COMBINATIONS

Abstract

This description outlines combinations of compounds for treating a disease or condition, such as cancer. A combination of compounds for treating a disease or condition may include a Bcl-2 inhibitor and a WEE1 inhibitor, along with pharmaceutically acceptable salts of either.

Description

COMBINATIONS Inclusion as a reference in any priority requests Each and every application for which a foreign or domestic priority claim is identified, e.g., in the Application Fact Sheet or application as filed with this application, is incorporated herein by reference pursuant to 37 CFR 1.57, and Rules 4.18 and 20.6, including U.S. Provisional Application No. 62 / 952,032, filed on December 20, 2019. Field This application relates to the fields of chemistry, biochemistry, and medicine. More specifically, this description outlines combination therapies and methods for treating diseases and / or conditions with the combination therapies described herein. Description Cancers are a family of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Currently, cancer treatments include surgery, hormone therapy, radiation, chemotherapy, immunotherapy, targeted therapy, and combinations thereof. Survival rates vary depending on the type of cancer and the stage at which it is diagnosed. In 2019, approximately 1.8 million people were diagnosed with cancer, and an estimated 606,880 people died from it in the United States. Therefore, there remains a need for effective cancer treatments. Summary Some of the forms described herein relate to a combination of compounds that may include an effective amount of Compound (A), or a pharmaceutically acceptable salt thereof, and an effective amount of one or more of Compound (B), or a pharmaceutically acceptable salt thereof. Some of the embodiments described herein relate to the use of a combination of compounds to treat a disease or condition, wherein the combination includes an effective amount of Compound (A), or a pharmaceutically acceptable salt thereof, and an effective amount of one or more of Compound (B), or a pharmaceutically acceptable salt thereof. Other embodiments described herein relate to the use of a combination of compounds in the manufacture of a medicament to treat a disease or condition, wherein the combination includes an effective amount of Compound (A), or a pharmaceutically acceptable salt thereof, and an effective amount of one or more of Compound (B), or a pharmaceutically acceptable salt thereof. In some forms, the disease or condition may be a cancer described in this description. Figures Figure 1 provides examples of Bcl-2 inhibitors. Figure 2 provides examples of Compound (A). Figure 3 shows the percentage of inhibition of Compound 1a and Compound 3 as single agents and in combination against DMS-53 (lung cancer cell line). Figure 4 shows the results of a study of tumor growth in response to monotherapy and combination therapy with Compound 1a and Compound 3 in an MV4-11 mouse model. Detailed description Definitions Unless otherwise defined, all technical and scientific terms used in this description have the same meaning commonly understood by those skilled in the art. All patents, applications, published applications, and other publications mentioned in this description are incorporated by reference in their entirety, unless otherwise specified. In the event of multiple definitions for a term in this description, the definitions contained in this section shall prevail, unless otherwise specified. When a group is described as “optionally substituted,” that group may be substituted or unsubstituted with one or more of the listed substituents. Similarly, when a group is described as “substituted or unsubstituted,” if it is substituted, the substituent(s) may be selected from one or more of the listed substituents.If no substituents are indicated, it means that the indicated “optionally substituted” or “substituted” group may be substituted with one or more groups selected individually and independently from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), cycloalkyl(alkyl), heteroaryl(alkyl), heterocyclyl(alkyl), hydroxy, alkoxy, acyl, cyano, halogen, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxyl, nitro, sulphenyl, sulfinyl, sulfonyl, haloalkyl, hydroxyalkyl, haloalkoxy, an amino, a monosubstituted amine group, a disubstituted amine group, and a amine(Ci-Ce alkyl). As used in the present description, “Caa Cb” where “a” and “b” are integers refers to the number of carbon atoms in a group. The indicated group may contain from “a” to “b”, inclusive, carbon atoms. Thus, for example, an “alkyl Ci to C4” group refers to all alkyl groups having from 1 to 4 carbons, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-. If “a” and “b” are not designated, the broader range described in these definitions should be assumed. If two “R” groups are described as “taken together,” the R groups and the atoms to which they are attached can form a cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocycle. For example, but not limited to, if Ray Rb of an NRaRb group is described as “taken together,” it means that they are covalently bonded to each other to form a ring. Ra—N. I Rb As used in this description, the term “alkyl” refers to a fully saturated aliphatic hydrocarbon group. The alkyl entity may be either branched or straight-chain. Examples of branched alkyl groups include, but are not limited to, isopropyl, sec-butyl, tert-butyl, and the like. Examples of straight-chain alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, and the like. The alkyl group can have from 1 to 30 carbon atoms (wherever it appears in the present description, a numerical range such as “1 to 30” refers to every whole number in the given range; e.g., “1 to 30 carbon atoms” means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 30 carbon atoms, although the present definition also covers the case of the term “alkyl” where no numerical range is designated).The alkyl group can also be a medium-sized alkyl group, having 1 to 12 carbon atoms. Alternatively, it can be a smaller alkyl group, having 1 to 6 carbon atoms. An alkyl group can be substituted or unsubstituted. The term “alkenyl” as used herein refers to a monovalent radical of linear or branched chain of two to twenty carbon atoms containing one or more carbon double bonds, including, but not limited to, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, and the like. An alkenyl group may be substituted or unsubstituted. The term “alkynyl” as used in this description refers to a monovalent, linear or branched chain radical of two to twenty carbon atoms containing one or more carbon triple bonds, including, but not limited to, 1-propynyl, 1-butynyl, 2-butynyl, and the like. An alkynyl group may be substituted or unsubstituted. As used herein, “cycloalkyl” refers to a fully saturated (without double or triple bonds) mono- or polycyclic hydrocarbon ring system. When composed of two or more rings, the rings may be joined together in a fused, bridged, or spiro manner. As used herein, the term “fused” refers to two rings that have two atoms and one bond in common. As used herein, the term “bridged cycloalkyl” refers to compounds in which the cycloalkyl contains a bond between one or more non-adjacent atoms. As used herein, the term “spiro” refers to two rings that have one atom in common and are not linked by a bridge.Cycloalkyl groups can contain 3 to 30 atoms in the ring(s), 3 to 20 atoms in the ring(s), 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s), or 3 to 6 atoms in the ring(s). A cycloalkyl group can be substituted or unsubstituted. Examples of monocycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of fused cycloalkyl groups are decahydronaphthalenyl, dodecahydro-1H-phenalenyl, and tetradecahydroanthracenyl; examples of bridging cycloalkyl groups are bicyclo[1.1.1]pentyl, adamantanyl, and norbornanyl; and examples of spiro cycloalkyl groups include spiro[3.3]heptane and spiro[4.5]decane. As used in this description, “cycloalkenyl” refers to a mono- or polycyclic hydrocarbon ring system containing one or more double bonds in at least one ring; however, if there is more than one, the double bonds cannot form a system of π electrons fully delocalized across all the rings (otherwise, the group would be “aryl,” as defined herein). Cycloalkenyl groups may contain 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s), or 3 to 6 atoms in the ring(s). When composed of two or more rings, the rings may be connected to each other in a fused, bridged, or spiro manner. A cycloalkenyl group may be substituted or unsubstituted. As used herein, “carbocyclyl” refers to a system of non-aromatic mono- or polycyclic hydrocarbon rings. When composed of two or more rings, the rings may be linked together in a fused, bridging, or spiro manner, as described herein. Carbocyclyl groups may contain 3 to 30 atoms in the ring(s), 3 to 20 atoms in the ring(s), 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s), or 3 to 6 atoms in the ring(s). A carbocyclyl group may be substituted or unsubstituted. Examples of carbocyclyl groups include, but are not in any way limited to, cycloalkyl groups and cycloalkenyl groups, as defined herein, and the non-aromatic portions of 1,2,3,4-tetrahydronaphthalene, 2,3-dihydro-1H-indene, 5,6,7,8-tetrahydroquinoline, and 6,7-dihydro-5Hcyclopenta[b]pyridine. non-adjacent. As used in this description, the term “spiro” refers to two rings that share one atom and are not bridged. Heterocyclyl and heteroalicyclyl groups may contain 3 to 30 atoms in the ring(s), 3 to 20 atoms in the ring(s), 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s), or 3 to 6 atoms in the ring(s). For example, five carbon atoms and one heteroatom; four carbon atoms and two heteroatoms; three carbon atoms and three heteroatoms; four carbon atoms and one heteroatom; three carbon atoms and two heteroatoms; two carbon atoms and three heteroatoms; one carbon atom and four heteroatoms; three carbon atoms and one heteroatom; two carbon atoms and one heteroatom. Furthermore, any nitrogen in a heteroalicyclyl group may be quaternized. Heterocyclyl or heteroalicyclyl groups may be substituted or unsubstituted.Examples of such “heterocyclyl” or “heteroalicyclyl” groups include, but are not limited to, 1,3-dioxin, 1,3-dioxane, 1,4-dioxane, 1,2-dioxolane, 1,3-dioxolane, 1,4-dioxolane, 1,3-oxathian, 1,4-oxathiin, 1,3-oxathiolane, 1,3-dithiol, 1,3-dithiolane, 1,4-oxathian, tetrahydro-1,4-thiazine, 2H-1,2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, trioxane, hexahydro-1,3,5-triazine, imidazoline, imidazolidine, isoxazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidine, morpholine, oxirane, piperidine N-oxide, piperidine, piperazine, pyrrolidine, azepane, pyrrolidone, pyrrolidione, 4-piperidone, pyrazoline, pyrazolidine, 2-oxopyrrolidine, tetrahydropyran, 4H-pyran, tetrahydrothiopyran, thiamorpholine, thiamorpholine sulfoxide, thiamorpholine sulfone and their benzofused analogues (e.g., benzimidazolidinone, tetrahydroquinoline and / or 3,4-methylenedioxyphenyl).Examples of spiro heterocyclyl groups include 2azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 2-oxa-6-azaspiro[3.3]heptane, 2,6-diazaspiro[3.3]heptane, 2oxaspiro[3.4]octane, and 2-azaspiro[3.4]octane. As used in this description, “aralkyl” and “aryl(alkyl)” refer to an aryl group connected, as a substituent, by means of a lower alkylene group. The lower alkylene and aryl groups of an aralkyl may be substituted or unsubstituted. Examples include, but are not limited to, benzyl, 2-phenylalkyl, 3-phenylalkyl, and naphthylalkyl. As used in this description, “heteroaralkyl” and “heteroaryl(alkyl)” refer to a heteroaryl group connected, as a substituent, by means of a lower alkylene group. The lower alkylene and heteroaryl groups of a heteroaralkyl may be substituted or unsubstituted. Examples include, but are not limited to, 2-thienylalkyl, 3-thienylalkyl, furylalkyl, thienylalkyl, pyrrolylalkyl, pyridylalkyl, isoxazolylalkyl, and imidazolylalkyl and their benzofused analogues. A “heteroalicyl(alkyl)” and “heterocyclyl(alkyl)” refer to a heterocyclic or heteroalicyclic group connected, as a substituent, by means of a lower alkylene group. The lower alkylene and the heterocyclyl of a (heteroalicyl(alkyl)) may be substituted or unsubstituted. Examples include, but are not limited to, tetrahydro-2H-pyran-4-yl(methyl), piperidin-4-yl(ethyl), piperidin-4-yl(propyl), tetrahydro-2H-thiopyran-4-yl(methyl), and 1,3-thiazinan-4-yl(methyl). As used in this description, “lower alkylene groups” are linear-chain anchoring groups (-CH2-) that form linkages to connect molecular fragments via their terminal carbon atoms. Examples include, but are not limited to, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), and butylene (-CH2CH2CH2CH2-). A lower alkylene group can be substituted by replacing one or more hydrogens of the lower alkylene group and / or MA / t / ZUZZ / UO 04 / or by substituting both hydrogens of the same carbon with a cycloalkyl group (e.g., -C-). As used in this description, the term “hydroxy” refers to an -OH group. As used in this description, “alkoxy” refers to the formula -OR, where R is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl) as defined herein. A non-limiting list of alkoxy compounds includes methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, phenoxy, and benzoxy. An alkoxy may be substituted or unsubstituted. As used in this description, “acyl” refers to a hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), and heterocyclyl(alkyl) group connected, as a substituent, by means of a carbonyl group. Examples include formyl, acetyl, propanoyl, benzoyl, and acryl. An acyl group may be substituted or unsubstituted. A “cyano” group refers to a “-CN” group. As used in the present description, the term “halogen atom” or “halogen” means any of the radiostable atoms in column 7 of the periodic table of elements, such as fluorine, chlorine, bromine, and iodine. A “thiocarbonyl” group refers to a “-C(=S)R” group in which R can be the same as that defined with respect to O-carboxyl. A thiocarbonyl group can be substituted or unsubstituted. An “O-carbamyl” group refers to a “-OC(=O)N(RaRb)” group in which Ra and Rb can independently be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). An O-carbamyl group can be substituted or unsubstituted. An “N-carbamyl” group refers to a “ROC(=O)N(RA)-” group in which R and RA can independently be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). An N-carbamyl group can be substituted or unsubstituted. An “O-thiocarbamyl” group refers to a “-OC(=S)-N(RaRb)” group in which RaRb can independently be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). An O-thiocarbamyl group can be substituted or unsubstituted. An “N-thiocarbamyl” group refers to a “ROC(=S)N(RA)-” group in which R and Ra can independently be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). An N-thiocarbamyl group can be substituted or unsubstituted. A “C-amido” group refers to a “-C(=O)N(RaRb)” group in which Ra and Rb can independently be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A C-amido can be substituted or unsubstituted. An “N-amido” group refers to a group “RC(=O)N(Ra)-” in which R and Ra can independently be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). An N-amido can be substituted or unsubstituted. An “S-sulfonamido” group refers to a “-SO2N(RaRb)” group in which Ra and Rb can independently be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). An S-sulfonamido can be substituted or unsubstituted. An “N-sulfonamido” group refers to an “RSO2N(Ra)-” group in which R and Ra can independently be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). An N-sulfonamido can be substituted or unsubstituted. An “O-carboxyl” group refers to a group “RC(=O)O-” in which R can be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl), as defined herein. An O-carboxyl group can be substituted or unsubstituted. The terms “ester” and “C-carboxyl” refer to a group “-C(=O)OR” in which R can be the same as that defined with respect to O-carboxyl. An ester and C-carboxyl can be substituted or unsubstituted. A “nitro” group refers to a “-NO2” group. A “sulfenyl” group refers to a “-SR” group in which R can be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A sulfenyl can be substituted or unsubstituted. A “sulfinyl” group refers to a “-S(=O)-R” group in which R can be the same as that defined with respect to sulphenyl. A sulfinil can be substituted or unsubstituted. A “sulfonyl” group refers to an “SO2R” group where R can be the same as that defined with respect to sulphenyl. A sulfonyl group can be substituted or unsubstituted. As used in this description, “haloalkyl” refers to an alkyl group in which one or more of the hydrogen atoms are replaced by a halogen (e.g., monohaloalkyl, dihaloalkyl, trihaloalkyl, and polyhaloalkyl). Such groups include, but are not limited to, chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloro-2-fluoromethyl, 2-fluoroisobutyl, and pentafluoroethyl. A haloalkyl may be substituted or unsubstituted. As used in this description, “haloalkoxy” refers to an alkoxy group in which one or more of the hydrogen atoms are replaced by a halogen (e.g., monohaloalkoxy, dihaloalkoxy, and trihaloalkoxy). Such groups include, but are not limited to, chloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1-chloro-2-fluoromethoxy, and 2-fluoroisobutoxy. A haloalkoxy may be substituted or unsubstituted. As used in the present description, the term “amino” refers to an -NH2 group. A “monosubstituted amine” group refers to a “-NHRa” group in which Ra can be an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl), as defined herein. The Ra group may be substituted or unsubstituted. Examples of monosubstituted amino groups include, but are not limited to, -NH(methyl), -NH(phenyl), and the like. A “disubstituted amine” group refers to a “-NRaRb” group in which Ra and Rb can be independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl), as defined herein. Ra and Rb can be independently substituted or unsubstituted. Examples of disubstituted amino groups include, but are not limited to, -N(methyl)2, -N(phenyl)(methyl), -N(ethyl)(methyl), and the like. As used in this description, the group “alkylamine” refers to a radical -(alkylene)-NR'R” where R' and R are independently hydrogen or alkyl as defined herein. An alkylamine may be substituted or unsubstituted. Examples of alkylamine groups include, but are not limited to, -CH2NH(methyl), -CH2NH(phenyl), -CH2CH2NH(methyl), -CH2CH2NH(phenyl), -CH2N(methyl)2, -CH2N(phenyl)(methyl), -NCH2(ethyl)(methyl), -CH2CH2N(methyl)2, -CH2CH2N(phenyl)(methyl), -NCH2CH2(ethyl)(methyl), and the like. Where the number of substituents is not specified (e.g., haloalkyl), there may be one or more substituents present. For example, “haloalkyl” may include one or more identical or different halogens. As another example, “C1-C3 alkoxyphenyl” may include one or more identical or different alkoxy groups containing one, two, or three atoms. As used in this description, a radical indicates a species with a single unpaired electron, such that the species containing the radical can covalently bond to another species. Hence, in this context, a radical is not necessarily a free radical. Rather, a radical indicates a specific portion of a larger molecule. The term “radical” can be used interchangeably with the term “group.” The term “pharmaceutically acceptable salt” refers to a salt of a compound that does not cause significant irritation to an organism to which it is administered and does not negate the biological activity and properties of the compound. In some embodiments, the salt is an acid addition salt of the compound. Pharmaceutical salts can be obtained by reacting a compound with inorganic acids such as hydrohalic acid (e.g., hydrochloric acid or hydrobromic acid), sulfuric acid, nitric acid, and phosphoric acid (such as 2,3-dihydroxypropyl dihydrogen phosphate). Pharmaceutical salts can also be obtained by reacting a compound with an organic acid such as aromatic or aliphatic sulfonic or carboxylic acids, for example, formic, acetic, succinic, lactic, malic, tartaric, citric, ascorbic, nicotinic, methanesulfonic, ethanesulfonic, p-toluenesulfonic, trifluoroacetic, benzoic, salicylic, 2-oxopentanedioic or naphthalenesulfonic acid.Pharmaceutical salts can also be obtained by reacting a compound with a base to form a salt such as an ammonium salt, an alkali metal salt (such as a sodium, potassium, or lithium salt), an alkaline earth metal salt (such as a calcium or magnesium salt), a carbonate salt, a bicarbonate salt, a salt of organic bases such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, C1-C7 alkylamine, cyclohexylamine, triethanolamine, ethylenediamine, and salts with amino acids such as arginine and lysine. Those skilled in the art understand that when a salt is formed by protonation of a nitrogen-based group (e.g., NH2), the nitrogen-based group can be associated with a positive charge (e.g., NH2 can be transformed into NFV), and the positive charge can be balanced by a negatively charged counterion (such as Cl1). It is understood that, in any compound described herein with one or more chiral centers, unless an absolute stereochemistry is expressly stated, then each center may independently be of the R configuration or the S configuration or a mixture thereof. Therefore, the compounds provided herein may be enantiomerically pure, enantiomerically enriched, a racemic mixture, diastereomerically pure, diastereomerically enriched, or a stereoisomeric mixture. Furthermore, it is understood that in any compound described herein with one or more double bonds generating geometric isomers that may be defined as E or Z, each double bond may independently be E or Z or a mixture thereof. Similarly, it is understood that all tautomeric forms are also included in any compound described herein. It is understood that when the compounds described in this description have free valences, then the valences must be occupied with hydrogen or isotopes of it, e.g., hydrogen 1 (protium) and hydrogen 2 (deuterium). It is understood that the compounds described herein may be isotopically labeled. Substitution with isotopes such as deuterium may provide certain therapeutic advantages resulting from increased metabolic stability, such as, for example, an increased in vivo half-life or reduced dosage requirements. Each chemical element represented in the structure of a compound may include any isotope of that element. For example, in the structure of a compound, a hydrogen atom may be explicitly described or understood as being present in the compound. In any position within the compound where a hydrogen atom may be present, the hydrogen atom may be any isotope of hydrogen, including, but not limited to, hydrogen-1 (protium) and hydrogen-2 (deuterium).Therefore, in the present description, reference to a compound encompasses all possible isotopic forms, unless the context clearly indicates otherwise. The methods and combinations described herein are understood to include crystalline forms (also known as polymorphs, which include different crystal packing arrangements of the same elemental composition of a compound), amorphous phases, salts, solvates, and hydrates. In some embodiments, the compounds described herein exist in solvated forms with pharmaceutically acceptable solvents such as water, ethanol, or the like. In other embodiments, the compounds described herein exist in non-solvated form. Solvates contain stoichiometric or non-stoichiometric amounts of a solvent and may form during the crystallization process with pharmaceutically acceptable solvents such as water, ethanol, or the like. Hydrates form when the solvent is water, and alcoholates form when the solvent is alcohol.Furthermore, the compounds provided in this description may exist in both solvated and unsolvated forms. Generally, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein. Where a range of values ​​is provided, it is understood that the upper and lower limits, and each intermediate value between the upper and lower limits of the range, are included within the modalities. Unless expressly stated otherwise, the terms and phrases used in this application and variations thereof, particularly in the appended claims, should be interpreted as without definite limits, as opposed to limiting. By way of examples, the term 'including' should be interpreted as 'including, but not limited to', 'including, but not limited to', or the like; as used herein, the term 'comprising' is synonymous with 'including', 'containing', or 'characterized by', and is inclusive or without definite limits, and does not exclude additional elements or method steps not mentioned; the term 'having' should be interpreted as 'having at least'; the term 'including' should be interpreted as 'including, but not limited to'; the term 'example' is used to provide illustrative instances of the element in question, not an exhaustive or limiting list thereof;The use of terms such as 'preferably', 'preferred', 'desired', or 'desirable', and words of similar meaning, should not be understood to imply that certain features are fundamental, essential, or even important to the structure or function, but rather simply to highlight alternative or additional features that may or may not be used in a particular modality. Furthermore, the term 'comprising' should be interpreted as synonymous with the phrases 'having at least' or 'including at least'. When used in the context of a compound, composition, or device, the term 'comprising' means that the compound, composition, or device includes at least the features or components mentioned, but may also include additional features or components. With respect to the use of any plural and / or singular term in this description, those skilled in the art may translate from plural to singular and / or from singular to plural as appropriate to the context and / or application. For the sake of clarity, various singular / plural permutations may be expressly stated in this description. The indefinite article "a" does not preclude plurality. The mere fact that certain measures are mentioned in different, mutually dependent claims does not indicate that a combination of these measures cannot be used. Any reference sign in the claims shall not be construed as limiting their scope. Compounds Some of the modalities described herein relate to the use of a combination of compounds to treat a disease or condition, wherein the combination may include an effective amount of Compound (A), or a pharmaceutically acceptable salt thereof, and an effective amount of one or more of Compound (B), or a pharmaceutically acceptable salt thereof, wherein: Compound (A) has the structure: where: R1 can be selected from hydrogen, halogen and a substituted or unsubstituted Ci-Ce alkyl; ring A can be selected from a substituted or unsubstituted phenyl and a substituted or unsubstituted 5-6 membered monocyclic heteroaryl; ring B can be selected from a substituted or unsubstituted 5-7 membered monocyclic carbocyclyl and a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl; R2 can be selected from (R3)m and R5; m can be 0, 1, 2 or 3; R3 can be selected from halogen and a substituted or unsubstituted Ci-Ce alkyl; X may be selected from hydrogen, halogen, hydroxy, cyano, a substituted or unsubstituted 4-6 membered monocyclic heterocycle, a substituted or unsubstituted amine (CrCe alkyl), a substituted or unsubstituted -NH-(CH2)i-6-amine, a monosubstituted amine, a disubstituted amine, an amino, a substituted or unsubstituted C3-Ce alkyl, a substituted or unsubstituted C3-C6 alkoxy, a substituted or unsubstituted C3-C6 cycloalkoxy, a substituted or unsubstituted acyl (C1C6 alkyl), a substituted or unsubstituted C-amido, a substituted or unsubstituted N-amido, a substituted or unsubstituted C-carboxy, a substituted or unsubstituted O-carboxy, a substituted or unsubstituted O-carbamyl, and a substituted or unsubstituted N-carbamyl; And it can be CH or N; Y1 can be CR4A or N; Y2 can be CR4Bo N;Ring C may be selected from a substituted or unsubstituted Ce-Cio aryl, a substituted or unsubstituted 5-10 membered monocyclic heteroaryl, a substituted or unsubstituted 5-7 membered monocyclic carbocyclyl, a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl, and a substituted or unsubstituted 7-10 membered bicyclic heterocyclyl; R4A and R4B may be independently selected from hydrogen, halogen, and an unsubstituted C1-4 alkyl; and R5 may be a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl; and one or more of Compound (B) may be a Bcl-2 inhibitor, or a pharmaceutically acceptable salt thereof. In some embodiments, R1 can be selected from hydrogen, halogen, and a substituted or unsubstituted Ci-Ce alkyl. In some embodiments, ring A can be selected from a substituted or unsubstituted phenyl and a substituted or unsubstituted 5-6-membered monocyclic heteroaryl. In some embodiments, ring B can be selected from a substituted or unsubstituted 5-7-membered monocyclic carbocyclyl and a substituted or unsubstituted 5-7-membered monocyclic heterocyclyl (R3)m. In some embodiments, R2 can be selected from Y—' X and Y2. In some embodiments, m can be 0, 1, 2, or 3. In some embodiments, R3 can be selected from a halogen and a substituted or unsubstituted Ci-Ce alkyl.In some embodiments, X may be selected from hydrogen, halogen, hydroxy, cyano, a substituted or unsubstituted 4-6 membered monocyclic heterocycle, a substituted or unsubstituted amine (C3-C6 alkyl), a substituted or unsubstituted -NH-(CH2)16-amine, a monosubstituted amine, a disubstituted amine, an amino, a substituted or unsubstituted C3-C6 alkyl, a substituted or unsubstituted C3-C6 alkoxy, a substituted or unsubstituted C3-C6 cycloalkoxy, a substituted or unsubstituted acyl (C3-C6 alkyl), a substituted or unsubstituted C-amido, a substituted or unsubstituted N-amido, a substituted or unsubstituted C-carboxyl, a substituted or unsubstituted O-carboxyl, a substituted or unsubstituted O-carbamyl, and a substituted or unsubstituted N-carbamyl. replaced. In some modalities, Y can be CH or N. In some modalities, Y1 can be CR4A or N. In some modalities, Y2 can be CR4 or N.In some embodiments, ring C can be selected from a substituted or unsubstituted Ce-Cio aryl, a substituted or unsubstituted 5- to 10-membered monocyclic heteroaryl, a substituted or unsubstituted 5- to 7-membered monocyclic carbocyclyl, a substituted or unsubstituted 5- to 7-membered monocyclic heterocyclyl, and a substituted or unsubstituted 7- to 10-membered bicyclic heterocyclyl. In some embodiments, R4A and R4B are independently selected from hydrogen, halogen, and an unsubstituted alkyl Cm. In some embodiments, R1 may be selected from hydrogen, halogen, and CrCe alkyl. In some embodiments, R1 may be hydrogen. In other embodiments, R1 may be halogen. In some embodiments, R1 may be fluoro. In still other embodiments, R1 may be an unsubstituted C1-Ce alkyl (such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, pentyl (linear or branched chain), or hexyl (linear or branched chain)). In some embodiments, R1 may be an unsubstituted methyl. In some embodiments, R1 may be a substituted C1-6 alkyl, such as those described herein. In some embodiments, R1 may be an unsubstituted CrCe haloalkyl (such as a CrCe fluoroalkyl, a Ci-Ce chloroalkyl, or a CrCe chlorofluoroalkyl). In some embodiments, R1 may be -CHF2, -CF3, -CF2CH3, or -CH2CF3. In some embodiments, ring A can be selected from a substituted or unsubstituted phenyl and a substituted or unsubstituted 5-6 membered monocyclic heteroaryl. In some embodiments, ring A may be a substituted phenyl group. In other embodiments, ring A may be an unsubstituted phenyl group. In some embodiments, ring A may be a substituted 5-6 membered monocyclic heteroaryl. In some embodiments, ring A may be an unsubstituted 5-6 membered monocyclic heteroaryl. In some embodiments, ring A may be selected from a substituted or unsubstituted pyrrole, a substituted or unsubstituted furan, a substituted or unsubstituted thiophene, a substituted or unsubstituted imidazole, a substituted or unsubstituted pyrazole, a substituted or unsubstituted oxazole, a substituted or unsubstituted thiazole, a substituted or unsubstituted pyridine, a substituted or unsubstituted pyrazine, a substituted or unsubstituted pyrimidine, and a substituted or unsubstituted pyridazine. When substituted, ring A can be substituted with one or more selected halogen substituents, a haloalkyl unsubstituted C1-C4 and an unsubstituted C1-C4 alkyl. In some embodiments, ring A is monosubstituted with a halogen (e.g., fluoro). Yb) each of the groups mentioned above is either substituted or unsubstituted. In some forms, i X, 5) Yb j WT) can be substituted or unsubstituted. In some forms, it can be a τ (aA Yb) substituted or unsubstituted, where ring A is unsubstituted. In other configurations, one can select replaced or not replaced, a replaced or not replaced and a replaced. As described herein, the portion of ring A of replaced or not may not be replaced. In some embodiments, ring B can be selected from a substituted or unsubstituted 5-7 membered monocyclic carbocyclyl and a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl. In some embodiments, ring B may be a substituted or unsubstituted 5- to 7-membered monocyclic carbocycline. In some embodiments, ring B may be a substituted or unsubstituted 5-membered monocyclic carbocycline. In other embodiments, ring B may be a substituted or unsubstituted 6-membered monocyclic carbocycline. In still other embodiments, ring B may be a substituted or unsubstituted 7-membered monocyclic carbocycline. In some modalities, it can be selected from: yx; where each of the groups mentioned above is either substituted or not substituted. In some embodiments, ring B may be a substituted or unsubstituted 5- to 7-membered monocyclic heterocycle. In some embodiments, ring B may be a substituted or unsubstituted 5-membered monocyclic heterocycle. In other embodiments, ring B may be a substituted or unsubstituted 6-membered monocyclic heterocycle. In still other embodiments, ring B may be a substituted or unsubstituted 7-membered monocyclic heterocycle. including any -NH group. t> or η ol>° In some embodiments, ring B can be selected from L~~~ú , , o--- / , \^°, hy (aA , where each of the groups mentioned above is substituted or unsubstituted, including any -NH group. In some embodiments, ring B can be substituted or unsubstituted. In some embodiments, when ring B is substituted, it may be substituted with one, two, or three substituents selected independently from halogen, hydroxyl, amino, an unsubstituted N-bonded amido (e.g., -NHC(O)C6-alkyl), an unsubstituted C6-haloalkyl (such as those described herein), and a substituted or unsubstituted CrC6-alkyl (such as those described herein).In some embodiments, ring B may be substituted with 1, 2, or 3 substituents independently selected from fluoro, hydroxy, amino acids, an unsubstituted -NHC(O)Ci-C6 alkyl, an unsubstituted Ci-Ce haloalkyl (such as those described herein), and an unsubstituted Ci-Ce alkyl (such as those described herein). In some embodiments, ring B may be substituted with 1 or 2 substituents independently selected from fluoro, hydroxyCF3, -CHF2, -CF2CH3, an unsubstituted methyl, an unsubstituted ethyl, and -NHC(O)CH3. mentioned above is substituted or not substituted, including any -NH group. ML / 04 / o replaced or not replaced. In some forms, not replaced. In some forms, Both ring A and ring B may be replaced or not replaced. In some forms, ring A and ring B are replaced. Bde They may be replaced or not replaced independently. In some forms, ring A and ring Bde They can both be non-replaceable. In some modalities, ring A and ring B of They can both be replaced independently. In some forms, ring A of and ring B of and ring B of ring B of It may not be replaced. In some models, ring A may be replaced. In some models, ring A of can be substituted and can be unsubstituted can be unsubstituted can be substituted with 1, 2 or 3 substituents selected independently from halogen, hydroxy and a substituted or unsubstituted Ci-Ce alkyl (such as those described herein). In some embodiments, ring A of may not be replaced and ring B of It may be substituted with 1, 2, or 3 independently selected substituents of fluoro, hydroxy, amino, an unsubstituted N-linked amido (e.g., alkyl -NHC(O)Ci-C6), an unsubstituted Ci-Ce haloalkyl (such as those described herein), and an unsubstituted CrC6 alkyl (such as those described herein). In some embodiments, the ring A of may not be replaced and ring B of can be substituted with 1 or 2 substituents independently selected from fluoro, hydroxy, amino, -CF3, -CHF2, -CF2CH3, an unsubstituted methyl, an unsubstituted ethyl and -NHC(O)CH3. In some modes, R2 can be ML / 04 / o (R3)m In some modes, R2 can be In some forms, Y can be CH or N (nitrogen). In some forms, Y can be CH. In some forms, Y can be N (nitrogen). In some embodiments, R3 may be selected from a halogen and a substituted or unsubstituted Ci-C6 alkyl (such as those described herein). In some embodiments, R3 may be a halogen. In some embodiments, R3 may be a substituted CrCe alkyl (such as those described herein). In some embodiments, R3 may be an unsubstituted Ci-Cs alkyl (such as those described herein). In some modalities, m can be 0, 1, 2, or 3. In some modalities, m can be 0. In some modalities, m can be 1. In some modalities, m can be 2. In some modalities, m can be 3. When m is 2 or 3, the R3 groups can be the same or different from each other. In some embodiments, X can be selected from hydrogen, halogen, hydroxy, cyano, a substituted or unsubstituted 4-6 member monocyclic heterocycle, a substituted or unsubstituted amine (CrCe alkyl), or -NH-(CH2)i.a substituted or unsubstituted 6-amine, a monosubstituted amine, a disubstituted amine, an amino, a C3-C6 alkyl (such as those described herein), a substituted or unsubstituted C3-C6 alkoxy (such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, t-butoxy, pentoxy (linear or branched chain) or hexoxy (linear or branched chain)), a substituted or unsubstituted C3-C6 cycloalkoxy (such as cyclopropoxy, cyclobutoxy, cyclopentoxy or cyclohexoxy), a substituted or unsubstituted acyl (C3-C6 alkyl), a substituted or unsubstituted C3-amido, a substituted or unsubstituted N-amido, a substituted or unsubstituted C3-carboxyl, a substituted or unsubstituted O-carboxyl, an O-carbamyl substituted or unsubstituted and a substituted or unsubstituted N-carbamyl. In some embodiments, X can be hydrogen. In other embodiments, X can be a halogen. In some embodiments, X can be fluorine. In some embodiments, X can be chlorine. In still other embodiments, X can be hydroxyl. In yet still other embodiments, X can be cyano. In some embodiments, X can be amino. In some embodiments, X may be an unsubstituted Ci-C6 alkyl (such as those described herein). In some embodiments, X may be an unsubstituted methyl, unsubstituted ethyl, or unsubstituted isopropyl group. In some embodiments, X may be a substituted CrCe alkyl (such as those described herein). In some embodiments, X may be an unsubstituted CrCe haloalkyl (such as a CrCe fluoroalkyl, a CrCe chloroalkyl, or a CrCe chlorofluoroalkyl). In some embodiments, X may be selected from -CHF2, -CF3, -CF2CH3, and -CH2CF3. In some embodiments, X may be an unsubstituted Ci-C6 hydroxyalkyl (such as a Ci-C6 monohydroxyalkyl or a Ci-C6 dihydroxyalkyl). In some embodiments, X can be selected from —CH2OH, -CH2CH2OH, -CH(OH)CH3 and -C(OH)(CH3)2. In some embodiments, X can be an unsubstituted Ci-Ce cyanoalkyl (such as a Ci-Ce mono-cyanoalkyl or a Ci-Ce di-cyanoalkyl).In some modes, X can be selected from , V^CN and In some modes, X can. MA / 04 / or be an unsubstituted Ci-Ce alkoxyalkyl (such as a CrCe mono-alkoxyalkyl or a CrCe di-alkoxyalkyl). In some embodiments, X may be selected from In some embodiments, X can be a substituted CrCe alkyl selected from In some embodiments, X may be an unsubstituted CY-C6 alkoxy (such as those described herein). In some embodiments, X may be an unsubstituted methoxy, an unsubstituted ethoxy, or an unsubstituted isopropoxy. In some embodiments, X may be a substituted CY-C6 alkoxy (such as those described herein). In some embodiments, X may be a CY-C3 alkoxy substituted with 1, 2, 3, or independently selected halogen substituents, an amino group, a monosubstituted amine (such as those described herein), and a disubstituted amine (such as those described herein). In some embodiments, X may be a Ci-Ce alkoxy substituted with 1 substituent selected from a halogen, an amino, a monosubstituted amine (such as those described herein) and a disubstituted amine (such as those described herein). V°^cf3 In some modalities, X can be selected from Ύ 3,Ύ In some forms, X may be a substituted C3-Ce cycloalkoxy (such as those described herein). In some forms, X may be an unsubstituted C3-C6 cycloalkoxy (such as those described herein). In some embodiments, X may be a substituted acyl (CrC6 alkyl), such as a substituted -(CO)-CH3. In some embodiments, X may be an unsubstituted acyl (CrC6 alkyl), such as an unsubstituted -(CO)-CH3. In some embodiments, X may be a substituted 4-6 membered monocyclic heterocycle. In some embodiments, X may be an unsubstituted 4-6 membered monocyclic heterocycle. In some embodiments, X may be selected from azetidine, oxethane, diazetidine, azaoxethane, pyrrolidine, tetrahydrofuran, imidazoline, pyrazolidine, piperidine, tetrahydropyran, piperazine, morpholine, and dioxane; wherein each of the aforementioned groups is either substituted or unsubstituted, N₂, N₂, N₂O, or any -NH group. In some embodiments, X may be selected from v, where each of the MA / 04 / or groups mentioned above is substituted or not substituted, including any -NH group. In some embodiments, X may be a 4-6 membered monocyclic heterocycle (such as those described herein) substituted with one or two substituents independently selected from halogen, a substituted or unsubstituted CrCe alkyl (such as those described herein), a monosubstituted amine (such as those described herein), a disubstituted amine (such as those described herein), an amino, a substituted or unsubstituted (CrCe alkyl) amine, and a substituted or unsubstituted (CrCe alkyl) acyl. In some embodiments, X may be a 4-6 membered monocyclic heterocycle substituted with one or two substituents independently selected from fluoro, an unsubstituted methyl, an unsubstituted ethyl, an unsubstituted isopropyl, —NN CH2OH and -N(CH3)2. In some embodiments, X can be selected from OH N— In some embodiments, X may be a substituted amine (Ci-Ce alkyl). In some embodiments, X may be an unsubstituted amine (CrCe alkyl). In some embodiments, X may be selected from Nri2 ; wherein each of the aforementioned groups is substituted or unsubstituted, including any -NH group. In some embodiments, X may be a substituted -NH-(CH2)i.6-amine. In some embodiments, X may be an unsubstituted -NH(CH2)i-6-amine. In some embodiments, X may be selected from nh2 NH2 ; wherein each of the aforementioned groups is substituted or unsubstituted, including any -NH group. ML / 04 / o In some embodiments, X may be a monosubstituted amine. In some embodiments, the substituent of the monosubstituted amine is an unsubstituted C3-C6 alkyl (such as those described herein) or an unsubstituted C3-C6 cycloalkyl (such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl). In some embodiments, X may be a disubstituted amine. In some embodiments, the two substituents of the disubstituted amine are independently selected from an unsubstituted C3-C6 alkyl (such as those described herein) and an unsubstituted C3-C6 cycloalkyl (such as those described herein). In some modes, X can be selected from In some embodiments, X may be a substituted or unsubstituted C-amido. In some embodiments, X may be a substituted or unsubstituted N-amido. In some embodiments, X may be a substituted or unsubstituted C-carboxyl. In some embodiments, X may be a substituted or unsubstituted O-carboxyl. In some embodiments, X may be a substituted or unsubstituted O-carbamyl. In some embodiments, X may be a substituted or unsubstituted N-carbamyl. In some embodiments, X may be monosubstituted with an unsubstituted C-Ce hydroxyalkyl (such as those described herein). In some forms, Y1 can be CR4A or N (nitrogen). In some forms, Y1 can be CR4A. In some forms, Y1 can be N (nitrogen). In some forms, Y2 can be CR4Bo N (nitrogen). In some forms, Y2 can be CR4B. In some forms, Y2 can be N (nitrogen). In some forms, each of Y1 and Y2 can be N (nitrogen). In some forms, Y1 can be CR4A and Y2 can be CR4B. In some forms, Y1 can be CR4A and Y2 can be N (nitrogen). In some forms, Y1 can be N (nitrogen) and Y2 can be CR4B. In some embodiments, R4A may be hydrogen. In some embodiments, R4A may be a halogen. In some embodiments, R4A may be an unsubstituted C1-4 alkyl (such as those described herein). In some embodiments, R4B may be hydrogen. In some embodiments, R4B may be a halogen. In some embodiments, R4B may be an unsubstituted C1,4 alkyl (such as those described herein). In some embodiments, each R4A and each R4B may be hydrogen. In some embodiments, each R4A and R4B may be a halogen (where the halogens may be the same or different from each other). In some embodiments, each R4A and R4B may be an unsubstituted Cm alkyl (such as those described herein, and where the Cm alkyls may be the same or different from each other). In some embodiments, each R4A and R4B may be hydrogen, and the other R4A and R4B may be a halogen. In some embodiments, one R4A and R4B may be hydrogen, and the other R4A and R4B may be an unsubstituted Cm alkyl (such as those described herein). In some embodiments, one of R4A and R4B may be a halogen, and the other of R4A and R4B may be an unsubstituted Cu alkyl (such as those described in the present description). II In some modes, R2 can be R5. For example, R2 can be r5. When, in some In N^Xí^ I embodiments, R2 is R5, and R5 can be a substituted 5-7 membered monocyclic heterocycle. In other embodiments, R5 can be an unsubstituted 5-7 membered monocyclic heterocycle. Examples of R5 groups include a substituted or unsubstituted piperidinyl, a substituted or unsubstituted pyrrolidinyl, and a substituted or unsubstituted azepanyl. When the R5 group is substituted, possible substituents include an unsubstituted C1-4 alkyl, halogen, hydroxy, and unsubstituted C1,4 haloalkyl. In some embodiments, ring C can be selected from a substituted or unsubstituted Ce-Cw aryl, a substituted or unsubstituted 5-10 membered monocyclic heteroaryl, a substituted or unsubstituted 5-7 membered monocyclic carbocyclyl, a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl, and a substituted or unsubstituted 7-10 membered bicyclic heterocyclyl. In some forms, ring C may be a substituted C6-Ci0 aryl group. In some forms, ring C may be an unsubstituted Ce-Cw aryl group. In some forms, ring C may be a substituted Ce aryl group. In some forms, ring C may be an unsubstituted Ce aryl group. In some embodiments, ring C may be a substituted 5-10 member heteroaryl. In some embodiments, ring C may be an unsubstituted 5-10 member heteroaryl. In some embodiments, ring C may be a substituted 5-6 member heteroaryl. In some embodiments, ring C may be an unsubstituted 5-6 member heteroaryl. In some embodiments, ring C may be selected from furan, thiophene, pyrrole, oxazole, thiazole, imidazole, benzimidazole, indole, pyrazole, isoxazole, pyridine, pyridazine, pyrimidine, pyrazine, purine, quinoline, isoquinoline, quinazoline, and quinoxaline; wherein each of the aforementioned groups is either substituted or unsubstituted, including any -NH group. In some embodiments, ring C may be a substituted or unsubstituted 5-membered monocyclic carbocyclyl. In some embodiments, ring C may be a substituted or unsubstituted 6-membered monocyclic carbocyclyl. In some embodiments, ring C may be a substituted or unsubstituted 7-membered monocyclic carbocyclyl. In some embodiments, ring C may be a substituted or unsubstituted 5-membered monocyclic heterocycle. In some embodiments, ring C may be a substituted or unsubstituted 6-membered monocyclic heterocycle. In some embodiments, ring C may be a substituted or unsubstituted 7-membered monocyclic heterocycle. In some embodiments, ring C may be selected from imidazoline, imidazolidine, isoxazoline, oxazolidine, oxazolidinone, thiazolidine, morpholine, piperidine, piperazine, pyrrolidine, pyrrolidone, 4-piperidone, pyrazoline, pyrazolidine, tetrahydropyran, azepine, oxepine, and diazepine; wherein each of the aforementioned groups is substituted or unsubstituted, including any -NH group. In some embodiments, ring C may be a substituted or unsubstituted 7-membered bicyclic heterocycle (e.g., a fused, bridged, or spiral heterocycle). In some embodiments, ring C may be a substituted or unsubstituted 8-membered bicyclic heterocycle, such as a fused, bridged, or spiral heterocycle. In some embodiments, ring C may be a substituted or unsubstituted 9-membered bicyclic heterocycle (e.g., a fused, bridged, or spiral heterocycle). In some embodiments, ring C may be a substituted or unsubstituted 10-membered bicyclic heterocycle, such as a fused, bridged, or spiral heterocycle. In some forms, ring C can be selected from pyrrolizidine, indoline, 1,2,3,4 tetrahydroquinoline, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 2-oxa-6-azaspiro[3.3]heptane, 2,6-diazaspiro[3.3]heptane, 2-oxaspiro[3.4]octane and 2-azaspiro[3.4]octane; wherein each of the above-mentioned groups is either substituted or unsubstituted, including any -NH group. In some embodiments, ring C may be substituted with one or more substituents selected independently from an unsubstituted Ci-Ce alkyl (as described herein) and an unsubstituted acyl (Ci-Ce alkyl). ML / 04 / o The groups mentioned above may or may not be replaced. A non-limiting list of Bcl-2 inhibitors is described herein, and includes those provided in Figure 1. Further information relating to the Bcl-2 inhibitors shown in Figure 1 is provided in the following publications: WO 2020 / 089286, WO 2015 / 011400, US 2014 / 0199234, WO 2018 / 027097, WO 2019 / 210828, WO 2018 / 192462, WO 2018 / 127130 and WO 2018 / 154004, each of which is incorporated by reference in this description for the limited purpose of describing each of the compounds shown in Figure 1. ML / t / ¿U¿¿ / UO 04 / O or a pharmaceutically acceptable salt of any of the above. Compound (A), together with pharmaceutically acceptable salts thereof, may be prepared as described herein and in WO 2019 / 173082, which is incorporated herein by reference in its entirety. As described in WO 2019 / 173082, Compound (A) is a WEE1 inhibitor. The possible combinations of Compound (A) and Compound (B), including pharmaceutically acceptable salts of either, are provided in Table 1. The numbers in Table 1 represent a compound as provided in Figures 1 and 2. For example, in Table 1, a combination represented by 3:5A corresponds to a combination of previous ones. , which includes pharmaceutically acceptable salts of any of the Table 1 CompComp - - - - - - : - - · > X * • — .. — - -- . — — Comp Comp — — : — r — . - . - - — W - - - “ __ _ . - Λ . — - . __ _ ·. “ : - - How: How - : í : - - - - -- í - * - - - - - - ' - The order of administration of compounds in a combination described herein may vary. In some formulations, Compound (A), including pharmaceutically acceptable salts thereof, may be administered before all of Compound (B), or a pharmaceutically acceptable salt thereof. In some formulations, Compound (A), including pharmaceutically acceptable salts thereof, may be administered before at least one Compound (B), or a pharmaceutically acceptable salt thereof. In still other formulations, Compound (A), including pharmaceutically acceptable salts thereof, may be administered concurrently with Compound (B), or a pharmaceutically acceptable salt thereof. In still other formulations, Compound (A), including pharmaceutically acceptable salts thereof, may be administered after the administration of at least one Compound (B), or a pharmaceutically acceptable salt thereof.In some formulations, Compound (A), which includes pharmaceutically acceptable salts thereof, may be administered after the administration of all of Compound (B), or a pharmaceutically acceptable salt thereof. There may be several advantages to using a combination of compounds described herein. For example, combining compounds that target multiple pathways simultaneously may be more effective in treating cancer, such as those described herein, compared to using the combination compounds as monotherapy. In some embodiments, a combination as described in the present description of Compound (A), which includes pharmaceutically acceptable salts, and one or more of Compound (B), or pharmaceutically acceptable salts thereof, may decrease the number and / or severity of side effects that can be attributed to a compound described in the present description, such as Compound (B), or a pharmaceutically acceptable salt thereof. The use of a combination of compounds described herein may result in an additive, synergistic, or strongly synergistic effect. A combination of compounds described herein may result in a non-antagonist effect. In some embodiments, a combination as described herein for Compound (A), including pharmaceutically acceptable salts thereof, and one or more of Compound (B), or pharmaceutically acceptable salts thereof, may result in an additive effect. In some embodiments, a combination as described herein for Compound (A), including pharmaceutically acceptable salts thereof, and one or more of Compound (B), or pharmaceutically acceptable salts thereof, may result in a synergistic effect. In some embodiments, a combination as described herein for Compound (A), including pharmaceutically acceptable salts thereof, and one or more of Compound (B), or pharmaceutically acceptable salts thereof, may result in a strongly synergistic effect.In some embodiments, a combination as described in the present description of Compound (A), which includes pharmaceutically acceptable salts thereof, and one or more of Compound (B), or pharmaceutically acceptable salts thereof, is not antagonistic. As used herein, the term “antagonist” means that the activity of the combination of compounds is lower compared to the sum of the activities of the compounds in combination when the activity of each compound is determined individually (i.e., as a single compound). As used herein, the term “synergistic effect” means that the activity of the combination of compounds is higher. ML / 04 / or that the sum of the individual activities of the compounds in the combination when the activity of each compound is determined individually. As used in the present description, the term “additive effect” means that the activity of the combination of compounds is almost equal to the sum of the individual activities of the compounds in the combination when the activity of each compound is determined individually. A potential advantage of using a combination as described herein may be a reduction in the amount(s) of the compound(s) required to treat a disease condition described herein compared to when each compound is administered as a monotherapy. For example, the amount of Compound (B), or a pharmaceutically acceptable salt thereof, used in a combination described herein may be less than the amount of Compound (B), or a pharmaceutically acceptable salt thereof, required to achieve the same reduction in a disease marker (e.g., tumor size) when administered as monotherapy.Another potential advantage of using a combination as described herein is that using two or more compounds with different mechanisms of action can create a higher barrier to the development of resistance compared to when a single compound is administered as monotherapy. Additional advantages of using a combination as described herein may include little or no cross-resistance among the compounds in such a combination; different pathways for eliminating the compounds; and / or little or no overlapping toxicity among the compounds. Pharmaceutical compositions Compound (A), including pharmaceutically acceptable salts thereof, may be provided in a pharmaceutical composition. Similarly, Compound (B), including pharmaceutically acceptable salts thereof, may be provided in a pharmaceutical composition. The term “pharmaceutical composition” refers to a mixture of one or more compounds and / or salts described herein with other chemical components, such as diluents, carriers, and / or excipients. The pharmaceutical composition facilitates the administration of the compound to an organism. Pharmaceutical compositions may also be obtained by reacting compounds with inorganic or organic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. Generally, pharmaceutical compositions will be adapted to the specific intended route of administration. As used in this description, a “carrier” refers to a compound that facilitates the incorporation of a compound into cells or tissues. For example, but not limited to, dimethyl sulfoxide (DMSO) MA / 04 / or English) is a commonly used carrier that facilitates the uptake of many organic compounds in cells or tissues of a subject. As used herein, a “diluent” refers to an ingredient in a pharmaceutical composition that lacks appreciable pharmacological activity but may be pharmaceutically necessary or desirable. For example, a diluent may be used to increase the volume of a potent drug whose mass is too small for manufacture and / or administration. It may also be a liquid for dissolving a drug to be administered by injection, ingestion, or inhalation. A common form of diluent in the art is an aqueous buffer solution such as, but not limited to, phosphate buffer saline solution, which limits the pH and isotonicity of human blood. As used herein, an “excipient” refers to an essentially inert substance added to a pharmaceutical composition to provide, but not be limited to, bulk, consistency, stability, binding capacity, lubrication, disintegration capacity, etc., to the composition. For example, stabilizers such as antioxidants and metal chelating agents are excipients. In one embodiment, the pharmaceutical composition comprises an antioxidant and / or a metal chelating agent. A “diluent” is a type of excipient. In some embodiments, Compounds (B), together with pharmaceutically acceptable salts thereof, may be administered in a pharmaceutical composition that includes Compound (A), which includes pharmaceutically acceptable salts thereof. In other embodiments, Compound (B), together with pharmaceutically acceptable salts thereof, may be administered in a pharmaceutical composition that is separate from a pharmaceutical composition that includes Compound (A), which includes pharmaceutically acceptable salts thereof. The pharmaceutical compositions described herein may be administered to a human patient on their own, or in pharmaceutical compositions where they are mixed with other active ingredients, such as in combination therapy, or with carriers, diluents, excipients, or combinations thereof. The correct formulation depends on the chosen route of administration. The formulation and administration techniques for the compounds described herein are known to those skilled in the art. The pharmaceutical compositions described herein can be manufactured in a known manner, e.g., by conventional processes of mixing, dissolving, granulating, preparing coated tablets, levigating, emulsifying, encapsulating, encapsulating, or forming tablets. Furthermore, the active ingredients are contained in an effective amount to achieve their intended purpose. Many of the compounds used in the pharmaceutical combinations described herein can be provided as salts with pharmaceutically compatible counterions. ML / 04 f or The technique encompasses many methods of administering a compound, salt, and / or composition, including, but not limited to, oral, rectal, pulmonary, topical, aerosol, injection, infusion, and parenteral administration, which includes intramuscular, subcutaneous, intravenous, intramedullary, intrathecal, direct intraventricular, intraperitoneal, intranasal, and infraocular injections. In some modalities, Compound (A), including pharmaceutically acceptable salts thereof, may be administered orally. In some modalities, Compound (A), including pharmaceutically acceptable salts thereof, may be administered to a subject via the same route as Compound (B), along with pharmaceutically acceptable salts thereof.In other embodiments, Compound (A), which includes pharmaceutically acceptable salts thereof, may be provided to a subject by a different route of administration than Compound (B), together with pharmaceutically acceptable salts thereof. The compound, salt, and / or composition can also be administered locally rather than systemically, for example, by injection or implantation directly into the affected area, often in a depot or sustained-release formulation. In addition, the compound can be delivered via a targeted drug delivery system, such as a liposome coated with a tissue-specific antibody. Liposomes are targeted to the organ and selectively taken up by it. For example, intranasal or pulmonary delivery may be desirable to target a respiratory disease or condition. If desired, the compositions may be presented in a package or dispensing device that may contain one or more dosage units containing the active ingredient. The package may comprise, for example, a metal or plastic foil, such as bubble wrap. The package or dispensing device may be accompanied by instructions for administration. The package or dispenser may also be accompanied by a notification associated with the container in the form prescribed by a government agency that regulates the manufacture, use, or sale of pharmaceutical products; the notification reflects the agency's approval of the drug form for human or veterinary administration. Such a notification, for example, may be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product information leaflet.Compositions that may include a compound and / or salt described herein formulated in a compatible pharmaceutical carrier may also be prepared, placed in a suitable container, and labelled for the treatment of an indicated condition. Uses and treatment methods As provided in the present description, in some modalities, a combination of compounds may be used that includes an effective amount of Compound (A), including pharmaceutically acceptable salts thereof, and an effective amount of one or more of Compound (B), or a pharmaceutically acceptable salt thereof, to treat a disease or condition. ML / 04 / o Examples of diseases or conditions that may be treated with a combination of compounds, along with pharmaceutically acceptable salts, include malignant neoplasms, cancers, and syndromes such as those described herein. In some cases, the disease or condition may be a hematologic malignancy. Illustrative hematologic malignancies include leukemia, lymphoma, or myeloma. In some cases, the hematologic malignancy may be refractory.In some modalities, the disease or condition may be a leukemia that includes, but is not limited to: acute myeloid leukemia (AML) (which includes its subtypes, such as, TP53 subtypes of wild-type AML, TP53 mutant AML, refractory AML, acute promyelocytic leukemia, acute basophilic leukemia and therapy-related AML), chronic lymphocytic leukemia (CLL) (which includes, but is not limited to, hairy cell leukemia and small lymphocytic lymphoma), acute lymphoblastic leukemia (ALL) (which includes, but is not limited to, B-cell, T-cell and ETP specification) and chronic myeloid leukemia (CML) (chronic myelogenous leukemia). In some cases, the disease or condition may be a myelodysplastic syndrome. In some cases, the disease or condition may be a myeloproliferative neoplasm (MPN), such as polycythemia vera (PV), myelofibrosis (MF), and essential thrombocythemia (ET). As described herein, a combination of the compounds described herein may be used to treat and / or ameliorate lymphoma. Illustrative lymphomas include, but are not limited to, non-Hodgkin lymphoma (NHL) (including, but not limited to, mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), peripheral T-cell lymphoma, cutaneous T-cell lymphoma, NK-cell lymphoma, Burkitt lymphoma, and Waldenstrom macroglobulinemia). A combination of compounds, including pharmaceutically acceptable salts thereof, may also be used to treat myeloma. Examples of myelomas that can be treated include, but are not limited to, multiple myeloma (MM) (which includes, but is not limited to, translocation (11;14) and non-translocation (11;14)).As described herein, a combination of compounds described herein may be used to treat and / or improve systemic mastocytosis and blastic plasmacytoid dendritic cell neoplasm. A disease or condition described herein may occur in an adult or pediatric subject. In some cases, the subject with the disease or condition, as described herein, may be a pediatric subject. In some cases, the disease or condition may be a pediatric hematologic malignancy, for example, pediatric AML and / or pediatric ALL. ML / 04 / o A combination of compounds described herein may be used to treat and / or enhance a solid tumor. For example, in some modalities, the solid tumor may be selected from an Ewing tumor and a Wilms cancer. Additional examples of a solid tumor that may be treated by a combination of compounds described herein, including pharmaceutically acceptable salts thereof, are bladder cancer, brain cancer, breast cancer (including, but not limited to, ER+ breast cancer and triple-negative breast cancer), cervical cancer, choriocarcinoma, cerebrospinal cancer, colon cancer, endometrial cancer, esophageal cancer, gallbladder / bile duct cancer, head and neck cancer (including oral cancer), hepatocellular cancer, lung cancer (including non-small cell lung cancer and small cell lung cancer), mesothelioma, ovarian cancer, and osteosarcoma.Pancreatic cancer, penile cancer, anal cancer, prostate cancer, small cell carcinoma, stomach cancer, rectal cancer, renal pelvis / ureter cancer, skin cancer, soft tissue sarcoma, stomach cancer, testicular cancer, thyroid cancer, uterine corpus cancer, and uterococcal cancer. In some forms, the disease or condition may be a cancer that expresses the Bel-2 protein. As used in this description, a “subject” refers to an animal that is the object of treatment, observation, or experimentation. “Animal” includes cold-blooded and warm-blooded vertebrates and invertebrates, such as fish, crustaceans, reptiles, and, in particular, mammals. “Mammal” includes, but is not limited to, mice, rats, rabbits, guinea pigs, dogs, cats, sheep, goats, cows, horses, primates such as monkeys, chimpanzees, and apes, and, in particular, humans. In some modalities, the subject may be a human. In some modalities, the subject may be a child and / or infant, for example, a child or infant with a fever. In other modalities, the subject may be an adult. As used in this description, the terms “treat,” “treating,” “treatment,” “therapeutic,” and “therapy” do not necessarily mean the cure or complete elimination of the disease or condition. Any relief from any unwanted sign or symptom of the disease or condition, to any degree, may be considered treatment and / or therapy. In addition, treatment may include actions that could worsen the subject’s appearance or overall well-being. The term “effective amount” is used to indicate the quantity of an active compound, or pharmaceutical agent, that elicits the indicated biological or medicinal response. For example, an effective amount of the compound, salt, or composition may be the amount necessary to prevent, alleviate, or improve the symptoms of the disease or condition, or to prolong the survival of the subject being treated. This response may occur in a tissue, system, animal, or human and includes the relief of the signs or symptoms of the disease or condition being treated. Determining an effective amount is within the capabilities of those skilled in the art, based on the description provided herein. The effective amount of the compounds described herein required as a dose will depend on the route of administration, the type of animal (including humans) being treated, and the specific physical characteristics of the animal in question.The dose may. ML / 04 / or adapt to achieve a desired effect, but will depend on factors such as weight, diet, simultaneous medication and other factors that will be recognized by experts in the medical technique. For example, an effective amount of a compound or radiation is the amount that results in: (a) the reduction, relief, or disappearance of one or more symptoms caused by cancer, (b) the reduction of tumor size, (c) the elimination of the tumor, and / or (d) the long-term stabilization (growth arrest) of the tumor. The amount of compound, salt, and / or composition required for treatment will vary not only with the specific compound or salt selected, but also with the route of administration, the nature and / or symptoms of the disease or condition being treated, and the patient's age and condition, and will ultimately be determined by the treating physician or clinician. When administering a pharmaceutically acceptable salt, dosages may be calculated on a free basis. As those skilled in the art will understand, in certain situations it may be necessary to administer the compounds described herein in amounts that exceed, or even greatly exceed, the dosage ranges described herein to effectively and aggressively treat particularly aggressive diseases or conditions. As will be readily apparent to someone skilled in the art, the effective in vivo dosage to be administered and the particular mode of administration will vary depending on age, weight, severity of the ailment, the mammalian species being treated, the specific compounds used, and the specific application for which these compounds are used. A person skilled in the art can determine the effective dosage levels—that is, the dosage levels required to achieve the desired outcome—by using routine methods, such as human clinical trials, in vivo studies, and in vitro studies. For example, the effective dosages of Compounds (A) and / or (B), or pharmaceutically acceptable salts of either, can be determined by comparing their in vitro activity with their in vivo activity in animal models.Such a comparison can be made by comparing it to an established drug, such as cisplatin and / or gemcitabine. The dosage and dosing interval can be individually adjusted to provide plasma levels of the active ingredient sufficient to maintain modulating effects, or the minimum effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vivo and / or in vitro data. The dosages required to achieve the MEC will depend on individual characteristics and the route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations. Dosing intervals can also be determined using the MEC value. Compositions should be administered using a regimen that maintains plasma levels above the MEC for 10–90% of the time, preferably between 30–90%, and ideally between 50–90%.In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to the plasma concentration. MA / t / ZUZZ / UO 04 f ó It should be noted that the treating physician should know how and when to terminate, discontinue, or adjust administration due to toxicity or organ dysfunction. Likewise, the treating physician should also know how to adjust the treatment to higher levels if the clinical response is inadequate (excluding toxicity). The magnitude of a dose administered in the treatment of the disorder of interest will vary with the severity of the disease or condition being treated and the route of administration. The severity of the disease or condition can, for example, be assessed, in part, using standard prognostic evaluation methods. Furthermore, the dose, and possibly the frequency of dosing, will also vary according to the age, body weight, and response of the individual patient. A comparable program to the one described above may be used in veterinary medicine. The compounds, salts, and compositions described herein can be evaluated using known methods to determine efficacy and toxicity. For example, the toxicology of a particular compound, or a subset of compounds sharing certain chemical entities, can be established by determining in vitro toxicity to a cell line, such as a mammalian cell line, and preferably a human cell line. The results of such studies are frequently predictive of toxicity in animals, such as mammals, or more specifically, humans. Alternatively, the toxicity of particular compounds in an animal model, such as mice, rats, rabbits, dogs, or monkeys, can be determined using known methods. The efficacy of a particular compound can be established using various recognized methods, such as in vitro methods, animal models, or clinical trials in humans.When selecting a model to determine efficacy, the expert can be guided by the state of the art to choose an appropriate model, dose, route of administration and / or regimen. Examples The following examples, which are in no way intended to limit the scope of the claims, describe other modalities in greater detail. CTG Trial Cell proliferation was measured using the CelITiter-Glo® luminescent cell viability assay. The assay involved the addition of a single reagent (CelITiter-Glo® reagent) directly to cells cultured in serum-supplemented medium. DMS-53 cells (ATCC, CRL-2062) were cultured according to ATCC recommendations and seeded at 20,000 cells per well. Each compound evaluated was prepared as a DMSO stock solution (10 mM). The compounds were tested in duplicate on each plate, using the concentration indicated in Table 2. The compound treatment (10.0 μL) was added to the cells ML / 04 f or from a 10x stock concentration of each compound. Plates were incubated at 37 °C, 5% CO2 for 72 h and then equilibrated at room temperature for approximately 30 min. An equal volume of CelITiter-Glo® reagent (100 µL) was added to each well. Plates were mixed for 2 min on an orbital shaker to induce cell lysis and then incubated at room temperature for 10 min to stabilize the luminescence signal. Luminescence was recorded using an M5e SpectraMAX plate reader, according to the CelITiter-Glo protocol. The percentage of inhibition was calculated using the following formula: % inhibition = (RLU*100 / (background cell RLU)). Figure 3 and Table 2 illustrate that the addition of Compound 3 to Compound 1A (alternatively referred to as “Compound 1 A” throughout the specification and figures) resulted in combination efficiency. MA / 04 f or Table 2 DMS-53 Concentration (uM) Inhibition (%) Compound 3 370 52 Compound 1A 650 33 Compound 3 + Compound 1A 370 + 650 74 Xenograft tumor model MV4-11 cells were cultured in vitro in IMDM medium supplemented with 10% fetal bovine serum at 37°C in a 5% CO2 atmosphere. Cells that grew in an exponential growth phase were collected and counted for tumor inoculation. Mice were inoculated subcutaneously in the right flank with MV4-11 cells using a single-cell suspension of 95% viable tumor cells (1 × 10⁷) in 100 µL IMDM without serum for tumor development. Treatment began when the mean tumor size reached approximately 230 mm³, with individual tumor sizes ranging from 200–260 mm³.The animals were randomly assigned to treatment groups of 10 animals each and dosed orally for 21 days as follows: the vehicle at the same volume as single-agent treatment; Compound 1A at 60 mg / kg, Compound 3 at 25 mg / kg, and the combination treatment of Compound 1A (60 mg / kg) and Compound 3 (25 mg / kg). Tumor volumes were assessed twice weekly to estimate tumor volume over time, and mice were weighed twice weekly as a surrogate for detecting signs of toxicity. Tumor growth inhibition (TGI) was calculated using the following equation: TGI = (1-(Td - T0) / (Cd - C0)) × 100%. Td and Cd are the mean tumor volumes of the treated and control animals, and T0 and C0 are the mean tumor volumes of the treated and control animals at the beginning of the experiment.Figure 4 illustrates that treatment with a single agent of Compound 1A at 60 mg / kg resulted in minor inhibition of tumor growth (20%), while treatment with a single agent of Compound 3 resulted in efficacy of approximately 50%. In Figure 4, the bottom row (squares) represents data for the combination of Compound 3 (25 mg / kg) and Compound 1A (60 mg / kg), and the third row at the bottom (squares) represents data for Compound 1A (60 mg / kg). The combination of Compound 3 (25 mg / kg) and Compound 1A (60 mg / kg) exhibited significant tumor growth inhibition (TGI) on day 22, demonstrating that a combination of a Bcl-2 inhibitor and a WEE1 inhibitor described herein can be used to treat the disease or condition described herein. Furthermore, although the foregoing has been described in some detail through illustrations and examples for the sake of clarity and understanding, those skilled in the art will understand that numerous and diverse modifications can be made without deviating from the spirit of this description. Therefore, it should be clearly understood that the forms described herein are merely illustrative and are not intended to limit the scope of this description, but rather encompass all modifications and alternatives that come with the true scope and spirit of the description.

Claims

1. Use of a combination of compounds to prepare a medicament to treat a disease or condition, wherein the combination includes an effective amount of Compound (A) and an effective amount of one or more of Compound (B), or a pharmaceutically acceptable salt thereof, wherein: Compound (A) has the structure: ML / 04V or wherein: R1 is selected from the group consisting of hydrogen, halogen and a substituted or unsubstituted Ci-Ce alkyl; ring A is selected from the group consisting of a substituted or unsubstituted phenyl and a substituted or unsubstituted 5-6 membered monocyclic heteroaryl; ring B is selected from the group consisting of a substituted or unsubstituted 5-7 membered monocyclic carbocyclyl and a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl; (R3)m is a compound R2 selected from the group consisting of YX, Y2 and R5; m is 0, 1, 2 or 3;R3 is selected from the group consisting of a halogen and a substituted or unsubstituted Ci-Ce alkyl; X is selected from the group consisting of hydrogen, halogen, hydroxy, cyano, a substituted or unsubstituted 4-6 membered monocyclic heterocycle, a substituted or unsubstituted amine (CrCe alkyl), a substituted or unsubstituted -NH-(CH2)i-6-amine, a monosubstituted amine, a disubstituted amine, an amino, a substituted or unsubstituted C3-Ce alkyl, a substituted or unsubstituted C3-C6 alkoxy, a substituted or unsubstituted C3-C6 cidoalkoxy, a substituted or unsubstituted acyl (C3-Ce alkyl), a substituted or unsubstituted C-amido, a substituted or unsubstituted N-amido, a substituted or unsubstituted C-carboxyl, a substituted or unsubstituted O-carboxyl, a substituted or unsubstituted O-carbamyl, and a substituted or unsubstituted N-carbamyl. replaced; YesCHoN; Y1 isCR4AoN; Y2 is CR4B or N;Ring C is selected from the group consisting of a substituted or unsubstituted Ce-Cw aryl, a substituted or unsubstituted 5-10 member monocyclic heteroaryl, a substituted or unsubstituted 5-7 member monocyclic carbocyclyl, a substituted or unsubstituted MA / 04 / O 5-7 member monocyclic heterocyclyl, and a substituted or unsubstituted 7-10 member bicyclic heterocyclyl; R4A and R4B are independently selected from the group consisting of hydrogen, halogen, and an unsubstituted CM alkyl; and R5 is a substituted or unsubstituted 5-7 member monocyclic heterocyclyl; and one or more of Compound (B) is a Bcl-2 inhibitor, or a pharmaceutically acceptable salt thereof; wherein the Bcl-2 inhibitor is selected from the group consisting of AZD0466, or a pharmaceutically acceptable salt thereof.

2. Use in accordance with claim 1, wherein Compound (A) is selected from the group consisting of: or a pharmaceutically acceptable salt of any of the foregoing.

4. Use in accordance with any one of claims 1-3, wherein the hematologic malignancy is acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).

5. Use in accordance with claim 4, wherein the hematologic malignancy is non-Hodgkin lymphoma.

6. Use in accordance with claim 4, wherein the hematologic malignancy is multiple myeloma and blastic plasmacytoid dendritic cell neoplasm.

7. Use in accordance with any one of claims 1-3, wherein the disease or condition is a solid tumor.

8. Use according to claim 7, wherein the disease or condition is selected from the group consisting of bladder cancer, brain cancer, breast cancer, cervical cancer, choriocarcinoma, cerebrospinal cancer, colon cancer, endometrial cancer, esophageal cancer, gallbladder / bile duct cancer, head and neck cancer (including oral cancer), hepatocellular cancer, lung cancer, non-small cell cancer, mesothelioma, ovarian cancer, osteosarcoma, pancreatic cancer, penile cancer, anal cancer, prostate cancer, testicular cancer, small cell cancer, small cell lung cancer, stomach cancer, rectal cancer, renal pelvis / ureter cancer, skin cancer, soft tissue sarcoma, stomach cancer, testicular cancer, thyroid cancer, and uterine body cancer.

9. Use in accordance with claim 8, wherein the disease or condition is breast cancer.

10. Use in accordance with claim 8, wherein the disease or condition is small cell lung cancer.

11. Use in accordance with claim 8, wherein the disease or condition is pancreatic cancer.

12. A combination of compounds comprising an effective amount of Compound (A) and an effective amount of one or more of Compound (B), or a pharmaceutically acceptable salt thereof, for use in treating a disease or condition, wherein: Compound (A) has the structure: wherein: R1 is selected from the group consisting of hydrogen, halogen, and a substituted or unsubstituted CrCe alkyl; ring A is selected from the group consisting of a substituted or unsubstituted phenyl and a substituted or unsubstituted 5-6-membered monocyclic heteroaryl; ring B is selected from the group consisting of a substituted or unsubstituted 5-7-membered monocyclic carbocyclyl and a substituted or unsubstituted 5-7-membered monocyclic heterocyclyl; or R3 is selected from the group consisting of a halogen and a substituted or unsubstituted Ci-Ce alkyl;X is selected from the group consisting of hydrogen, halogen, hydroxy, cyano, a substituted or unsubstituted 4-6 membered monocyclic heterocycle, a substituted or unsubstituted amine (Ci-Ce alkyl), a substituted or unsubstituted -NH-(CH2)u-amine, a monosubstituted amine, a disubstituted amine, an amino, a substituted or unsubstituted Ci-Ce alkyl, a substituted or unsubstituted CrC6 alkoxy, a substituted or unsubstituted C3-C6 cycloalkoxy, a substituted or unsubstituted acyl (Ci-Ce alkyl), a substituted or unsubstituted C-amido, a substituted or unsubstituted N-amido, a substituted or unsubstituted C-carboxyl, a substituted or unsubstituted O-carboxyl, a substituted or unsubstituted O-carbamyl, and a substituted or unsubstituted N-carbamyl; YesCHoN; Y1 is CR4A or N; Y2 is CR4B or N;Ring C is selected from the group consisting of a substituted or unsubstituted Ce-Cw aryl, a substituted or unsubstituted 5-10 member monocyclic heteroaryl, a substituted or unsubstituted 5-7 member monocyclic carbocyclyl, a substituted or unsubstituted 5-7 member monocyclic heterocyclyl, and a substituted or unsubstituted 7-10 member bicyclic heterocyclyl; R4A and R4B are independently selected from the group consisting of hydrogen, halogen, and an unsubstituted Cu alkyl; and R5 is a substituted or unsubstituted 5-7 member monocyclic heterocyclyl; and one or more of Compound (B) is a Bcl-2 inhibitor, or a pharmaceutically acceptable salt thereof; wherein the Bcl-2 inhibitor is selected from the group consisting of AZD0466, or a pharmaceutically acceptable salt thereof.

13. The combination for use according to claim 12, wherein Compound (A) is selected from the group consisting of: or a pharmaceutically acceptable salt of any of the foregoing.

14. The combination for use in accordance with claim 12 or 13, wherein Compound (A) is selected from the group consisting of ΙΧ 1 / = ΧΝχΧ· Ti JOO^ Ti Η Χ-Μ \ Τ°Η 5 F ο F / = ΧΝΧ\ Τι Τ' Η )—Μ / -ν 10 i ο HN^V i XNXX ν^-Λ / = L II ΐ J ,Ν^ Γ I s—ζ Η Τ ΖΖ Ν V d ΟΗ , 15 ΝΝ^ι ο ΤΙ Πη Η >Ν V \ί ΟΗ , 20 >Χ ο ΧΤ Τχ^ Η Τμ 0Η X / X-CFsH 25 ^Ν^ι ο ΧνT| L .Ν. g. JJ .-- Γ II ίι J n^ Γ —1 H XM \^Τθίζ\ 30 XX ν η 0 ν η XN^<^ n^X / = Xn^^~ L II Jn J μ-' L 1 s—^ν^ν^-ν Η X. ΖΖ'Ν V d OH o ^ClXL 1 ΤΙ!. ^N^N^NHH xXp o Χ7^Ί 1 P JJ . L. .NA s^JJ , L ϊ XI ÍI>-r H XN OH H \ ')XH \ °H / 0 H7X I o ι Ν ^ιΆ / Ϊ1 N VA / = 1 XJN^ Γ Η X 1 N^ HLHLV Ó OH, y \\ OH , 0 XN N^rA / = L II ι X p-' HVM (Z \\ OH X / X-CFsH o zx JJ ,— Ti ÍXV^ H Xn v \V OH / \ o O n Va / = n VA / = II x JN^ Γ II x 1 N^ H VM H 3—M i ν XX* 0 Χ^Ί 0 ¡i xTcS^ ¡ TT TT^n^ Η L Η L ΖΖ'Ν Ζ>Ν r Ü ΟΗ V ¿ ΟΗ ΜΛ / t / ¿U¿¿ / U0 0410 ΜΛ / t / ¿U¿¿ / UO 0410 aceptable de cualquiera de los anteriores. MA / 04 / or 15. The combination for use in accordance with any one of claims 12-14, wherein the hematologic malignancy is acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).

16. The combination for use according to claim 15, wherein the hematologic malignancy is non-Hodgkin lymphoma.

17. The combination for use according to claim 15, wherein the hematologic malignancy is multiple myeloma and blastic plasmacytoid dendritic cell neoplasm.

18. The combination for use in accordance with any one of claims 12-14, wherein the disease or condition is a solid tumor.

19. The combination for use according to claim 18, wherein the disease or condition is selected from the group consisting of bladder cancer, brain cancer, breast cancer, cervical cancer, choriocarcinoma, cerebrospinal cancer, colon cancer, endometrial cancer, esophageal cancer, gallbladder / bile duct cancer, head and neck cancer (including oral cancer), hepatocellular cancer, lung cancer, non-small cell cancer, mesothelioma, ovarian cancer, osteosarcoma, pancreatic cancer, penile cancer, anal cancer, prostate cancer, testicular cancer, small cell cancer, small cell lung cancer, stomach cancer, rectal cancer, renal pelvis / ureter cancer, skin cancer, soft tissue sarcoma, stomach cancer, testicular cancer, thyroid cancer, and uterine body cancer.

20. The combination for use in accordance with claim 19, wherein the disease or condition is breast cancer.

21. The combination for use in accordance with claim 19, wherein the disease or condition is small cell lung cancer.

22. The combination for use in accordance with claim 19, wherein the disease or condition is pancreatic cancer.