POLYMORPHIC CARBAZOLE DERIVATIVES AND THEIR USES

Abstract

The present invention provides salt and freebase forms, and compositions and methods thereof, useful for treating various conditions in which the aryl hydrocarbon receptor (AHR) is involved, by administering small molecule therapeutic products that act as AHR inhibitors.

Description

POLYMORPHOUS CARBAZOLE DERIVATIVES AND USES THEREOF Qncann / zznz / E / YiAi FIELD OF THE INVENTION The present application relates to various forms and compositions, and methods, useful for treating various conditions in which the aryl hydrocarbon receptor (AHR) is involved, by administering small molecule therapeutic agents that They act as AHR inhibitors. BACKGROUND OF THE INVENTION The aryl hydrocarbon receptor (AHR) is a transcription factor that exists unliganded in the inactive state in the cytoplasm bound to HSP90. Upon ligand binding, AHR translocates to the nucleus where it dimerizes with ARNT forming a functional transcription factor. AHR / tRNA binds to dioxin response elements (DREs) in the promoter of many genes where it modulates gene transcription. The most well-documented genes regulated by AHR are the cytochrome P450 genes Cyplbl and Cyplal, where AHR activation greatly increases the expression of these genes. Therefore, the levels of Cyplbl and Cyplal mRNA are a selective readout of AHR activation (reviewed in Murray et al., 2014). There are many exogenous and endogenous AHR agonists that activate the receptor. The best exogenous ligand class Ref. 334495 characterized are dioxins. One of the first endogenous ligands to be characterized is kynurenine, generated by TDO (Opitz 2011) or IDO (Mezrich 2010). Kynurenine is a stable metabolite in the IDO / TDO pathway and is the degradation product of tryptophan. Kynurenine has been shown to activate the AHR as measured by an increase in Cyplal and / or Cyplbl mRNA levels in multiple cell types, along with other DRE-driven genes. Activation of the AHR has pro-tumor effects by acting directly on humoral cells and indirectly by causing immunosuppression, thereby not allowing the body's own immune system to attack the tumor. For example, activation of AHR through multiple ligands leads to increased expression of FoxP3 and results in polarization of CD4+ T cells toward a suppressive subset called Foxp3+ regulatory T cells (Tregs). These T-reg cells inhibit the proliferation of activated T cells (Funatake 2005, other authors). Interestingly, kynurenine has been shown to induce immunosuppressive Tregs through AHR. Kynurenine does not affect the generation of T recordings in AHR-null T cells or when an AHR antagonist (Mezrich) is added. In addition to T registers, AHR activation also leads to the expansion of suppressive Trl T cells (Gandhi 2010). IDO expression has also been shown to be regulated by AHR activation in both tumor cells and T cells, leading to increased immune suppression (Vogel). There is also likely a role for AHR in immunosuppressive myeloid cells (Nguyen 2013). Immune suppression is often associated with high levels of anti-inflammatory cytokines and there is evidence that AHR is involved in the activation of many of these cytokines, such as IL-10 (Gandhi 2010, Wagage 2014). There remains an unmet need to develop AHR inhibitors for the treatment of diseases, disorders and conditions associated with it. BRIEF DESCRIPTION OF THE INVENTION It has now been discovered that the compounds of the present invention, and their compositions, are useful for treating, preventing and / or reducing a risk of a disease, disorder or condition in which aldehyde toxicity is involved in the pathogenesis. In general, salt forms or free base forms, and pharmaceutically acceptable compositions thereof, are useful for treating or lessening the severity of a variety of diseases or disorders as described in detail herein. These compounds are represented by the chemical structure below, Qncann / zznz / E / YiAi denoted as compound A: Qncann / zznz / E / YiAi The compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful for treating a variety of diseases, disorders or conditions, associated with AHR. These diseases, disorders or conditions include those described herein. The compounds provided by the present invention are also useful for the study of AHR in biological and pathological phenomena; the study of intracellular signal transduction pathways; and the comparative evaluation of new AHR inhibitors in vitro or in vivo. BRIEF DESCRIPTION OF THE FIGURES Figure 1 illustrates the XRPD pattern of Compound A, Form B. Figure 2 illustrates a TG / DTA trace of Compound A, Form B. Figure 3 illustrates the XRPD pattern of Compound A, Form C. Figure 4 illustrates an A, Form C. Figure 5 illustrates 1, Form A. Figure 6 illustrates a 1, Form A. Figure 7 illustrates 1, Form B. Figure 8 illustrates 2, Form A. Figure 9 illustrates a 2, Form A. Figure 10 illustrates 3, Form A. Figure 11 illustrates Compound 3, Form A. Figure 12 illustrates 3, Form B. Figure 13 illustrates Compound 3, Form B. Figure 14 illustrates 4, Form A. Figure 15 illustrates Compound 4, Form A. Figure 16 illustrates the TG / DTA trace of the XRPD Standard Compound of the TG / DTA Compound trace of the XRPD Standard Compound of the / DTA of the XRPD pattern of the Compound a trace of TG / DTA of the XRPD pattern of the Compound a trace of TG / DTA of the XRPD pattern of the Compound 5, Form A. Figure 17 illustrates a TG / DTA trace of Compound 5, Form A. Figure 18 illustrates the XRPD pattern of Compound 6, Form A. Figure 19 illustrates a TG / DTA trace of Compound 6, Form A. Figure 20 illustrates the XRPD pattern of Compound 6, Form B. Figure 21 illustrates a TG / DTA trace of Compound 6, Form B. Figure 22 illustrates the XRPD pattern of Compound 7, Form A. Figure 23 illustrates a TG / DTA trace of Compound 7, Form A. Figure 24 illustrates the XRPD pattern of a mixture of Form A and Form B of Compound A. Figure 25 illustrates TGA / DSC of a mixture of Form A and Form B of Compound A. DETAILED DESCRIPTION OF THE INVENTION General description of certain aspects of the invention United States Patent Application No. 15 / 958,586, filed on April 20, 2018 and published as United States Patent Application No. 2018-0327411 on November 15, 2018 (the publication Qncann / zznz / E / YiAi '411, the entirety of which is incorporated herein by reference), describes certain AHR inhibitory compounds. These compounds include compound A: > u N C N N C C σ Ca c a Compound A, (3R)-N-[2-(5-fluoro-3-pyridyl)-8isopropyl-pyrazolo[1,5-a][l,3,5]triazin-4-yl]-2,3 ,4,9tetrahydro-1H-carbazole-3-amine, is designated as compound I40 in the '411 publication and the synthesis of compound A is described in detail in Example 39 of the '411 publication and is reproduced herein for convenience. The reference. It would be desirable to provide a solid form of compound A (for example, as a free base thereof or salt thereof) that imparts characteristics such as improved aqueous solubility, stability and ease of formulation. Accordingly, the present invention provides both free base forms and salt forms of compound A: Free base forms of compound A It is contemplated that compound A may exist in a variety of physical forms. For example, compound A may be in solution, suspension or solid form. In certain embodiments, compound A is in solid form. When compound A is in solid form, the compound may be amorphous, crystalline, or a mixture thereof. Example solid shapes are described in more detail below. In some embodiments, the present invention provides a form of compound A substantially free of impurities. As used herein, the term substantially free of impurities means that the compound does not contain a significant amount of foreign matter. This foreign matter may include different forms of compound A, residual solvents or any other impurities that may result from the preparation and / or isolation of compound A. In certain embodiments, at least about 95% by weight of a form of compound A is present. . In still other embodiments of the invention, at least about 99% by weight of one form of compound A is present. According to one embodiment, a form of compound A is present in an amount of at least about 97, 97.5, 98.0, 98.5, 99, 99.5, 99.8 weight percent where Qncann / zznz / E / YiAi percentages are based on the total weight of the composition. According to another embodiment, a form of compound A contains no more than about 3.0 HPLC area percent total organic impurities and, in certain embodiments, no more than about 1.5 HPLC area percent total organic impurities with respect to to the total area of ​​the HPLC chromatogram. In other embodiments, a form of compound A contains no more than about 1.0% HPLC area percent of any individual impurity; no more than about 0.6 HPLC area percent of any individual impurity and, in certain embodiments, no more than about 0.5 HPLC area percent of any individual impurity, relative to the total area of ​​the HPLC chromatogram. The structure depicted for one form of compound A is also intended to include all tautomeric forms of compound A. Additionally, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen with deuterium or tritium, or the replacement of one carbon with a carbon enriched with 13C or C14C are within the scope of this invention. It has been found that compound A can exist in a variety of solid forms. Examples of these forms include polymorphs such as those described herein. As used herein, the term polymorph refers to the different crystal structures in which a compound, or a salt or solvate thereof, can crystallize. In certain embodiments, compound A is a crystalline solid. In other embodiments, compound A is a crystalline solid substantially free of amorphous compound A. As used herein, the term substantially free of amorphous compound A means that the compound does not contain a significant amount of amorphous compound A. In certain embodiments, at least about 95% by weight of crystalline compound A is present. In still other embodiments of the invention, at least about 99% by weight of crystalline compound A is present. It has been found that compound A can exist in at least three different polymorphic forms. In certain embodiments, the present invention provides a polymorphic form of compound A referred to herein as Form A. In certain embodiments, the present invention provides a polymorphic form of compound A referred to herein as Form A. present as Form B. In certain embodiments, the present invention provides a Qncann / zznz / E / YiAi mixture of Form A and Form B of compound A. In certain embodiments, the present invention provides a polymorphic form of compound A referred to herein as Form C. In some embodiments, compound A is amorphous. In some embodiments, compound A is amorphous, and is substantially free of crystalline compound A. Form B of Compound A In some embodiments, Form B of compound A has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table B below. Table B - XRPD Peak Positions for Form B of Compound A Qncann / zznz / E / YiAi Position [°2Θ]Χ spacing d [Á] Intensity [%] 8.5 10.3405 0.8 9.2 9.5896 11 9.5 9.3466 100 9.8 8.9763 26.3 11.3 7.7944 4 12.8 6.907 9.6 13.7 6.443 8 3.9 14.2 6.2284 10 14.7 6.0202 27.4 15.4 5.7663 3.5 16.8 5.2862 13.9 17.5 5.0495 7.6 17.9 4.9378 1 18.5 4.8002 0.7 19.0 4.6705 1.3 19.2 4.6159 2 19.8 4.485 9.8 20.1 4.4138 14.2 20.9 4.2497 1.1 21.6 4.1169 2.3 21.8 4.073 1.4 22.5 3.9481 44 23.6 3.7662 1 .5 24.2 3.6729 5.8 24.6 3.6111 1.5 25.7 3.4637 6.2 26.0 3.4299 3.1 27.3 3.2589 1.8 27.7 3.2135 3.4 28.1 3.1726 1.4 28.6 3.1 145 1.6 29.1 3.0612 1 29.7 3.0045 4.8 31.5 2.8379 3.4 Qncann / zznz / E / YiAi1In this and all subsequent tables, the 2Θ position is within ± 0.2. In some embodiments, Form B of compound A is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 9.5, about 9.8, and about 14.7 degrees 2-theta. In some embodiments, Form B of compound A is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 9.5, about 9.8, and about 14.7 degrees 2-theta. In some embodiments, Form B of compound A is characterized by having three peaks in its X-ray powder diffraction pattern selected from those at about 9.5, about 9.8, and about 14.7 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern of Form B of Compound A is substantially similar to the XRPD provided in Figure 1. Methods for preparing Form B of compound A are described below. Form C of Compound A In some embodiments, Form C of compound A has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table C below. Table C – XRPD Peak Positions for Form C of the Qncann / zznz / E / YiAi Compound A Position [“Σθ]1 spacing d [Á] Intensity [%] 6.02 14.6575 100 7.34 12.0353 37.5 8.45 10.4488 5.5 8.60 10.275 13.5 8.61 10.2605 39.2 9.03 9.7846 1 6.8 10.29 8.5906 81.2 13.27 6.668 12.9 14.28 6.1968 3 14.45 6.1252 21.4 14.86 5.9561 26 15.20 5.8241 4.8 15.53 5.6994 11.5 15.80 5.6027 3.6 16.54 5.3548 1.3 16.85 5.256 2.6 17.26 5.1331 28.9 17.69 5.0108 1.4 18.10 4.8972 8.1 1 8.29 4.8453 8.7 18.59 4.7689 1.4 19.09 4.6451 3.1 19.43 4.5653 6.3 19.61 4.5233 11.2 19.89 4.4608 5 20.25 4.3824 18.9 21.18 4.191 21.9 22.30 3.984 3.1 22.41 3.9644 6.2 22.90 3.881 2.5 23.53 3.7773 2.5 24.44 3.6389 1.2 24.82 3.5836 3.6 25.39 3.5055 1.3 25.66 3.4686 2.3 26.00 3.4238 9.4 26.14 3.4064 8.8 26.69 3.3367 4 27.04 3.2951 8.6 27.35 3.2585 7.9 28.02 3.1813 2 29.12 3.0638 2 1In this and all subsequent tables, the 2Θ position is within ±0.2. In some embodiments, Form C of compound A is characterized by having one or more peaks in its pattern. Qncann / zznz / E / YiAi X-ray powder diffraction selected from those at approximately 6.02, approximately 8.61 and approximately 10.29 degrees 2-theta. In some embodiments, Form C of compound A is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 6.02, about 8.61, and about 10.29 degrees 2-theta. In some embodiments, Form C of compound A is characterized by having three peaks in its X-ray powder diffraction pattern selected from those at about 6.02, about 8.61, and about 10.29 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern of Form C of compound A is substantially similar to the XRPD provided in Figure 3. Methods for preparing Form C of compound A are described below. Mixture of Form A and Form B of Compound A In some embodiments, the present invention provides a mixture of Form A and Form B of compound A, which has an X-ray powder diffraction pattern substantially similar to the XRPD provided in Figure 2-4. In some embodiments, a mixture of Form A and Form B of compound A has a substantially similar TGA. Qncann / zznz / E / YiAi to the TGA provided in Figure 25. In some embodiments, a mixture of Form A and Form B of compound A has a DSC substantially similar to the DSC provided in Figure 25. Methods for preparing a mixture of Form A and Form B of compound A are described below. In some embodiments, the present invention provides compound A: TO. Qncann / zznz / E / YiAi where the compound is crystalline. In some embodiments, the present invention provides compound A, wherein the compound is substantially free of amorphous compound A. In some embodiments, the present invention provides compound A, wherein the compound is substantially free of impurities. In some embodiments, the present invention provides compound A, wherein the compound has an XRPD substantially similar to that depicted in Figure 1. In some embodiments, the present invention provides compound A, wherein the compound has a XRPD substantially similar to that depicted in Figure 3. In some embodiments, the present invention provides compound A, wherein the compound has an XRPD substantially similar to that depicted in Figure 24. In some embodiments, the present invention provides a composition comprising compound A and a pharmaceutically acceptable carrier or excipient. In some embodiments, the present invention provides a method of inhibiting AHR comprising administering compound A or composition thereof to the patient. In some embodiments, the present invention provides a method of inhibiting AHR in a patient comprising administering compound A or composition thereof to the patient. In some embodiments, the present invention provides a method of treating one or more disorders associated with AHR activity comprising administering compound A or composition thereof to the patient. In some embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need of the same compound A or composition thereof. In some embodiments, the AHR-mediated disorder is a Qncann / zznz / E / YiAi proliferative disease such as cancer or an inflammatory disorder. Salt Forms of Compound A In some embodiments, an acid and compound A are ionically bonded to form one of compounds 1 through 7, described below. It is contemplated that compounds 1 through 7 may exist in a variety of physical forms. For example, compounds 1 through 7 may be in solution, suspension or solid form. In certain embodiments, compounds 1 through 7 are in solid form. When compounds 1 through 7 are in solid form, the compounds may be amorphous, crystalline or a mixture thereof. Examples of these solid forms of compounds 1 to 7 are described in more detail below. Compound 1 (Esylate Salts of Compound A) According to one embodiment, the present invention provides an esylate salt of compound A, represented by compound 1: 1. Qncann / zznz / E / YiAi One skilled in the art will appreciate that ethanesulfonic acid and compound A bond ionically to form compound 1. It is contemplated that compound 1 may exist in a variety of physical forms. For example, compound 1 may be in solution, suspension or solid form. In certain embodiments, compound 1 is in solid form. When compound 1 is in solid form, the compound may be amorphous, crystalline or a mixture thereof. Example solid shapes are described in more detail below. In some embodiments, the present invention provides compound 1 substantially free of impurities. As used herein, the term substantially free of impurities means that the compound does not contain a significant amount of foreign matter. This foreign matter may include excess methanesulfonic acid, excess compound A, residual solvents or any other impurities that may result from the preparation and / or isolation of compound 1. In certain embodiments, at least about 95% by weight of compound 1 is present. In still other embodiments of the invention, at least about 99% by weight of compound 1 is present. According to one embodiment, compound 1 is present in an amount of at least about 97, 97.5, 98.0, 98.5, 99, 99.5, 99.8 weight percent where Qncann / zznz / E / YiAi percentages are based on the total weight of the composition. According to another embodiment, compound 1 contains no more than about 3.0 HPLC area percent of total organic impurities and, in certain embodiments, no more than about 1.5 HPLC area percent of total organic impurities with respect to the area total HPLC chromatogram. In other embodiments, compound 1 contains no more than about 1.0% HPLC area percent of any individual impurity; no more than about 0.6 HPLC area percent of any individual impurity and, in certain embodiments, no more than about 0.5 HPLC area percent of any individual impurity, relative to the total area of ​​the HPLC chromatogram. The structure depicted for compound 1 is also intended to include all tautomeric forms of compound 1. Additionally, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen with deuterium or tritium, or the replacement of one carbon with a carbon enriched with 13C or C14C are within the scope of this invention. It has been found that compound 1 can exist in a variety of solid forms. Examples of these forms include polymorphs such as those described herein. In certain embodiments, compound 1 is a crystalline solid. In other embodiments, compound 1 is a crystalline solid substantially free of amorphous compound 1. As used herein, the term substantially free of amorphous compound 1 means that the compound does not contain a significant amount of amorphous compound 1. In certain embodiments, at least about 95% by weight of the crystalline compound 1 is present. In still other embodiments of the invention, at least about 99% by weight of the crystalline compound 1 is present. It has been found that compound 1 can exist in at least one different polymorphic form. In some embodiments, the present invention provides a polymorphic form of Compound 1 referred to herein as Form A. In some embodiments, the present invention provides a polymorphic form of Compound 1 referred to herein. present as Form B. In some embodiments, compound 1 is amorphous. In some embodiments, compound 1 is amorphous and substantially free of crystalline compound 1. Form A of Compound 1 In some embodiments, Form A of compound 1 has at least 1, 2, 3, 4 or 5 selected spectral peaks. Qncann / zznz / E / YiAi from the peaks listed in Table 1 below. Qncann / zznz / E / YiAi Table 1 – XRPD Peak Positions for Form A of the Compound 1 Position [°2θ]1 spacing d [Á] Intensity [%] 5.8 15.3556 100 9.0 9.7887 4.8 11.6 7.6552 50.4 12.7 6.9761 2.4 13.5 6.5581 7.2 13.9 6.3739 6.4 14.2 6.2271 20 15.0 5.8855 16 15.3 5.7732 2.3 16.2 5.467 5 16.9 5.2552 1.1 17.4 5.099 4 18.1 4.8971 2.6 18.8 4.7082 32.3 19.4 4.5638 1.8 20.7 4.2954 6.3 23.2 3.8286 2.6 23.9 3.716 1.7 24.4 3.6524 2.1 24.5 3. 6304 2.1 24.9 3.5667 1.7 25.5 3.4859 12.2 25.9 3.4353 14 26.5 3.3649 0.6 27.2 3.2797 3.6 27.6 3.2317 2.6 28.1 3.1783 1.1 28.3 3.1519 4.2 28.7 3.1126 1.9 29.2 3.0595 3.8 29.5 3.02 12 0.9 31.1 2.8721 0.8 32.8 2.7304 0.8 33.1 2.7026 0.6 35.1 2.5538 1 35.9 2.4998 1.1 39.5 2.282 0.7 Qncann / zznz / E / YiAi1In this and all subsequent tables, the 2Θ position is within ± 0.2. In some embodiments, Form A of compound 1 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 5.8, about 11.6, and about 18.8 degrees 2-theta. In some embodiments, Form A of compound 1 is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 5.8, about 11.6, and about 18.8 degrees 2-theta. In some embodiments, Form A of compound 1 is characterized by having all three peaks in its X-ray powder diffraction pattern selected from those at about 5.8, about 11.6, and about 18.8 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 5. Methods for preparing Form A of compound 1 are described below. Form B of Compound 1 In some embodiments, Form B of compound 1 has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table 2 below. Table 2 - XRPD peak positions for Form B of Compound 1 Qncann / zznz / E / YiAi Position d Intensity 5.1 17.2744 1.5 5.6 15.7493 100 8.9 9.9195 1.3 9.5 9.3413 1.2 9.9 8 . 965 0.1 10.2 8.7059 0.4 10.9 8.1087 1.8 11.2 7.8636 60 12.2 7.2352 0.1 12.8 6.9174 0 13.2 6.6957 3 14.0 6.3029 1.3 14.7 6 .0184 0.3 15.0 5.9183 3.2 15.7 5.643 1 16.2 5.4526 0.1 16.9 5.2422 6.7 17.5 5.0508 0 17.9 4.9563 0.2 18.5 4.7908 1.1 19.8 4.4798 0.3 20.9 4.238 1.2 21.6 4.1127 0.1 22.0 4.0401 0.1 22.5 3.9459 0.6 23.7 3.7457 0.3 24.2 3.6719 0.1 24.6 3.6151 0.3 25.6 3.4774 1.8 26.0 3.4236 0.2 26.6 3.3461 0.8 26.8 3. 321 0.2 28.4 3.1454 3.2 29.2 3.0548 0.5 Qncann / zznz / E / YiAi1In this and all subsequent tables, the 2Θ position is within ± 0.2. In some embodiments, Form B of compound 1 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 5.6, about 11.2, and about 16.9 degrees 2-theta. In some embodiments, Form B of compound 1 is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 5.6, about 11.2, and about 16.9 degrees 2-theta. In some embodiments, Form B of compound 1 is characterized by having all three peaks in its X-ray powder diffraction pattern selected from those at about 5.6, about 11.2, and about 16.9 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 7. Methods for preparing Form B of compound 1 are described below. In some embodiments, the present invention provides compound 1: Qncann / zznz / E / YiAi In some embodiments, the present invention provides compound 1, wherein the compound is crystalline. In some embodiments, the present invention provides compound 1, wherein the compound is a crystalline solid substantially free of amorphous compound 1. In some embodiments, the present invention provides compound 1, wherein the compound is substantially free of impurities. In some embodiments, the present invention provides compound 1, wherein the compound has one or more peaks in its XRPD selected from those at 5.8, about 11.6 and about 18.8 degrees 2-theta. In some of these embodiments, the present invention provides compound 1, wherein the compound has at least two peaks in its XRPD selected from those at about 5.8, about 11.6 and about 18.8 degrees 2-theta. In some of these embodiments, the present invention provides compound 1, wherein the compound is Form A. In some embodiments, the present invention provides compound 1, wherein the compound has an XRPD substantially similar to that depicted in Figure 5. In some embodiments, the present invention provides compound 1, wherein the compound has one or more peaks in its XRPD selected from those at 5.6, about 11.2 and about 16.9 degrees 2-theta. In some of these embodiments, the present invention provides compound 1, wherein the compound has at least two peaks in its XRPD selected from those at about 5.6, about 11.2 and about 16.9 degrees 2-theta. In some of these embodiments, the present invention provides compound 1, wherein the Qncann / zznz / E / YiAi compound is of Form B. In some embodiments, the present invention provides compound 1, wherein the compound has an XRPD substantially similar to that depicted in Figure 7. In some embodiments, the present invention provides a composition comprising compound 1 and a pharmaceutically acceptable carrier or excipient. In some embodiments, the present invention provides a method of inhibiting AHR comprising administering compound 1 or composition thereof to the patient. In some embodiments, the present invention provides a method of inhibiting AHR in a patient comprising administering compound 1 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating one or more disorders associated with AHR activity comprising administering compound 1 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need of the same compound 1 or composition thereof. In some embodiments, the AHR-mediated disorder is a proliferative disease such as cancer or a disorder Qncann / zznz / E / YiAi inflammatory . Compound 2 (Maleate Salts of Compound A) According to one embodiment, the present invention provides a maleate salt of compound A, represented by compound 2: Qncann / zznz / E / YiAi where approximately 1 < x < approximately 2. One skilled in the art will appreciate that maleic acid and compound A bond ionically to form compound 2. In some embodiments, compound A and maleic acid are in a ratio of approximately 1:1. In some embodiments, compound A and maleic acid are in a ratio of approximately 2:1. It is contemplated that compound 2 may exist in a variety of physical forms. For example, compound 2 may be in solution, suspension or solid form. In certain embodiments, compound 2 is in solid form. When compound 2 is in solid form, the compound may be amorphous, crystalline or a mixture thereof. Example solid shapes are described in more detail below. In some embodiments, the present invention provides compound 2 substantially free of impurities. As used herein, the term substantially free of impurities means that the compound does not contain a significant amount of foreign matter. This foreign matter may include excess benzenesulfonic acid, excess compound A, residual solvents or any other impurities that may result from the preparation and / or isolation of compound 2. In certain embodiments, at least about 95% by weight of compound 2 is present. In still other embodiments of the invention, at least about 99% by weight of compound 2 is present. According to one embodiment, compound 2 is present in an amount of at least about 97, 97.5, 98.0, 98.5, 99, 99.5, 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, compound 2 contains no more than about 3.0 HPLC area percent of total organic impurities and, in certain embodiments, no more than about 1.5 HPLC area percent of total organic impurities with respect to the area total HPLC chromatogram. In other embodiments, compound 2 contains no more than about 1.0% HPLC area percent of Qncann / zznz / E / YiAi any individual impurities; no more than about 0.6 HPLC area percent of any individual impurity and, in certain embodiments, no more than about 0.5 HPLC area percent of any individual impurity, relative to the total area of ​​the HPLC chromatogram. The structure depicted for compound 2 is also intended to include all tautomeric forms of compound 2. Additionally, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen with deuterium or tritium, or the replacement of one carbon with a carbon enriched with 13C or C14C are within the scope of this invention. It has been found that compound 2 can exist in at least one different polymorphic form. In some embodiments, the present invention provides a polymorphic form of Compound 2 referred to herein as Form A. In some embodiments, Form A of Compound 2 comprises compound A and maleic acid in a ratio of about 2:1. In certain embodiments, compound 2 is a crystalline solid. In other embodiments, compound 2 is a crystalline solid substantially free of amorphous compound 2. As Qncann / zznz / E / YiAi As used herein, the term substantially free of amorphous compound 2 means that the compound does not contain a significant amount of amorphous compound 2. In certain embodiments, at least about 95% by weight of the crystalline compound 2 is present. In still other embodiments of the invention, at least about 99% by weight of the crystalline compound 2 is present. It has been found that compound 2 can exist in at least one different polymorphic form. In some embodiments, the present invention provides a polymorphic form of Compound 2 referred to herein as Form A. In some embodiments, compound 2 is amorphous. In some embodiments, compound 2 is amorphous and substantially free of crystalline compound 2. Form A of Compound 2 In some embodiments, Form A of compound 2 has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table 3 below. Table 3 - XRPD peak positions for Form A of Compound 2 Position [ °2Θ]1 spacing d [Á] Intensity [%] 5.3 16.6727 100 6.6 13.3333 3.8 8.0 11.0992 4 9.6 9.2459 3.9 10.6 8.3351 3.2 11.3 7.8022 40.9 13.3 6.6763 10.7 14.1 6.2596 1.9 14.7 6.0118 1.1 16.0 5.5517 24.5 16.8 5. 2683 2 17.4 5.1039 1.3 17.8 4.9827 3.6 18.7 4.7433 1.2 19.2 4.6251 2.2 19.9 4.4483 0.6 20.7 4.293 3.4 21.3 4.1699 5.6 22.7 3.9225 2.3 24.0 3.7105 3.1 24.5 3.6303 2.4 26.3 3.3879 1. 6 26.7 3.3409 2.1 27.1 3.2939 2 27.6 3.2338 0.6 28.1 3.1769 0.9 28.8 3.1015 0.3 29.3 3 .0447 0.6 31.8 2.8079 0.5 32.2 2.7771 0.5 Qncann / zznz / E / YiAi1In this and all subsequent tables, the 2Θ position is within ± 0.2. In some embodiments, Form A of compound 2 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 5.3, about 11.3, and about 16.0 degrees 2-theta. In some embodiments, Form A of compound 2 is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 5.3, about 11.3, and about 16.0 degrees 2-theta. In some embodiments, Form A of compound 2 is characterized by having all three peaks in its X-ray powder diffraction pattern selected from those at about 5.3, about 11.3, and about 16.0 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 9. Methods for preparing Form A of compound 2 are described below. In some embodiments, the present invention provides compound 2: Qncann / zznz / E / YiAi where approximately 1 < x < approximately 2. In some embodiments, the present invention provides compound 2, wherein the compound is crystalline. In some embodiments, the present invention provides compound 2, wherein the compound is a crystalline solid substantially free of amorphous compound 2. In some embodiments, the present invention provides compound 2, wherein the compound is substantially free of impurities. In some embodiments, the present invention provides compound 2, wherein the compound has one or more peaks in its XRPD selected from those at about 5.3, about 11.3 and about 16.0 degrees 2-theta. In some of these embodiments, the present invention provides compound 2, wherein the compound has at least two peaks in its XRPD selected from those at about 5.3, about 11.3 and about 16.0 degrees 2-theta. In some of these embodiments, the present invention provides compound 2, wherein the compound is Form A. In some embodiments, Form A of Compound 2 comprises compound A and maleic acid in a ratio of approximately 2:1. In some embodiments, the present invention provides compound 2, wherein the compound has an XRPD substantially similar to that depicted in Figure Qncann / zznz / E / YiAi 9. In some embodiments, the present invention provides a composition comprising compound 2 and a pharmaceutically acceptable carrier or excipient. In some embodiments, the present invention provides a method of inhibiting AHR comprising administering compound 2 or composition thereof to the patient. In some embodiments, the present invention provides a method of inhibiting AHR in a patient comprising administering compound 2 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating one or more disorders associated with AHR activity comprising administering compound 2 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need of the same compound 2 or composition thereof. In some embodiments, the AHR-mediated disorder is a proliferative disease such as cancer or an inflammatory disorder. Compound 3 (Mesylate Salts of Compound A) According to one embodiment, the present invention provides a mesylate salt of compound A, represented Qncann / zznz / E / YiAi for compound 3: Qncann / zznz / E / YiAi 3. One skilled in the art will appreciate that methanesulfonic acid and compound A bond ionically to form compound 3. It is contemplated that compound 3 may exist in a variety of physical forms. For example, compound 3 may be in solution, suspension or solid form. In certain embodiments, compound 3 is in solid form. When compound 3 is in solid form, the compound may be amorphous, crystalline or a mixture thereof. Example solid shapes are described in more detail below. In some embodiments, the present invention provides compound 3 substantially free of impurities. As used herein, the term substantially free of impurities means that the compound does not contain a significant amount of foreign matter. This foreign matter may include excess sulfuric acid, excess compound A, residual solvents or any other impurities that may result from the preparation and / or isolation of compound 3. In certain embodiments, at least about 95% by weight of compound 3 is present. In still other embodiments of the invention, at least about 99% by weight of compound 3 is present. According to one embodiment, compound 3 is present in an amount of at least about 97, 97.5, 98.0, 98.5, 99, 99.5, 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, compound 3 contains no more than about 3.0 HPLC area percent of total organic impurities and, in certain embodiments, no more than about 1.5 HPLC area percent of total organic impurities with respect to the area total HPLC chromatogram. In other embodiments, compound 3 contains no more than about 1.0% HPLC area percent of any individual impurity; no more than about 0.6 HPLC area percent of any individual impurity and, in certain embodiments, no more than about 0.5 HPLC area percent of any individual impurity, relative to the total area of ​​the HPLC chromatogram. The structure depicted for compound 3 is also intended to include all tautomeric forms of compound 3. Additionally, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more Qncann / zznz / E / YiAi isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen with deuterium or tritium, or the replacement of one carbon with a carbon enriched with 13C or C14C are within the scope of this invention. It has been found that compound 3 can exist in at least two different polymorphic forms. In some embodiments, the present invention provides a polymorphic form of Compound 3 referred to herein as Form A. In some embodiments, the present invention provides a polymorphic form of Compound 3 referred to herein. present as Form B. In certain embodiments, compound 3 is a crystalline solid. In other embodiments, compound 3 is a crystalline solid substantially free of amorphous compound 3. As used herein, the term substantially free of amorphous compound 3 means that the compound does not contain a significant amount of amorphous compound 3. In certain embodiments, at least about 95% by weight of the crystalline compound 3 is present. In still other embodiments of the invention, at least about 99% by weight of the crystalline compound 3 is present. In some embodiments, compound 3 is amorphous. In some embodiments, compound 3 is amorphous and substantially free of crystalline compound 3. Form A of Compound 3 In some embodiments, Form A of compound 3 has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table 4 below. Table 4 – XRPD Peak Positions for Form A of the Qncann / zznz / E / YiAi Compound 3 Position [“Ζθ]1 spacing d [Á] Intensity [%] 5.1 17.2728 1.2 5.6 15.7025 100 9.0 9.7695 3.6 10.2 8.7061 0.3 11.0 8.0007 2.7 11.2 7.8648 35 12.1 7 .3154 0.4 12.4 7.1465 0.3 13.3 6.6505 2.9 14.0 6.313 3.2 14.3 6.1969 2.1 15.3 5.7988 6.3 15.8 5.6164 1.7 16.3 5.4343 0.4 16.9 5.2456 8 18.0 4.9265 0.4 18.4 4.8306 0.6 18.7 4.7514 1 . 9 18.9 4.7028 1.8 19.5 4.5477 0.7 20.0 4.4386 0.4 21.0 4.229 1.2 22.0 4.0295 0.4 24.2 3.6743 0.5 25.5 3.4972 5.3 25.9 3.4328 0.7 26.7 3.3316 1.6 28.3 3.150 6 2.5 29.2 3,053 0.5 Qnconn / zznz / E / YiAi1In this and all subsequent tables, the 2Θ position is within ± 0.2. In some embodiments, Form A of compound 3 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 5.6, about 11.2, and about 16.9 degrees 2-theta. In some embodiments, Form A of compound 3 is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 5.6, about 11.2, and about 16.9 degrees 2-theta. In some embodiments, Form A of compound 3 is characterized by having three peaks in its X-ray powder diffraction pattern selected from those at about 5.6, about 11.2, and about 16.9 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 11. Methods for preparing Form A of compound 3 are described below. Form B of Compound 3 In some embodiments, Form B of compound 3 has at least 1, 2, 3, 4 or 5 spectral peaks selected from the peaks listed in Table 5 below. Table 5 - XRPD peak positions for Form B of Compound 3 Qncann / zznz / E / YiAi Position [ °2Θ]1 d (Angstroms) Intensity [%] 6.0 14.7036 100 11.6 7.6195 10 12.1 7.3357 32.3 13.6 6.5115 2.1 14.6 6.0801 3.1 15.6 5.66 2 16.1 5. 514 0.6 17.6 5.0376 4.5 18.1 4.8948 12.5 19.8 4.4702 1 20.1 4.4033 3.3 20.8 4.2687 0.2 21.1 4.2034 1.3 21.9 4.0542 2.2 22.2 4.0022 4.2 22.6 3.9386 0.5 23.0 3.8694 0.3 23.5 3.7822 1.2 24.3 3.6649 0.3 25.1 3.54 65 1.8 26.9 3.3177 1.9 27.4 3.2583 3 28.3 3.1563 0.9 29.4 3.0401 0.9 Qncann / zznz / E / YiAi1In this and all subsequent tables, the 2Θ position is within ± 0.2. In some embodiments, Form B of compound 3 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 6.0, about 12.1, and about 18.1 degrees 2-theta. In some embodiments, Form B of compound 3 is characterized by having two or more peaks in its powder X-ray diffraction pattern selected from those at about 6.0, about 12.1, and about 18.1 degrees 2-theta. In some embodiments, Form B of compound 3 is characterized by having all three peaks in its X-ray powder diffraction pattern selected from those at about 6.0, about 12.1, and about 18.1 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 13. Methods for preparing Form B of compound 3 are described below. In some embodiments, the present invention provides compound 3: Qncann / zznz / E / YiAi 3. In some embodiments, the present invention provides compound 3, wherein the compound is crystalline. In some embodiments, the present invention provides compound 3, wherein the compound is a crystalline solid substantially free of amorphous compound 3. In some embodiments, the present invention provides compound 3, wherein the compound is substantially free of impurities. In some embodiments, the present invention provides compound 3, wherein the compound has one or more peaks in its XRPD selected from those at about 5.6, about 11.2 and about 16.9 degrees 2-theta. In some of these embodiments, the present invention provides compound 3, wherein the compound has at least two peaks in its XRPD selected from those at about 5.6, about 11.2 and about 16.9 degrees 2-theta. In some of these embodiments, the present invention provides compound 3, wherein the compound is Form A. In some embodiments, the present invention provides compound 3, wherein the compound has an XRPD substantially similar to that depicted in Figure 11. In some embodiments, the present invention provides compound 3, wherein the compound has one or more peaks in its XRPD selected from those at about 6.0, about 12.1 and about 18.1 degrees 2-theta. In some of these embodiments, the present invention provides compound 3, wherein the compound has at least two peaks in its XRPD selected from those at about 6.0, about 12.1 and about 18.1 degrees 2-theta. In some of these embodiments, the present invention provides compound 3, wherein the compound is Form B. In some embodiments, the present invention provides compound 3, wherein the compound has an XRPD substantially similar to that depicted in Figure 13. In some embodiments, the present invention provides a composition comprising compound 3 and a pharmaceutically acceptable carrier or excipient. In some embodiments, the present invention provides a method of inhibiting AHR comprising administering to the patient the compound 3 or composition of the Qncann / zznz / E / YiAi himself. In some embodiments, the present invention provides a method of inhibiting AHR in a patient comprising administering compound 3 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating one or more disorders associated with AHR activity comprising administering compound 3 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need of the same compound 3 or composition thereof. In some embodiments, the AHR-mediated disorder is a proliferative disease such as cancer or an inflammatory disorder. Compound 4 (Napsilate Salts of Compound A) According to one embodiment, the present invention provides a napsilate salt of compound A, represented by compound 4: Qncann / zznz / E / YiAi . 97.5, 98.0, 98.5, 99, 99.5, 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, compound 4 contains no more than about 3.0 HPLC area percent of total organic impurities and, in certain embodiments, no more than about 1.5 HPLC area percent of total organic impurities with respect to the area total HPLC chromatogram. In other embodiments, compound 4 contains no more than about 1.0% HPLC area percent of any individual impurity; no more than about 0.6 HPLC area percent of any individual impurity and, in certain embodiments, no more than about 0.5 HPLC area percent of any individual impurity, relative to the total area of ​​the HPLC chromatogram. The structure depicted for compound 4 is also intended to include all tautomeric forms of compound 4. Additionally, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen with deuterium or tritium, or the replacement of one carbon with a carbon enriched with 13C or C14C are within the scope of this invention. It has been found that compound 4 can exist in at least a different solid form. Examples of these forms include polymorphs such as those described herein. It has been found that compound 4 can exist in at least one distinct polymorphic form. In some embodiments, the present invention provides a polymorphic form of Compound 4 referred to herein as Form A. In certain embodiments, compound 4 is a crystalline solid. In other embodiments, compound 4 is a crystalline solid substantially free of amorphous compound 4. As used herein, the term substantially free of amorphous compound 4 means that the compound does not contain a significant amount of amorphous compound 4. In certain embodiments, at least about 95% by weight of the crystalline compound 4 is present. In still other embodiments of the invention, at least about 99% by weight of the crystalline compound 4 is present. In some embodiments, compound 4 is amorphous. In some embodiments, compound 4 is amorphous and substantially free of crystalline compound 4. Form A of Compound 4 In some embodiments, Form A of compound 4 has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table 6 below. Table 6 – XRPD Peak Positions for Form A of the Compound 4 Position d Intensity 6.8 13.0644 1.1 7.5 11.81 100 7.8 11.2555 9.4 8.4 10.5306 78.5 9.5 9.3437 5.7 9.8 9.0463 7.2 9.9 8.8891 7.5 11.1 7. 9975 8.2 11.9 7.404 5.2 12.6 7.0284 1.4 12.9 6.8706 1 . 6 13.5 6.5355 5 13.8 6.4284 11 . 9 14.5 6.1263 26.4 14.7 6.029 1.2 15.1 5.8748 8.3 15.8 5.6186 10.1 16.1 5.5086 4 16.5 5.3844 20.1 16.6 5.3221 1.8 16.8 5. 2691 1.7 17.3 5.1223 1.3 18.1 4.9044 11. 6 19.1 4.6279 4.7 19.6 4.5254 11.4 19.7 4.496 9.8 20.1 4.424 47.9 20.6 4.2976 7 . 6 20.9 4.2364 2.5 21.5 4.1352 0.3 21.8 4.0652 1.1 22.0 4.0293 5.8 22.4 3.9624 28.3 22.9 3.8768 1.7 23.7 3.745 7.5 24.6 3.6159 5.8 24.8 3.5884 3.8 25.2 3.5259 2.9 Qncann / zznz / E / YiAi1In this and all subsequent tables, the 2Θ position is within ± 0.2. In some embodiments, Form A of compound 4 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 7.5, about 8.4, and about 20.1 degrees 2-theta. In some embodiments, Form A of compound 4 is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 7.5, about 8.4, and about 20.1 degrees 2-theta. In some embodiments, Form A of compound 4 is characterized by having all three peaks in its X-ray powder diffraction pattern selected from those at about 7.5, about 8.4, and about 20.1 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 15. Methods for preparing Form A of compound 4 are described below. In some embodiments, the present invention provides compound 4: Qncann / zznz / E / YiAi In some embodiments, the present invention provides compound 4, wherein the compound is crystalline. In some embodiments, the present invention provides compound 4, wherein the compound is a crystalline solid substantially free of amorphous compound 4. In some embodiments, the present invention provides compound 4, wherein the compound is substantially free of impurities. In some embodiments, the present invention provides compound 4, wherein the compound has one or more peaks in its XRPD selected from those at about 7.5, about 8.4 and about 20.1 degrees 2-theta. In some of these embodiments, the present invention provides compound 4, wherein the compound has at least two peaks in its XRPD selected from those at about 7.5, about 8.4 and about 20.1 degrees 2-theta. In some of these embodiments, the present invention provides compound 4, wherein the compound is Form A. In some embodiments, the present invention provides compound 4, wherein the compound has an XRPD substantially similar to that depicted in Figure 15. In some embodiments, the present invention provides a composition comprising compound 4 and a pharmaceutically acceptable carrier or excipient. In some embodiments, the present invention provides a method of inhibiting AHR comprising administering compound 4 or composition thereof to the patient. In some embodiments, the present invention provides a method of inhibiting AHR in a patient comprising administering compound 4 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating one or more disorders associated with AHR activity comprising administering compound 4 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need of the same compound 4 or composition thereof. In Qncann / zznz / E / YiAi In some embodiments, the AHR-mediated disorder is a proliferative disease such as cancer or an inflammatory disorder. Compound 5 (Oxalate Salts of Compound A) According to one embodiment, the present invention provides an oxalate salt of compound A, represented by compound 5: Qncann / zznz / E / YiAi One skilled in the art will appreciate that oxalic acid and compound A bond ionically to form compound 5. It is contemplated that compound 5 may exist in a variety of physical forms. For example, compound 5 may be in solution, suspension or solid form. In certain embodiments, compound 5 is in solid form. When compound 5 is in solid form, the compound may be amorphous, crystalline or a mixture thereof. Example solid shapes are described in more detail below. In some embodiments, the present invention provides compound 5 substantially free of impurities. As used herein, the term substantially free of impurities means that the compound does not contain a significant amount of foreign matter. This foreign matter may include excess hydrochloric acid, excess compound A, residual solvents or any other impurities that may result from the preparation and / or isolation of compound 5. In certain embodiments, at least about 95% by weight of compound 5 is present. In still other embodiments of the invention, at least about 99% by weight of compound 5 is present. According to one embodiment, compound 5 is present in an amount of at least about 97, 97.5, 98.0, 98.5, 99, 99.5, 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, compound 5 contains no more than about 3.0 HPLC area percent of total organic impurities and, in certain embodiments, no more than about 1.5 HPLC area percent of total organic impurities with respect to the area total HPLC chromatogram. In other embodiments, compound 5 contains no more than about 1.0% HPLC area percent of any individual impurity; no more than about 0.6 HPLC area percent of any individual impurity and, in certain embodiments, no more than about 0.5 percent Qncann / zznz / E / YiAi HPLC area percent of any individual impurity, relative to the total area of ​​the HPLC chromatogram. The structure depicted for compound 5 is also intended to include all tautomeric forms of compound 5. Additionally, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen with deuterium or tritium, or the replacement of one carbon with a carbon enriched with 13C or C14C are within the scope of this invention. It has been found that compound 5 can exist in at least one distinct polymorphic form. In some embodiments, the present invention provides a polymorphic form of Compound 5 referred to herein as Form A. In certain embodiments, compound 5 is a crystalline solid. In other embodiments, compound 5 is a crystalline solid substantially free of amorphous compound 5. As used herein, the term substantially free of amorphous compound 5 means that the compound does not contain a significant amount of amorphous compound 5. In certain embodiments, at least about 95% by weight of the crystalline compound 5 is present. In still other embodiments of the invention, at least about 99% by weight of the crystalline compound 5 is present. In some embodiments, compound 5 is amorphous. In some embodiments, compound 5 is amorphous and substantially free of crystalline compound 5. Form A of Compound 5 In some embodiments, Form A of compound 5 has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table 7 below. Table 7 - XRPD Peak Positions for Form A of Compound 5 Qncann / zznz / E / YiAi Position [“Σθ]1 spacing d [Á] Intensity [%] 6.4 13.7901 100 7.1 12.4378 20.2 11.4 7.7871 4 . 9 12.7 6.9614 63.9 14.4 6.1639 6 17.5 5.0766 16.5 18.3 4.8405 3.3 19.2 4.6288 3.2 21.1 4.2167 2.7 22.3 3.9765 1.7 23.1 3. 8472 8.2 27.3 3.2647 1.7 29.0 3.0719 0.9 1In this and all subsequent tables, the 2Θ position is within ±0.2. In some embodiments, Form A of compound 5 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 6.4, about 7.1, and about 12.7 degrees 2-theta. In some embodiments, Form A of compound 5 is characterized by having two or more peaks in its powder X-ray diffraction pattern selected from those at about 6.4, about 7.1, and about 12.7 degrees 2-theta. In some embodiments, Form A of compound 5 is characterized by having all three peaks in its X-ray powder diffraction pattern selected from those at about 6.4, about 7.1, and about 12.7 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 17. Methods for preparing Form A of compound 5 are described below. In some embodiments, the present invention provides compound 5: Qncann / zznz / E / YiAi 5. In some embodiments, the present invention provides compound 5, wherein the compound is crystalline. In some embodiments, the present invention provides compound 5, wherein the compound is a crystalline solid substantially free of amorphous compound 5. In some embodiments, the present invention provides compound 5, wherein the compound is substantially free of impurities. In some embodiments, the present invention provides compound 5, wherein the compound has one or more peaks in its XRPD selected from those at about 6.4, about 7.1 and about 12.7 degrees 2-theta. In some of these embodiments, the present invention provides compound 5, wherein the compound has at least two peaks in its XRPD selected from those at about 6.4, about 7.1 and about 12.7 degrees 2-theta. In some of these embodiments, the present invention provides compound 5, wherein the compound is Form A. In some embodiments, the present invention provides compound 5, wherein the compound has an XRPD substantially similar to that depicted in Figure 17. Qncann / zznz / E / YiAi In some embodiments, the present invention provides a composition comprising compound 5 and a pharmaceutically acceptable carrier or excipient. In some embodiments, the present invention provides a method of inhibiting AHR comprising administering compound 5 or composition thereof to the patient. In some embodiments, the present invention provides a method of inhibiting AHR in a patient comprising administering compound 5 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating one or more disorders associated with AHR activity comprising administering compound 5 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need of the same compound or composition thereof. In some embodiments, the AHR-mediated disorder is a proliferative disease such as cancer or an inflammatory disorder. Compound 6 (Tartrate Salts of Compound A) According to one embodiment, the present invention provides a tartrate salt of compound A, represented Qncann / zznz / E / YiAi for compound 6: Qncann / zznz / E / YiAi where approximately 1 < x < approximately 2. One skilled in the art will appreciate that tartaric acid and compound A bond ionically to form compound 6. In some embodiments, compound A and tartaric acid are in a ratio of approximately 1:1. In some embodiments, compound A and tartaric acid are in a ratio of approximately 2:1. It is contemplated that compound 6 may exist in a variety of physical forms. For example, compound 6 may be in solution, suspension or solid form. In certain embodiments, compound 6 is in solid form. When compound 6 is in solid form, the compound may be amorphous, crystalline or a mixture thereof. Example solid shapes are described in more detail below. In some embodiments, the present invention provides compound 6 substantially free of impurities. As used herein, the term substantially free of impurities means that the compound does not contain a significant amount of foreign matter. This foreign matter may include excess oxalic acid, excess compound A, residual solvents or any other impurities that may result from the preparation and / or isolation of compound 6. In certain embodiments, at least about 95% by weight of compound 6 is present. In still other embodiments of the invention, at least about 99% by weight of compound 6 is present. According to one embodiment, compound 6 is present in an amount of at least about 97, 97.5, 98.0, 98.5, 99, 99.5, 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, compound 6 contains no more than about 3.0 HPLC area percent of total organic impurities and, in certain embodiments, no more than about 1.5 HPLC area percent of total organic impurities with respect to the area total HPLC chromatogram. In other embodiments, compound 6 contains no more than about 1.0% HPLC area percent of any individual impurity; no more than about 0.6 HPLC area percent of any individual impurity and, in certain embodiments, no more than about 0.5 percent Qncann / zznz / E / YiAi HPLC area percent of any individual impurity, relative to the total area of ​​the HPLC chromatogram. The structure depicted for compound 6 is also intended to include all tautomeric forms of compound 6. Additionally, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen with deuterium or tritium, or the replacement of one carbon with a carbon enriched with 13C or C14C are within the scope of this invention. It has been found that compound 6 can exist in at least two different polymorphic forms. In some embodiments, the present invention provides a polymorphic form of Compound 6 referred to herein as Form A. In some embodiments, the present invention provides a polymorphic form of Compound 6 referred to herein. as Form B. In some embodiments, Form A of Compound 6 comprises compound A and tartaric acid in a ratio of approximately 1:1. In some embodiments, Form B of Compound 6 comprises compound A and tartaric acid in a ratio of about 2:1. In certain embodiments, compound 6 is a crystalline solid. In other embodiments, compound 6 is a crystalline solid substantially free of amorphous compound 6. As used herein, the term substantially free of amorphous compound 6 means that the compound does not contain a significant amount of amorphous compound 6. In certain embodiments, at least about 95% by weight of the crystalline compound 6 is present. In still other embodiments of the invention, at least about 99% by weight of the crystalline compound 6 is present. In some embodiments, compound 6 is amorphous. In some embodiments, compound 6 is amorphous and substantially free of crystalline compound 6. Form A of Compound 6 In some embodiments, Form A of compound 6 has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table 8 below. Table 8 - XRPD Peak Positions for Form A of Compound 6 Position [°2θ]1 spacing d [Á] Intensity [%] 5.5 16.1924 100 7.0 12.6864 1.4 8.2 10.8305 7.5 8.4 10.5158 9 9.1 9.6845 0.7 10.3 8.5415 1.6 11.1 7.9331 15.7 13.4 6.6022 1.1 14.5 6.1046 5 15.6 5.6633 4.8 16.3 5.4202 4.5 17.4 5.1082 13.5 17.6 5.03 75 6.7 18.9 4.7033 17.7 20.3 4.371 4 22.3 3.976 5.8 23.1 3.8469 6.6 24.5 3.6371 4.1 26.3 3.3865 8.3 26.7 3.3422 5.9 27.0 3. 2941 2.6 29.9 2.9861 3.4 Qncann / zznz / E / YiAi1In this and all subsequent tables, position 2Θ is within + 0.2. In some embodiments, Form A of compound 6 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 5.5, about 11.1, and about 18.9 degrees 2-theta. In some embodiments, Form A of compound 6 is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 5.5, about 11.1, and about 18.9 degrees 2-theta. In some embodiments, Form A of compound 6 is characterized by having all three peaks in its X-ray powder diffraction pattern selected from those at about 5.5, about 11.1, and about 18.9 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 19. Methods for preparing Form A of compound 6 are described below. Form B of Compound 6 In some embodiments, Form B of compound 6 has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table 9 below. Table 9 - XRPD Peak Positions for Form B of Compound 6 Qncann / zznz / E / YiAi Position [°2Θ]1 spacing d [Á] Intensity [%] 5.3 16.5046 1.7 6.2 14.2356 74.6 6.8 13.0713 100 7.2 12.183 2.4 8 . 6 10.2145 5 9.5 9.2819 0.6 10.7 8.2682 8.2 11.5 7.7192 4.5 12.4 7.1588 12.4 13.5 6.5301 24.8 14.6 6.0796 6.9 16.3 5.4162 2.1 17.1 5.1667 11.2 17.7 5.0058 3.2 18.7 4.7289 9.7 19.3 4 .5962 3 20.6 4.3182 15.7 20.9 4.2371 11.5 21.8 4.0643 5.9 23.2 3.8387 0.8 24.3 3.6659 1.8 25.3 3.5112 1 26.1 3.4101 1.3 Qncann / zznz / E / YiAi1In this and all subsequent tables, the 2Θ position is within ± 0.2. In some embodiments, Form B of compound 6 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 6.2, about 6.8, and about 13.5 degrees 2-theta. In some embodiments, Form B of compound 6 is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 6.2, about 6.8, and about 13.5 degrees 2-theta. In some embodiments, Form B of compound 6 is characterized in that it has all three peaks in its X-ray powder diffraction pattern selected from those at about 6.2, about 6.8, and about 13.5 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 21. Methods for preparing Form B of compound 6 are described below. In some embodiments, the present invention provides compound 6: Qnconn / zznz / E / YiAi where approximately 1 < x < approximately 2. In some embodiments, the present invention provides compound 6, wherein the compound is crystalline. In some embodiments, the present invention provides compound 6, wherein the compound is a crystalline solid substantially free of amorphous compound 6. In some embodiments, the present invention provides compound 6, wherein the compound is substantially free of impurities. In some embodiments, the present invention provides compound 6, wherein the compound has one or more peaks in its XRPD selected from those at about 5.5, about 11.1 and about 18.9 degrees 2-theta. In some of these embodiments, the present invention provides compound 6, wherein the compound has at least two peaks in its XRPD selected from those at about 5.5, about 11.1 and about 18.9 degrees 2-theta. In some of these embodiments, the present invention provides compound 6, wherein the compound is Form A. In some embodiments, Form A of Compound 6 comprises compound A and tartaric acid in a ratio of approximately 1:1. In some embodiments, the present invention provides compound 6, wherein the compound has an XRPD substantially similar to that depicted in Figure 19. In some embodiments, the present invention provides compound 6, wherein the compound has one or more peaks in its XRPD selected from those at about 6.2, about 6.8 and about Qncann / zznz / E / YiAi 13.5 degrees 2-theta. In some of these embodiments, the present invention provides compound 6, wherein the compound has at least two peaks in its XRPD selected from those at about 6.2, about 6.8 and about 13.5 degrees 2-theta. In some of these embodiments, the present invention provides compound 6, wherein the compound is Form B. In some embodiments, Form B of Compound 6 comprises compound A and tartaric acid in a ratio of approximately 2:1. In some embodiments, the present invention provides compound 6, wherein the compound has an XRPD substantially similar to that depicted in Figure 21. In some embodiments, the present invention provides a composition comprising compound 6 and a pharmaceutically acceptable carrier or excipient. In some embodiments, the present invention provides a method of inhibiting AHR comprising administering compound 6 or composition thereof to the patient. In some embodiments, the present invention provides a method of inhibiting AHR in a patient comprising administering compound 6 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating one or more Qncann / zznz / E / YiAi disorders associated with AHR activity comprising administering compound 6 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need of the same compound 6 or composition thereof. In some embodiments, the AHR-mediated disorder is a proliferative disease such as cancer or an inflammatory disorder. Compound 7 (Edisylate Salts of Compound A) According to one embodiment, the present invention provides an edisylate salt of compound A, represented by compound 7: Qncann / zznz / E / YiAi where approximately 1 < x < approximately 2. One skilled in the art will appreciate that ethanedisulfonic acid and compound A are ionically linked to form compound 7. In some embodiments, compound A and ethanedisulfonic acid are in a ratio of approximately 1:1. In some embodiments, compound A and ethanedisulfonic acid are in a ratio of approximately 2:1. It is contemplated that compound 7 may exist in a variety of physical forms. For example, compound 7 may be in solution, suspension or solid form. In certain embodiments, compound 7 is in solid form. When compound 7 is in solid form, the compound may be amorphous, crystalline or a mixture thereof. Example solid shapes are described in more detail below. In some embodiments, the present invention provides compound 7 substantially free of impurities. As used herein, the term substantially free of impurities means that the compound does not contain a significant amount of foreign matter. This foreign matter may include excess phosphoric acid, excess compound A, residual solvents or any other impurities that may result from the preparation and / or isolation of compound 7. In certain embodiments, at least about 95% by weight of compound 7 is present. In still other embodiments of the invention, at least about 99% by weight of compound 7 is present. According to one embodiment, compound 7 is Qncann / zznz / E / YiAi present in an amount of at least about 97, 97.5, 98.0, 98.5, 99, 99.5, 99.8 weight percent where the percentages are based on the total weight of the composition. According to another embodiment, compound 7 contains no more than about 3.0 HPLC area percent of total organic impurities and, in certain embodiments, no more than about 1.5 HPLC area percent of total organic impurities with respect to the area total HPLC chromatogram. In other embodiments, compound 7 contains no more than about 1.0% HPLC area percent of any individual impurity; no more than about 0.6 HPLC area percent of any individual impurity and, in certain embodiments, no more than about 0.5 HPLC area percent of any individual impurity, relative to the total area of ​​the HPLC chromatogram. The structure depicted for compound 7 is also intended to include all tautomeric forms of compound 7. Additionally, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structure except for the replacement of hydrogen with deuterium or tritium, or the replacement of one carbon with a carbon enriched with 13C or C14C are within the scope of this invention. Qncann / zznz / E / YiAi It has been found that compound 7 can exist in at least one distinct polymorphic form. In some embodiments, the present invention provides a polymorphic form of Compound 7 referred to herein as Form A. In some embodiments, Form A of Compound 7 comprises compound A and ethanedisulfonic acid in a ratio of about 2:1. In certain embodiments, compound 7 is a crystalline solid. In other embodiments, compound 7 is a crystalline solid substantially free of amorphous compound 7. As used herein, the term substantially free of amorphous compound 7 means that the compound does not contain a significant amount of amorphous compound 7. In certain embodiments, at least about 95% by weight of the crystalline compound 7 is present. In still other embodiments of the invention, at least about 99% by weight of the crystalline compound 7 is present. In some embodiments, compound 7 is amorphous. In some embodiments, compound 7 is amorphous and substantially free of crystalline compound 7. Form A of Compound 7 In some embodiments, Form A of compound 7 has at least 1, 2, 3, 4, or 5 spectral peaks selected from the peaks listed in Table 10 below. Qncann / zznz / E / YiAi Table 10 – XRPD Peak Positions for Form A of the Compound 7 Qncann / zznz / E / YiAi Position [°2θ]1 spacing d [Á] Intensity [%] 6.6 13.4754 100 8.0 11.0262 0.7 10.4 8.5378 5 13.2 6.7031 7.3 16.0 5.5191 2.4 18.2 4.871 0.8 19.1 4.6 422 1.8 19.3 4.5954 1.7 20.4 4.3516 0.7 22.4 3.9584 1.5 26.5 3.3549 0.6 1In this and all subsequent tables, position 2Θ is within +0.2. In some embodiments, Form A of compound 7 is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 6.6, about 10.4, and about 13.2 degrees 2-theta. In some embodiments, Form A of compound 7 is characterized by having two or more peaks in its X-ray powder diffraction pattern selected from those at about 6.6, about 10.4, and about 13.2 degrees 2-theta. In some embodiments, Form A of compound 7 is characterized by having all three peaks in its X-ray powder diffraction pattern selected from those at about 6.6, about 10.4, and about 13.2 degrees 2-theta. In certain embodiments, the X-ray powder diffraction pattern is substantially similar to the XRPD provided in Figure 23. Methods for preparing Form A of compound 7 are described below. Qncann / zznz / E / YiAi In some embodiments, the present invention provides compound 7: where approximately 1 < x < approximately 2. In some embodiments, the present invention provides compound 7, wherein the compound is crystalline. In some embodiments, the present invention provides compound 7, wherein the compound is a crystalline solid substantially free of amorphous compound 7. In some embodiments, the present invention provides compound 7, wherein the compound is substantially free of impurities. In some embodiments, the present invention provides compound 7, wherein the compound has one or more peaks in its XRPD selected from those at about 6.6, about 10.4 and about 13.2 degrees 2-theta. In some of these embodiments, the present invention provides compound 7, wherein the compound has at least two peaks in its XRPD selected from those at about 6.6, about 10.4 and about 13.2 degrees 2-theta. In some of these embodiments, the present invention provides compound 7, wherein the compound is Form A. In some embodiments, Form A of Compound 7 comprises compound A and ethanedisulfonic acid in a ratio of about 2:1. In some embodiments, the present invention provides compound 7, wherein the compound has an XRPD substantially similar to that depicted in Figure 23. In some embodiments, the present invention provides a composition comprising compound 7 and a pharmaceutically acceptable carrier or excipient. In some embodiments, the present invention provides a method of inhibiting AHR comprising administering compound 7 or composition thereof to the patient. In some embodiments, the present invention Qncann / zznz / E / YiAi provides a method of inhibiting AHR in a patient comprising administering compound 7 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating one or more disorders associated with AHR activity comprising administering compound 7 or composition thereof to the patient. In some embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need of the same compound 7 or composition thereof. In some embodiments, the AHR-mediated disorder is a proliferative disease such as cancer or an inflammatory disorder. In some embodiments, the present invention provides a compound selected from: compound A, Form B; compound A, Form C; compound 1, Form A; compound 1, Form B; compound 2, Form A; compound 3, Form A; compound 3, Form B; compound 4, Form A; compound 5, Form A; compound 6, Form A; compound 6, Form B; and compound 7, Form A. In some of these embodiments, the present invention provides a composition comprising one of the above compound forms and a pharmaceutically acceptable carrier or excipient. In some of these embodiments, the present invention provides a method of inhibiting AHR comprising administering to the patient a compound of the present invention or composition thereof. In some of these embodiments, the present invention provides a method of inhibiting AHR in a patient comprising administering to the patient a compound of the present invention or composition thereof. In some of these embodiments, the present invention provides a method of treating one or more disorders associated with AHR activity comprising administering to the patient a compound of the present invention or composition thereof. In some of these embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need thereof a compound of the present invention or composition thereof. In some of these embodiments, the AHR-mediated disorder is a proliferative disease such as cancer or an inflammatory disorder. General methods of providing a salt compound Compound A is prepared according to the methods described in detail in the '411 publication, all of which are incorporated herein by reference. The salt compounds of general formula Qncann / zznz / E / YiAi combine compound A: Qnconn / zznz / E / YiAi with a suitable acid and optionally a suitable solvent under suitable conditions to form a salt compound of general formula X. In some embodiments, a suitable acid is ethanesulfonic acid. In some embodiments, the present invention provides a method for making an esylate salt of compound A. In certain embodiments, the esylate salt of compound A is Compound 1. In certain embodiments, the esylate salt of compound A is Form A of compound 1. In certain embodiments, the esylate salt of compound A is Form B of compound 1. In some embodiments, a suitable acid is maleic acid. In some embodiments, the present invention provides a method for making a maleate salt of compound A. In certain embodiments, the maleate salt of compound A is Compound 2. In certain embodiments, the maleate salt of compound A is Form A of compound 2. In some embodiments, a suitable acid is methanesulfonic acid. In some embodiments, the present invention provides a method for making a mesylate salt of compound A. In certain embodiments, the mesylate salt of compound A is Compound 3. In certain embodiments, the mesylate salt of compound A is Form A of compound 3. In certain embodiments, the mesylate salt of compound A is Form B of compound 3. In some embodiments, a suitable acid is naphthalenesulfonic acid. In some embodiments, the present invention provides a method for making a napsylate salt of compound A. In certain embodiments, the napsylate salt of compound A is Compound 4. In certain embodiments, the napsylate salt of compound A is Form A of compound 4. In some embodiments, a suitable acid is oxalic acid. In some embodiments, the present invention provides a method for making an oxalate salt of compound A. In certain embodiments, the oxalate salt of compound A is Compound 5. In certain embodiments, the oxalate salt of compound A is Form A of compound 5. In some embodiments, a suitable acid is tartaric acid. In some embodiments, the present invention provides a method for making a tartrate salt of compound A. In certain embodiments, the tartrate salt of compound A is Compound 6. In certain embodiments, the tartrate salt of compound A is Form A of compound 6. In certain embodiments, the tartrate salt of compound A is Form B of compound 6. In some embodiments, a suitable acid is ethanedisulfonic acid. In some embodiments, the present invention provides a method for making an edisylate salt of compound A. In certain embodiments, the edisylate salt of compound A is Compound 7. In certain embodiments, the edisylate salt of compound A is Form A of compound 7. A suitable solvent may be any solvent system (for example, a solvent or a mixture of solvents) in which compound A and / or an acid are soluble, or are at least partially soluble. Examples of suitable solvents useful in the present invention include, but are not limited to, protic solvents, aprotic solvents, polar aprotic solvents or mixtures thereof. In certain embodiments, suitable solvents include an ether, an ester, an alcohol, a ketone, or a mixture thereof. In some embodiments, the solvent is one or more organic alcohols. In some embodiments, the solvent is treated with chlorine. In some embodiments, the solvent is an aromatic solvent. In certain embodiments, a suitable solvent is methanol, ethanol, isopropanol or acetone where the solvent is Qncann / zznz / E / YiAi anhydrous or in combination with water or heptane. In some embodiments, suitable solvents include tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, glyme, diglyme, methyl t-butyl ether, t-butanol, n-butanol and acetonitrile. In some embodiments, a suitable solvent is ethanol. In some embodiments, a suitable solvent is anhydrous ethanol. In some embodiments, the suitable solvent is MTBE. In some embodiments, a suitable solvent is ethyl acetate. In some embodiments, a suitable solvent is a mixture of methanol and methylene chloride. In some embodiments, a suitable solvent is a mixture of acetonitrile and water. In certain embodiments, a suitable solvent is methyl acetate, isopropyl acetate, acetone or tetrahydrofuran. In certain embodiments, a suitable solvent is diethyl ether. In certain embodiments, a suitable solvent is water. In certain embodiments, a suitable solvent is methyl ethyl ketone. In certain embodiments, a suitable solvent is toluene. In some embodiments, the present invention provides a method for preparing a salt compound of general formula X, which comprises one or more steps of removing a solvent and adding a solvent. In some embodiments, a solvent added is the same as the solvent removed. In some embodiments, an added solvent is different Qncann / zznz / E / YiAi of the removed solvent. Solvent removal means are known in the synthetic and chemical arts and include, but are not limited to, any of those described herein and in the Exemplification. In some embodiments, a method for preparing a salt compound of general formula X comprises one or more steps of heating or cooling a preparation. In some embodiments, a method for preparing a salt compound of general formula In some embodiments, a method for preparing a salt compound of general formula X comprises a step of adding a suitable acid to a solution or suspension of compound A. In some embodiments, a method for preparing a salt compound of general formula X comprises a heating step. In certain embodiments, a salt compound of formula X is precipitated from the mixture. In another embodiment, a salt compound of formula X crystallizes from the mixture. In other embodiments, a salt compound of formula X crystallizes from the solution after seeding the solution (i.e., adding crystals of a salt compound of formula A salt compound of formula Qncann / zznz / E / YiAi by removing part or all of the solvent by methods such as evaporation, distillation, filtration (e.g., nanofiltration, ultrafiltration), reverse osmosis, absorption and reaction, by adding an antisolvent such as heptane, by cooling or by different combinations of these methods. As generally described above, a salt compound of formula X is optionally isolated. It will be appreciated that a salt compound of formula X can be isolated by any suitable physical means known to one skilled in the art. In certain embodiments, the precipitated solid salt compound of formula X is separated from the supernatant by filtration. In other embodiments, the precipitated solid salt compound of formula X is separated from the supernatant by decanting the supernatant. In certain embodiments, a salt compound of formula X is separated from the supernatant by filtration. In certain embodiments, an isolated salt compound of formula In other embodiments, the isolated salt compound of formula X is dried under reduced pressure, optionally at elevated temperature. Uses, formulation and administration and pharmaceutically acceptable compositions According to another embodiment, the invention provides a composition comprising a compound of the Qncann / zznz / E / YiAi present invention or a pharmaceutically acceptable salt, ester or ester salt thereof and a pharmaceutically acceptable carrier, adjuvant or vehicle. The amount of compound in the compositions of the present invention is such that it is effective to measurably inhibit AHR, in a biological sample or in a patient. In certain embodiments, the amount of compound in the compositions of this invention is such that it is effective to measurably inhibit AHR, in a biological sample or in a patient. In certain embodiments, a composition of this invention is formulated for administration to a patient in need of this composition. In some embodiments, a composition of the present invention is formulated for oral administration to a patient. The term patient, as used herein, means an animal, preferably a mammal, and more preferably a human. The term pharmaceutically acceptable carrier, adjuvant or vehicle refers to a non-toxic carrier, adjuvant or vehicle that does not destroy the pharmacological activity of the compound with which it is formulated. Pharmaceutically acceptable carriers, adjuvants or vehicles that can be used in the compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, proteins Serum Qncann / zznz / E / YiAi, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, mixtures of partial glycerides of saturated vegetable fatty acids, water, salts or electrolytes, such as sulfate protamine, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, block polymers polyethylene-polyoxypropylene, polyethylene glycol and wool. A pharmaceutically acceptable derivative means any salt, ester, non-toxic salt of an ester or other derivative of a compound of the present invention that, upon administration to a recipient, is capable of providing, either directly or indirectly, a compound of the present invention or an inhibitory active metabolite or residue thereof. The compositions of the present invention can be administered orally, parenterally, by aerosol inhalation, topically, rectally, nasally, buccally, vaginally or through an implanted reservoir. The term parenteral as used herein includes subcutaneous, intravenous, intramuscular, intra-articular, intrasynovial, intrasternal, intrathecal, infusion or injection techniques. Qncann / zznz / E / YiAi intrahepatic, intralesional and intracranial. Preferably, the compositions are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of the present invention may be aqueous or oleaginous suspension. These suspensions can be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable suspension or solution in a non-toxic parenterally acceptable solvent or diluent, for example, as a solution in 1,3-butanediol. Acceptable vehicles and solvents that can be used include water, Ringer's solution, and isotonic sodium chloride solution. Furthermore, sterile non-volatile oils are conventionally employed as a solvent or suspending medium. For this purpose, any soft fixed oil that includes synthetic mono- or diglycerides can be used. Fatty acids, such as oleic acid and its glyceride derivatives, are useful in the preparation of injectables, as are pharmaceutically acceptable natural oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain an alcohol diluent or dispersant. Long chain Qncann / zznz / E / YiAi, such as carboxymethylcellulose or similar dispersing agents that are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tweens, Spans and other emulsifying agents or bioavailability enhancers that are commonly used in the preparation of solids, liquids or other pharmaceutically acceptable dosage forms may also be used for formulation purposes. The pharmaceutically acceptable compositions of this invention may be administered in any pharmaceutically acceptable oral dosage form including, but not limited to, capsules, tablets, suspensions or aqueous solutions. In the case of tablets for oral use, commonly used carriers include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also usually added. For oral administration in capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents can also be added. Alternatively, the compositions Pharmaceutically acceptable Qncann / zznz / E / YiAi of this invention can be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non-irritant excipient that is solid at room temperature but liquid at rectal temperature and will therefore melt in the rectum to release the drug. These materials include cocoa butter, beeswax, and polyethylene glycols. The pharmaceutically acceptable compositions of this invention may also be administered topically, especially when the target of treatment includes areas or organs easily accessible by topical application, including diseases of the eye, skin or lower intestinal tract. Topical formulations suitable for each of these areas or organs are easily prepared. Topical application to the lower intestinal tract can be effected in a rectal suppository formulation (see above) or in a suitable enema formulation. Topical transdermal patches can also be used. For topical applications, pharmaceutically acceptable compositions may be formulated provided in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of compounds of the Qncann / zznz / E / YiAi present invention include, but are not limited to, mineral oil, liquid petroleum jelly, white petroleum jelly, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, the provided pharmaceutically acceptable compositions may be formulated into a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl ester wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. For ophthalmic use, the provided pharmaceutically acceptable compositions may be formulated as micronized suspensions in sterile isotonic pH-adjusted saline or, preferably, as solutions in sterile isotonic pH-adjusted saline, either with or without a preservative such as benzylalkonium chloride. . Alternatively, for ophthalmic uses, pharmaceutically acceptable compositions may be formulated in an ointment such as petrolatum. The pharmaceutically acceptable compositions of this invention may also be administered by inhalation or nasal spray. These compositions are prepared Qncann / zznz / E / YiAi according to techniques well known in the art of pharmaceutical formulation and can be prepared as solutions in saline, using benzyl alcohol or other suitable preservatives, absorption promoters to improve bioavailability, fluorocarbons and / or others conventional solubilizing or dispersing agents. More preferably, the pharmaceutically acceptable compositions of this invention are formulated for oral administration. These formulations can be administered with or without food. In some embodiments, the pharmaceutically acceptable compositions of the present invention are administered without food. In other embodiments, the pharmaceutically acceptable compositions of the present invention are administered with food. The amount of compounds of the present invention that can be combined with the carrier materials to produce a composition in an individual dosage form will vary depending on the host treated, the particular mode of administration. Preferably, the compositions provided should be formulated so that a dosage of between 0.01 - 100 mg / kg body weight / day of the inhibitor can be administered to a patient receiving these compositions. It should also be understood that a specific dosage and specific treatment regimen for any particular patient will depend on a variety of factors, which Qncann / zznz / E / YiAi include the activity of the specific compound used, age, body weight, general health, gender, diet, timing of administration, rate of excretion, drug combination, and the treating physician's judgment and severity of the particular disease being treated. The amount of a compound of the present invention in the composition will also depend on the particular compound in the composition. Uses of pharmaceutically acceptable compounds and compositions The activity of a compound used in the present invention as an AHR inhibitor can be evaluated in vitro or in vivo. An in vivo evaluation of the efficacy of the compounds of the invention can be performed using an animal model of obesity or metabolic syndrome, for example, a rodent or primate model. Cell-based assays can be performed using, for example, a cell line isolated from a tissue that expresses AHR. Additionally, biochemical or mechanism-based assays can be performed, for example, transcription assays using a purified protein, Northern blotting, RT-PCR, etc. In vitro assays include assays that determine cell morphology, protein expression and / or cytotoxicity, enzyme inhibitory activity and / or subsequent functional consequences of treating cells with compounds of the invention. In vitro tests Alternative Qncann / zznz / E / YiAi quantify the ability of the inhibitor to bind to protein or nucleic acid molecules within the cell. Inhibitor binding can be measured by radiolabeling the inhibitor prior to binding, isolating the inhibitor / target molecule complex, and determining the amount of binding to the radiolabel. Alternatively, inhibitor binding can be determined by performing a competition experiment where new inhibitors are incubated with purified proteins or nucleic acids bound to known radioligands. Detailed conditions for evaluating a compound used in the present invention as an AHR inhibitor are set forth in the Examples below. The tests mentioned above are examples and are not intended to limit the scope of the invention. One skilled in the art can appreciate that modifications can be made to conventional tests to develop equivalent tests that obtain the same result. As used herein, the terms treatment, treating and treating refer to reversing, alleviating, delaying the onset or inhibiting the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some embodiments, the treatment may be administered after one or more symptoms have developed. In other modalities, the Qnconn / zznz / E / YiAi treatment can be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in view of a history of symptoms and / or in view of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example to prevent or delay their recurrence. The compounds and compositions, according to the method of the present invention, can be administered using any amount and any route of administration effective to treat or lessen the severity of a metabolic disorder or condition, cancer, a bacterial infection, a fungal infection, a parasitic infection (for example, malaria), an autoimmune disorder, a neurodegenerative or neurological disorder, schizophrenia, a bone-related disorder, liver disease, or a heart disorder. In some embodiments, the compounds and compositions, according to the method of the present invention, can be administered using any amount and any route of administration effective to treat or lessen the severity of a disease associated with AHR. The exact amount needed will vary from subject to subject, depending on species, age and general condition. Qncann / zznz / E / YiAi of the subject, the severity of the infection, the particular agent, its mode of administration and the like. The compounds of the invention are preferably formulated in unit dosage form for ease of administration and dosage uniformity. The term dosage unit form as used herein refers to a physically discrete unit of agent appropriate for the patient to be treated. It will be understood, however, that the total daily use of the compounds and compositions of the present invention will be decided by the treating physician within the scope of good medical judgment. The specific effective dose level for any particular patient or organism will depend on a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound used; the specific composition used; the patient's age, body weight, general health, sex, and diet; the time of administration, route of administration and rate of excretion of the specific compound used; the duration of treatment; drugs used in combination or coincidence with the specific compound used and similar factors known in the medical arts. The term patient, as used herein, means an animal, preferably a mammal, and more preferably a human. The pharmaceutically acceptable compositions of Qncann / zznz / E / YiAi This invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (such as by powders, ointments or drops), orally, as an oral spray or nasally. , or similar, depending on the severity of the infection being treated. In certain embodiments, the compounds of the invention can be administered orally or parenterally at dosage levels of about 0.01 mg / kg to about 50 mg / kg and preferably from about 1 mg / kg to about 25 mg / kg, by weight. body of the subject per day, one or more times a day, to obtain the desired therapeutic effect. Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing and emulsifying agents such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate , benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular cottonseed, peanut, corn, germ, olive, castor and sesame oils), glycerol, alcohol Qncann / zznz / E / YiAi tetrahydrofurfuryl, polyethylene glycols and sorbitan fatty acid esters, and mixtures thereof. In addition to inert diluents, oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening agents, flavorings and perfuming agents. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a non-toxic parenterally acceptable solvent or diluent, for example, as a solution in 1,3-butanediol. Acceptable vehicles and solvents that can be used include water, Ringer's solution, USP, and isotonic sodium chloride solution. Furthermore, sterile non-volatile oils are conventionally employed as a solvent or suspending medium. For this purpose, any soft fixed oil that includes synthetic mono- or diglycerides can be used. Additionally, fatty acids such as oleic acid are used in the preparation of injectables. Injectable formulations can be sterilized, for example, by filtration through a bacteria-containing filter or by incorporating agents 100 sterilants in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium before use. To prolong the effect of a compound of the present invention, it is often desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of crystalline or amorphous material with poor solubility in water. The absorption rate of the compound then depends on its dissolution rate which, in turn, may depend on the crystal size and crystal form. Alternatively, delayed absorption of a parenterally administered form of the compound is achieved by dissolving or suspending the compound in a petroleum carrier. Injectable depot forms are made by forming microcapsule matrices of the compound in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of the compound to the polymer and the nature of the particular polymer employed, the rate of release of the compound can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Injectable depot formulations are also prepared by trapping the compound in liposomes or microemulsions that are compatible with body tissues. 101 Compositions for rectal or vaginal administration are preferably suppositories that can be prepared by mixing the compounds of the present invention with suitable non-irritant excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax that are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In these solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and / or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato starch or tapioca, alginic acid, certain silicates and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monosteate , h) absorbents such as clay 102 bentonite and kaolin, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard gelatin capsules using excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like. Solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared with coatings and coatings such as enteric coatings and other coatings known in the art of pharmaceutical formulation. They may optionally contain opacifying agents and may also be of a composition that releases the active ingredient(s) alone, or preferably, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard gelatin capsules using excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like. Qncann / zznz / E / YiAi 103 The active compounds may also be in microencapsulated form with one or more excipients as indicated above. Solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared with coatings and coatings such as enteric coatings, release control coatings and other coatings known in the art of pharmaceutical formulation. In these solid dosage forms, the active compound can be mixed with at least one inert diluent such as sucrose, lactose or starch. These dosage forms may also comprise, as is common practice, additional substances other than inert diluents, for example, tablet lubricants and other tablet aids such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and may also be of a composition that releases the active ingredient(s) alone, or preferably, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Dosage forms for topical or transdermal administration of a compound of the present 104 invention include ointments, pastes, creams, lotions, gels, powders, solutions, aerosols, inhalants or patches. The active component is mixed under sterile conditions with a pharmaceutically acceptable carrier and any necessary preservatives or buffers as required. It is also contemplated that ophthalmic formulation, ear drops and eye drops are within the scope of this invention. Furthermore, the present invention contemplates the use of transdermal patches, which have the additional advantage of providing controlled delivery of a compound to the body. These dosage forms can be made by dissolving or dispensing the compound into the appropriate medium. Absorption enhancers can also be used to increase the flow of the compound through the skin. The rate can be controlled by providing a rate control membrane or by dispersing the compound in a polymer matrix or gel. Uses and treatment methods According to one embodiment, the invention relates to a method for inhibiting AHR in a biological sample comprising the step of contacting the biological sample with a compound of the present invention, or a composition comprising the compound. The term biological sample, as used herein, includes, but is not limited to, cell cultures or 105 extracts thereof; biopsy material obtained from a mammal or extracts thereof; and blood, saliva, urine, feces, semen, tears or other bodily fluids or extracts thereof. Inhibition of enzymes in a biological sample is useful for a variety of purposes that are known to one skilled in the art. Examples of such purposes include, but are not limited to, biological assays, gene expression studies and identification of biological targets. Another embodiment of the present invention relates to a method of inhibiting AHR in a patient comprising the step of administering to the patient a compound of the present invention, or a composition comprising the compound. The compounds provided are AHR inhibitors and are therefore useful for treating one or more disorders associated with AHR activity. Therefore, in certain embodiments, the present invention provides a method of treating an AHR-mediated disorder comprising the step of administering to a patient in need thereof a compound of the present invention, or pharmaceutically acceptable composition thereof. In some embodiments, the present invention provides a use of a compound or solid form of the present invention, or a pharmaceutically acceptable composition thereof, for the treatment of a disease. Qncann / zznz / E / YiAi disorder or condition as described in the 106 present. As used herein, the terms AHR-mediated disorders, diseases and / or conditions as used herein mean any disease or other deleterious condition in which AHR, or a mutant thereof, is known to play a role. Accordingly, another embodiment of the present invention relates to treating or lessening the severity of one or more diseases in which AHR, or a mutant thereof, is known to play a role. AHR-mediated disorders are well established in the art. The link between AHR and AHR-mediated diseases and / or disorder conditions as mentioned herein is well established in the relevant arts. For example, see: Uyttenhove et al., Evidence for a tumor immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase Nature Medicine, 2003 vol. 9(10), 1038; Murray et al., AH RECEPTOR LIGANDS IN CANCER: FRIEND AND FOE Nat. Rev. Cancer December 2014, vol. 14(12), pages 801-814; Moon et al., Targeting the indoleamine 2,3-dioxygenase pathway in cancer J. ImmunoTherapy of Cancer, 2015 vol 3, page 51; Ishida et al., Activation of aryl hydrocarbon receptor promotes invasion of clear cell renal cell carcinoma and is associated with poor prognosis and cigarette smoke Int. J. Cancer July 2015 vol. 15, no. 137(2), pages 299-310; Ishida et al., 107 Activation of the aryl hydrocarbon receptor pathway enhances cancer cell invasion by upregulating the MNP expression and is associated with poor prognosis in upper urinary tract urothelial cancerCarcinogenesis February 2010 vol. 31(2), pages 287-295. Su et al., Prognostic value of nuclear translocation of aryl hydrocarbon receptor for non-mall cell lung cancer Anticancer Res. September 2013, vol. 33(9), pages 3953-3961; Peng et al., Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9 BMC Cell Biol. April 2009, vol. 16; pages 10-27; Jin et al., Aryl Hydrocarbon Receptor Activation Reduces Dendritic Cell Function During Influenza Virus Infection Toxicol Sci. August 2010, vol. 116(2), pages 514-522; Head et al., The aryl hydrocarbon receptor is a modulator of anti-viral immunity Biochem. Pharmacol. February 2009, vol. fifteen; No. 77(4), pages 642-53; Jin et al., The aryl hydrocarbon receptor is a modulator of antiviral immunity Biochem. J. Immunol. June 2014, vol. 44(6), pages 1685-98; Nguyen et al., Aryl hydrocarbon receptor and kynurenine: recent advances in autoimmune disease research Front Immunol. October 2014, vol. 29, no. 5, page 551; Esser et al., The aryl hydrocarbon receptor in immunity Trends in Immunology, Vol.30, No. 9. In some embodiments, the present invention 108 provides a method of treating one or more disorders, diseases and / or conditions wherein the disorder, disease or condition is a proliferative disease such as cancer, an inflammatory disorder or a viral infection. In certain embodiments, the present invention provides a method of treating cancer or another proliferative disorder, comprising administering a compound or composition of the present invention to a patient with cancer or another proliferative disorder. In certain embodiments, the method of treating cancer or other proliferative disorder comprises administering compounds and compositions of the present invention to a mammal. In certain embodiments, the mammal is a human. As used herein, the terms cancer inhibition and cancer cell proliferation inhibition refer to inhibiting the growth, division, maturation or viability of cancer cells, and / or causing the death of cancer cells, individually or in conjunction with other cancer cells, by cytotoxicity, nutrient depletion or the induction of apoptosis. Examples of tissues containing cancer cells whose proliferation is inhibited by the compounds and compositions described herein and against which the methods described herein are useful include, but are not limited to, breast, prostate, brain, blood, marrow Qncann / zznz / E / YiAi 109 bone, liver, pancreas, skin, kidney, colon, ovary, lung, testicle, penis, thyroid, parathyroid, pituitary, thymus, retina, uvea, conjunctiva, spleen, head, neck, trachea, gallbladder, rectum, salivary gland , adrenal gland, throat, esophagus, lymph nodes, sweat glands, sebaceous glands, muscle, heart and stomach. In some embodiments, the cancer treated by compounds or compositions of the invention is a melanoma, liposarcoma, lung cancer, breast cancer, prostate cancer, leukemia, kidney cancer, esophageal cancer, brain cancer, lymphoma or breast cancer. colon. In certain embodiments, the cancer is a primary effusion lymphoma (PEL). The compounds of the present invention are useful in the treatment of a proliferative disease selected from a benign or malignant tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate , pancreas, lung, vagina, cervix, testicle, genitourinary tract, esophagus, larynx, skin, bone or thyroid, sarcoma, glioblastomas, neuroblastomas, multiple myeloma or gastrointestinal cancer, especially colon carcinoma or colorectal adenoma or a tumor of the neck and head, epidermal hyperproliferation, psoriasis, hyperplasia of Qnconn / zznz / E / YiAi 110 prostate, a neoplasm, a neoplasm of an epithelial nature, adenoma, adenocarcinoma, keratoacanthoma, squamous cell carcinoma, large cell carcinoma, non-small cell lung carcinoma, lymphomas, Hodgkins and non-Hodgkins, Waldenstrom, macroglobulinemia, a breast carcinoma, carcinoma follicular, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, a MYD88-driven disorder, DLBCL, ABC DLBCL, an IL-1-driven disorder, Smoldering of indolent multiple myeloma or a leukemia. Cancer includes, in some embodiments, but is not limited to, leukemias (e.g., acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroleukemia, leukemia chronic myelocytic leukemia, chronic lymphocytic leukemia), polycythemia vera, lymphoma (e.g., Hodgkin's disease or non-Hodgkin's disease), Waldenstrom's macroglobulinemia, multiple myeloma, heavy chain disease, and solid tumors such as sarcomas and carcinomas (e.g. example, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer , cancer Qncann / zznz / E / YiAi 111 prostate, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma , choriocarcinoma, seminoma, embryonal carcinoma, Wilm's tumor, cervical cancer, testicular cancer, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, glioblastoma multiforme (GBM, also known such as glioblastoma), medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, schwannoma, neurofibrosarcoma, meningioma, melanoma, neuroblastoma and retinoblastoma). In some embodiments, the cancer is glioma, astrocytoma, glioblastoma multiforme (GBM, also known as glioblastoma), medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, schwannoma, neurofibrosarcoma, meningioma, melanoma, neuroblastoma or retinoblastoma. In some embodiments, the cancer is acoustic neuroma, astrocytoma (e.g., grade I - pilocytic astrocytoma, grade II - low grade astrocytoma, grade III anaplastic astrocytoma or grade IV - glioblastoma (GBM)), 112 chordoma, CNS lymphoma, craniopharyngioma, brainstem glioma, ependymoma, mixed glioma, optic nerve glioma, subependymoma, medulloblastoma, meningioma, metastatic brain tumor, oligodendroglioma, pituitary tumors, primitive neuroectodermal tumor (PNET) or schwannoma. In some embodiments, the cancer is a type more commonly found in children than adults, such as brainstem glioma, craniopharyngioma, ependymoma, juvenile pilocytic astrocytoma (JPA), medulloblastoma, optic nerve glioma, pineal tumor, neuroectodermal tumors. primitive (PNET) or rhabdoid tumor. In some embodiments, the patient is an adult human. In some embodiments, the patient is a child or pediatric patient. Cancer includes, but is not limited to, mesothelioma, hepatobiliary (hepatic and bile duct), bone cancer, pancreatic cancer, skin cancer, head or neck cancer, cutaneous or infraocular melanoma, ovarian cancer, cancer colon, rectal cancer, cancer of the anal region, stomach cancer, gastrointestinal (gastric, colorectal and duodenal), uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the Qncann / zznz / E / YiAi 113 parathyroid gland, adrenal gland cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, testicular cancer, chronic or acute leukemia, chronic myeloid leukemia, lymphocytic lymphomas, bladder cancer, kidney or ureter, renal cell carcinoma, renal pelvis carcinoma, non-Hodgkin lymphoma, spinal axis tumors, brainstem glioma, pituitary adenoma, adrenocortical cancer, gallbladder cancer, multiple myeloma, cholangiocarcinoma, fibrosarcoma, neuroblastoma, retinoblastoma , or a combination of one or more of the above cancers. In some embodiments, the cancer is selected from hepatocellular carcinoma, ovarian cancer, ovarian epithelial cancer or fallopian tube cancer; papillary serous cystadenocarcinoma or uterine papillary serous carcinoma (UPSC); prostate cancer; Testicular cancer; gallbladder cancer; hepatocholangiocarcinoma; synovial sarcoma of bone and soft tissue; rhabdomyosarcoma; osteosarcoma; chondrosarcoma; Ewing sarcoma; anaplastic thyroid cancer; adrenocortical adenoma; pancreatic cancer; pancreatic ductal carcinoma or pancreatic adenocarcinoma; gastrointestinal / stomach cancer (GIST); lymphoma; squamous cell carcinoma of the head and neck Qncann / zznz / E / YiAi 114 (SCCHN); salivary gland cancer; glioma, or brain cancer; malignant peripheral nerve sheath tumors associated with neurofibromatosis1 (MPNST); macroglobulinemia or medulloblastoma. In some embodiments, the cancer is selected from hepatocellular carcinoma (HCC), hepatoblastoma, colon cancer, rectal cancer, ovarian cancer, ovarian epithelial cancer, fallopian tube cancer, papillary serous cystadenocarcinoma, carcinoma Uterine papillary serous (UPSC), hepatocholangiocarcinoma, bone and soft tissue synovial sarcoma, rhabdomyosarcoma, osteosarcoma, anaplastic thyroid cancer, adrenocortical adenoma, pancreatic cancer, pancreatic ductal carcinoma, pancreatic adenocarcinoma, glioma, associated malignant peripheral nerve sheath tumors to neurofibromatosis-1 (MPNST); macroglobulinemia or medulloblastoma. In some embodiments, the cancer is a solid tumor, such as a sarcoma, carcinoma or lymphoma. Solid tumors generally comprise an abnormal mass of tissue that usually does not include cysts or fluid areas. In some embodiments, the cancer is selected from renal cell carcinoma or kidney cancer; hepatocellular carcinoma (HCC) or hepatoblastoma or liver cancer; melanoma; cancer Qncann / zznz / E / YiAi 115 breast; colorectal carcinoma or colorectal cancer; colon cancer; rectal cancer; anal cancer; lung cancer, such as non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC); ovarian cancer, ovarian epithelial cancer, ovarian carcinoma or fallopian tube cancer; papillary serous cystadenocarcinoma or uterine papillary serous carcinoma (UPSC); prostate cancer; Testicular cancer; gallbladder cancer; hepatocholangiocarcinoma; synovial sarcoma of bone and soft tissue; rhabdomyosarcoma; osteosarcoma; chondrosarcoma; Ewing sarcoma; anaplastic thyroid cancer; adrenocortical carcinoma; pancreatic cancer; pancreatic ductal carcinoma or pancreatic adenocarcinoma; gastrointestinal / stomach cancer (GIST); lymphoma; squamous cell carcinoma of the head and neck (SCCHN); salivary gland cancer; glioma, or brain cancer; neurofibromatosis-1-associated malignant peripheral nerve sheath tumors (MPNST); macroglobulinemia or medulloblastoma. In some embodiments, the cancer is selected from renal cell carcinoma, hepatocellular carcinoma (HCC), hepatoblastoma, colorectal carcinoma, colorectal cancer, colon cancer, rectal cancer, anal cancer, ovarian cancer, ovarian epithelial cancer, ovarian carcinoma, cancer Qncann / zznz / E / YiAi 116 fallopian tube, papillary serous cystadenocarcinoma, uterine papillary serous carcinoma (UPSC), hepatocholangiocarcinoma, synovial sarcoma of bone and soft tissue; rhabdomyosarcoma, osteosarcoma, chondrosarcoma, anaplastic thyroid cancer, adrenocortical carcinoma, pancreatic cancer, pancreatic ductal carcinoma, pancreatic adenocarcinoma, glioma, brain cancer, malignant peripheral nerve sheath tumors associated with neurofibromatosis1 (MPNST), Walstden's macroglobulinemia, or medulloblastoma. In some embodiments, the cancer is selected from hepatocellular carcinoma (HCC), hepatoblastoma, colon cancer, rectal cancer, ovarian cancer, ovarian epithelial cancer, ovarian carcinoma, fallopian tube cancer, papillary serous cystadenocarcinoma, papillary serous carcinoma. uterine (UPSC), hepatocholangiocarcinoma, synovial sarcoma of bone and soft tissue; rhabdomyosarcoma, osteosarcoma, anaplastic thyroid cancer, adrenocortical carcinoma, pancreatic cancer, pancreatic ductal carcinoma, pancreatic adenocarcinoma, glioma, malignant peripheral nerve sheath tumors associated with neurofibromatosis1 (MPNST), Waldenstrom macroglobulinemia or medulloblastoma. In some embodiments, the cancer is hepatocellular carcinoma (HCC). In some embodiments, the cancer is hepatoblastoma. In some embodiments, the cancer is colon cancer. In some embodiments, the cancer is cancer of 117 straight. In some embodiments, the cancer is ovarian cancer or ovarian carcinoma. In some embodiments, the cancer is ovarian epithelial cancer. In some embodiments, the cancer is fallopian tube cancer. In some embodiments, the cancer is papillary serous cystadenocarcinoma. In some embodiments, the cancer is uterine papillary serous carcinoma (UPSC). In some embodiments, the cancer is hepatocholangiocarcinoma. In some embodiments, the cancer is synovial sarcoma of bone and soft tissue; rhabdomyosarcoma. In some embodiments, the cancer is rhabdomyosarcoma. In some embodiments, the cancer is osteosarcoma. In some embodiments, the cancer is anaplastic thyroid cancer. In some embodiments, the cancer is adrenocortical carcinoma. In some embodiments, the cancer is pancreatic cancer or pancreatic ductal carcinoma. In some embodiments, the cancer is pancreatic adenocarcinoma. In some embodiments, the cancer is glioma. In some embodiments, the cancer is malignant peripheral nerve sheath tumors (MPNST). In some embodiments, the cancer is MPNST associated with neurofibromatosis-1. In some embodiments, the cancer is Waldenstrom's macroglobulinemia. In some embodiments, the cancer is medulloblastoma. In some embodiments, the cancer is Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Carcinoma Qncann / zznz / E / YiAi 118 adrenocortical, Anal cancer. Appendix cancer, Atypical teratoid / rhabdoid tumor, Basal cell carcinoma, Bile duct cancer, Bladder cancer, Bone cancer, Brain tumor, Astrocytoma, Brain and spinal cord tumor, Brainstem glioma, Teratoid / rhabdoid tumor atypical central nervous system, Embryonal tumors of the central nervous system, Breast cancer, Bronchial tumors, Burkitt's lymphoma, Carcinoid tumor, Unknown primary cell carcinoma, Cancer of the central nervous system, Cervical cancer, Childhood cancers, Chordoma, Chronic lymphocytic leukemia (CLL), Chronic myeloid leukemia (CML), Chronic myeloproliferative disorders, Colon cancer, Colorectal cancer, Craniopharyngioma, Cutaneous T-cell lymphoma, Ductal carcinoma in situ (DCIS) its acronym in English), Embryonal tumors, Endometrial cancer, Ependymoblastoma, Ependymoma, Esophageal cancer, Esthesioneuroblastoma, Ewing sarcoma, Extracranial germ cell tumor, Extragonadal germ cell tumor, Extrahepatic bile duct cancer, Eye cancer, Fibrous histiocytoma of bone , Gallbladder cancer, Gastric cancer, Gastrointestinal carcinoid, Gastrointestinal stromal tumors (GIST), Germ cell tumor, Ovarian germ cell tumor, Gestational trophoblastic tumor, Glioma, Leukemia 119 capillary cell cancer, Head and neck cancer Heart cancer, Hepatocellular cancer, Histiocytiosis, Langerhans cell cancer Hodkin lymphoma, Hypopharyngeal cancer, Intraocular melanoma, Islet cell tumors, Kaposi's sarcoma, Kidney cancer, Histiocytosis Langerhans cells, Laryngeal cancer, Leukemia, Lip and oral cavity cancer, Liver cancer, Lobular carcinoma in situ (LCIS), Lung cancer, Lymphoma, AIDS-related lymphoma, Macroglobulinemia, Male breast cancer, Medulloblastoma, Medulloepithelioma , Melanoma, Merkel cell carcinoma, Malignant mesothelioma, Metastatic squamous neck cancer with occult primary, Midline tract carcinoma involving the NUT gene, Oral cancer, Multiple endocrine neoplasia syndrome, Multiple myeloma / Plasma cell neoplasia , Mycosis fungoides, Myelodysplastic syndrome, Myelodysplastic / neuroliferative neoplasm, Chronic myelogenous leukemia (CML), Acute myeloid leukemia (AML), Myeloma, Multiple myeloma, Chronic myeloproliferative disorder, Nasal cavity cancer, Paranasal sinus cancer, Nasopharyngeal cancer, Neuroblastoma, Non-Hodgkin lymphoma, Non-small cell lung cancer, Oral cancer, Oral cavity cancer, Lip cancer, Oropharyngeal cancer, Osteosarcoma, Ovarian cancer, Pancreatic cancer, Papillomatosis, Paraganglioma, Paranasal sinus cancer, Nasal cavity cancer , Cancer Qncann / zznz / E / YiAi 120 parathyroid, Penile cancer, Pharyngeal cancer, Pheochromocytoma, Pineal parenchymal tumors of intermediate differentiation, Pineoblastoma, Pituitary tumor, Plasma cell neoplasm, Pleuropulmonary blastema, Breast cancer, Central Nervous System (CNS), Lymphoma , Prostate Cancer, Rectal Cancer, Renal Cell Cancer, Renal Clear Cell Carcinoma Renal Pelvic Cancer, Ureter Cancer, Transitional Cell Cancer, Retinoblastoma, Rhabdomyosarcoma, Salivary Gland Cancer, Sarcoma, Sézary Syndrome, Cancer skin, Small cell lung cancer, Small intestine cancer, Soft tissue sarcoma, Squamous cell carcinoma, Squamous neck cancer with occult primary, Head and neck squamous cell cancer (HNSCC) , Stomach cancer, Supratentorial primitive neuroectodermal tumors, T-cell lymphoma, Testicular cancer, Throat cancer, Thymoma, Thymic carcinoma, Thyroid cancer, Transitional cell cancer of the renal pelvis and ureter, Triple negative breast cancer (TNBC , for its acronym in English), Gestational trophoblastic tumor, Unknown primary, Unusual cancer of childhood, Urethral cancer, Uterine cancer, Uterine sarcoma, Waldenstrom's macroglobulinemia, 0 Wilms tumor. The compounds according to the invention are useful Qncann / zznz / E / YiAi 121 in the treatment of inflammatory or obstructive airway diseases, resulting, for example, in the reduction of tissue damage, airway inflammation, bronchial hyperreactivity, remodeling or disease progression. Inflammatory or obstructive diseases of the airways to which the present invention is applied include asthma of any type or genesis that includes both intrinsic (non-allergic) asthma and extrinsic (allergic) asthma, mild asthma, moderate asthma, severe asthma, asthma bronchitis, exercise-induced asthma, occupational asthma and asthma induced after bacterial infection. The treatment of asthma should also be understood as encompassing the treatment of subjects, for example, less than 4 or 5 years of age, who exhibit symptoms of wheezing and diagnosed or diagnosable as wheezing infants, an established patient category of greatest concern. and now often identified as incipient or early-stage asthmatics. Prophylactic efficacy in the treatment of asthma will be evidenced by the reduction in the frequency or severity of the symptomatic attack, for example, acute asthmatic attack or bronchoconstrictor, improvement in lung function or improvement in airway hyperreactivity. Additionally, it may be evidenced by reducing the requirement for other symptomatic therapy, such as therapy for or with the intent Qnconn / zznz / E / YiAi 122 to restrict or abort the symptomatic attack when it occurs, for example, anti-inflammatory or bronchodilator. The prophylactic benefit in asthma may be evident, particularly in subjects prone to morning immersion. Morning dipping is a recognized asthmatic syndrome, common to a substantial percentage of asthmatics and characterized by an asthma attack, for example, between the hours of about 4 to 6 am, i.e. at a time normally substantially distant from any asthma therapy. previously administered symptomatic asthma. The compounds of the present invention can be used for other inflammatory or obstructive airway diseases and conditions to which the present invention is applied and include acute lung injury (ALT), acute / adult respiratory distress syndrome (ARDS), chronic obstructive pulmonary, airway or lung disease (COPD, COAD or COLD), including chronic bronchitis or dyspnea associated with it, emphysema, as well as exacerbation of airway hyperresponsiveness as a consequence of other drug therapy, in particular other therapy inhaled pharmacology. The invention is also applicable to the treatment of bronchitis of any type or genesis including, but not limited to, acute, arachidic, catarrhal, croupus, chronic or phtinoid bronchitis. Other inflammatory diseases Qncann / zznz / E / YiAi 123 or obstructive airways to which the present invention is applied include pneumoconiosis (an inflammatory, commonly occupational, disease of the lungs, frequently accompanied by airway obstruction, whether chronic or acute, and caused by repeated inhalation of dusts) of any type or genesis, including, for example, aluminosis, anthracosis, asbestosis, calicosis, ptylosis, siderous, silicosis, tobaccose and byssinosis. With respect to their anti-inflammatory activity, in particular in relation to the inhibition of eosinophil activation, the compounds of the invention are also useful in the treatment of eosinophil-related disorders, for example, eosinophilia, in particular eosinophil-related disorders of the airways (for example, involving morbid eosinophilic infiltration of lung tissues) including hypereosinophilia as it affects the airways and / or lungs as well as, for example, eosinophil-related disorders of the airways consequent or concomitant with the syndrome Loffler, eosinophilic pneumonia, parasitic (particularly metazoan) infestation (including tropical eosinophilia), bronchopulmonary aspergillosis, polyarteritis nodosa (including Churg-Strauss), eosinophilic granuloma disorders Qncann / zznz / E / YiAi 124 related to eosinophils that affect the airways caused by the reaction to the drug. The compounds of the invention are also useful in the treatment of inflammatory or allergic skin conditions, for example, psoriasis, contact dermatitis, atopic dermatitis, alopecia areata, erythema multiforme, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, urticaria , bullous pemphigoid, lupus erythematosus, systemic lupus erythematosus, pemphigus vulgaris, foliar pemphigus, paraneoplastic pemphigus, epidermolysis bullosa acquisita, acne vulgaris and other inflammatory or allergic skin conditions. The compounds of the invention can also be used for the treatment of other diseases or conditions, such as diseases or conditions that have an inflammatory component, for example, treatment of diseases and conditions of the eye such as ocular allergy, conjunctivitis, keratoconjunctivitis sicca and conjunctivitis. vernal, diseases affecting the nose including allergic rhinitis and inflammatory disease in which autoimmune reactions are involved or have an autoimmune component or etiology, including autoimmune hematologic disorders (e.g., hemolytic anemia, aplastic anemia, pure red cell anemia and idiopathic thrombocytopenia), lupus erythematosus 125 systemic, rheumatoid arthritis, polychondritis, scleroderma, Wegener's granulamatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Steven-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), irritable bowel, celiac disease, periodontitis, hyaline membrane disease, kidney disease, glomerular disease, alcoholic liver disease, multiple sclerosis, endocrine ophthalmopathy, Graves' disease, sarcoidosis, alveolitis, chronic hypersensitivity pneumonitis, multiple sclerosis, primary biliary cirrhosis, uveitis (anterior and posterior), Sjogren's syndrome, keratoconjunctivitis sicca and vernal keratoconjunctivitis, interstitial pulmonary fibrosis, psoriatic arthritis, systemic juvenile idiopathic arthritis, cryopyrin-associated periodic syndrome, nephritis, vasculitis, diverticulitis, interstitial cystitis, glomerulonephritis (with and without syndrome nephrotic, for example, including idiopathic nephrotic syndrome or minimal change nephropathy), chronic granulomatous disease, endometriosis, leptospiriosis kidney disease, glaucoma, retinal disease, aging, headache, pain, complex regional pain syndrome, cardiac hypertrophy, wasting muscle, catabolic disorders, obesity, fetal growth retardation, hypercholesterolemia, heart disease, failure Qncann / zznz / E / YiAi 126 chronic cardiac, mesothelioma, anhydrous ecodermal dysplasia, Behcet's disease, incontinence pigmenti, Paget's disease, pancreatitis, hereditary periodic fever syndrome, asthma (allergic and non-allergic, mild, moderate, severe, bronchial and exercise-induced), acute lung injury, acute respiratory distress syndrome, eosinophilia, hypersensitivity, anaphylaxis, nasal sinusitis, ocular allergy, silica-induced diseases, COPD (damage reduction, airway inflammation, bronchial hyperresponsiveness, remodeling or disease progression) , lung disease, cystic fibrosis, acid-induced lung injury, pulmonary hypertension, polyneuropathy, cataracts, muscle inflammation in relation to systemic sclerosis, dermatomyositis, polymyositis, inclusion body myositis, myasthenia gravis, thyroiditis, Addison's disease, lichen planus , type 1 or type 2 diabetes. In some embodiments, the inflammatory disease that can be treated according to the methods of the present invention is selected from acute and chronic gout, chronic gouty arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, systemic juvenile idiopathic arthritis (SJIA). , for its acronym in English), cryopyrin-associated periodic syndromes (CAPS), or osteoarthritis. 127 In some embodiments, the inflammatory disease that can be treated according to the methods of the present invention is selected from a TH17-mediated disease. In some embodiments, the TH17-mediated disease is selected from systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease including ulcerative colitis or Crohn's. In some embodiments, the inflammatory disease that can be treated according to the methods of the present invention is selected from allergic disorders of Sjogren's syndrome, osteoarthritis. Eye conditions such as ocular allergy, conjunctivitis, keratoconjunctivitis sicca and vernal conjunctivitis, diseases that affect the nose, including allergic rhinitis. In some embodiments, the inflammatory disease that can be treated according to the methods of the present invention is selected from contact dermatitis, atopic dermatitis, alopecia areata, erythema multiforma, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, urticaria, bullous pemphigoid. , pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, epidermolysis bullosa acquisita and other inflammatory or allergic skin conditions. In certain embodiments, a provided compound is useful for treating an infection, disease or condition. 128 viral. In some embodiments, the present invention provides a method of treating a viral disease selected from retroviral diseases, such as HIV-1, HIV-2, human T cell leukemia virus-I (HTLV-I). , HTLV-II, HTLV-III, simian immunodeficiency virus (SIV), lymphadenopathy-associated virus (LAV-2), simian T-lymphotrophy virus ( STLV-I), STLV-II, STLV-III, simian B lymphotrophy virus (SBL), gibbon monkey leukemia virus (GALV) bovine leukemia virus (BLV), equine infectious anemia virus (EIAV), feline leukemia virus (FELV), murine leukemia virus (MuLV), avian leukosis virus (ALV); other viral infections such as hepadnaviridae (Hepatitis B); herpesviridae (Herpes simplex I, Herpes simplex II, Varicella-Zoster, Epstein-Barr virus and cytomegalovirus); parvoviridae (human parvovirus B-19); papovaviridae (human papillomavirus types 1 to 60, JC and BK viruses); poxviruses (smallpox, smallpox, vaccinia, monkeypox, cowpox, paravaccinia or milk nodule virus, parapox or ORF virus, molluscum contagiosum) and cancers, lymphomas and other leukemias. Qncann / zznz / E / YiAi 129 Combination therapies Depending on the particular condition or disease to be treated, additional therapeutic agents, which are normally administered to treat that condition, may be administered in combination with compounds and compositions of the present invention. As used herein, additional therapeutic agents that are typically administered to treat a particular disease or condition are known to be appropriate for the disease or condition being treated. In certain embodiments, a provided compound, or a composition thereof, is administered in combination with another chemotherapeutic, anti-cancer or cytotoxin agent, to a patient in need thereof. In certain embodiments, the anti-cancer or chemotherapeutic agents used in combination with compounds or compositions of the invention including, but not limited to, metformin, phenformin, buformin, imatinib, nilotinib, gefitinib, sunitinib, carfilzomib, salinosporamide A, acid retinoic acid, cisplatin, carboplatin, oxaliplatin, mechlorethamine, cyclophosphamide, chlorambucil, ifosfamide, azathioprine, mercaptopurine, doxyfluridine, fluorouracil, gemcitabine, methotrexate, thioguanine, vincristine, vinblastine, vinorelbine, vindesine, podophyllotoxin, etoposide, teniposide, tafluposide, paclitaxel , docetaxel, Qncann / zznz / E / YiAi 130 irinotecan, Topotecan, amsacrine, actinomycin, doxorubicin, daunorubicin, valrubicin, idarubicine, epirubicine, plicamycin, mitomycin, mitoxantrone, melfalano, busulfan, capecitabine, pemetrexed, epylon, acid 13-cis-retinoic eoiyadenosina, 5-Azacytidine, 5-Fluorouracil, 5-FU, 6-Mercaptopurine, 6-MP, 6-TG, 6-Thioguanine, Abraxane, Accutane ®, Actinomycin-D, Adriamycin ®, Adrucil ®, Afinitor ®, Agrylin ®, Ala -Cort ®, Aldesleukin, Alemtuzumab, ALIMTA, Alitretinoin, Alkaban-AQ ®, Alkeran ®, Todotransretinoic acid, Alpha Interferon, Altretamine, Ametopterin, Amifostine, Aminoglutethimide, Anagrelide, Anandron ®, Anastrozole, Arabinosylcytosine, Ara-C, Aranesp ®, Aredia ®, Arimidex ®, Aromasin ®, Arranon ®, Arsenic Trioxide, Arzerra™, Asparaginase, ATRA, Avastin ®, Azacitidine, BCG, BCNU, Bendamustine, Bevacizumab, Bexarotene, BEXXAR ®, Bicalutamide, BiCNU, Blenoxane ®, Bleomycin, Bortezomib, Busulfan, Busulfex ®, C225, Calcium Leucovorin, Campath ®, Camptosar ®, Camptothecin-11, Capecitabine, Carac ™, Carboplatin, Carmustine, Carmustine Wafer, Casodex ®, CC5013, CCI-779, CCNU, CDDP, CeeNU , Cerubidine ®, Cetuximab, Chlorambucil, Citrovorum Factor, Cladribine, Cortisone, Cosmegen ®, CPT-11, Cytadren ®, Cytosar-U ®, Cytoxan ®, Dacarbazine, Dacogen, Dactinomycin, Darbepoetin Alfa, Dasatinib, Daunomycin, Daunorubicin Hydrochloride , Daunorubicin Liposomal, DaunoXome ®, Decadron, Decitabine, Qncann / zznz / E / YiAi 131 Delta-Cortef ®, Deltasone ®, Denileukin, Diftitox, DepoCyt™, Dexamethasone, Dexamethasone Acetate, Dexamethasone Sodium Phosphate, Dexasone, Dexrazoxane, DHAD, DIC, Diodex, Docetaxel, Doxil ®, Doxorubicin, Liposomal Doxorubicin, Droxia™, DTIC, DTIC-Dome ®, Duralone ®, Efudex ®, Eligard ™, Ellence ™, Eloxatin ™, Elspar ®, Emcyt ®, Epirubicin, Epoetin Alfa, Erbitux, Erlotinib, Erwinia L-asparaginase, Estramustine, Ethiol, Etopophos ®, Etoposide , Etoposide Phosphate, Eulexin ®, Everolimus, Evista ®, Exemestane, Fareston ®, Faslodex ®, Femara ®, Filgrastim, Floxuridine, Fludara ®, Fludarabine, Fluoroplex ®, Fluorouracil, Fluorouracil (cream), Fluoxymesterone, Flutamide, Folinic Acid, FUDR ®, Fulvestrant, G-CSF, Gefitinib, Gemcitabine, Gemtuzumab, ozogamicin, ,Gemzar Gleevec ™, Gliadel ® Wafer, GM-CSF, Goserelin, Granulocyte - Colony Stimulating Factor, Granulocyte and Macrophage Colony Stimulating Factor, Halotestin ® , Herceptin ®, Hexadrol, Hexalen ®, Hexamethylmelamine, HMM, Hycamtin ®, Hydrea ®, Hydrocort Acétate ®, Hydrocortisone, Hydrocortisone Sodium Phosphate, Hydrocortisone Sodium Succinate, Hydrocortone Phosphate, Hydroxyurea, Ibritumomab, Ibritumomab, Tiuxetan, Idamycin ®, Idarubicin Ifex ®, IFN-alpha, Ifosfamide, IL-11, IL-2, Imatinib mesylate, Imidazole Carboxamide, Interferon alfa, Interferon Alfa-2b (PEG Conjugated), Interleukin-2, Interleukin-11, Intron A® (interferon alfa-2b), Iressa ®, 132 Irinotecan, Isotretinoin, Ixabepilone, Ixempra ™, Kidrolase ®, Lanacort ®, Lapatinib, L-asparaginase, LCR, Lenalidomide, Letrozole, Leucovorin, Leukeran, Leukine ™, Leuprolide, Leurocristine, Leustatin ™, Liposomal Ara-C, Liquid Pred ®, Lomustine, L-PAM, L-Sarcolysin, Lupron ®, Lupron Depot ®, Matulane ®, Maxidex, Mechlorethamine, Mechlorethamine Hydrochloride, Medralone ®, Medrol ®, Megace ®, Megestrol, Megestrol Acetate, Melphalan, Mercaptopurine, Mesna, Mesnex ™ , Mehotrexate, Methotrexate Sodium, Methylprednisolone, Meticorten ®, Mitomycin, Mitomycin-C, Mitoxantrone, MPrednisol ®, MTC, MTX, Mustargen ®, Mustina, Mutamycin ®, Myleran ®, Mylocel ™, Mylotarg ®, Navelbine ®, Nelarabine, Neosar ® , Neulasta ™, Neumega ®, Neupogen ®, Nexavar ®, Nilandron ®, Nilotinib, Nilutamide, Nipent ®, Nitrogen Mustard, Novaldex ®, Novantrone ®, Nplate, Octreotide, Octreotide Acetate, Ofatumumab, Oncospar ®, Oncovin ®, Ontak ®, Onxal ™, Oprelvekin, Orapred ®, Orasone ®, Oxaliplatin, Paclitaxel, Protein-Bound Paclitaxel, Pamidronate, Panitumumab, Panretin ®, Paraplatin ®, Pazopanib, Pediapred ®, PEG Interferon, Pegaspargase, Pegfilgrastim, PEG-INTRON ™, PEG -L-asparaginase, PEMETREXED, Pentostatin, Phenylalanine Mozzate, Platinol ®, PlatinolAQ ®, Prednisolone, Prednisone, Prelone ®, Procarbazine, PROCRIT ®, Proleukin ®, Prolifeprospan 20 with Carmustine Implant, Purinethol ®, Raloxifene, Revlimid ®, Rheumatrex Qncann / zznz / E / YiAi 133 ®, Rituxan ®, Rituximab, Roferon-A ® (Inferred Alfa-2a), Romiplostim, Rubex ®, Rubidomycin hydrochloride, Sandostatin ®, Sandostatin LAR ®, Sargramostim, Solu-Cortef ®, Solu-Medrol ®, Sorafenib, SPRYCEL ™, STI-571, Streptozocin, SU11248, Sunitinib, Sutent ®, Tamoxifen, Tarceva ®, Targretin ®, Tasigna ®, Taxol ®, Taxotere ®, Temodar ®, Temozolomide, Temsirolimus, Teniposide, TESPA, Thalidomid, Thalomid ®, TheraCys ® , Thioguanine, Thioguanine Tabloid ®, Thiofosfoamide, Thioplex ®, Tiotepa, TICE ®, Toposar ®, Topotecan, Toremifeno, Torisel ®, Tositumomab, Trastuzumab, Treanda ®, Tretinoina, Trexall ™, Trisenox ®, TSPA, TYKERB ®, VCR, Vectibix ™, Velban ®, Velcade ®, VePesid ®, Vesanoid ®, Viadur ™, Vidaza ®, Vinblastine, Vinblastine Sulfate, Vincasar Pfs ®, Vincristine, Vinorelbine, Vinorelbine tartrate, VLB, VM-26, Vorinostat, Votrient, VP- 16, Vumon ®, Xeloda ®, Zanosar ®, Zevalin ™, Zinecard ®, Zoladex ®, Zoledronic acid, Zolinza, Zometa ®, or combinations of any of the above. In certain embodiments, an immuno-oncological agent can be administered with a compound as described herein for the treatment of a proliferative disorder as described herein. As used herein, the term an immuno-oncological agent refers to an agent that is effective in enhancing, stimulating and / or up-regulating immune responses in a subject. In Qncann / zznz / E / YiAi In some embodiments, the administration of an immuno-oncological agent with a compound as described herein has a synergistic effect in the treatment of cancer. In some embodiments, a compound as described herein is administered sequentially prior to the administration of an immuno-oncological agent. In some embodiments, a compound as described herein is administered simultaneously with an immuno-oncological agent. In some embodiments, a compound as described herein is administered sequentially after administration of an immuno-oncological agent. In some embodiments, a compound as described herein may be formulated with an immuno-oncology agent. An immuno-oncological agent may be, for example, a small molecule drug, an antibody or a biological or small molecule. Examples of biological immuno-oncology agents include, but are not limited to, cancer vaccines, antibodies, and cytokines. In some embodiments, an antibody is a monoclonal antibody. In some embodiments, a monoclonal antibody is humanized or human. In some embodiments, an immuno-oncological agent is (i) an agonist of a stimulatory receptor (including a costimulant) or (ii) an antagonist of an inhibitory signal. Qncann / zznz / E / YiAi 135 (which includes a co-inhibitor) in T cells, both of which result in amplifying antigen-specific T cell responses. Some of the stimulatory and inhibitory molecules are members of the immunoglobulin superfamily (IgSF). An important family of membrane-bound ligands that bind to costimulatory or coinhibitory receptors is the B7 family, which includes B7-1, B7-2, B7-H1 (PD-L1), B7-DC (PDL2), B7-H2 (ICOS-L), B7-H3, B7-H4, B7-H5 (VISTA) and B7-H6. Another family of membrane-bound ligands that bind to costimulatory or co-inhibitory receptors is the family of TNF molecules that bind to members of the cognate TNF receptor family, which includes CD40 and CD40L, 0X40, OX-40L, CD70, CD27L, CD30, CD30L, 4-1BBL, CD137 (4-1BB), TRAIL / Apo2-L, TRAILR1 / DR4, TRAILR2 / DR5, TRAILR3, TRAILR4, OPG, RANK, RANKL, TWEAKR / Fnl4, TWEAK, BAFFR , WWTP, XEDAR, TACI, APRIL, BOMA, ΕΤβΡ, LIGHT, DcR3, HVEM, VEGI / TL1A, TRAMP / DR3, WWTP, EDA1, , FAS, FASL, RELT, DR6, TROY, NGFR. In some embodiments, an immuno-oncological agent is a cytokine that inhibits the activation of T cells (for example, IL-6, IL-10, TGF-β, VEGF and other immunosuppressive cytokines) or a cytokine that stimulates the activation of T cells. T, to stimulate an immune response. 136 In some embodiments, a combination of a compound as described herein, and an immuno-oncological agent can stimulate T cell responses. In some embodiments, an immuno-oncological agent is: (i) an antagonist of a protein that inhibits activation of T cells (e.g. immune checkpoint inhibitors) such as CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, TIM-3, Galectin 9, CEACAM-1, BTLA , CD69, Galectin-1, TIGIT, CD113, GPR56, VISTA, 2B4, CD48, GARP, PD1H, LAIR1, TIM-1, and TIM-4; or (ii) an agonist of a protein that stimulates T cell activation such as B7-1, B7-2, CD28, 4-1BB (CD137), 4-1BBL, ICOS, ICOS-L, 0X40, OX40L, GITR , GITRL, CD70, CD27, CD40, DR3 and CD28H. In some embodiments, an immuno-oncological agent is an antagonist of inhibitory receptors on NK cells or an agonist of activating receptors on NK cells. In some embodiments, an immuno-oncological agent is a KIR antagonist, such as lirilumab. In some embodiments, an immuno-oncological agent is an agent that inhibits or depletes macrophages or monocytes, including but not limited to CSF-1R antagonists such as CSF-1R antagonist antibodies including RG7155 (WO11 / 70024, WO11 / 107553, WO11 / 131407, WO13 / 87699, WO13 / 119716, WO13 / 132044) or FPA-008 (WO11 / 140249; WO13169264; WO14 / 036357). Qnconn / zznz / E / YiAi 137 In some embodiments, an immuno-oncological agent is selected from agonist agents that bind positive costimulatory receptors, blocking agents that attenuate signaling through inhibitory receptors, antagonists and one or more agents that systemically increase the frequency of antitumor T cells, agents that overcome distinct immunosuppressive pathways within the tumor microenvironment (e.g., block inhibitory receptor engagement (e.g., PD-L1 / PD-1 interactions), deplete or inhibit Tregs (e.g., using an anti-CD25 monoclonal antibody (e.g. example, daclizumab) or by depletion of anti-CD25 beads ex vivo), inhibit metabolic enzymes such as IDO, or reverse / prevent energy or T cell exhaustion) and agents that trigger innate immune activation and / or inflammation at tumor sites . In some embodiments, an immuno-oncological agent is a CTLA-4 antagonist. In some embodiments, a CTLA-4 antagonist is a CTLA-4 antagonist antibody. In some embodiments, an antagonistic CTLA-4 antibody is YERVOY (ipilimumab) or tremelimumab. In some embodiments, an immuno-oncological agent is a PD-1 antagonist. In some embodiments, a PD-1 antagonist is administered by infusion. In some embodiments, an immuno-oncological agent is an antibody or an antigen-binding portion thereof that is Qncann / zznz / E / YiAi 138 specifically binds to a Programmed Death-1 (PD1) receptor and inhibits PD-1 activity. In some embodiments, a PD-1 antagonist is an antagonistic PD-1 antibody. In some embodiments, an antagonistic PD-1 antibody is OPDIVO (nivolumab), KEYTRUDA (pembrolizumab), or MEDI-0680 (AMP-514; WO2012 / 145493). In some embodiments, an immuno-oncology agent may be pidilizumab (CT-011). In some embodiments, an immuno-oncological agent is a recombinant protein composed of the extracellular domain of PD-L2 (B7-DC) fused to the Fe part of IgGl, designated AMP-224. In some embodiments, an immuno-oncological agent is a PD-L1 antagonist. In some embodiments, a PD-L1 antagonist is an antagonistic PD-L1 antibody. In some embodiments, a PD-L1 antibody is MPDL3280A (RG7446; W02010 / 077634), durvalumab (MEDI4736), BMS-936559 (WO2007 / 005874) and MSB0010718C (W02013 / 79174). In some embodiments, an immuno-oncological agent is an antagonist of LAG-3. In some embodiments, a LAG-3 antagonist is an antagonistic LAG-3 antibody. In some embodiments, a LAG3 antibody is BMS-986016 (WO10 / 19570, WO14 / 08218), or IMP-731 or IMP-321 (WO08 / 132601, WO009 / 44273). In some embodiments, an immuno-oncological agent is a CD137 (4-1BB) agonist. In some embodiments, a CD137 agonist (4-1BB) is an agonistic CD137 antibody. Qncann / zznz / E / YiAi 139 In some embodiments, a CD137 antibody is urelumab or PF05082566 (WO12 / 32433). In some embodiments, an immuno-oncological agent is a GITR agonist. In some embodiments, a GITR agonist is a GITR agonist antibody. In some embodiments, a GITR antibody is BMS-986153, BMS-986156, TRX-518 (WOO06 / 105021, WOO09 / 009116) or MK-4166 (WO11 / 028683). In some embodiments, an immuno-oncological agent is an IDO antagonist. In some embodiments, an IDO antagonist is INCB-024360 (WO2006 / 122150, WO07 / 75598, WO08 / 36653, WO08 / 36642), indoximod, or NLG-919 (WO09 / 73620, WOO09 / 1156652, WO11 / 56652, WO12). / 142237). In some embodiments, an immuno-oncological agent is an 0X40 agonist. In some embodiments, an 0X40 agonist is an 0X40 agonist antibody. In some embodiments, an 0X40 antibody is MEDI-6383 or MEDI-6469. In some embodiments, an immuno-oncological agent is an OX40L antagonist. In some embodiments, an OX40L antagonist is an 0X40 antagonist antibody. In some embodiments, an antagonist of 0X4OL is RG-7888 (WOO6 / 029879). In some embodiments, an immuno-oncological agent is a CD40 agonist. In some embodiments, a CD40 agonist is an agonist CD40 antibody. In some embodiments, an immuno-oncological agent is an antagonist of Qncann / zznz / E / YiAi 140 CD40. In some embodiments, a CD40 antagonist is an antagonistic CD40 antibody. In some embodiments, a CD40 antibody is lucatumumab or dacetuzumab. In some embodiments, an immuno-oncological agent is a CD27 agonist. In some embodiments, a CD27 agonist is an agonist CD27 antibody. In some embodiments, a CD27 antibody is varlilumab. In some embodiments, an immuno-oncological agent is MGA271 (a B7H3) (WO11 / 109400). In some embodiments, an immuno-oncologic agent is abagovomab, adecatumumab, afutuzumab, alemtuzumab, anatumomab mafenatox, apolizumab, atezolimab, avelumab, blinatumomab, BMS-936559, catumaxomab, durvalumab, epacadostat, epratuzumab, indoximod, inotuzumab ozogamicin, intelumumab, ipil imumab, isatuximab, lambrolizumab, MED14736, MPDL3280A, nivolumab, obinutuzumab, ocaratuzumab, ofatumumab, olatatumab, pembrolizumab, pidilizumab, rituximab, ticilimumab, samalizumab, or tremelimumab. In some embodiments, an immuno-oncological agent is an immunostimulatory agent. For example, antibodies that block the PD-1 and PD-L1 inhibitory axis can trigger activated tumor-reactive T cells and have been shown in clinical trials to induce durable antitumor responses in increasing numbers of tumor histologies, including some types of tumors 142 genetically approved for the treatment of unresectable cutaneous, subcutaneous and lymph node lesions in melanoma. In some embodiments, an immuno-oncology agent is selected from an oncolytic viral therapy such as pexastimogene devacirepvec (PexaVec / JX-594, SillaJen / formerly Jennerex Biotherapeutics), a thymidine kinase (TK-) deficient vaccinia virus genetically modified to express GM-. CSF, for hepatocellular carcinoma (NCT02562755) and melanoma (NCT00429312); pelareorep (Reolysin ®, Oncolytics Biotech), a variant of respiratory enteric orphan virus (reovirus) that does not replicate in cells that are not activated by RAS, in numerous cancers, including colorectal cancer (NCT01622543); prostate cancer (NCT01619813); squamous cell and head cancer (NCT01166542) ; pancreatic adenocarcinoma (NCT00998322) ; and non-small cell lung cancer (NSCLC) (NCT 00861627); enadenotucirev (NG-348, PsiOxus, formerly known as ColoAdl), an adenovirus modified to express a full-length CD80 and an antibody fragment specific for the T-cell receptor protein CD3, in ovarian cancer (NCT02028117); metastatic or advanced epithelial tumors such as colorectal cancer, bladder cancer, head and neck squamous cell carcinoma, and salivary gland cancer Qncann / zznz / E / YiAi (NCT02636036); ONCOS-102 (Targovax / formerly Oncos), a 143 adenovirus modified to express GM-CSF, in melanoma (NCT03003676); and peritoneal disease, colorectal cancer, or ovarian cancer (NCT02963831); GL-0NC1 (GLV-168 / GLH-1153, Genelux GmbH), vaccinia viruses genetically modified to express beta-galactosidase (betagal) / beta-glucoronidase or beta-gal / human sodium iodide symporter (hNIS) were studied. respectively, in peritoneal carcinomatosis (NCT01443260); fallopian tube cancer, ovarian cancer (NCT 02759588); or CG0070 (Coid Genesys), an adenovirus genetically modified to express GM-CSF, in bladder cancer (NCT02365818). In some embodiments, an immuno-oncology agent is selected from JX-929 (SillaJen / formerly Jennerex Biotherapeutics), a vaccinia TK growth factor-deficient vaccinia virus modified to express cytosine deaminase, which is capable of converting the prodrug. 5-fluorocytosine in the cytotoxic drug 5fluorouracil; TG01 and TG02 (Targovax / formerly Oncos), peptide-based immunotherapy agents targeting difficult-to-treat RAS mutations; and TILT-123 (TILT Biotherapeutics), a modified adenovirus designated: Ad5 / 3E2F-delta24-hTNFa-IRES-hIL20; and VSV-GP (ViraTherapeutics) a vesicular stomatitis virus (VSV) modified to express the lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP), which can be further modified Qncann / zznz / E / YiAi 144 to express modified antigens to raise an antigen-specific CD8+ T cell response. In some embodiments, an immuno-oncological agent is a T cell genetically modified to express a chimeric antigen receptor, or CAR. T cells genetically modified to express the chimeric antigen receptor are called CAR-T cells. Cars have been constructed consisting of binding domains, which may be derived from natural ligands, single chain variable fragments (scFv) derived from monoclonal antibodies specific for cell surface antigens, fused to endodomains that are the functional end of the T cell receptor. (TCR), such as the CD3-zeta signaling domain of TCR, which is capable of generating an activation signal in T cells. Upon antigen binding, these CARs bind to endogenous signaling pathways in the effector cell and generate activation signals similar to those initiated by the TCR complex. For example, in some embodiments, the CAR-T cell is one of those described in US Patent 8,906,682 (June; which is incorporated by reference in its entirety), which describes CAR-T cells genetically modified to comprise an extracellular domain. having an antigen-binding domain (such as a CD19-binding domain), fused to a signaling domain Qncann / zznz / E / YiAi 145 intracellular zeta chain of the T cell antigen receptor complex (such as CD3 zeta). When expressed in the T cell, CAR is capable of redirecting antigen recognition based on antigen-binding specificity. In the case of CD19, the antigen is expressed on malignant B cells. There are currently more than 200 ongoing clinical trials employing CAR-T in a wide range of indications. [https: / / clinicaltrials.gov / ct2 / results?term=chimeric+antigen +receptors&pg=l]. In some embodiments, an immunostimulatory agent is a retinoic acid receptor-related orphan receptor (RORyt) activator. RORyt is a transcription factor with key roles in the differentiation and maintenance of type 17 effector subsets of CD4+ (Thl7) and CD8+ (Tcl7) T cells, as well as the differentiation of subpopulations of innate immune cells that express IL-17, such as NK cells. In some embodiments, an activator of RORyt is LYC-55716 (Lycera), which is currently being evaluated in clinical trials for the treatment of solid tumors (NCT02929862). In some embodiments, an immunostimulatory agent is a toll-like receptor (TLR) agonist or activator. Suitable TLR activators include an agonist or Qncann / zznz / E / YiAi 146 TLR9 activator such as SD-101 (Dynavax). SD-101 is an immunostimulatory CpG that is being studied for B-cell, follicular, and other lymphomas (NCT02254772). TLR8 agonists or activators that can be used in the present invention include motolimod (VTX-2337, VentiRx Pharmaceuticals) which is being studied for head and neck squamous cell cancer (NCT02124850) and ovarian cancer (NCT02431559). Other immuno-oncological agents that can be used in the present invention include urelumab (BMS-663513, Bristol-Myers Squibb), an anti-CD137 monoclonal antibody; varlilumab (CDX-1127, Celldex Therapeutics), an anti-CD27 monoclonal antibody; BMS-986178 (Bristol-Myers Squibb), an anti-OX40 monoclonal antibody; lirilumab (IPH2102 / BMS986015, Innate Pharma, Bristol-Myers Squibb), an anti-KIR monoclonal antibody; monalizumab (IPH2201, Innate Pharma, AstraZeneca), an anti-NKG2A monoclonal antibody; andecaliximab (GS-5745, Gilead Sciences), an anti-MMP9 antibody; MK-4166 (Merck & Co.), an anti-GITR monoclonal antibody. In some embodiments, an immunostimulatory agent is selected from elotuzumab, mifamurtide, a toll-like receptor agonist or activator, and a RORyt activator. In some embodiments, a therapeutic agent Qncann / zznz / E / YiAi immunostimulator is recombinant human interleukin 15 147 (rhIL-15). rhIL-15 has been tested in the clinic as a therapy for melanoma and renal cell carcinoma (NCT01021059 and NCT01369888) and leukemias (NCT02689453). In some embodiments, an immunostimulatory agent is recombinant human interleukin-12 (rhIL-12). In some embodiments, an IL-15-based immunotherapeutic agent is heterodimeric IL-15 (hetIL-15, Novartis / Admune), a fusion complex composed of a synthetic form of endogenous IL-15 complexed with the alpha chain of the IL receptor. -15 soluble IL-15 binding protein (IL15: SIL-15RA), which has been evaluated in Phase 1 clinical trials for melanoma, renal cell carcinoma, non-small cell lung cancer, and squamous cell carcinoma. head and neck (NCT02452268) . In some embodiments, a recombinant human interleukin 12 (rhIL-12) is NM-IL-12 (Neumedicines, Inc.), NCT02544724 or NCT02542124. In some embodiments, an immuno-oncological agent is selected from those described in Jerry L. Adams ET. AL., Big opportunities for small molecules in immuno-oncology, Cancer Therapy 2015, Vol. 14, pages 603-622, the contents of which are incorporated herein by reference in their entirety. In some embodiments, an immuno-oncological agent is selected from the examples described in Table 1 of Jerry L. Adams ET. TO THE. In some embodiments, an immuno-oncology agent is a targeted small molecule. 148 immuno-oncology selected from those listed in Table 2 of Jerry L. Adams ET. TO THE. In some embodiments, an immuno-oncology agent is a small molecule agent selected from those listed in Table 2 of Jerry L. Adams ET. TO THE. In some embodiments, an immuno-oncology agent is selected from the small molecule immuno-oncology agents described in Peter L. Toogood, Small molecule immuno-oncology therapeutic agents, Bioorganic & Medicinal Chemistry Letters 2018, Vol. 28, pages 319-329 , the contents of which are incorporated herein by reference in their entirety. In some embodiments, an immuno-oncology agent is a pathway-targeting agent as described in Peter L. Toogood. In some embodiments, an immuno-oncological agent is selected from those described in Sandra L. Ross et al., Bispecific T-Cell Engaging (BiTE®) Antibody Constructs Can Mediate Non-Specific Tumor Cell Killing, PLOS One 12 (8) : e0183390, the contents of which are incorporated herein by reference in their entirety. In some embodiments, an immuno-oncology agent is a bispecific T cell engagement (BiTE®) antibody construct. In some embodiments, a bispecific T cell engaging antibody construct (BiTE®) is an antibody construct. 149 bispecific CD19 / CD3. In some embodiments, a bispecific T cell engagement (BiTE®) antibody construct is an EGFR / CD3 bispecific antibody construct. In some embodiments, a bispecific T cell engagement antibody construct (BiTE®) activates T cells. In some embodiments, a bispecific T cell engagement antibody construct (BiTE®) activates T cells, which release cytokines that induce upregulation of intercellular adhesion molecule 1 (ICAM-1) and FAS in nonspecific cells. In some embodiments, a bispecific T cell engaging (BiTE®) antibody construct activates T cells resulting in induced non-specific cell lysis. In some embodiments, non-specific cells are found in solid tumors. In some embodiments, the non-specific cells that are lysed are in proximity to the BiTE® activated T cells. In some embodiments, the non-specific cells comprise tumor-associated antigen (TAA)-negative cancer cells. In some embodiments, the non-specific cells comprise EGFR-negative cancer cells. In some embodiments, an immuno-oncological agent is an antibody that blocks the PD-L1 / PD1 and / or CTLA4 axis. In some embodiments, an immuno-oncological agent is an infiltrating T cell of Qncann / zznz / E / YiAi 150 tumor expanded ex vivo. In some embodiments, an immuno-oncological agent is a bispecific antibody or chimeric antigen receptor (CAR) construct that directly connects T cells to tumor-associated surface antigens (TAA). In certain embodiments, a combination of 2 or more therapeutic agents can be co-administered with compounds of the invention. In certain embodiments, a combination of 3 or more therapeutic agents can be administered with compounds of the invention. Other examples of agents with which the inhibitors of the present invention may also be combined include, but are not limited to: vitamins and nutritional supplements, cancer vaccines, treatments for neutropenia (e.g., G-CSF, filgrastim, lenograstim ), treatments for thrombocytopenia (e.g., blood transfusion, erythropoietin), PI3 kinase (PI3K) inhibitors, MEK inhibitors, mTOR inhibitors, CPT1 inhibitors, AMPK activators, PCSK9 inhibitors, site 1 protease inhibitors of SREBP, HMG CoAreductase inhibitors, antiemetics (for example, 5-HT3 receptor antagonists, dopamine antagonists, NK1 receptor antagonists, histamine receptor antagonists, cannabinoids, benzodiazepines or anticholinergics), treatments for Alzheimer's such as Qncann / zznz / E / YiAi 151 Aricept® and Excelon®; treatments for Parkinson's disease such as L-DOPA / carbidopa, entacapone, ropinrol, pramipexole, bromocriptine, pergolide, trihexependyl and amantadine; agents for treating multiple sclerosis (MS) such as interferon beta (eg, Avonex® and Rebif®), Copaxone® and mitoxantrone; asthma treatments such as albuterol and Singulair®; agents to treat schizophrenia such as zyprexa, risperdal, seroquel and haloperidol; anti-inflammatory agents such as corticosteroids, TNF blockers, IL-1 RA, azathioprine, cyclophosphamide and sulfasalazine; immunomodulatory and immunosuppressive agents such as cyclosporine, tacrolimus, rapamycin, mycophenolate mofetil, interferons, corticosteroids, cyclophofamide, azathioprine and sulfasalazine; neurotrophic factors such as acetylcholinesterase inhibitors, MAO inhibitors, interferons, anticonvulsants, ion channel blockers, riluzole and anti-Parkinsonian agents; agents for the treatment of cardiovascular diseases such as beta-blockers, ACE inhibitors, diuretics, nitrates, calcium channel blockers and statins, fibrates, cholesterol absorption inhibitors, bile acid sequestrants and niacin; agents for the treatment of liver diseases such as corticosteroids, cholestyramine, interferons and antiviral agents; agents Qncann / zznz / E / YiAi 152 for the treatment of blood disorders such as corticosteroids, antileukemic agents and growth factors; agents for the treatment of immunodeficiency disorders such as gamma globulin; and antidiabetic agents such as biguanides (metformin, phenformin, buformin), thiazolidinediones (rosiglitazone, pioglitazone, troglitazone), sulfonylureas (tolbutamide, acetohexamide, tolazamide, chlorpropamide, glipizide, glibenclamide, glimepiride, gallinazide), meglitinides (repaglinide, nateglinide), alfa -glucosidase inhibitors (miglitol, acarbose), incretin mimetics (exenatide, liraglutide, taspoglutide), gastric inhibitory peptide analogues, DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin, alogliptin), amylin analogues (pramlintide), and insulin and insulin analogues. In certain embodiments, the compounds of the present invention, or a pharmaceutically acceptable composition thereof, are administered in combination with antisense agents, a monoclonal or polyclonal antibody, or a therapeutic siRNA. In another embodiment, the present invention provides a method of treating an inflammatory disease, disorder or condition by administering to a patient in need thereof a compound of the present invention and one or more additional therapeutic agents. These additional therapeutic agents may be small molecules or 153 recombinant biological agents and include, for example, acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, etodolac (Lodine®) and celecoxib, colchicine (Colcrys®), corticosteroids such as prednisone, prednisolone, methylprednisolone, hydrocortisone and the like, probenecid, allopurinol, febuxostat (Uloric®), sulfasalazine (Azulfidine ®), antimalarials such as hydroxychloroquine (Plaquenil ®) and chloroquine (Aralen®), methotrexate (Rheumatrex ®), gold salts such as thioglucose gold ( Solganal®), gold thiamalate (Myochysrine®) and auranofin (Ridaura®), D-penicillamine (Depen® or Cuprimine®), azathioprine (Imuran®), cyclophosphamide (Cytoxan®), chlorambucil (Leukeran®), cyclosporine (Sandimmune ®), leflunomide (Arava®) and anti-TNF agents such as etanercept (Enbrel®), infliximab (Remicade®), golimumab (Simponi®), certolizumab pegol (Cimzia®) and adalimumab (Humira®), anti-IL -1 agents such as anakinra (Kineret®) and rilonacept (Arcalyst®), canakinumab (Ilaris®), anti-Jak inhibitors such as tofacitinib, antibodies such as rituximab (Rituxan®), anti-T cell agents such as abatacept ( Orencia®), anti-IL-6 agents such as tocilizumab (Actemra®), diclofenac, cortisone, hyaluronic acid (Synvisc® or Hyalgan®), monoclonal antibodies such as tanezumab, anticoagulants such as heparin (Calcinparine® or Liquaemin®), and warfarin (Coumadin®), antidiarrheals such as 154 diphenoxylate (Lomotil®) and loperamide (Imodium®), bile acid binding agents such as cholestyramine, alosetron (Lotronex®), lubiprostone (Amitiza®), laxatives such as Milk of Magnesia, polyethylene glycol (MiraLax®), Dulcolax® , Correctol® and Senokot®, anticholinergics or antispasmodics such as dicyclomine (Bentyl®), Singulair®, beta-2 agonists such as albuterol (Ventolín® HFA, Proventil® HFA), levalbuterol (Xopenex®), metaproterenol (Alupent®), pirbuterol acetate (Maxair®), terbutaline sulfate (Brethaire®), salmeterol xinafoate (Serevent®) and formoterol (Foradil®), anticholinergic agents such as ipratropium bromide (Atrovent®) and tiotropium (Spiriva®), corticosteroids such such as beclomethasone dipropionate (Beclovent®, Qvar®, and Vanceril®), triamcinolone acetonide (Azmacort®), mometasone (Asthmanex®), budesonide (Pulmocort®), and flunisolide (Aerobid®), Afviar®, Symbicort®, Dulera ®,cromolin sodium (Intal®), methylxanthines such as theophylline (Theo-Dur®, Theolair®, Slo-bid®, Uniphyl®, Theo24®) and aminophylline, IgE antibodies such as omalizumab (Xolair®), transcriptase inhibitors nucleoside reverse drug such as zidovudine (Retrovir®), abacavir (Ziagen®), abacavir / lamivudine (Epzicom®), abacavir / lamivudine / zidovudine (Trizivir®), didanosine (Videx®), emtricitabine (Emtriva®), lamivudine (Epivir ®), lamivudine / zidovudine (Combivir®), stavudine (Zerit®), and Qncann / zznz / E / YiAi 155 zalcitabine (Hivid®), non-nucleoside reverse transcriptase inhibitors such as delavirdine (Rescriptor®), efavirenz (Sustiva®), nevairapine (Viramune®) and etravirine (Intelence®), nucleotide reverse transcriptase inhibitors such as tenofovir (Viread®), protease inhibitors such as amprenavir (Agenerase®), atazanavir (Reyataz®), darunavir (Prezista®), fosamprenavir (Lexiva®), indinavir (Crixivan®), lopinavir and ritonavir (Kaletra®), nelfinavir (Viracept®), ritonavir (Norvir®), saquinavir (Fortovase® or Invirase®), and tipranavir (Aptivus®), entry inhibitors v enfuvirtide (Fuzeon®) and maraviroc (Selzentry®), integrase inhibitors such as raltegravir (Isentress®), doxorubicin (Hydrodaunorubicin®), vincristine (Oncovin®), bortezomib (Velcade®), and dexamethasone (Decadron ®) in combination with lenalidomide (Revlimid ®), or any combination(s) thereof. In some embodiments, a provided compound is administered in combination with an antiviral agent, including, for example, acyclovir, penciclovir, cidofovir, idoxuridine, zidovudine, ribavarin, amantadine, foscarnet, didanosine, acyclovir, ganciclovir, cidofovir, zalcitabine, rimantadine, calacyclovir, famicyclovir, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zalcitabine, zidovudine, zidovudine-lamivudine, TRIZIVIR (zidovudine, lamivudine, abacavir), EPZICOM (aba-cavir Qncann / zznz / E / YiAi 156 lamivudine), TRUVADA (tenofovir-emtricitabine), ephenzine, neapine, and delavirdine, amenprenavir, atavir, fosamprenavir, indinavir, lopinavir-ritonavir, nelfinavir, ritonavir, saquinavir and tipranavir. In some embodiments, the antiviral agent is an anti-influenza agent that includes, for example, rimantadine, amantadine, oseltamivir and zanamivir. These additional agents can be administered separately from a composition containing the compound of the invention, as part of a multiple dosage regimen. Alternatively, these agents may be part of an individual dosage form, mixed together with a compound of the present invention in an individual composition. If administered as part of a multiple-dose regimen, the two active agents may be presented simultaneously, sequentially, or within a period of time of each other, typically within five hours of each other. As used herein, the term combination, combined and related terms refer to the simultaneous or sequential administration of therapeutic agents in accordance with the present invention. For example, a compound of the present invention may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a unit dosage form. Qncann / zznz / E / YiAi 157 individual. Accordingly, the present invention provides an individual unit dosage form comprising a compound of the present invention, an additional therapeutic agent and a pharmaceutically acceptable carrier, adjuvant or vehicle. The amount of both a provided compound and an additional therapeutic agent (in those compositions comprising an additional therapeutic agent as described above) that can be combined with the carrier materials to produce an individual dosage form will vary depending on the host treated and the particular mode of administration. Preferably, the compositions of this invention should be formulated so that a dosage of between 0.01 - 100 mq / kg body weight / day of an invention can be administered. In those compositions comprising an additional therapeutic agent, that additional therapeutic agent and the compound of the present invention may act synergistically. Therefore, the amount of additional therapeutic agent in these compositions will be less than that required in a monotherapy using only that therapeutic agent. In these compositions a dosage of between 0.01 - 100 gg / kg body weight / day of the additional therapeutic agent can be administered. The amount of additional therapeutic agent present Qncann / zznz / E / YiAi 158 in the compositions of the present invention will not be greater than the amount that would normally be administered in a composition comprising that therapeutic agent as the only active agent. Preferably, the amount of additional therapeutic agent in the compositions described herein will vary from about 50% to 100% of the amount normally present in a composition comprising that agent as the only therapeutically active agent. In one embodiment, the present invention provides a composition comprising a compound of the present invention and one or more additional therapeutic agents. The therapeutic agent may be administered concomitantly with a compound of the present invention, or may be administered before or after administration of a compound of the present invention. Suitable therapeutic agents are described in more detail below. In certain embodiments, a compound of the present invention can be administered up to 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5, hours, 6 hours, 7 hours, 8 hours , 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours or 18 hours before the therapeutic agent. In other embodiments, a compound of the present invention can be administered up to 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5, hours, 6 hours, 7 hours, 8 hours , 159 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours or 18 hours after the therapeutic agent. In some embodiments, the present invention provides a medicament comprising at least one compound of the present invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. All features of each aspect of the invention apply to all other aspects mutatis mutandis. In order that the invention described herein can be understood more completely, the following examples are set forth. It should be understood that these examples are for illustrative purposes only and should not be construed as limiting the present invention in any way. Exemplification As illustrated in the Examples below, in certain exemplary embodiments, the compounds are prepared according to the following general processes. It will be appreciated that, although the general methods represent the synthesis of certain compounds of the present invention, the following general methods, and other methods known to one skilled in the art, can be applied to all compounds and subclasses and species of each of these Qncann / zznz / E / YiAi 160 compounds, as described herein. General processes X-ray powder diffraction (XRPD) An X-ray diffraction system is set up for Bragg-Brentano reflection geometry using a line source X-ray beam. That source provides a beam profile incident on the sample that changes from a narrow line at high angles to a wide rectangle at low angles. Beam conditioning slits are used in the line X-ray source to ensure that the maximum beam size is less than 10 mm both along the line and normal to the line. The Bragg-Brentano geometry is a para-focusing geometry controlled by passive divergence and receiving slits with the sample itself acting as the focusing component for the optics. The inherent resolution of the Bragg-Brentano geometry is governed in part by the diffractometer radius and the width of the receiving slit used. Typically, an X-ray diffraction system is operated to provide peak widths of 0.1 °2θ or less. The axial divergence of the X-ray beam is controlled by 5.0 degree Soller slits in both the incident and diffracted beam paths. Powder samples are prepared in a low-bottom Si holder using light hand pressure to keep the sample surfaces flat and level with the Qncann / zznz / E / YiAi 161 reference surface of the sample holder. Each sample is analyzed from 2 to 40 °2Θ using a continuous scan of 602Θ per minute with an effective step size of 0.02 °2θ. Differential scanning calorimetry (DSC) DSC analyzes are carried out using a TA instrument. Temperature calibration of the instrument is performed using indium. The DSC cell is maintained under a nitrogen purge of ~50 mL per minute during each analysis. The sample is placed in a normalized, folded aluminum tray and heated from 25°C to 350°C at a rate of 10°C per minute. Thermogravimetric Analysis (TG) TG analysis is carried out using a TA instrument. The instrument balance is calibrated using class M weights and temperature calibration is performed using alumel. Nitrogen purge is ~40 ml per minute at equilibrium and ~60 ml per minute in the furnace. Each sample is placed on a preheated platinum tray and heated from 20°C to 350°C at a rate of 10°C per minute. Nuclear Magnetic Resonance (NMR) Spectroscopy Samples are prepared by dissolving the material in a solvent. The solutions are filtered and placed into individual 5 mm NMR tubes for later acquisition. Qncann / zznz / E / YiAi 162 spectral. Primary Salt Detection Qncann / zznz / E / YiAi Salt detection experiments were carried out using twelve (12) acid salt formers, with a variety of crystallization techniques (cooling, suspension, evaporation and vapor diffusion) being employed. The experimental details for each salt formation attempt are described in Table 11. Table 11. Salt Detection Experiments Salt former (X: Y)1 Crystallization Technique Results Aspartic acid (1:1) Suspension in 1:1 acetone:water at RT. Compound A Form B Ethanesulfonic acid (1:1) Suspension in 1:1 THE:water at RT. Compound A Form C Dissolve in acetone 9:1:water at 50 °C. Slowly cool to RT. 1:1 Compound Form A without residual solvent by NMR Ethanedisulfonic acid (1:1) Suspension in EtOH at 65°C, added EtOAc did not dissolve. Slowly cool to RT. 1:0.64 Compound 7 Form A with 0.11 equiv. EtOAc and 0.33 equiv. EtOH Suspension in EtOH at 65°C, added EtOAc did not dissolve. Slowly cool to RT. 1:0.75 Compound 7 Form A without EtOH by NMR 1 M hydrochloric acid (1:1) Dissolve in THE at RT. Vapor diffusion in heptane. Residual oil formed. Suspension in EtOH at 65°C. Slowly cool to RT. Form B Free Base 163 Suspension in acetone at RT. Free Base Form B + peaks Maleic acid (1:1) Dissolve in acetone at RT. Vapor diffusion in heptane. 1:0.6 Compound 2 Form A with 0.02 equiv. Acetone by NMR Dissolve in THF at RT. Vapor diffusion in heptane. There are not enough solids to collect. Dissolve in acetone at 50°C. Slowly cool to RT. Add an equal volume of heptane and shake at 5°C. Partially evaporate to obtain solids. 1:0.58 Compound 2 Form A with 0.025 equiv. acetone and 0.72 equiv. heptane by NMR Methanesulfonic acid (1:1) Suspension in EtOH at RT. 1:1 Compound 3 Form A with 0.9 equiv. EtOH by NMR Suspension in EtOH at RT. Vacuum dry. 1:1 Compound 3 Form A + Form B without EtOH by NMR Naphthalenesulfonic acid (1:1) Dissolve in EtOH at 65°C. Slowly cool to RT. 1:1 Compound 4 Form A with 0.05 equiv. EtOH by NMR Oxalic acid (1:1) Dissolve in acetone at 50°C. Slowly cool to RT. Compound 5 Form A Salt formation cannot be confirmed by NMR 1M phosphoric acid (1:1) Suspension in EtOH at RT. Compound A Form B Phosphoric acid 1 M (1:2) Stir in water at RT. The solids remained floating. Solids were not collected. Sulfuric acid 1 M (1:1) Suspension in IDA at RT. Compound A Form B Suspension in EtOH at RT. Compound A Form B οηραηη / ζζηζ / Ε / γίΛΐ 164 Dissolve in acetone 9:1:water at 50 °C. Slowly cool to RT. Compound A Form B Tartaric acid (1:1) Suspension in 9:1 acetone:water at RT. Compound A Form B Dissolve in THF at RT. Filter and rapid evaporation. 1:1 Compound 6 Form A with 0.48 equiv. THF Dissolve in EtOH + EtOAc at 65°C. Slowly cool to RT. Compound A Form B Tartaric acid (1:4) Dissolve in EtOH + EtOAc at 65°C. Slowly cool to RT. 1:0.66 Compound 6 Form B with 0.12 equiv. EtOAc by NMR Toluenesulfonic acid (1:1) Suspension in MeOH at RT. Compound A Form B Dissolve in acetone 9:1:water at 50 °C. Slowly cool to RT. No solids formed. Qncann / zznz / E / YiAi Secondary Salt Detection Compound 1, Form A, Compound 2, Form A, Compound 3, Form B and Compound 4, Form A were expanded and the experimental details are described below in Table 12. Table 12. Secondary Salt Detection Experiments Salt former (X:Y)1 Crystallization Technique Results Ethanesulfonic Acid (1:1) Suspension 500 mg of free base in 15 mL 9:1 acetone:water at 50°C. Add 93 pL of acid at 50°C. Slowly cool to RT while stirring and then refrigerate at 5°C overnight. 1:1 Compound 1 Form B without residual acetone Methanesulfonic Acid (1:1) Suspension of 500 mg of free base in 15 mL of EtOH at RT. Add 74 pL of acid and continue stirring overnight. Secaral empty for 3 days at ~40°C. Compound 3 1:1 Form B without residual EtOH 165 Maleic acid (1:1) Dissolve 500 mg of free base and 132 mg of acid in 7 mL of acetone at 50°C. Slowly cool to RT and then add the same volume of heptane (7 mL) and refrigerate at 50 C overnight. The suspension is allowed to partially evaporate for 2 hours. 1:0.54 Compound 2 Form A with acetone 0.02 equiv. Naphthalenesulfonic acid (1:1) Suspension 500 mg of free base and 236 mg of acid in 10 mL of EtOH at 65°C. Refrigerate slowly at RT and then refrigerate at 5°C overnight. 1:1 Compound 4 Form A with 0.07 equiv. EtOH Example A - General Preparation of Compound A Qnconn / zznz / E / YiAi The title compound was prepared according to the steps and intermediates (e.g., Reaction Scheme 1) described below and in the '411 publication, the entirety of which is incorporated herein by reference. Reaction Scheme 1 - Synthesis of Compound A 6 Step 1: (3R)-N-[2-(5-Fluoro-3-pyrid.yl)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-2, 3,4,9-tetrahydro-lHcarbazole-3-amine (compound A) Qncann / zznz / E / YiAi A mixture of 4-chloro-2-(5-fluoro-3-pyridyl)-8isopropyl-pyrazolo[1,5-a][1,3,5] triazine (60.00 mg, 205.68 mol, 1 eg), (3R )-2,3,4, 9-tetrahydro-lH-carbazole-3-amine (42.14 mg, 226.25 mol, 1.1 eq), DIEA (79.75 mg, 617.05 mol, 107.48 L, 3 eg) in í-PrOH (4 mL) was degassed and purged with N2 for 3 times. The mixture was stirred at 55°C for 3 hours under N2 atmosphere. The reaction mixture was concentrated under reduced pressure to give a residue that was purified by preparative HPLC (column: Phenomenex Gemini 150*25mm*10um; mobile phase: [water(0.05%HCl)-ACN];B%: 70%- 100%, 10 min), followed by lyophilization to give (3R)-N-[2-(5-fluoro-3-pyridyl)-8isopropyl-pyrazolo[1,5-a][l,3,5]triazin- 4-yl]-2,3,4,9tetrahydro-lH-carbazole-3-amine (42.07 mg, 75.45 mol, 36.7% yield, 98.8% purity, 3HC1) as a yellow solid. NMRτΗ (400 MHz, CD3OD) δ ppm 9.46 (s, 1H), 8.81 (d, J = 9.3 Hz, 1H), 8.76 (s, 1H), 8.12-7.92 (m, 1H), 7.37 (d, J= 7.7 Hz, 1H), 7.27 (d, J= 7.9 Hz, 1H), 7.08-7.00 (m, 1H), 6.99 167 6.90 (m, 1H), 3.34 (s, 1H), 3.31-3.25 (m, 2H), 3.18-2.79 (m, 3H), 2.44-2.21 (m, 2H), 1.42 (d, J = 7.1 Hz, 6H) ; ES-LCMS m / z 442.2 [M+H]+. Example 1 - Preparation of free base forms A, B and C of compound A Qncann / zznz / E / YiAi Form B of Compound A Form B of compound A was prepared as described above. Table B, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form B of compound A. Table B – XRPD Peak Positions for Form B of the Compound A Position [°2θ]1 spacing d [Á] Intensity [%] 8.5 10.3405 0.8 9.2 9.5896 11 9.5 9.3466 100 9.8 8.9763 26.3 11.3 7.7944 4 12.8 6.907 9.6 168 13.7 6.4438 3.9 14.2 6.2284 10 14.7 6.0202 27.4 15.4 5.7663 3.5 16.8 5.2862 13.9 17.5 5.0495 7.6 17.9 4.9378 1 18.5 4.800 2 0.7 19.0 4.6705 1.3 19.2 4.6159 2 19.8 4.485 9.8 20.1 4.4138 14.2 20.9 4.2497 1.1 21.6 4.1169 2.3 21.8 4.073 1.4 22.5 3.9 481 44 23.6 3.7662 1.5 24.2 3.6729 5.8 24.6 3.6111 1.5 25.7 3.4637 6.2 26.0 3.4299 3.1 27.3 3.2589 1.8 27.7 3.2135 3.4 28.1 3.1726 1.4 28.6 3.1145 1.6 29.1 3.0612 1 29.7 3.0045 4.8 31.5 2.8379 3.4 1In this and all subsequent tables, position 20 is within ±0.2. Figure 1 illustrates an XRPD pattern of Form B of compound A. Figure 2 illustrates a TG / DTA trace of Form B of compound A. Qncann / zznz / E / YiAi 169 Form C of Compound A Form C of compound A was prepared as described above. Table C, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form C of compound A. Table C - XRPD Peak Positions for Form C of Compound A Qncann / zznz / E / YiAi Position [°2Θ]1 d spacing [Á] Intensity [%] 6.02 14 . 6575 100 7.34 12.0353 37.5 8.45 10.4488 5.5 8.60 10.275 13.5 8.61 10.2605 39.2 9.03 9.7846 16.8 10.29 8.5906 81.2 13.27 6 .668 12.9 14.28 6.1968 3 14.45 6.1252 21.4 14.86 5.9561 26 15.20 5.8241 4.8 15.53 5.6994 11.5 15.80 5.6027 3.6 16.54 5.3548 1.3 16.85 5.256 2.6 17.26 5.1331 28.9 170 17.69 5.0108 1.4 18.10 4.8972 8.1 18.29 4.8453 8.7 18.59 4.7689 1.4 19.09 4.6451 3.1 19.43 4.5653 6.3 19.61 4.5233 11.2 1 9.89 4.4608 5 20.25 4.3824 18 . 9 21.18 4.191 21.9 22.30 3.984 3.1 22.41 3.9644 6.2 22.90 3.881 2.5 23.53 3.7773 2.5 24.44 3.6389 1.2 24.82 3.5836 3.6 25 .39 3.5055 1.3 25.66 3.4686 2.3 26.00 3.4238 9.4 26.14 3.4064 8.8 26.69 3.3367 4 27.04 3.2951 8.6 27.35 3.2585 7.9 28.02 3. 1813 2 29.12 3.0638 2 1In this and all subsequent tables, the 2Θ position is within ±0.2. Figure 3 illustrates an XRPD pattern of Form C of compound A. Qnconn / zznz / E / YiAi 171 Figure 4 represents a TG / DTA trace of Form C of compound A. Mixture of Form Ά and Form B of Compound A The hydrochloride salt of compound A (7.0 g) was dissolved in the mixture of EtOAc (150 mL) and saturated NaHCOa solution (200 mL) and stirred at 28 °C for 30 min. The mixture was extracted with EtOAc (150 mL x 3). The combined organic layers were washed with brine (200 mL x 2), dried over Na^SCg and concentrated to provide a residue which was added to MeOH (150 mL) and stirred for 30 min. The mixture was filtered and the filtered cake was concentrated to give the desired product which was lyophilized to give a mixture of Form A and Form B of compound A (6.7 g) as a solid. Figure 24 illustrates an XRPD pattern of a mixture of Form A and Form B of compound A. Figure 25 illustrates TGA / DSC of a mixture of Form A and Form B of compound A. Example 2 - Preparation of Form A of Compound 1 1. Qncann / zznz / E / YiAi 172 Form A of Compound 1 Form A of compound 1 was prepared as described above. Table 1, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form A of compound 1. Table 1 - XRPD peak positions for Form A of Compound 1 Qncann / zznz / E / YiAi Position [°2Θ] d spacing [Á] Intensity [%] 5.8 15.3556 100 9.0 9.7887 4.8 11.6 7.6552 50.4 12.7 6.9761 2.4 13.5 6.5581 7.2 13.9 6.3739 6.4 14.2 6 .2271 20 15.0 5.8855 16 15.3 5.7732 2.3 16.2 5.467 5 16.9 5.2552 1.1 17.4 5.099 4 18.1 4.8971 2.6 18.8 4.7082 32.3 19.4 4.5638 1.8 20.7 4.2954 6.3 23.2 3.8286 2.6 23.9 3.716 1.7 24.4 3.6524 2.1 24.5 3.6304 2.1 24.9 3.5667 1.7 25.5 3.4859 12.2 25.9 3.4353 14 26.5 3.3649 0.6 27.2 3.279 7 3.6 27.6 3.2317 2.6 28.1 3.1783 1.1 28.3 3.1519 4.2 28.7 3.1126 1 . 9 29.2 3.0595 3.8 29.5 3.0212 0.9 31.1 2.8721 0.8 32.8 2.7304 0.8 33.1 2.7026 0.6 35.1 2.5538 1 35.9 2.4998 1.1 39.5 2.28 2 0.7 Qncann / zznz / E / YiAi Figure 5 illustrates an XRPD pattern of Form A of compound 1. Figure 6 illustrates a TG / DTA trace of Form A of compound 1. Form B of Compound 1 Form B of compound 1 was prepared as described above. 174 Table 2, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form B of compound 1. Table 2 - XRPD peak positions for Form B of Compound 1 Qncann / zznz / E / YiAi Position [°20] d (Angstroms) Intensity [%] 5.1 17.2744 1.5 5.6 15.7493 100 8.9 9.9195 1.3 9.5 9.3413 1.2 9.9 8 . 965 0.1 10.2 8.7059 0.4 10.9 8.1087 1.8 11.2 7.8636 60 12.2 7.2352 0.1 12.8 6.9174 0 13.2 6.6957 3 14.0 6.3029 1.3 14.7 6 .0184 0.3 15.0 5.9183 3.2 15.7 5.643 1 16.2 5.4526 0.1 16.9 5.2422 6.7 17.5 5.0508 0 17.9 4.9563 0.2 18.5 4.7908 1.1 19.8 4 .4798 0.3 20.9 4.238 1.2 21.6 4.1127 0.1 22.0 4.0401 0.1 22.5 3.9459 0.6 23.7 3.7457 0.3 24.2 3.6719 0.1 24.6 3.6151 0.3 25.6 3.477 4 1.8 26.0 3.4236 0.2 26.6 3.3461 0.8 26.8 3.321 0.2 175 28.4 3.1454 3.2 29.2 3.0548 0.5 Qncann / zznz / E / YiAi Figure 7 illustrates an XRPD pattern of Form B of compound 1. Example 3 - Preparation of Form A of Compound 2 Form A of Compound 2 Form A of compound 2 was prepared as described above. Table 3, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form A of compound 2. Table 3 - XRPD peak positions for Form A of Compound 2 Position [°2θ] d spacing [Á] Intensity [%] 5.3 16.6727 100 6.6 13.3333 3.8 8.0 11.0992 4 9.6 9.2459 3.9 10.6 8.3351 3.2 11.3 7.8022 40.9 176 13.3 6.6763 10.7 14.1 6.2596 1.9 14.7 6.0118 1.1 16.0 5.5517 24.5 16.8 5.2683 2 17.4 5.1039 1.3 17.8 4.9827 3.6 18.7 4.74 33 1.2 19.2 4.6251 2.2 19.9 4.4483 0.6 20.7 4.293 3.4 21.3 4.1699 5.6 22.7 3.9225 2.3 24.0 3.7105 3.1 24.5 3.6303 2.4 26.3 3.3879 1.6 26.7 3.3409 2.1 27.1 3.2939 2 27.6 3.2338 0.6 28.1 3.1769 0.9 28.8 3.1015 0.3 29.3 3.0447 0.6 31.8 2.8079 0.5 32.2 2.7771 0.5 Figure 8 illustrates an XRPD pattern of Form A of compound 2. Figure 9 illustrates a TG / DTA trace of Form A of compound 2. Qnconn / zznz / E / YiAi 177 Example 4 - Preparation of Form A of Compound 3 Qncann / zznz / E / YiAi Form A of Compound 3 Form A of compound 3 was prepared as described above. Table 4, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form A of compound 3. Table 4 - XRPD peak positions for Form A of Compound 3 Position [°2Θ] d spacing [Á] Intensity [%] 5.1 17.2728 1.2 5.6 15.7025 100 9.0 9.7695 3.6 10.2 8.7061 0.3 11.0 8.0007 2.7 11.2 7.8648 35 12.1 7.3 154 0.4 12.4 7.1465 0.3 13.3 6.6505 2.9 14.0 6.313 3.2 178 14.3 6.1969 2.1 15.3 5.7988 6.3 15.8 5.6164 1.7 16.3 5.4343 0.4 16.9 5.2456 8 18.0 4.9265 0.4 18.4 4.8306 0.6 18.7 4.7514 1.9 18.9 4.7028 1.8 19.5 4.5477 0.7 20.0 4.4386 0.4 21.0 4.229 1.2 22.0 4.0295 0.4 24.2 3.6743 0.5 25.5 3.4972 5.3 25.9 3. 4328 0.7 26.7 3.3316 1.6 28.3 3.1506 2.5 29.2 3.053 0.5 Qncann / zznz / E / YiAi Figure 10 illustrates an XRPD pattern of Form A of compound 3. Figure 11 illustrates a TG / DTA trace of Form A of compound 3. Form B of Compound 3 Form B of compound 3 was prepared as described above. Table 5 above is reproduced below and 179 establishes the X-ray diffraction peaks observed for Form B of compound 3. Table 5 – XRPD Peak Positions for Form B of the Qncann / zznz / E / YiAi Compound 3 Position [°2Θ] d (Angstroms) Intensity [%] 6.0 14.7036 100 11.6 7.6195 10 12.1 7.3357 32.3 13.6 6.5115 2.1 14.6 6.0801 3.1 15.6 5.66 2 16.1 5.5 14 0.6 17.6 5.0376 4.5 18.1 4.8948 12.5 19.8 4.4702 1 20.1 4.4033 3.3 20.8 4.2687 0.2 21.1 4.2034 1.3 21.9 4.0542 2.2 22.2 4.0022 4.2 22.6 3.9386 0.5 23.0 3.8694 0.3 23.5 3.7822 1.2 24.3 3.6649 0.3 25.1 3.5465 1. 8 26.9 3.3177 1. 9 27.4 3.2583 3 28.3 3.1563 0.9 29.4 3.0401 0.9 Figure 12 illustrates an XRPD pattern of Form B of compound 3. Figure 13 represents a TG / DTA trace of the Form B of compound 3. 180 Example 5 - Preparation of Form A of Compound 4 Qncann / zznz / E / YiAi 4. Form A of Compound 4 Form A of compound 4 was prepared as described above. Table 6, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form A of compound 4. Table 6 - XRPD Peak Positions for Form A of Compound 4 Position [°2Θ] d (Angstroms) Intensity [%] 6.8 13.0644 1.1 7.5 11.81 100 7.8 11.2555 9.4 8.4 10.5306 78.5 9.5 9.3437 5.7 9.8 9.0463 7.2 9.9 8.8 891 7.5 11.1 7.9975 8.2 11.9 7.404 5.2 12.6 7.0284 1.4 12.9 6.8706 1 . 6 13.5 6.5355 5 13.8 6.4284 11 . 9 14.5 6.1263 26.4 181 14.7 6.029 1.2 15.1 5.8748 8.3 15.8 5.6186 10.1 16.1 5.5086 4 16.5 5.3844 20.1 16.6 5.3221 1.8 16.8 5.2691 1.7 17.3 5.122 3 1.3 18.1 4.9044 11 . 6 19.1 4.6279 4.7 19.6 4.5254 11.4 19.7 4.496 9.8 20.1 4.424 47.9 20.6 4.2976 7 . 6 20.9 4.2364 2.5 21.5 4.1352 0.3 21.8 4.0652 1.1 22.0 4.0293 5.8 22.4 3.9624 28.3 22.9 3.8768 1.7 23.7 3.745 7.5 24.6 3. 6159 5.8 24.8 3.5884 3.8 25.2 3.5259 2.9 Figure 14 illustrates an XRPD pattern of Form A of compound 4. Figure 15 illustrates a TG / DTA trace of the Form A of compound 4. Example 6 - Preparation of Form A of Compound 5 5. Qncann / zznz / E / YiAi 182 Form A of Compound 5 Form A of compound 5 was prepared as described above. Table 7, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form A of compound 5. Table 7 - XRPD Peak Positions for Form A of Compound 5 Qncann / zznz / E / YiAi Position [°2Θ] d spacing [Á] Intensity [%] 6.4 13.7901 100 7.1 12.4378 20.2 11.4 7.7871 4 . 9 12.7 6.9614 63.9 14.4 6.1639 6 17.5 5.0766 16.5 18.3 4.8405 3.3 19.2 4.6288 3.2 21.1 4.2167 2.7 22.3 3.9765 1.7 23.1 3. 8472 8.2 27.3 3.2647 1.7 29.0 3.0719 0.9 Figure 16 illustrates an XRPD pattern of Form A of compound 5. Figure 17 illustrates a TG / DTA trace of Form A of compound 5. 183 Example 7 - Preparation of Forms A and B of Compound 6 Qncann / zznz / E / YiAi where X is approximately 1 or 2. Form A of Compound 6 Form A of compound 6 was prepared as described above. Form A of compound 6 was determined to comprise compound A and ethanedisulfonic acid in a ratio of approximately 1:1. Table 8, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form A of compound 6. Table 8 - XRPD Peak Positions for Form A of Compound 6 Position [°2Θ] d spacing [Á] Intensity [%] 5.5 16.1924 100 7.0 12.6864 1.4 8.2 10.8305 7.5 8.4 10.5158 9 9.1 9.6845 0.7 10.3 8.5415 1 . 6 11.1 7.9331 15.7 184 13.4 6.6022 1.1 14.5 6.1046 5 15.6 5.6633 4.8 16.3 5.4202 4.5 17.4 5.1082 13.5 17.6 5.0375 6.7 18.9 4.7033 17.7 20.3 4.37 1 4 22.3 3.976 5.8 23.1 3.8469 6.6 24.5 3.6371 4.1 26.3 3.3865 8.3 26.7 3.3422 5.9 27.0 3.2941 2.6 29.9 2.9861 3.4 Qncann / zznz / E / YiAi Figure 18 illustrates an XRPD pattern of Form A of compound 6. Figure 19 illustrates a TG / DTA trace of Form A of compound 6. Form B of Compound 6 Form B of compound 6 was prepared as described above. Form B of compound 6 was determined to comprise compound A and ethanedisulfonic acid in a ratio of approximately 2:1. Table 9, above, is reproduced below and sets out the X-ray diffraction peaks observed for Form B of compound 6. 185 Table 9 – XRPD Peak Positions for Form B of the Qncann / zznz / E / YiAi Compound 6 Position [°2Θ] d spacing [Á] Intensity [%] 5.3 16.5046 1.7 6.2 14.2356 74.6 6.8 13.0713 100 7.2 12.183 2.4 8.6 10.2145 5 9.5 9.2819 0.6 10.7 8.26 82 8.2 11.5 7.7192 4.5 12.4 7.1588 12.4 13.5 6.5301 24.8 14.6 6.0796 6.9 16.3 5.4162 2.1 17.1 5.1667 11.2 17.7 5.0058 3.2 18.7 4.7289 9.7 19.3 4.5962 3 20.6 4.3182 15.7 20.9 4.2371 11.5 21.8 4.0643 5.9 23.2 3.8 387 0.8 24.3 3.6659 1.8 25.3 3.5112 1 26.1 3.4101 1.3 Figure 20 illustrates a Form B XRPD pattern. 186 of compound 6. Figure 21 represents a TG / DTA trace of the Form B of compound 6. Example 8 - Preparation of Form A of Compound 7 Qnconn / zznz / E / YiAi HO. . Aoo ° OH J2 Form A of Compound 7 Form A of the described above. Table 10, below, sets out observations for Form A of compound 7. Table 10 – XRPD peak positions for Form A of compound prepared as above, reproduces the ray diffraction peaks Compound 7 Position [°2Θ] d spacing [Á] Intensity [%] 6.6 13.4754 100 8.0 11.0262 0.7 10.4 8.5378 5 13.2 6.7031 7.3 16.0 5.5191 2.4 187 18.2 4.871 0.8 19.1 4.6422 1.8 19.3 4.5954 1.7 20.4 4.3516 0.7 22.4 3.9584 1.5 26.5 3.3549 0.6 Qncann / zznz / E / YiAi Figure 22 illustrates an XRPD pattern of Form A of compound 7. Figure 23 illustrates a TG / DTA trace of Form A of compound 7. Example 9 - Solubility studies Solubility studies of Compound A, Form B, Compound 1, Form B, Compound 2, Form A, Compound 3, Form B and Compound 4, Form A were determined in water, simulated intestinal fluid in fasting state (FaSSIF), simulated intestinal fluid in the fed state (FeSSIF) and simulated gastric fluid in the fasted state (FaSSGF). Simulated fluids were obtained and prepared according to biorelevant.com using their FaSSIF / FeSSIF / FaSSGF powder (vi, formerly known as SIF powder). The samples were prepared by adding excess solids to 5 mL of medium at 37 °C. Samples were extracted and filtered at 30 minutes, 120 minutes and 24 hours and analyzed for solution concentration using the HPLC parameters described below in Table 13. 188 Qncann / zznz / E / YiAi Table 13 - HPLC parameters HPLC Method Condition Parameter Value Column Waters of Seal 10% Acetonitrile in water Needle Wash Solvent 50% Tetrahydrofuran in Water Diluent 1:1 Tetrahydrofuran (not stabilized): Water Injection Volume 5 pL Detection Wavelength 345 nm Target Analytical Concentration 0.5 mg / mL Profile Gradient Time (min) Mobile Phase A Mobile Phase B Flow (mL / min) 0 95 5 1.00 7 5 95 1.00 7.1 95 5 1.00 10 95 5 1.00 The pH of the samples was also measured at each time point; pH paper was used at 30 minutes and 120 minutes due to the small sample size, and a pH meter was used at 24 hours. The remaining material from all assays was analyzed by XRPD after 24 hours to determine if changes in polymorphic form had occurred. The remaining material from the water tests was analyzed by NMR after 24 hours to determine if dissociation had occurred. Compound 1, Form B, does not 189 was analyzed by NMR at 24 hours due to low availability of material. The results are shown below in Table 14. Qncann / zznz / E / YiAi Table 14 - Solubility Studies Medium Material 30 minutes 120 minutes 24 hours Solubility (mg / mL) pH Solubility (mg / mL) pH Solubility (mg / mL) pH FaSSIF Compound 1 Form B 0.045 6 0.034 6 0.018 6.2 Compound 3 Form B 0.065 6 0.034 6 0.016 5.7 Compound 2 Form A 0.078 6 0.040 6 0.014 5.0 Compound 4 Form A 0.071 6 0.038 5.5 0.025 1.9 Compound A Form B 0.0049 6 0.011 6 0.0095 6.4 FeSSIF Compound 1 Form B 0.058 5 0.056 5 0.063 4.8 Compound 3 Form B 0.027 5 0.043 5 0.16 4.4 Compound 2 Form A 0.058 5 0.16 5 0.12 4.7 Compound 4 Form A 0.048 5 0.11 4.5 0.033 4.4 Compound A Form B <0.0001 5 0.027 5 0.021 4.8 FaSSGF Compound 1 Form B <0.0001 1.5 <0. 0001 1.5 <0.0001 1.2 Compound 3 Form B <0.0001 1.5 <0.0001 1.5 <0.0001 1.2 Compound 2 Form A <0.0001 1.5 <0.0001 1.5 <0.0001 1.2 Compound 4 Form A <0.0001 1.5 <0.0001 1.5 <0.0001 1.1 Compound A Form B <0.000 1 1.5 <0.0001 1.5 <0.0001 1.1 Compound 1 Form B <0.0001 4.5 <0.0001 4.5 <0.0001 3.4 190 Compound 3 Form B <0.0001 4 <0.0001 4 <0.0001 2.4 Compound 2 Form A <0.0001 3.5 <0.0001 4 <0.0001 2.9 Compound 4 Form A <0.0001 4.5 <0.0001 3 <0.0001 1.5 Compound A Form B <0.0001 4.5 <0.0001 4.5 < 0.0001 7.7 Qncann / zznz / E / YiAi As can be seen, Compound 2, Form A and Compound 3, Form B showed the highest solubility at 24 hours in FeSSIF. Example 10 - Stability Studies Stability studies of Compound A, Form B, Compound 1, Form B, Compound 2, Form A, Compound 3, Form B and Compound 4, Form A were carried out at 40 °C / 75% RH. Samples were stored in vials with loose caps in a chamber containing a saturated NaCl solution to achieve approximately 75% RH within the chamber. The chamber was stored in an oven at 40 °C. Samples were analyzed at time 0, 1 week, 2 weeks and 4 weeks using the HPLC parameters described above in Table 13. The results are shown below in Table 13. Table 15. 191 oncann / zznz / E / YiAi Table 15 - Stability Studies Material Time Point % Area Composite 1 Form B Time 0 9 9.90 1 Week 99.59 2 weeks 99.53 4 weeks 9 9.46 Composite 3 Form B Time 0 99.88 1 Week 91.60 2 weeks 6 9.61 4 weeks 16.23 Composite 2 Form A Time 0 99.87 1 Week 99.20 2 weeks 98.30 4 weeks 98.58 Compound 4 Form A Time 0 99.77 1 Week 94.31 2 weeks 94.20 4 weeks 99.37 Compound A Form B Time 0 99.62* 1 Week 99.22 2 weeks 99.05 4 weeks 99.58 *1 mg / mL Overall, significant degradation over time was observed for Form B of Compound 3. It was confirmed that the solids at the end of the study lost all crystallinity and became X-ray amorphous. Compound A Form B and Compound 1 Form B appear equally stable at 40°C / 75% 192 HR. Compound 4 Form A exhibited degradation at 1 and 2 weeks, but the degradative peaks were no longer present at 4 weeks, which enhanced the percentage area of ​​the main peak. Compound 2 Form A is quite stable under these accelerated conditions, losing only ~1.5% area over four weeks. While we have described a number of embodiments of this invention, it is evident that our basic examples can be altered to provide other embodiments utilizing the compounds and methods of this invention. Therefore, it will be appreciated that the scope of this invention will be defined by the application and claims rather than by the specific embodiments that have been represented by way of example. It is stated that in relation to this date, the best method known to the applicant to put the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

CLAIMS Qnconn / zznz / E / YiAi Having described the invention as above, the following claims are claimed as property:

1. Compound 2 in a solid form: characterized in that approximately 1 < X < approximately 2 .

2. The compound according to claim 1, characterized in that it is crystalline.

3. The compound according to claim 1, characterized in that it is a crystalline solid substantially free of the amorphous compound 2.

4. The compound according to claim 1, characterized in that it is substantially free of impurities.

5. The compound according to claim 1, characterized in that it has one or more peaks in its XRPD selected from those at approximately 5.3, approximately 11.3 and approximately 16.0 degrees 2-theta. 194 6. The compound according to claim 5, characterized in that it has at least two peaks in its XRPD selected from those at approximately 5.3, approximately 11.3 and approximately 16.0 degrees 2-theta.

7. The compound according to claim 6, characterized in that it is of Form A, and wherein x is approximately 2.

8. The compound according to claim 1, characterized in that it has an XRPD substantially similar to that depicted in Figure 9.

9. A composition, characterized in that it comprises the compound according to claim 1 and a pharmaceutically acceptable carrier or excipient.

10. A method for inhibiting AHR in a patient in need thereof, characterized in that it comprises administering to the patient the compound according to claim 1 or a composition thereof.

11. A method for inhibiting AHR in a biological sample, characterized in that it comprises contacting the biological sample with the compound according to claim 1 or a composition thereof.

12. A method for treating an AHR-mediated disorder in a patient in need thereof, characterized in that it comprises administering to the patient the compound according to claim 1 or a composition thereof.

13. The method according to claim 12, characterized in that the AHR-mediated disorder is a cancer.

14. The method according to claim 12, characterized in that the AHR-mediated disorder is an inflammatory disorder.

15. The method according to claim 12, characterized in that the compound or composition thereof is administered orally.

16. The method according to claim 12, characterized in that the compound or composition thereof is administered in a range of 0.01 - 100 mg / kg of the patient's body weight.

17. The method according to claim 12, characterized in that it further comprises administering an additional therapeutic agent to the patient.

18. A compound, characterized in that it is selected from: Compound A: Qncann / zznz / E / YiAi A of Form A, Compound 1: of Form A or Compound 3: of Form A or Compound 4: 196 Form B or Form C; HN''' T SA 1 7° AY * AC A^ |j NX)H Ί< / 1 Form B; hn-HX yox JA Aw · wx° Yf NN / 3 Form B; -NH AL HN' Λ n^x-'XA=z N / O=S=O HO 4 of Form A; Qncann / zznz / E / YiAi 197 Compound 5: Qncann / zznz / E / YiAi Form A; Compound 6: Form A or Form B, where approximately 1 < x < approximately 2; or Compound 7: 198 of Form A, where approximately 1 < x < approximately 2.

19. A pharmaceutically acceptable composition, characterized in that it comprises a compound according to claim 18, and a pharmaceutically acceptable carrier, excipient or vehicle.

20. A method for treating an AHR-mediated disorder in a patient in need thereof, characterized in that it comprises administering to the patient the compound according to claim 18 or a composition thereof.

21. The method according to claim 20, characterized in that the AHR-mediated disorder is a cancer or an inflammatory disorder.

22. The method according to claim 20, characterized in that the compound or composition thereof is administered orally.

23. The method according to claim 20, characterized in that the compound or composition thereof is administered in a range of 0.01 - 100 mg / kq of the patient's body weight.

24. The method according to claim 20, characterized in that it further comprises administering an additional therapeutic agent to the patient.

25. A method for the preparation of a Qncann / zznz / E / YiAi salt compound of formula X: 199 Qncann / zznz / E / YiAi X characterized in that it comprises the steps of: combining A: with an acid and optionally a solvent under conditions to form a salt compound of formula X.

26. The method according to claim 25, characterized in that: (a) the suitable acid is methanesulfonic acid, thereby forming a mesylate salt of compound A and optionally crystallizing the mesylate salt to form Form A or Form B; (b) the suitable acid is ethanesulfonic acid, thereby forming an esylate salt of compound A and optionally crystallizing the esylate salt to form Form A or Form B; (c) the suitable acid is naphthalenesulfonic acid, thereby forming a napsilate salt of compound A and optionally crystallizing the napsilate salt to form Form A; (d) the suitable acid is tartaric acid, thereby forming a tartrate salt of compound A and optionally crystallizing the tartrate salt to form Form A or Form B; (e) the suitable acid is oxalic acid, thereby forming an oxalate salt of compound A and optionally crystallizing the oxalate salt to form Form A;or (f) the suitable acid is ethanedisulfonic acid, thereby forming an edisylate salt of compound A and optionally crystallizing the edisylate salt to form Qncann / zznz / E / YiAi the Form A.;