 1-(2,2,2-trifluoroethyl)piperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8- methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy- tetrahydrofurane, azepan-2-one, azabicyclohexane, 4,4-difluorocyclohexane, substituted or unsubstituted aryl, or substituted or unsubstituted benzyl; each represents a separate embodiment according to this invention. In some embodiments, R6may be further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear 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(e.g., N(CH3)2, NH2), NH(R10), N(R10)(R11), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), halophenyl, (benzyloxy)phenyl, CN, and NO2; each represents a separate embodiment according to this invention.

[0078] In some embodiments, R6of formula I(b) and / or I(l) is -R8-O-R10. In some embodiments, -R8- O-R10is CH2-O-CH3. In some embodiments, R6is R8-S-R10. In some embodiments, R8-S-R10is (CH2)3- S-(CH2)2CH3. In some embodiments, R6is R8-NHC(O)-R10. In some embodiments, R6is R8-(substituted or unsubstituted C3-C8cycloalkyl). In some embodiments, the R8-(substituted or unsubstituted C3-C8cycloalkyl) is CH2-cyclobutanol, CH2-difluorocyclopropyl, CH2-methylcyclopropyl, CH2- dimethylamino-cyclohexyl, (CH2)2-cyclopentanole, CH2-cyclohexanol), (CH2)3-pyran, CH2- tetrahydrofurane, CH2-dioxane, CH2-methyl-THF, CH2-oxa-azaspirodecane, (CH2)3-dimethylpyrazole, CH2-methyl-azetidine, or CH2-azaspiroheptane; each represents a separate embodiment according to this invention. In some embodiments, R6is C1-C5linear or branched, substituted or unsubstituted alkyl. In some embodiments, R6is C1-C5linear or branched, substituted alkyl. In some embodiments, the substituted alkyl is 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), CH2-OCH2-CH2-O-CH3or benzyl; each represents a separate embodiment according to this invention. In some embodiments, R6is C1-C5linear or branched, unsubstituted alkyl. In some embodiments, the unsubstituted alkyl is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, or neopentyl; each represents a separate embodiment according to this invention. In some embodiments, R6is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, R6is substituted C3-C8cycloalkyl. In some embodiments, the substituted cycloalkyl is methoxycyclopropyl, methylcyclobutyl,aminomethyl-cyclobutyl, or methoxycyclobutyl, 2,3-dihydro-1H-indenol; each represents a separate embodiment according to this invention. In some embodiments, R6is unsubstituted C3-C8cycloalkyl. In some embodiments, the unsubstituted cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; each represents a separate embodiment according to this invention. In some embodiments, R6is substituted or unsubstituted saturated or unsaturated, single fused, bridged or spiro 3-10 membered carbocyclic or heterocyclic ring. In some embodiments, R6the carbocyclic or heterocyclic ring as defined in R6is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide , C(O)N(R)2, C(O)-alkyl, C(O)- pyrrolidine, C(O)-piperidine, N(R)2, NH(R10), N(R10)(R11), N(CH3)2, NH2, CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., pyran, oxetane, piperidine, pyrazole, triazole, imidazole), C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), halophenyl, (benzyloxy)phenyl, CN, and NO2. In some embodiments, R6is substituted or unsubstituted 3-10 membered heterocyclic ring. In some embodiments, the substituted heterocyclic ring is piperidine, 1-methylpiperidine, 3-fluoro-1- methylpiperidine, 1-(2,2,2-trifluoroethyl)piperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8- methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy- tetrahydrofurane, azepan-2-one, azabicyclohexane; each represents a separate embodiment according to this invention. In some embodiments, R6is piperidine. In some embodiments, R6is 1-methylpiperidine. In some embodiments, R6is 3-fluoro-1-methylpiperidine. In some embodiments, R6is 1-(2,2,2- trifluoroethyl)piperidine, In some embodiments, R6is azetidine. In some embodiments, R6is 1-methyl- azetidine. In some embodiments, R6is morpholine. In some embodiments, R6is pyrrolidine. In some embodiments, R6is pyrrolidinone. In some embodiments, R6is tetrahydropyran. In some embodiments, R6is tetrahydrofurane. In some embodiments, R6is 8-methyl-8-azabicyclo[3.2.1]octane. In some embodiments, R6is dioxane. In some embodiments, R6is 1,3-dioxane. In some embodiments, R6is substituted or unsubstituted saturated or unsaturated, single fused, bridged or spiro 3-10 membered carbocyclic ring. In some embodiments, R6is 4,4-difluorocyclohexane.

[0079] In some embodiments, R7of formula I, II, I(a)-I(f) and / or I(i) is H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, SR10, -R8-O-R10, -R8-S-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, - C(O)Ph, C(O)O-R10, COO-CH3, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)- haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl, methylimidazole, methyl, ethyl, C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, C1- C5linear or branched, or C3-C8cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkyl, C1-C5linear or branchedthioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl, cyclopropyl-1-ol, cyclopropylamine, oxetane-3-ol, bicyclo[1.1.1]pentane, substituted or unsubstituted 4-7 membered heterocyclic ring, morpholine, 3,3- dimethylmorpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2- ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, pyrrolidine-3-carbonitrile, 3-cyanopyrrolidine, 1- methylpyrrolidine, 2,2-dimethylpyrrolidine, 3,3-difluoropyrrolidine, difluoromethylpyrrolidine, pyrrolidin-3-one-O-methyloxime, pyrrolidin-2-one, pyrrolidin-3-one, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperazine-2-one, 1-methylpiperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4-carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, 2- oxopyrrolidine, isoxazolidine, piperazine-2-one, substituted or unsubstituted 3-10 membered bridged, fused or spiro heterocyclic ring, 4-azaspiro[2.4]heptane, 2-oxa-5-azaspiro[3.4]octane, 1,4-dioxa-6- azaspiro[4.4]nonane, 4,7-diazaspiro[2.5]octane, 2,5-diazabicyclo[2.2.1]heptane, R8-(substituted or unsubstituted single, fused or spiro 3-8 membered heterocyclic ring), substituted or unsubstituted aryl, or substituted or unsubstituted benzyl; each represents a separate embodiment according to this invention. In some embodiments, R7is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear 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)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl- pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0080] In some embodiments, R7of formula I, II, I(b), I(d)-I(f) and / or I(i) is H. In some embodiments, R7is F. In some embodiments, R7is Cl. In some embodiments, R7is Br. In some embodiments, R7is I. In some embodiments, R7is OH. In some embodiments, R7is O-R20. In some embodiments, R7is CF3. In some embodiments, R7is CN. In some embodiments, R7is NH2. In some embodiments, R7is NHR. In some embodiments, R7is N(R)2. In some embodiments, R7is NH(R10). In some embodiments, R7is N(R10)(R11). In some embodiments, R7is NHC(O)-R10. In some embodiments, R7is COOH. In some embodiments, R7is -C(O)Ph. In some embodiments, R7is C(O)O-R10. In some embodiments, R7is COO-CH3.In some embodiments, R7is C(O)H. In some embodiments, R7is C(O)-R10. In some embodiments, R7is C1-C5linear or branched C(O)-haloalkyl. In some embodiments, R7is -C(O)NH2. In some embodiments, R7is C(O)NHR. In some embodiments, C(O)NHR is C(O)NH(CH3). In some embodiments, R7is C(O)N(R10)(R11). In some embodiments, C(O)N(R10)(R11) is C(O)NH(CH3), C(O)NH(CH2CH2OCH3), or C(O)NH(CH2CH2OH); each represents a separate embodiment according to this invention. In some embodiments, R7is SO2R. In some embodiments, R7is C1-C5linear or branched, substituted or unsubstituted alkyl. In some embodiments, the alkyl is methylimidazole, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl or hexyl; each represents a separate embodiment according to this invention. In some embodiments, R7is C1-C5linear orbranched, or C3-C8cyclic haloalkyl. In some embodiments, R7is C1-C5linear haloalkyl. In some embodiments, the haloalkyl is CHF2. In some embodiments, R7is C1-C5branched haloalkyl. In some embodiments, R7is C3-C8cyclic haloalkyl. In some embodiments, R7is C1-C5linear or branched, or C3- C8 cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom. In some embodiments, R7is C1-C5linear alkoxy. In some embodiments, the alkoxy is methoxy. In some embodiments, the alkoxy is ethoxy. In some embodiments, R7is C1-C5branched alkoxy. In some embodiments, R7is C3-C8cyclic alkoxy. In some embodiments, R7is C1-C5linear or branched thioalkyl. In some embodiments, R7is C1-C5linear or branched haloalkoxy. In some embodiments, R7is C1-C5linear haloalkoxy. In some embodiments, R7is C1-C5branched haloalkoxy. In some embodiments, R7is C1-C5linear or branched alkoxyalkyl. In some embodiments, R7is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, the cycloalkyl is cyclopropyl, cyclopropanol, cyclobutyl, cyclopentyl, bicyclo[1.1.1]pentane, cyclohexyl, cycloheptyl or cyclooctyl; each represents a separate embodiment according to this invention. In some embodiments, R7is substituted or unsubstituted 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In some embodiments, R7is substituted or unsubstituted 3- 10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic heterocyclic ring. In some embodiments, R7is substituted or unsubstituted 4-7 membered heterocyclic ring. In some embodiments, R7is unsubstituted 4-7 membered heterocyclic ring. In some embodiments, the heterocyclic ring is morpholine, tetrahydrofuran, tetrahydropyran, oxetane, pyrrolidine, pyrrolidin-3- one, pyrrolidin-2-one, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperazine-2-one, piperidine, piperidine-2-one, oxadiazole, triazole, isoxazolidine, or 2-oxopyrrolidine; each represents a separate embodiment according to this invention. In some embodiments, R7is substituted 4-7 membered heterocyclic ring. In some embodiments, the heterocyclic ring is 3,3-dimethylmorpholine, oxetan-3-ol, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, pyrrolidine-3-carbonitrile, 3-cyanopyrrolidine, 1-methylpyrrolidine, 2,2-dimethylpyrrolidine, 3,3-difluoropyrrolidine, difluoromethylpyrrolidine, pyrrolidin-3-one-O-methyloxime, pyrrolidin-3-one O-methyl oxime, 1-methylpiperazine, 1- methylpiperazine, piperidin-3-ol, piperidin-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine; each represents a separate embodiment according to this invention. In some embodiments, R7is a substituted or unsubstituted 3-10 membered bridged, fused or spiro heterocyclic ring. In some embodiments, the ring is 4-azaspiro[2.4]heptane, 2-oxa-5-azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane, 4,7- diazaspiro[2.5]octane, 2,5-diazabicyclo[2.2.1]heptane; each represents a separate embodiment according to this invention. In some embodiments, R7is R8-(substituted or unsubstituted single, fused or spiro 3-8 membered heterocyclic ring). In some embodiments, R7is R8-(unsubstituted single 3-8 membered heterocyclic ring). In some embodiments, R7is R8-(unsubstituted fused 3-8 membered heterocyclic ring). In some embodiments, R7is R8-(unsubstituted spiro 3-8 membered heterocyclic ring). In some embodiments, R7is R8-(substituted single 3-8 membered heterocyclic ring). In some embodiments, R7is R8-(substituted fused 3-8 membered heterocyclic ring). In some embodiments, R7isR8-(substituted spiro 3-8 membered heterocyclic ring). In some embodiments, the heterocyclic ring may be saturated. In some embodiments, the heterocyclic ring may be unsaturated. In some embodiments, the hetrocyclic ring may be aromatic. In some embodiments, R7is substituted or unsubstituted aryl. In some embodiments, R7is phenyl. In some embodiments, R7may be further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0081] In some embodiments, R7of formula I(a) is O-R20. In some embodiments, R7is substituted or unsubstituted 4-7 membered heterocyclic ring. In some embodiments, R7is substituted or unsubstituted 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In some embodiments, R7is substituted or unsubstituted 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic heterocyclic ring. In some embodiments, R7is substituted or unsubstituted 4-7 membered heterocyclic ring. In some embodiments, R7is unsubstituted 4-7 membered heterocyclic ring. In some embodiments, the heterocyclic ring is morpholine, tetrahydrofuran, tetrahydropyran, oxetane, pyrrolidine, pyrrolidin-3-one, pyrrolidin-2-one, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidine-2-one, oxadiazole, triazole, isoxazolidine, or 2-oxopyrrolidine; each represents a separate embodiment according to this invention. In some embodiments, R7is substituted 4-7 membered heterocyclic ring. In some embodiments, the heterocyclic ring is 3,3-dimethylmorpholine, oxetan-3-ol, pyrrolidin-2-ol, pyrrolidin- 3-ol, 3-methoxypyrrolidine, pyrrolidine-3-carbonitrile, 3-cyanopyrrolidine, 1-methylpyrrolidine, 2,2- dimethylpyrrolidine, 3,3-difluoropyrrolidine, difluoromethylpyrrolidine, pyrrolidin-3-one-O- methyloxime, pyrrolidin-3-one O-methyl oxime, 1-methylpiperazine, 1-methylpiperazine, piperidin-3- ol, piperidin-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine; each represents a separate embodiment according to this invention. In some embodiments, R7is a substituted or unsubstituted 3-10 membered bridged, fused or spiro heterocyclic ring. In some embodiments, the ring is 4-azaspiro[2.4]heptane, 2- oxa-5-azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane; each represents a separate embodiment according to this invention. In some embodiments, R7is morpholine. In some embodiments, R7is tetrahydrofuran. In some embodiments, R7is tetrahydropyran. In some embodiments, R7is oxetane. In some embodiments, R7is oxetan-3-ol. In some embodiments, R7is pyrrolidine. In some embodiments, R7is pyrrolidin-2-ol. In some embodiments, R7is pyrrolidin-3-ol. In some embodiments, R7is 3- methoxypyrrolidine. In some embodiments, R7is pyrrolidine-3-carbonitrile. In some embodiments, R7is 1-methylpyrrolidine. In some embodiments, R7is pyrrolidin-2-one. In some embodiments, R7is pyrrolidin-3-one. In some embodiments, R7is pyrrolidinone. In some embodiments, R7is imidazole. Insome embodiments, R7is pyrazole. In some embodiments, R7is isoxazolidine. In some embodiments, R7is piperazine. In some embodiments, R7is piperidine. In some embodiments, R7is piperidin-3-ol. In some embodiments, R7is piperidin-4-ol. In some embodiments, R7is piperidine-2-one. In some embodiments, R7is piperazine-2-one. In some embodiments, R7is piperidine-4-carbonitrile. In some embodiments, R7is 4-fluoropiperidine. In some embodiments, R7is 2,2-dimethylpyrrolidine. In some embodiments, R7is pyrrolidin-3-one O-methyl oxime. In some embodiments, R7is a substituted or unsubstituted 3-10 membered bridged, fused or spiro heterocyclic ring. In some embodiments, R7is 4- azaspiro[2.4]heptane. In some embodiments, R7is 2-oxa-5-azaspiro[3.4]octane. In some embodiments, R7is 1,4-dioxa-6-azaspiro[4.4]nonane. In some embodiments, R7is 4,7-diazaspiro[2.5]octane. In some embodiments, R7is 2,5-diazabicyclo[2.2.1]heptane. In some embodiments, R7is 3,3- dimethylmorpholine. In some embodiments, R7is 1-methylpiperazine. In some embodiments, R7is oxadiazole. In some embodiments, R7is triazole. In some embodiments, R7is substituted or unsubstituted aryl. In some embodiments, R7is phenyl. In some embodiments, R7may be further substituted with at least one substitution selected from F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0082] In some embodiments, R7of formula I(c) is not H, F, Cl, C1-C5linear or branched, or C3-C8cyclic alkoxy, C1-C5linear or branched haloalkoxy or C1-C5linear or branched, substituted or unsubstituted alkyl.

[0083] In some embodiments, R7of formula I, II, I(a)-I(f) and / or I(i) is represented by the structure of formula A:wherein X1is N or O; R1and R2are each independently H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH, CH2OCH3), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy, 3-8 membered carbocyclic or heterocyclic ring (e.g., oxetane);or R1and R2are joined to form a C3-C8carbocyclic or heterocyclic ring (e.g., cyclopropyl); R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); or R2and R4are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring (e.g., pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin- 2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, pyrazole); wherein if X1is O then R4is absent;

[0084] In some embodiments, X1of formula A is N. In other embodiments X1is O.

[0085] In some embodiments, R1of formula A, I(h), I(m), and / or I(o) is H. In other embodiments, R1is F. In other embodiments R1is CF3. In other embodiments, R1is Cl. In other embodiments, R1is Br. In other embodiments, R1is I. In other embodiments, R1is OH. In other embodiments, R1is SH. In other embodiments, R1is substituted or unsubstituted C1-C5alkyl. In other embodiments, R1is CH2OH. In other embodiments, R1is CH2OCH3. In other embodiments, R1is C1-C5linear or branched, or C3-C8cyclic haloalkyl. In other embodiments, R1is substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy. In other embodiments, R1is 3-8 membered carbocyclic or heterocyclic ring. In other embodiments, R1is 3-8 membered heterocyclic ring. In other embodiments, R1is oxetane. In other embodiments, R1is 3-8 membered carbocyclic ring.

[0086] In some embodiments, R2of formula A, I(h), I(m), and / or I(o) is H. In other embodiments R2is F. In other embodiments R2is CF3. In other embodiments, R2is Cl. In other embodiments, R2is Br. In other embodiments, R2is I. In other embodiments, R2is OH. In other embodiments, R2is SH. In other embodiments, R2is substituted or unsubstituted C1-C5alkyl. In other embodiments, R2is CH2OH. In other embodiments, R2is CH2OCH3. In other embodiments, R2is C1-C5linear or branched, or C3-C8cyclic haloalkyl. In other embodiments, R2is substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy. In other embodiments, R2is 3-8 membered carbocyclic or heterocyclic ring. In other embodiments, R2is 3-8 membered heterocyclic ring. In other embodiments, R2is oxetane. In other embodiments, R2is 3-8 membered carbocyclic ring.

[0087] In some embodiments, R1and R2of formula A, I(h), I(m), and / or I(o) are joined to form =O. In other embodiments, R1and R2are joined to form a 3-8 membered carbocyclic or heterocyclic ring. In other embodiments, R1and R2are joined to form a 3-8 membered carbocyclic ring. In someembodiments, the carbocyclic ring is cyclopropyl. In other embodiments, R1and R2are joined to form a 3-8 membered heterocyclic ring.

[0088] In some embodiments, R1and R2of formula A or formula I(a) and / or I(h), are not joined to form =O.

[0089] In some embodiments, R3of formula A, I(h), I(m), and / or I(o) is H. In some embodiments, R3is methyl. In some embodiments, R3is substituted or unsubstituted C1-C5alkyl. In some embodiments, the alkyl is methoxyethylene, methylaminoethylene, aminoethylene; each represents a separate embodiment according to this invention. In some embodiments, R3is -R8-O-R10. In some embodiments, R3is (CH2)2-O-CH3). In some embodiments, R3is R8-N(R10)(R11). In some embodiments, R3is (CH2)2- NH(CH3). In some embodiments, R3is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, the cycloalkyl is cyclopropyl. In some embodiments, R3is substituted or unsubstituted 5- 7 membered heterocyclic ring. In some embodiments, the heterocyclic ring is pyrrolidine, methylpyrrolidine, or piperidine; each represents a separate embodiment according to this invention. In some embodiments, R3is pyrrolidine. In some embodiments, R3is methylpyrrolidine. In some embodiments, R3is piperidine. In some embodiments, R3is R20as defined hereinbelow.

[0090] In some embodiments, R4of formula A, I(h), I(m), and / or I(o) is H. In some embodiments, R4is methyl. In some embodiments, R4is substituted or unsubstituted C1-C5alkyl. In some embodiments, the alkyl is methoxyethylene, methylaminoethylene, aminoethylene; each represents a separate embodiment according to this invention. In some embodiments, R4is -R8-O-R10. In some embodiments, R4is (CH2)2-O-CH3). In some embodiments, R4is R8-N(R10)(R11). In some embodiments, R4is (CH2)2- NH(CH3). In some embodiments, R4is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, the cycloalkyl is cyclopropyl. In some embodiments, R4is substituted or unsubstituted 5- 7 membered heterocyclic ring. In some embodiments, the heterocyclic ring is pyrrolidine, methylpyrrolidine, or piperidine; each represents a separate embodiment according to this invention. In some embodiments, R4is pyrrolidine. In some embodiments, R4is methylpyrrolidine. In some embodiments, R4is piperidine. In some embodiments, R4is R20as defined hereinbelow.

[0091] In some embodiments, R3and R4of formula A, I(h), I(m), and / or I(o) are joined to form a 3-8 membered heterocyclic ring. In some embodiments, the heterocyclic ring is imidazole, pyrrolidine, pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, or piperazine; each represents a separate embodiment according to this invention.

[0092] In some embodiments, R2and R4of formula A, I(h) and / or I(m) are joined to form Ring F. In some embodiments, Ring F is absent. In some embodiments, Ring F is a substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring. In some embodiments, R2and R4are joined to form pyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyridine, piperidine, imidazole, pyrimidine, triazole, oxadiazole, pyrazole; each represents a separate embodiment according to this invention. In some embodiments, Ring F is unsubstituted, saturated 4-8 membered heterocyclic ring. In some embodiments, Ring F is pyrrolidine, morpholine or piperidine; each represents a separate embodimentaccording to this invention. In some embodiments, Ring F is a substituted saturated 4-8 membered heterocyclic ring. In some embodiments, Ring F is 1-methylpyrrolidine, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3-(difluoromethyl)pyrrolidine, or pyrrolidine-3-carbonitrile; each represents a separate embodiment according to this invention. In some embodiments, Ring F is a substituted or unsubstituted unsaturated, 4-8 membered heterocyclic ring. In some embodiments, Ring F is pyrrolidin-2-one, pyrrolidin-3-one, pyridine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, or pyrazole; each represents a separate embodiment according to this invention. In some embodiments, if Ring F is aromatic, then R1is absent. In some embodiments, if Ring F is aromatic, then R3is absent. In some embodiments, if Ring F is aromatic, then R1and / or R3are absent.

[0093] In some embodiments, R2and R4of formula A, I(h) and / or I(m) are joined to form substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring. In some embodiments, the heterocyclic ring is pyrrolidine, morpholine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3-(difluoromethyl)pyrrolidine, pyrrolidine-3-carbonitrile, pyridine, piperidine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, or pyrazole; each represents a separate embodiment according to this invention.

[0094] In some embodiments, if X1of formula A is O then R4is absent.

[0095] In some embodiments, R2and R4of formula I(h) and / or I(m) are joined to form Ring F. In some embodiments, Ring F is absent. In some embodiments, Ring F is a substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring. In some embodiments, Ring F is unsubstituted, saturated 4-8 membered heterocyclic ring. In some embodiments, Ring F is pyrrolidine, morpholine or piperidine; each represents a separate embodiment according to this invention. In some embodiments, Ring F is a substituted saturated 4-8 membered heterocyclic ring. In some embodiments, Ring F is 1-methylpyrrolidine, 3,3-difluoropyrrolidine, pyrrolidine-3-ol, 3-methoxypyrrolidine, 3- (difluoromethyl)pyrrolidine, or pyrrolidine-3-carbonitrile; each represents a separate embodiment according to this invention. In some embodiments, Ring F is a substituted or unsubstituted unsaturated, 4-8 membered heterocyclic ring. In some embodiments, Ring F is pyrrolidin-2-one, pyrrolidin-3-one, pyridine, piperidine-2-one, imidazole, pyrimidine, triazole, oxadiazole, or pyrazole; each represents a separate embodiment according to this invention.

[0096] In some embodiments, Ring F of formula I(h) and / or I(m) is absent. In some embodiments, Ring F is a substituted or unsubstituted, saturated or unsaturated, 4-8 membered heterocyclic ring. In some embodiments, Ring F is a substituted, saturated, 4-8 membered heterocyclic ring. In some embodiments, Ring F is a substituted unsaturated, 4-8 membered heterocyclic ring. In some embodiments, Ring F is an unsubstituted, saturated, 4-8 membered heterocyclic ring. In some embodiments, Ring F is an unsubstituted, unsaturated, 4-8 membered heterocyclic ring. In some embodiments, Ring F is pyrrolidine. In some embodiments, Ring F is pyrrolidine-2-one. In some embodiments, Ring F is piperidine. In some embodiments, Ring F is piperazine. In some embodiments, Ring F is morpholine. In some embodiments, Ring F is a pyridinyl. In other embodiments, Ring F is2-pyridinyl. In other embodiments, Ring F is pyrimidine. In other embodiments, Ring F is imidazole. In other embodiments, Ring F is pyridazine. In other embodiments, Ring F is pyrazine. In other embodiments, Ring F is pyrazole. In other embodiments, Ring F is thiazole. In other embodiments, Ring F is isothiazolyl. In other embodiments, Ring F is thiadiazolyl. In other embodiments, Ring F is triazolyl. In other embodiments, Ring F is thiazolyl. In other embodiments, Ring F is oxazolyl. In other embodiments, Ring F is isoxazolyl. In other embodiments, Ring F is pyrrolyl. In other embodiments, Ring F is oxadiazolyl. In other embodiments, Ring F is 1,2,3-, 1,2,4-, 1,2,5- or 1,3,4- oxadiazolyl; each is a separate embodiment according to this invention. In other embodiments, Ring F is oxazolonyl. In other embodiments, Ring F is oxazolidonyl. In other embodiments, Ring F is thiazolonyl. In other embodiments, Ring F is isothiazolinonyl. In other embodiments, Ring F is isoxazolidinonyl. In other embodiments, Ring F is imidazolidinonyl. In other embodiments, Ring F is pyrazolonyl. In other embodiments, Ring F is 2H-pyrrol-2-onyl. In other embodiments, Ring F is triazolopyrimidine. In other embodiments, Ring F is 3H-[1,2,3]triazolo[4,5-d]pyrimidine, 1H-[1,2,3]triazolo[4,5-d]pyrimidine, [1,2,4]triazolo[4,3-c]pyrimidine, [1,2,4]triazolo[4,3-a]pyrimidine, [1,2,3]triazolo[1,5-a]pyrimidine, [1,2,3]triazolo[1,5-c]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine or [1,2,4]triazolo[1,5-c]pyrimidine; each is a separate embodiment according to this invention. In other embodiments, Ring F is 6,7-dihydro- 5H-pyrazolo[5,1-b][1,3]oxazine.

[0097] In some embodiments, R7of formula I(a) is O-R20, substituted or unsubstituted 4-7 membered heterocyclic ring (e.g., morpholine, tetrahydrofuran, tetrahydropyran, oxetane, oxetan-3-ol, pyrrolidine, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 1-methylpyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, pyrrolidine-3-carbonitrile, 3-cyanopyrrolidine, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidin-3-ol, piperidin-4-ol, piperidine-2-one, piperidine-4- carbonitrile, 4-fluoropiperidine, oxadiazole, triazole, pyrazole, 2-oxopyrrolidine; each represents a separate embodiment according to this invention), or substituted or unsubstituted aryl. In some embodiments, R7of formula I(a) is represented by formula A, wherein X1, R1, R2, R3and R4are as defined above except that R1and R2cannot be joined to form =O.

[0098] In some embodiments, R7’ of formula I(c) is not H.

[0099] In some embodiments, R7’ of formula I, II, I(a)-I(b) and / or I(d)-I(o) is H. In some embodiments, R7’ of formula I, II and / or I(a)-I(o) is F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8- O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, - CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl, C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, C1-C5linear or branched, or C3-C8cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, methoxy, C1-C5linear or branchedthioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl, cyclopropyl, cyclohexyl, substituted or unsubstituted 3-8 membered heterocyclic ring, morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine, substituted or unsubstituted aryl, or substituted or unsubstituted benzyl; each represents a separate embodiment according to this invention. In some embodiments, the heterocyclic ring is morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2- one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine; each represents a separate embodiment according to this invention. In some embodiments, R7’ is morpholine, pyran, oxetane, pyrrolidine, 3,3- difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4- ol, dioxazole, 2-oxopyrrolidine; each represents a separate embodiment according to this invention. In some embodiments, R7’ is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0100] In some embodiments, R7’ of formula I, II and / or I(a)-I(o) is H. In some embodiments, R7’ is F. In some embodiments, R7’ is Cl. In some embodiments, R7’ is Br. In some embodiments, R7’ is I. In some embodiments, R7’ is CF3. In some embodiments, R7’ is C1-C5linear or branched, substituted or unsubstituted alkyl. In some embodiments, R7’ is C1-C5linear or branched unsubstituted alkyl. In some embodiemnts, the alkyl is isopropyl, methyl, ethyl; each represents a separate embodiment according to this invention. In some embodiments, R7’ is C1-C5linear or branched substituted alkyl. In some embodiments, R7’ is isopropyl. In some embodiments, R7’ is methyl. In some embodiments, R7’ is ethyl. In some embodiments, R7’ is C1-C5linear or branched, or C3-C8cyclic haloalkyl. In some embodiments, R7’ is C1-C5linear or branched haloalkyl. In some embodiments, the haloalkyl is CHF2. In some embodiments, R7’ is C3-C8cyclic haloalkyl. In some embodiments, R7’ is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, the cycloalkyl is cyclopropyl, cyclpbutyl, cyclopentyl, cyclohexyl, or cycloheptyl; each represents a separate embodiment according to this invention. In some embodiments, the cycloalkyl is cyclopropyl. In some embodiments, the cycloalkyl is cyclohexyl. In some embodiments, R7’ is morpholine. In some embodiments, R7’ is pyran. In some embodiments, R7’ is oxetane. In some embodiments, R7’ is pyrrolidine. In some embodiments, R7’ is 3,3- difluoropyrrolidine. In some embodiments, R7’ is imidazole. In some embodiments, R7’ is pyrazole. In some embodiments, R7’ is triazole. In some embodiments, R7’ is piperazine. In some embodiments, R7’ is piperidine. In some embodiments, R7’ is piperidin-2-one. In some embodiments, R7’ is piperidin-4- ol. In some embodiments, R7’ is dioxazole. In some embodiments, R7’ is 2-oxopyrrolidine.

[0101] In some embodiments, R7and R7’ of formula I, II, and / or I(a)-I(f) are joined to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring including but not limited to: cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine; each represents a separate embodiment according to this invention. In some embodiments, R7and R7’ are joined to form a 5 or 6 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In some embodiments, R7and R7’ are joined to form a 5 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7and R7’ are joined to form 6 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7and R7’ are joined to form a cyclohexyl. In some embodiments, R7and R7’ are joined to form a 5 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7and R7’ are joined to form a cyclopentyl. In some embodiments, R7and R7’ are joined to form 6 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7and R7’ are joined to form a 6 membered substituted or unsubstituted, aromatic, carbocyclic ring. In some embodiments, R7and R7’ are joined to form a 5 or 6 membered substituted or unsubstituted, aromatic, heterocyclic ring. In some embodiments, R7and R7’ are joined to form a 5 or 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7and R7’ are joined to form a 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7and R7’ are joined to form a piperidine. In some embodiments, R7and R7’ are joined to form a tetrahydropyran. In some embodiments, R7and R7’ are joined to form a 5 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7and R7’ are joined to form a pyrrolidine. In some embodiments, R7and R7’ are joined to form a tetrahydrofuran.

[0102] In some embodiments, R7and R7’ of formula I(c) are different. In some embodiments, R7and R7’ of formula I(c) are not H, F, Cl, C1-C5linear or branched, or C3-C8cyclic alkoxy , C1-C5linear or branched haloalkoxy or C1-C5linear or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to this invention.

[0103] In some embodiments, R7’’ of formula I(i)-I(o) is H. In some embodiments, R7’’ of formula I(i)-I(m) is F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO- N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl, C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, C1-C5linear or branched, or C3-C8cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic ring, substituted or unsubstituted aryl, or substituted orunsubstituted benzyl; each represents a separate embodiment according to this invention. In some embodiments, R7’’ is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)- piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0104] In some embodiments, R7’’ of formula I(i)-I(o) is H. In some embodiments, R7’’ is F. In some embodiments, R7’’ is Cl. In some embodiments, R7’’ is Br. In some embodiments, R7’’ is I. In some embodiments, R7’’ is CF3. In some embodiments, R7’’ is C1-C5linear or branched, substituted or unsubstituted alkyl. In some embodiments, R7’’ is C1-C5linear or branched unsubstituted alkyl. In some embodiemnts, the alkyl is isopropyl, methyl, ethyl; each represents a separate embodiment according to this invention. In some embodiments, R7’’ is C1-C5linear or branched substituted alkyl. In some embodiments, R7’’ is isopropyl. In some embodiments, R7’’ is methyl. In some embodiments, R7’’ is ethyl. In some embodiments, R7’’ is C1-C5linear or branched, or C3-C8cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom. In some embodiments, R7’’ is C1-C5linear or branched alkoxy. In some embodiments, R7’’ is methoxy. In some embodiments, R7’’ is C1-C5linear or branched, or C3-C8cyclic haloalkyl. In some embodiments, R7’’ is C1-C5linear or branched haloalkyl. In some embodiments, the haloalkyl is CHF2. In some embodiments, R7’’ is C3-C8cyclic haloalkyl. In some embodiments, R7’’ is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, the cycloalkyl is cyclopropyl, cyclpbutyl, cyclopentyl, cyclohexyl, or cycloheptyl; each represents a separate embodiment according to this invention. In some embodiments, the cycloalkyl is cyclopropyl. In some embodiments, the cycloalkyl is cyclohexyl. In some embodiments, R7’’ is a substituted or unsubstituted 3-8 membered heterocyclic ring. In some embodiments, R7’’ is morpholine. In some embodiments, R7’’ is pyran. In some embodiments, R7’’ is oxetane. In some embodiments, R7’’ is pyrrolidine. In some embodiments, R7’’’’ is 3,3- difluoropyrrolidine. In some embodiments, R7’’ is imidazole. In some embodiments, R7’’’’ is pyrazole. In some embodiments, R7’’ is triazole. In some embodiments, R7’’ is piperazine. In some embodiments, R7’’ is piperidine. In some embodiments, R7’’ is piperidin-2-one. In some embodiments, R7’’ is piperidin-4-ol. In some embodiments, R7’’ is dioxazole. In some embodiments, R7’’ is 2-oxopyrrolidine.

[0105] In some embodiments, R7’ and R7’’ of formula I(j)-I(o) are joined to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring including but not limited to: cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, pyrrolidine; each represents a separate embodiment according to this invention. In some embodiments, R7’ and R7’’ are joined to form a 5 or 6 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a5 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form 6 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a cyclohexyl. In some embodiments, R7’ and R7’’ are joined to form a 5 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a cyclopentyl. In some embodiments, R7’ and R7’’ are joined to form 6 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 6 membered substituted or unsubstituted, aromatic, carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 5 or 6 membered substituted or unsubstituted, aromatic, heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 5 or 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a piperidine. In some embodiments, R7’ and R7’’ are joined to form a tetrahydropyran. In some embodiments, R7’ and R7’’ are joined to form a 5 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a pyrrolidine. In some embodiments, R7’ and R7’’ are joined to form a tetrahydrofuran.

[0106] In some embodiments, R7’ and R7’’ of formula I(c) and / or I(i)-I(o) are different. In some embodiments, R7and R7’ of formula I(c) and / or I(i)-I(n) are not H, F, Cl, C1-C5linear or branched, or C3-C8cyclic alkoxy , C1-C5linear or branched haloalkoxy or C1-C5linear or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to this invention.

[0107] In some embodiments, R7’’’ of formula I(i) is H. In some embodiments, R7’’’ of formula I(i) is F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO- N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl, C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, C1-C5linear or branched, or C3-C8cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic ring, substituted or unsubstituted aryl, or substituted or unsubstituted benzyl; each represents a separate embodiment according to this invention. In some embodiments, R7’’’ is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)- piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole),halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0108] In some embodiments, R7’’’ of formula I(i) is H. In some embodiments, R7’’’ is F. In some embodiments, R7’’’ is Cl. In some embodiments, R7’’’ is Br. In some embodiments, R7’’’ is I. In some embodiments, R7’’’ is CF3. In some embodiments, R7’’’ is C1-C5linear or branched, substituted or unsubstituted alkyl. In some embodiments, R7’’’ is C1-C5linear or branched unsubstituted alkyl. In some embodiemnts, the alkyl is isopropyl, methyl, ethyl; each represents a separate embodiment according to this invention. In some embodiments, R7’’’ is C1-C5linear or branched substituted alkyl. In some embodiments, R7’’’ is isopropyl. In some embodiments, R7’’’ is methyl. In some embodiments, R7’’’ is ethyl. In some embodiments, R7’’’ is C1-C5linear or branched, or C3-C8cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom. In some embodiments, R7’’’ is C1-C5linear or branched alkoxy. In some embodiments, R7’’’ is methoxy. In some embodiments, R7’’’ is C1-C5linear or branched, or C3-C8cyclic haloalkyl. In some embodiments, R7’’’ is C1-C5linear or branched haloalkyl. In some embodiments, the haloalkyl is CHF2. In some embodiments, R7’’’ is C3-C8cyclic haloalkyl. In some embodiments, R7’’’ is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, the cycloalkyl is cyclopropyl, cyclpbutyl, cyclopentyl, cyclohexyl, or cycloheptyl; each represents a separate embodiment according to this invention. In some embodiments, R7’’’ is a substituted or unsubstituted 3-8 membered heterocyclic ring. In some embodiments, R7’’’ is morpholine. In some embodiments, R7’’’ is pyran. In some embodiments, R7’’’ is oxetane. In some embodiments, R7’’’ is pyrrolidine. In some embodiments, R7’’’ is 3,3- difluoropyrrolidine. In some embodiments, R7’’’ is imidazole. In some embodiments, R7’’’ is pyrazole. In some embodiments, R7’’’ is triazole. In some embodiments, R7’’’’ is piperazine. In some embodiments, R7’’’ is piperidine. In some embodiments, R7’’’ is piperidin-2-one. In some embodiments, R7’’’’ is piperidin-4-ol. In some embodiments, R7’’’ is dioxazole. In some embodiments, R7’’’ is 2- oxopyrrolidine.

[0109] In some embodiments, R7’’’’ of formula I(i) is H. In some embodiments, R7’’’’ of formula I(i) is F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, -R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, -OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO- N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl, C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl, C1-C5linear or branched, or C3-C8cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic ring, substituted or unsubstituted aryl, or substituted orunsubstituted benzyl; each represents a separate embodiment according to this invention. In some embodiments, R7’’’’ is further substituted with at least one substitution selected from: F, Cl, Br, I, C1- C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)- piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0110] In some embodiments, R7’’’’ of formula I(i) is H. In some embodiments, R7’’’’ is F. In some embodiments, R7’’’’ is Cl. In some embodiments, R7’’’’ is Br. In some embodiments, R7’’’’ is I. In some embodiments, R7’’’’ is CF3. In some embodiments, R7’’’’ is C1-C5linear or branched, substituted or unsubstituted alkyl. In some embodiments, R7’’’’ is C1-C5linear or branched unsubstituted alkyl. In some embodiments, the alkyl is isopropyl, methyl, ethyl; each represents a separate embodiment according to this invention. In some embodiments, R7’’’’ is C1-C5linear or branched substituted alkyl. In some embodiments, R7’’’’ is isopropyl. I’n some embodiments, R7’’’’ is methyl. In some embodiments, R7’’’’ is ethyl. In some embodiments, R7’’’’ is C1-C5linear or branched, or C3-C8cyclic alkoxy optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom. In some embodiments, R7’’’’ is C1-C5linear or branched alkoxy. In some embodiments, R7’’ is methoxy. In some embodiments, R7’’’’ is C1-C5linear or branched, or C3-C8cyclic haloalkyl. In some embodiments, R7’’’’ is C1-C5linear or branched haloalkyl. In some embodiments, the haloalkyl is CHF2. In some embodiments, R7’’’’ is C3-C8cyclic haloalkyl. In some embodiments, R7’’’’ is substituted or unsubstituted C3-C8cycloalkyl. In some embodiments, the cycloalkyl is cyclopropyl, cyclpbutyl, cyclopentyl, cyclohexyl, or cycloheptyl; each represents a separate embodiment according to this invention. In some embodiments, R7’’’’ is a substituted or unsubstituted 3-8 membered heterocyclic ring. In some embodiments, R7’’’’ is morpholine. In some embodiments, R7’’’’ is pyran. In some embodiments, R7’’’’ is oxetane. In some embodiments, R7’’’’ is pyrrolidine. In some embodiments, R7’’’’ is 3,3-difluoropyrrolidine. In some embodiments, R7’’’’ is imidazole. In some embodiments, R7’’’’ is pyrazole. In some embodiments, R7’’’’ is triazole. In some embodiments, R7’’’’ is piperazine. In some embodiments, R7’’’’ is piperidine. In some embodiments, R7’’’’ is piperidin-2-one. In some embodiments, R7’’’’ is piperidin-4-ol. In some embodiments, R7’’’’ is dioxazole. In some embodiments, R7’’’’ is 2-oxopyrrolidine.

[0111] In some embodiments, R7’ and R7’’ of formula I(i) are joined to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 5 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a cyclopentane. In some embodiments, R7’ and R7’’ are joined to form 6 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a cyclohexane. In someembodiments, R7’ and R7’’ are joined to form a 5 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form 6 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 6 membered substituted or unsubstituted, aromatic, carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 5 or 6 membered substituted or unsubstituted, aromatic, heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 5 or 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a piperidine. In some embodiments, R7’ and R7’’ are joined to form a tetrahydropyran. In some embodiments, R7’ and R7’’ are joined to form a 5 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a tetrahydrofuran. In some embodiments, R7’ and R7’’ are joined to form a pyrrolidine.

[0112] In some embodiments, R7’ and R7’’ of formula I(i) are different. In some embodiments, R7’ and R7’’ of formula I(i) are not H, F, Cl, C1-C5linear or branched, or C3-C8cyclic alkoxy, C1-C5linear or branched haloalkoxy or C1-C5linear or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to this invention.

[0113] In some embodiments, R7’’ and R7of formula I(i) are joined to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In some embodiments, R7’’ and R7are joined to form a 5 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’’ and R7are joined to form a cyclopentane. In some embodiments, R7’’ and R7are joined to form 6 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’’ and R7are joined to form a cyclohexane. In some embodiments, R7’’ and R7are joined to form a 5 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’’ and R7are joined to form 6 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’ and R7’’ are joined to form a 6 membered substituted or unsubstituted, aromatic, carbocyclic ring. In some embodiments, R7’’ and R7are joined to form a 5 or 6 membered substituted or unsubstituted, aromatic, heterocyclic ring. In some embodiments, R7’’ and R7are joined to form a 5 or 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’’ and R7are joined to form a 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’’ and R7are joined to form a piperidine. In some embodiments, R7’’ and R7are joined to form a tetrahydropyran. In some embodiments, R7’’ and R7are joined to form a 5 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’’ and R7are joined to form a tetrahydrofuran. In some embodiments, R7’’ and R7are joined to form a pyrrolidine.

[0114] In some embodiments, R7’’ and R7of formula I(i) are different. In some embodiments, R7’’ and R7of formula I(i) are not H, F, Cl, C1-C5linear or branched, or C3-C8cyclic alkoxy , C1-C5linear orbranched haloalkoxy or C1-C5linear or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to this invention.

[0115] In some embodiments, R7and R7’’’ of formula I(i) are joined to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In some embodiments, R7and R7’’’ are joined to form a 5 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7and R7’’’ are joined to form 6 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7and R7’’’ are joined to form a 5 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7and R7’’’ are joined to form 6 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7and R7’’’ are joined to form a 6 membered substituted or unsubstituted, aromatic, carbocyclic ring. In some embodiments, R7and R7’’’ are joined to form a 5 or 6 membered substituted or unsubstituted, aromatic, heterocyclic ring. In some embodiments, R7and R7’’’ are joined to form a 5 or 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7and R7’’’ are joined to form a 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7and R7’’’ are joined to form a piperidine. In some embodiments, R7and R7’’’ are joined to form a tetrahydrofuran. In some embodiments, R7and R7’’’ are joined to form a tetrahydropyran. In some embodiments, R7and R7’’’ are joined to form a 5 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7and R7’’’ are joined to form a pyrrolidine. In some embodiments, R7and R7’’’ are joined to form a cyclopentane. In some embodiments, R7and R7’’’ are joined to form a cyclohexane.

[0116] In some embodiments, R7and R7’’’ of formula I(i) are different. In some embodiments, R7and R7’’’ of formula I(i) are not H, F, Cl, C1-C5linear or branched, or C3-C8cyclic alkoxy , C1-C5linear or branched haloalkoxy or C1-C5linear or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to this invention.

[0117] In some embodiments, R7’’’ and R7’’’’ of formula I(i) are joined to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form a 5 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form 6 membered unsubstituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form a 5 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form 6 membered substituted saturated or unsaturated carbocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form a 6 membered substituted or unsubstituted, aromatic, carbocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form a 5 or 6 membered substituted or unsubstituted, aromatic, heterocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form a 5 or 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form a 6 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form a piperidine. In some embodiments, R7’’’ and R7’’’’ are joined to form a tetrahydrofuran. In some embodiments, R7’’’ and R7’’’’ are joined to form atetrahydropyran. In some embodiments, R7’’’ and R7’’’’ are joined to form a 5 membered substituted or unsubstituted, heterocyclic ring. In some embodiments, R7’’’ and R7’’’’ are joined to form a pyrrolidine. In some embodiments, R7’’’ and R7’’’’ are joined to form a cyclopentane. In some embodiments, R7’’’ and R7’’’’ are joined to form a cyclohexane.

[0118] In some embodiments, R7’’’ and R7’’’’ of formula I(i) are different. In some embodiments, R7’’’ and R7’’’’ of formula I(i) are not H, F, Cl, C1-C5linear or branched, or C3-C8cyclic alkoxy , C1- C5linear or branched haloalkoxy or C1-C5linear or branched, substituted or unsubstituted alkyl; each represents a separate embodiment according to this invention.

[0119] In some embodiments, at least two of R7, R7’, R7’’, R7’’’ and R7’’’’ are not H. In some embodiments, at least three of R7, R7’, R7’’, R7’’’ and R7’’’’ are not H

[0120] In some embodiments, R30of formula I, II and / or I(a)-I(o) is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl, methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3, C1-C5linear or branched alkoxy, C1-C5linear or branched haloalkyl, CHF2, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2,CF(CH3)-CH(CH3)2, R8-aryl, -R8-O-R8-O-R10, (CH2)2-O-(CH2)2-O-CH3, - R8-O-R10, -R8-R10, (CH2)2-O-CH3, substituted or unsubstituted aryl, phenyl, CH2-Ph, substituted or unsubstituted heteroaryl, or pyridine; each represents a separate embodiment according to this invention. In some embodiments, R30is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention. In some embodiments, R30is H. In some embodiments, R30is alkyl. In some embodiments, R30is methyl. In some embodiments, R30is R20.

[0121] In some embodiments, R of formula I, II and / or I(a)-I(o) is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl, C1-C5linear or branched alkoxy, C1-C5linear or branched haloalkyl, R8-aryl, -R8-O-R8-O-R10, - R8-O-R10, -R8-R10, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; each represents a separate embodiment according to this invention. In some embodiments, R is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention. In some embodiments, R is H. In some embodiments, R is NH(R10). In some embodiments, R is NH-CH2-cyclopropyl. In someembodiments, R is C1-C5linear or branched, substituted or unsubstituted alkyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. In some embodiments, R is propyl. In some embodiments, R is isopropyl. In some embodiments, R is butyl. In some embodiments, R is substituted alkyl. In some embodiments, R is CH2-OH. In some embodiments, R is CH2-CH2-OH. In some embodiments, R is C3- C8 substituted or unsubstituted cycloalkyl. In some embodiments, R is cyclopropyl. In some embodiments, R is C1-C5linear or branched alkoxy. In some embodiments, R is methoxy. In some embodiments, R is ethoxy. In some embodiments, R is propoxy. In some embodiments, R is isopropoxy. In some embodiments, R is COOH. In some embodiments, R is R8-O-R10. In some embodiments, R is CH2-OH. In some embodiments, R is CH2-CH2-OH.

[0122] In various embodiments, each R8of compound of formula I, II and / or I(a)-I(o) is independently CH2. In some embodiments, R8is CH2CH2. In some embodiments, R8is CH2CH2CH2. In some embodiments, R8is CH2CH2CH2CH2.

[0123] In some embodiments, p of formula I, II and / or I(a)-I(o) is 1. In other embodiments, p is 2. In other embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 5. In some embodiments, p is between 1 and 3. In some embodiments, p is between 1 and 5. In some embodiments, p is between 1 and 10.

[0124] In some embodiments, R9of formula I, II and / or I(a)-I(o) is C≡C. In some embodiments, R9is C≡C-C≡C. In some embodiments, R9is CH=CH. In some embodiments, R9is CH=CH-CH=CH.

[0125] In some embodiments, q of formula I, II and / or I(a)-I(o) is 2. In some embodiments, q is 4. In some embodiments, q is 6. In some embodiments, q is 8. In some embodiments, q is between 2 and 6.

[0126] In some embodiments, R10of formula I, II and / or I(a)-I(o) is H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3; each represents a separate embodiment according to this invention), C1-C5substituted or unsubstituted linear or branched haloalky, CH2CF3, C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; each represents a separate embodiment according to this invention. In some embodiments, R10is H. In some embodiments, R10is C1-C5substituted or unsubstituted linear or branched alkyl. In some embodiments, R10is C1-C5unsubstituted linear or branched alkyl. In other embodiments, R10is CH3. In other embodiments, R10is CH2CH3.In other embodiments, R10is CH2CH2CH3. In some embodiments, R10is isopropyl. In some embodiments, R10is butyl. In some embodiments, R10is isobutyl. In some embodiments, R10is t-butyl. In some embodiments, R10is pentyl. In some embodiments, R10is isopentyl. In some embodiments, R10is neopentyl. In some embodiments, R10is benzyl. In some embodiments, R10is C1-C5substituted linear or branched alkyl. In other embodiments, R10is CH2-CH2-O-CH3. In other embodiments, R10is CH2CF3. In other embodiments, R10is C1-C5substituted or unsubstituted linear or branched haloalkyl. In other embodiments, R10is C1-C5linear or branched alkoxy. In other embodiments, R10is O-CH3. In other embodiments, R10is R20. In other embodiments, R10is C(O)R. In other embodiments, R10is S(O)2R. In some embodiments, R10is further substituted with at lest one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide(e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0127] In some embodiments, R11of formula I, II and / or I(a)-I(o) is H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH3, CH2CF3, C1-C5linear or branched alkoxy (e.g., O-CH3), C(O)R, or S(O)2R; each represents a separate embodiment according to this invention. In some embodiments, R11is H. In some embodiments, R11is C1-C5substituted or unsubstituted linear or branched alkyl. In some embodiments, R11is C1-C5unsubstituted linear or branched alkyl. In other embodiments, R11is CH3. In other embodiments, R11is CH2CH3. In other embodiments, R11is CH2CH2CH3. In some embodiments, R11is isopropyl. In some embodiments, R11is butyl. In some embodiments, R11is isobutyl. In some embodiments, R11is t-butyl. In some embodiments, R11is pentyl. In some embodiments, R11is isopentyl. In some embodiments, R11is neopentyl. In some embodiments, R11is benzyl. In some embodiments, R11is C1-C5substituted linear or branched alkyl. In other embodiments, R11is CH2-CH2-O-CH3. In other embodiments, R11is CH2CF3. In other embodiments, R11is C1-C5substituted or unsubstituted linear or branched haloalkyl. In other embodiments, R11is C1-C5linear or branched alkoxy. In other embodiments, R11is O-CH3. In other embodiments, R11is R20. In other embodiments, R11is C(O)R. In other embodiments, R11is S(O)2R. In some embodiments, R11is further substituted with at lest one substitution selected from: F, Cl, Br, I, C1- C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)- piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0128] In some embodiments, R10and R11of formula I, II and / or I(a)-I(o) are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring. In other embodiments, R10and R11are joined to form a piperazine ring. In other embodiments, R10and R11are joined to form a piperidine ring. In some embodiments, substitutions include: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy , OMe, amide , C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2, NH(R10), N(R10)(R11), N(CH3)2, NH2, CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl , cyclobutanol, substituted or unsubstituted 3-8 membered heterocyclic ring pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole, halophenyl, (benzyloxy)phenyl, CN, and NO2; each represents a separate embodiment according to this invention.

[0129] In some embodiments, n of formula I, II, I(a)-I(h) and / or I(j)-I(o) is an integer between 0 and 4. In some embodiments, n of formula I(c) is an integer between 1 and 4. In some embodiments, n offormula I, II, I(a)-I(h) and / or I(j)-I(n) is 0. In some embodiments, n of formula I, II, I(a)-I(h) and / or I(j)-I(n) is 1. In some embodiments, n of formula I, II, I(a)-I(h) and / or I(j)-I(n) is 2. In some embodiments, n of formula I, II, I(a)-I(h) and / or I(j)-I(n) is 3. In some embodiments, n of formula I, II, I(a)-I(h) and / or I(j)-I(n) is 4. In some embodiments, n of formula I, II, I(a)-I(h) and / or I(j)-I(n) is 1 or 2.

[0130] In some embodiments, A’ of formula I(f) is a 3-8 membered single or fused saturated, unsaturated or aromatic heterocyclic ring. In some embodiments, A’ is a 3-8 membered single heterocyclic ring. In some embodiments, A’ is a fused 4-10 membered heterocyclic ring. In some embodiments, A’ is a single aromatic 3-8 membered heterocyclic ring. In some embodiments, A’ is a fused aromatic 3-10 membered heterocyclic ring. In some embodiments, A’ is a saturated 3-8 membered single heterocyclic ring. In some embodiments, A’ is piperidine. In some embodiments, A’ is pyrrolidine. In some embodiments, A’ is piperazine. In some embodiments, A’ is morpholine. In some embodiments, A’ is a pyridinyl. In other embodiments, A’ is 2-pyridinyl. In other embodiments, A’ is 3-pyridinyl. In other embodiments, A’ is 4-pyridinyl. In other embodiments, A’ is pyrimidine. In other embodiments, A’ is pyridazine. In other embodiments, A’ is pyrazine. In other embodiments, A’ is pyrazole. In other embodiments, A’ is benzothiazolyl. In other embodiments, A’ is benzimidazolyl. In other embodiments, A’ is quinolinyl. In other embodiments, A’ is isoquinolinyl. In other embodiments, A’ is indolyl. In other embodiments, A’ is indenyl. In other embodiments, A’ is benzofuran-2(3H)-one. In other embodiments, A’ is benzo[d][1,3]dioxole. In other embodiments, A’ is tetrahydrothiophene1,1- dioxide. In other embodiments, A’ is thiazole. In other embodiments, A’ is benzimidazole. In others embodiment, A’ is piperidine. In other embodiments, A’ is imidazole. In other embodiments, A’ is thiophene. In other embodiments, A’ is isoquinoline. In other embodiments, A’ is indole. In other embodiments, A’ is 1,3-dihydroisobenzofuran. In other embodiments, A’ is benzofuran. In other embodiments, A’ is tetrahydro-2H-pyran. In other embodiments, A’ is isothiazolyl. In other embodiments, A’ is thiadiazolyl. In other embodiments, A’ is triazolyl. In other embodiments, A’ is thiazolyl. In other embodiments, A’ is oxazolyl. In other embodiments, A’ is isoxazolyl. In other embodiments, A’ is pyrrolyl. In other embodiments, A’ is furanyl. In other embodiments, A’ is oxadiazolyl. In other embodiments, A’ is 1,2,3-, 1,2,4-, 1,2,5- or 1,3,4- oxadiazolyl; each is a separate embodiment according to this invention. In other embodiments, A’ is tetrahydrofuranyl. In other embodiments, A’ is oxazolonyl. In other embodiments, A’ is oxazolidonyl. In other embodiments, A’ is thiazolonyl. In other embodiments, A’ is isothiazolinonyl. In other embodiments, A’ is isoxazolidinonyl. In other embodiments, A’ is imidazolidinonyl. In other embodiments, A’ is pyrazolonyl. In other embodiments, A’ is 2H-pyrrol-2-onyl. In other embodiments, A’ is furanonyl. In other embodiments, A’ is thiophenonyl. In other embodiments, A’ is thiane 1,1 dioxide. In other embodiments, A’ is triazolopyrimidine. In other embodiments, A’ is 3H-[1,2,3]triazolo[4,5-d]pyrimidine, 1H- [1,2,3]triazolo[4,5-d]pyrimidine, [1,2,4]triazolo[4,3-c]pyrimidine, [1,2,4]triazolo[4,3-a]pyrimidine, [1,2,3]triazolo[1,5-a]pyrimidine, [1,2,3]triazolo[1,5-c]pyrimidine, [1,2,4]triazolo[1,5-a]pyrimidine or[1,2,4]triazolo[1,5-c]pyrimidine; each is a separate embodiment according to this invention. In other embodiments, A’ is 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine. In other embodiments, A’ is 1,2,3,4- tetrahydronaphthalene. In other embodiments, A’ is chroman. In other embodiments, A’ is isochroman. In other embodiments, A’ is 1,2,3,4-tetrahydroquinoline. In other embodiments, A’ is 1,2,3,4- tetrahydroisoquinoline. In other embodiments, A’ is 2,3-dihydro-1H-indene. In other embodiments, A’ is 2,3-dihydrobenzofuran. In other embodiments, A’ is 1,3-dihydroisobenzofuran. In other embodiments, A’ is isoindoline. In other embodiments, A’ is indoline. In some embodiments, A’ of formula I(f) is not a phenyl.

[0131] In some embodiments, R100of formula I(g) is H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl), R8-OH (e.g., (CH2)2-OH), -R8-O-R10(e.g., (CH2)2-O-CH3), R8- N(R10)(R11) (e.g., (CH2)2-NH(CH3), (CH2)2-NH2), R20, or a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., pyrrolidine, piperidine); each represents a separate embodiment according to this invention. In some embodiments, R100is H. In some embodiments, R100is C1-C5substituted or unsubstituted linear or branched alkyl. In some embodiments, R100is C1-C5unsubstituted linear or branched alkyl. In other embodiments, R100is CH3. In other embodiments, R100is CH2CH3. In other embodiments, R100is CH2CH2CH3. In some embodiments, R100is isopropyl. In some embodiments, R100is butyl. In some embodiments, R100is isobutyl. In some embodiments, R100is t-butyl. In some embodiments, R100is pentyl. In some embodiments, R100is isopentyl. In some embodiments, R100is neopentyl. In some embodiments, R100is benzyl. In some embodiments, R100is C1-C5substituted linear or branched alkyl. In other embodiments, R100is CH2-CH2-O-CH3. In other embodiments, R100is CH2- CH2-OH. In other embodiments, R100is R8-OH. In other embodiments, R100is (CH2)2-OH. In other embodiments, R100is -R8-O-R10.In other embodiments, R100is (CH2)2-O-CH3. In other embodiments, R100is R8-N(R10)(R11). In other embodiments, R100is (CH2)2-NH(CH3). In other embodiments, R100is (CH2)2-NH2. In other embodiments, R100is R20as defined hereinabove. In other embodiments, R100is a substituted or unsubstituted 3-8 membered heterocyclic ring. In other embodiments, R100is pyrrolidine. In other embodiments, R100is piperidine. In other embodiments, R100is C1-C5substituted or unsubstituted linear or branched haloalkyl. In other embodiments, R100is C1-C5linear or branched alkoxy. In other embodiments, R100is O-CH3. In other embodiments, R100is C(O)R. In other embodiments, R100is S(O)2R. In some embodiments, R100is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide (e.g., C(O)N(R)2, C(O)-pyrrolidine, C(O)-piperidine, N(R)2NH(R10), N(R10)(R11), (e.g., N(CH3)2, NH2), CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g. pyran, oxetane, piperidine, pyrazole, methyl-pyrrazole, triazole, imidazole), halophenyl, (benzyloxy)phenyl, CN and NO2; each represents a separate embodiment according to this invention.

[0132] In some embodiments, Ring W of formula I(j) and / or I(n) is a 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring. In someembodiments, Ring W is a 3-8 membered single saturated heterocyclic ring. In some embodiments, Ring W is morpholine (e.g., 2 or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, pyrrolidine, piperazine, piperidine; each represents a separate embodiment according to this invention. In some embodiments, Ring W is further substituted with R200to form a substituted heterocyclic ring, including but not limited to: oxetan-3-ol, pyrrolidin-2-ol, pyrrolidin-3-ol, 3-methoxypyrrolidine, 3- cyanopyrrolidine, 1-methylpyrrolidine, 3-(difluoromethyl)pyrrolidine, 3,3-difluoropyrrolidine, piperidin-3-ol, piperidin-4-ol, piperidine-4-carbonitrile, 4-fluoropiperidine, 2,2-dimethylpyrrolidine, pyrrolidin-3-one-O-methyloxime, 3,3-dimethylmorpholine or 1-methylpiperazine; each represents a separate embodiment according to this invention. In some embodiments, Ring W is a 3-8 membered single unsaturated heterocyclic ring. In some embodiments, Ring W is a pyrrolidin-2-one, pyrrolidin-3- one, pyrrolidinone, pyrrolidin-3-one-O-methyloxime, imidazole, pyrazole, isoxazolidine, piperidine-2- one, piperazine-2-one, oxadiazole, triazole, 2-oxopyrrolidine; each represents a separate embodiment according to this invention. In some embodiments, Ring W is a 3-10 membered spiro, saturated, heterocyclic ring. In some embodiments, Ring W is 4-azaspiro[2.4]heptane, 2-oxa-5- azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane, 4,7-diazaspiro[2.5]octane; each represents a separate embodiment according to this invention. In some embodiments, Ring W is a 3-10 membered bridged, saturated, heterocyclic ring. In some embodiments, Ring W is bicyclo[1.1.1]pentane, 2,5- diazabicyclo[2.2.1]heptane; each represents a separate embodiment according to this invention.In some embodiments, Ring W is a 3-8 membered single saturated carbocyclic ring (i.e., cycloalkyl). In some embodiments, Ring W is cyclopropyl.

[0133] In some embodiments, R200of formula I(j), I(k), I(l) and / or I(n) is H, R20, F, Cl, Br, I, OH, SH, alkoxy, NH2, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl, methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3, C1-C5linear or branched alkoxy, methoxy, C1-C5linear or branched haloalkyl, CHF2, CF3, CF2CH3, CH2CF3,CF2CH2CH3,CH2CH2CF3,CF2CH(CH3)2,CF(CH3)-CH(CH3)2, R8-aryl, CH2-Ph, -R8-O-R8-O-R10, (CH2)2-O-(CH2)2-O-CH3, -R8-O-R10, -R8-R10, (CH2)2-O-CH3, substituted or unsubstituted aryl, phenyl, substituted or unsubstituted heteroaryl, pyridine, 2, 3, or 4-pyridine; each represents a separate embodiment according to this invention. In some embodiments, R200is H. In some embodiments, R200is F. In some embodiments, R200is Cl. In some embodiments, R200is Br. In some embodiments, R200is I. In some embodiments, R200is OH. In some embodiments, R200is SH. In some embodiments, R200is alkoxy. In some embodiments, R200is NH2. In some embodiments, R200is N(R10)(R11) . In some embodiments, R200is CF3. In some embodiments, R200is CN. In some embodiments, R200is NO2. In some embodiments, R200is C1-C5linear or branched, substituted or unsubstituted alkyl. In some embodiments, R200is methyl or ethyl. In some embodiments, R200is C1-C5linear or branched alkoxy. In some embodiments, R200is methoxy. In some embodiments, R200is C1-C5linear or branched haloalkyl. In some embodiments, R200is CHF2. In some embodiments, R200and the carbon atom to which it is connected are C=O. In some embodiments, R200and the carbon atom to which it is connected are C=N-O(R). In some embodiments, R200and the carbon atom to which it is connected are C=N-O-CH3. In some embodiments, R200and the carbon atom to which it is connected are C(R)2. In some embodiments, R200and the carbon atom to which it is connected are C(CH3)2. In some embodiments, R200and the carbon atom to which it is connected are CF2.

[0134] In some embodiments, W1of formula I(j), I(k) and / or I(m) is CH2. In some embodiments, W1is C=O. In some embodiments, W1is CH(R10). In some embodiments, W1is CHCH3.

[0135] In some embodiments, Q1of formula I(k) is O. In some embodiments, Q1is NH. In some embodiments, Q1is CH2. In some embodiments, Q1is CH(R). In some embodiments, Q1is C(R)2. In some embodiments, Q1is S. In some embodiments, Q1is S=O. In some embodiments, Q1is SO2. In some embodiments, Q1is C=O.

[0136] In some embodiments, Q2of formula I(k) is C=O. In some embodiments, Q2is NH. In some embodiments, Q2is CH2. In some embodiments, Q2is O. In some embodiments, Q2is CH(R). In some embodiments, Q2is C(R)2. In some embodiments, Q2is S. In some embodiments, Q2is S=O. In some embodiments, Q2is SO2.

[0137] In some embodiments, t of formula I(k) is a...

Claims

WHAT IS CLAIMED:

1. A compound represented by the structure of formula I(j):wherein X2, X3, and X4, are each independently nitrogen or CH; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); Ring W is a 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring (e.g., morpholine (2 or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidine-2-one, oxadiazole, triazole, 2-oxopyrrolidine, cyclopropyl, 2,2-dimethylpyrrolidine, 4-azaspiro[2.4]heptane, pyrrolidin-3-one-O-methyloxime, 2-oxa- 5-azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane, 3,3-dimethylmorpholine, 1-methylpiperazine, 4,7-diazaspiro[2.5]octane, bicyclo[1.1.1]pentane, 2,5-diazabicyclo[2.2.1]heptane, piperazine, piperazine-2-one); W1is CH2, C=O or CH(R10) (e.g., CHCH3); R7’ and R7’’ are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl,cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7’ and R7’’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10(CH2-OH, CH2-CH2-OH), -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R200is H, R20, F, Cl, Br, I, OH, SH, alkoxy, NH2, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2- O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy (e.g., methoxy), C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); or R200and the carbon atom to which it is connected are C=O, C=N-O(R) (e.g, C=N-O-CH3) or C(R)2(e.g., C(CH3)2, CF2); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

2. The compound of claim 1, wherein Ring W is a 3-8 membered single saturated heterocyclic ring, preferably morpholine (2 or 3- morpholine), tetrahydrofuran, tetrahydropyran, oxetane, pyrrolidine, isoxazolidine, piperazine, piperidine; a 3-8 membered single unsaturated heterocyclic ring, preferably pyrrolidin-2-one, pyrrolidin-3- one, imidazole, pyrazole, piperidine-2-one, piperazine-2-one, oxadiazole, triazole, 2-oxopyrrolidine; a 3-10 membered spiro saturated heterocyclic ring, preferably 4-azaspiro[2.4]heptane, 2-oxa-5- azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane, 4,7-diazaspiro[2.5]octane; a 3-10 membered bridged saturated heterocyclic ring, preferably bicyclo[1.1.1]pentane, 2,5- diazabicyclo[2.2.1]heptane; or a 3-8 membered single saturated carbocyclic ring (i.e., cycloalkyl), preferably cyclopropyl; R200is H, OH, F, NH2, C1-C5linear or branched alkoxy, methoxy, CN, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl), C1-C5linear or branched haloalkyl, CHF2, or R200and the carbon atom to which it is connected are C=O, C=N-O(R) (e.g, C=N-O-CH3) or C(R)2(e.g., C(CH3)2, CF2) X2, and X3are CH; X4, is N or CH; X10is N, CH, C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy) or C(COOH); R7' is H, F, Cl, CF3, C1-C5linear or branched, substituted or unsubstituted alkyl, preferably methyl, C1-C5linear or branched, or C3-C8cyclic alkoxy, preferably methoxy, substituted orunsubstituted C3-C8cycloalkyl, preferably cyclopropyl or cyclohexyl, or substituted or unsubstituted aryl; R7’’ is H or F; n is 1 or 2; or any combination thereof.

3. The compound of claim 1 or 2, selected from the following:

4. The compound of any one of claims 1-3, wherein the compounds is not (R)-2-(2-fluoro-4-(pyrrolidin- 2-yl)phenyl)-N-(3-(4-fluoropiperidin-1-yl)propyl) benzo[d]imidazo [2,1-b] thiazole-7-carboxamide, (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3-(4-fluoropiperidin-1-yl)propyl)benzo[d]imidazo[2,1- b]thiazole-7-carboxamide or 2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-N-(3-(4-fluoropiperidin-1- yl)propyl) benzo[d]imidazo[2,1-b]thiazole-7-carboxamide.

5. A compound represented by the structure of formula I(n):wherein X2, X3, and X4, are each independently nitrogen or CH; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); Ring W is a 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring (e.g., morpholine (2 or 3-morpholine), tetrahydrofuran, tetrahydropyran, oxetane, pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, pyrrolidinone, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidine-2-one, oxadiazole, triazole, 2-oxopyrrolidine,cyclopropyl, 4-azaspiro[2.4]heptane, pyrrolidin-3-one-O-methyloxime, 2-oxa-5-azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane, 4,7-diazaspiro[2.5]octane, bicyclo[1.1.1]pentane, 2,5- diazabicyclo[2.2.1]heptane, piperazine, piperazine-2-one); R200is H, R20, F, Cl, Br, I, OH, SH, alkoxy, methoxy, NH2, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O- CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy (e.g., methoxy), C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); or R200and the carbon atom to which it is connected are C=O, C=N-O(R) (e.g, C=N-O-CH3) or C(R)2(e.g., C(CH3)2, CF2); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, C1-C5linear or branched alkyl (e.g., methyl, ethyl, iso-propyl), CD3, or substituted or unsubstituted, saturated or unsaturated, single, fused, bridged or spiro 3-10 membered carbocyclic or heterocyclic ring (e.g., piperidine (2, 3, or 4-piperidine), 1-methylpiperidine (1-methyl-3-piperidine, 1-methyl-4-piperidine), 3-fluoro-1-methylpiperidine, 1-(2,2,2-trifluoroethyl)piperidine, azetidine, 1- methyl-azetidine (1-methyl-3-azetidine), morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran (4 or 3-tetrahydropyrane), tetrahydrofurane, azaspiro[3.3]heptane, 8-methyl-8- azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy- tetrahydrofurane, azepan-2-one, azabicyclohexane, 4,4-difluorocyclohexane, cyclopropyl); R7’ and R7’’ are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl;or R7’ and R7’’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH, CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

6. The compound of claim 5, wherein X2and X3are CH; X4is CH or nitrogen; Ring W is a 3-10 membered single, saturated, heterocyclic ring, preferably morpholine (e.g., 2 or 3-morpholine), tetrahydrofuran, tetrahydropyran, pyrrolidine, isoxazolidine, piperazine, piperidine; 3-10 membered single, unsaturated, heterocyclic ring, preferably piperazine-2-one; 3-10 membered spiro, heterocyclic ring, preferably 4-azaspiro[2.4]heptane, 2-oxa-5- azaspiro[3.4]octane, 1,4-dioxa-6-azaspiro[4.4]nonane, 4,7-diazaspiro[2.5]octane; 3-10 membered bridged, heterocyclic ring, preferably bicyclo[1.1.1]pentane, 2,5- diazabicyclo[2.2.1]heptane; or 3-10 membered single, unsaturated heterocyclic ring, preferably pyrrolidin-2-one, pyrrolidin-3-one, piperazine-2-one, piperidine-2-one, pyrrolidin-3-one-O-methyloxime; R200is H, OH, CN, NH2, C1-C5linear or branched, substituted or unsubstituted alkyl, C1-C5linear or branched alkoxy (e.g., methoxy), C1-C5linear or branched haloalkyl (e.g., CHF2); or R200and the carbon atom to which it is connected are C=O, C=N-O(R) (e.g, C=N- O-CH3) or C(R)2(e.g., C(CH3)2, CF2); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, C1-C5linear or branched, substituted or unsubstituted alkyl, preferably methyl, ethyl, or iso-propyl, CD3, a substituted or unsubstituted saturated single, 3-10 membered heterocyclic ring, preferably piperidine (e.g., 2, 3, or 4-piperidine), 1-methylpiperidine (e.g., 1-methyl-3- piperidine, 1-methyl-4-piperidine), 3-fluoro-1-methylpiperidine, 1-(2,2,2- trifluoroethyl)piperidine, azetidine, 1-methyl-azetidine (e.g., 1-methyl-3-azetidine), morpholine, tetrahydropyran (e.g., 4 or 3-tetrahydropyrane), tetrahydrofurane, dioxane, or 1,3- dioxane saturated bridged or spiro 3-10 membered heterocyclic ring, preferably 8-methyl-8- azabicyclo[3.2.1]octane, or substituted or unsubstituted, saturated single, 3-10 membered carbocyclic ring (i.e., cycloalkyl), preferably 4,4-difluorocyclohexane, cyclopropyl; R7’ and R7’’ are each independently H or F; or any combination thereof.

7. The compound of claim 5 or 6, wherein the carbocyclic or heterocyclic ring as defined in R6is further substituted with at least one substitution selected from: F, Cl, Br, I, C1-C5linear or branched alkyl, OH, alkoxy (e.g., OMe), amide , C(O)N(R)2, C(O)-alkyl, C(O)-pyrrolidine, C(O)-piperidine, N(R)2, NH(R10), N(R10)(R11), N(CH3)2, NH2, CF3, aryl, phenyl, heteroaryl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclobutanol), substituted or unsubstituted 3-8 memberedheterocyclic ring (e.g., pyran, oxetane, piperidine, pyrazole, triazole, imidazole), C1-C5linear or branched haloalkyl (e.g., CH2CF3, CHF2), halophenyl, (benzyloxy)phenyl, CN, and NO2.

8. The compound of any one of claims 5-7, wherein the substituted or unsubstituted ring of R6is piperidine (e.g., 2, 3, or 4-piperidine), 1-methylpiperidine (e.g., 1-methyl-3-piperidine, 1-methyl-4- piperidine), 3-fluoro-1-methylpiperidine, 1-(2,2,2-trifluoroethyl)piperidine, azetidine, 1-methyl- azetidine (e.g., 1-methyl-3-azetidine), morpholine, tetrahydropyran (e.g., 4 or 3-tetrahydropyrane), tetrahydrofurane, dioxane, or 1,3-dioxane, 8-methyl-8-azabicyclo[3.2.1]octane, 4,4- difluorocyclohexane, or cyclopropyl.

9. The compound of any one of claims 5-8, selected from the following:

10. A compound represented by the structure of formula I(o): RI(o) wherein X2, X3, and X4are each independently nitrogen or CH; X5, X6, X7, X8and X9are each independently nitrogen or carbon atoms; X10is N, CH, or C(R) (e.g., C(CH2)OH, C(CH2)2OH, C(NH-CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), C(COOH)); R1is H, F, Cl, Br, I, OH, SH, or CF3, substituted or unsubstituted C1-C5alkyl (e.g., CH2OH), C1-C5linear or branched, or C3-C8cyclic haloalkyl, substituted or unsubstituted C1-C5linear or branched, or C3-C8cyclic alkoxy; R2is substituted or unsubstituted C1-C5alkyl (e.g., CH2OH, CH2OCH3), 3-8 membered carbocyclic or heterocyclic ring (e.g., oxetane); or R1and R2are joined to form a 3-8 membered carbocyclic or heterocyclic ring (e.g., cyclopropyl, oxetane);R3and R4are each independently H, Me, substituted or unsubstituted C1-C5alkyl (e.g., methoxyethylene, methylaminoethyl, aminoethyl), -R8-O-R10(e.g., (CH2)2-O-CH3), R8-N(R10)(R11) (e.g., (CH2)2-NH(CH3)), substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl), substituted or unsubstituted 5-7 membered heterocyclic ring (e.g., pyrrolidine, methylpyrrolidine, piperidine), or R20; or R3and R4are joined to form a 3-8 membered heterocyclic ring (e.g., pyrrolidine, , pyrrolidone, 2-oxopyrrolidine, piperidine, morpholine, piperazine, imidazole); R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is H, C1-C5linear or branched alkyl (e.g., methyl, ethyl), substituted or unsubstituted, saturated or unsaturated, single fused, bridged or spiro 3-10 membered heterocyclic ring (e.g., piperidine, 1-methylpiperidine, 3-fluoro-1-methylpiperidine, azetidine, 1-methyl-azetidine, morpholine, pyrrolidine, pyrrolidinone, quinuclidine, tetrahydropyran, tetrahydrofurane, azaspiro[3.3]heptane, 8- methyl-8-azabicyclo[3.2.1]octane, dioxane, 1,3-dioxane, imidazole, trifluoromethyl-oxetane, hydroxy- tetrahydrofurane, azepan-2-one, azabicyclohexane) or (CH2)3-4-fluoro-piperidine; R7’ and R7’’ are each independently H, F, Cl, Br, I, OH, O-R20, SH, R8-OH, R8-SH, -R8-O-R10, R8-(C3-C8cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, -CH2CN, - R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8-N(R10)(R11), R9-R8-N(R10)(R11), B(OH)2, - OC(O)CF3, -OCH2Ph, NHC(O)-R10, NHCO-N(R10)(R11), COOH, -C(O)Ph, C(O)O-R10, R8-C(O)-R10, C(O)H, C(O)-R10, C1-C5linear or branched C(O)-haloalkyl, -C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH-R10), C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., isopropyl, methyl, ethyl), C1-C5linear or branched, substituted or unsubstituted alkenyl, C1-C5linear or branched, or C3-C8cyclic haloalkyl (e.g., CHF2), C1-C5linear or branched, or C3-C8cyclic alkoxy (e.g. methoxy), optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5linear or branched thioalkoxy, C1-C5linear or branched haloalkoxy, C1-C5linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclohexyl), substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine), substituted or unsubstituted aryl, substituted or unsubstituted benzyl; or R7’ and R7’’ are joined 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); R20is represented by the following structure:R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH-CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-OH,CH2-CH2-OH, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C3-C8substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5linear or branched alkoxy, isopropoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O- CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O-CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); R30is H, R20, F, Cl, Br, I, OH, SH, alkoxy, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5linear or branched, substituted or unsubstituted alkyl (e.g., methyl, ethyl, CH2-CH2-O-CH2-CH2-O-CH3, CH2-O-CH2-CH2-O-CH3), C1-C5linear or branched alkoxy, C1-C5linear 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-O-R10(e.g. (CH2)2-O-(CH2)2-O-CH3), -R8-O-R10, -R8-R10(e.g., (CH2)2-O- CH3), substituted or unsubstituted aryl (e.g., phenyl), substituted or unsubstituted heteroaryl (e.g., pyridine (2, 3, and 4-pyridine); each R8is independently [CH2]pwherein p is between 1 and 10; R9is [CH]q, [C]qwherein q is between 2 and 10; R10and R11are each independently H, C1-C5substituted or unsubstituted linear or branched alkyl (e.g., methyl, ethyl, CH2-cyclopropyl, CH2-CH2-O-CH3), C1-C5substituted or unsubstituted linear or branched haloalky (e.g., CH2CF3), C1-C5linear or branched alkoxy (e.g., O-CH3), R20, C(O)R, or S(O)2R; or R10and R11are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring (e.g., piperazine, piperidine), n is an integer between 0 and 4 (e.g., 1, 2); or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

11. The compound of claim 10, wherein R1is H; R2is a substituted C1-C5alkyl (e.g., CH2OH, CH2OCH3), or 3-8 membered heterocyclic ring (e.g., oxetane); R3and R4are each independently H; R5is H or C1-C5linear or branched alkyl (e.g. methyl); R6is C1-C5linear or branched alkyl (e.g., methyl, ethyl), (CH2)3-4-fluoro-piperidine, or tetrahydropyran; R7’ is F; R7’’ is H;n is 1; or any combination thereof.

12. The compound of claim 10 or 11, wherein the compound is represented by the structure of any one of the following compounds:

13. A compound represented by the structure of any one of the following compounds:or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant (e.g., deuterated analog), PROTAC, pharmaceutical product or any combination thereof.

14. The compound according to any one of claims 1-13, wherein the compound is a c-MYC mRNA translation modulator, a c-MYC mRNA transcription regulator, a c-MYC inhibitor or any combination thereof.

15. A pharmaceutical composition comprising the compound of any one of claims 1-14 and a pharmaceutically acceptable carrier.

16. The compound according to any one of claims 1-14 or the pharmaceutical composition according to claim 15, for use in treating, suppressing, reducing the severity, reducing the risk of developing or inhibiting cancer in a subject.

17. The compound of claim 16, wherein the cancer is selected from the list of: breast cancer, ovarian carcinoma, acute myeloid leukemia, chronic myelogenous leukemia, Hodgkin’s and Burkitt’s lymphoma, diffuse large Bcell lymphoma, prostate cancer, colon cancer, gastric cancer, primary central nervous system lymphoma, glioblastoma, medulloblastoma, melanoma, non-small cell lung carcinoma, germinal center-derived lymphomas, 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 early cancer, advanced cancer, invasive cancer, metastatic cancer, drug resistant cancer or any combination thereof; wherein the subject has been previously treated with chemotherapy, immunotherapy, radiotherapy, biological therapy, surgical intervention, or any combination thereof; wherein the compound is administered in combination with an anti-cancer therapy; or any combination thereof.

18. The compound of claim 17, wherein the anti-cancer therapy is chemotherapy, immunotherapy, radiotherapy, biological therapy, surgical intervention, or any combination thereof.

19. The compound according to any one of claims 1-14 or the pharmaceutical composition according to claim 15, for use in suppressing, reducing or inhibiting tumor growth in a subject.

20. A method of modulating c-MYC mRNA translation, or regulating c-MYC mRNA transcription in a cell, comprising contacting a compound according to any one of claims 1-14 with a cell, thereby modulating c-MYC mRNA translation, or regulating c-MYC mRNA transcription in said cell.

21. The method of claim 20, wherein said method is carried out(a) by regulating c-MYC mRNA splicing (inclusion or exclusion of untranslated region or alternative usage of exons); (b) by regulation of c-MYC mRNA modifications; (c) by regulation of the interaction of RNA binding protein with c-MYC mRNA thereby changing mRNA localization; (d) by regulating c-MYC mRNA localization in the cytoplasm; (e) by regulating ribosomes or ribosome accessory factor to c-MYC mRNA; (f) by reducing the amount of c-MYC protein in the cell; or any combination thereof.

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