SELECTIVE CANCER THERAPEUTIC AGENTS CDK4 / 6 INHIBITORS

Abstract

The description discloses selective and potent CDK 4 / 6 inhibitors that exhibit advantageous inhibition of cancer growth, even at low concentrations. One class of CDK 4 / 6 inhibitors refers to substituted pyrrolopyrimidine compounds having a fatty acid moiety and specifically derived from Palbociclib of the general formula [2A], where R1 is hydrogen, aryl, alkyl, alkoxy, cycloalkyl, or heterocyclyl; R2 is hydrogen, halogen, alkyl, acyl, cycloalkyl, alkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, nitrile, or nitro; R3 is hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, or cycloalkyl; yn is an integer from 9 to 20. These compounds can be used as pharmaceutical compounds for anticancer therapies and are useful for the treatment, prevention and / or improvement of cancer.

Description

SELECTIVE CANCER THERAPEUTIC AGENTS CDK4 / 6 INHIBITORS FIELD OF INVENTION This description refers to pharmaceutical compounds for anticancer therapies, and more specifically to substituted pyrrolopyrimidine compounds, substituted pyridopyrimidine compounds and substituted benzimidazole compounds, which as potent inhibitors of CDK 4 / 6 are useful for the treatment, prevention and / or improvement of cancer. BACKGROUND OF THE INVENTION Cancer stem cells (CSCs) are tumor-initiating cells (TICs) that are resistant to conventional cancer therapies, such as chemotherapy and radiation treatment. Consequently, CSCs are responsible for both tumor recurrence and distant metastasis, leading to treatment failure and poor clinical outcomes in cancer patients. Therefore, innovative strategies are needed to understand how to address the challenge posed by CSCs. Mechanistically, this may be related to the ability of CSCs to survive and thrive under adverse conditions and in different microenvironments. Because CSCs are a particularly small subset of the tumor cell population, their metabolic and phenotypic properties have remained largely uncharacterized until recently. On the other hand, CSCs are surprisingly resilient and highly resistant to cellular stress, allowing them to undergo anchorage-independent growth, especially under low-adhesion conditions. As a result, they form 3D spheroids, which retain the properties of both CSCs and stem cell progenitors. In contrast, when subjected to suspension growth, most bulk cancer cells die via anoikis—a specialized type of apoptosis. Thus, clonal propagation from an individual CSC results in the production of a 3D spheroid and does not involve cancer cell self-aggregation. Therefore, 3D spheroid formation is a functional readout for stem cell development in epithelial cancer cells and allows for the enrichment of an epithelioid cell population with a stem cell-like phenotype.These 3D spheroids are also known as mammospheres when prepared using breast cancer cells, such as MCF7, among others. Previously, 3D spheroids have been generated from 2 different ER(+) cell lines (MCF7 and MA / t / ZUZZ / UOZO I4 T47D) and have been subjected to unbiased, label-free proteomic analysis. This work initiated the analysis of the phenotypic behavior of CSCs at the molecular level. The 3D spheroids were directly compared with monolayers from these cell lines and processed in parallel. This allowed for the identification of proteomic elements characteristic of the CSC phenotype in 3D spheroids, relative to monolayers. Based on this molecular analysis, it was observed that the mammospheres are significantly enriched in mitochondrial proteins. These mitochondria-related proteins included molecules involved in beta-oxidation and ketone metabolism / recycling, mitochondrial biogenesis, electron transport, ADP / ATP exchange / transport, CoQ synthesis and ROS production, as well as the suppression of mitophagy.As such, increased synthesis of mitochondrial proteins or decreased mitophagy could allow for the accumulation of mitochondrial mass in CSCs. Given the increases in CSCs, mitochondrial mass is being considered as a novel metabolic biomarker for CSC purification. Using this comprehensive approach, it has been observed that it was possible to significantly enrich CSC activity using only MitoTrackerMR as a single marker for both ER(+)(MCF7) and ER(-)(MDA-MB-231) breast cancer cell lines. Notably, cells high in MitoTrackerMR were found to be chemoresistant to paclitaxel, exhibiting resistance to the paclitaxel-induced DNA damage response. However, what is needed are new pharmaceutical compounds for anticancer therapies that eradicate cancer stem cells (CSCs), prevent or reduce the likelihood of metastasis and / or recurrence, and reduce or eliminate cancer resistance to chemotherapy and other anticancer therapies. Additionally, what is needed are therapeutic strategies and anticancer therapies that specifically target the most adapted CSCs and eliminate further cancer growth, including attachment-independent growth, tumor recurrence, and distant metastasis. SUMMARY OF THE INVENTION Cancer stem cells (CSCs) are now believed to be a major cause of treatment failure in cancer patients worldwide. Mechanistically, this may be related to the ability of CSCs to survive and thrive under harsh conditions and in different microenvironments. The inventors proposed the theory that CSCs could become resistant to conventional therapies by MA / 14 stimulate ATP production using elevated mitochondrial OXIDATIVE PHOSPHORYLATION metabolism. In accordance with this view, a variety of mitochondrial inhibitors successfully blocked the formation of 3D tumor spheres, including i) FDA-approved antibiotics (doxycycline, tigecycline, azithromycin, pyrvinium pamoate, atovaquone, bedaquiline), ii) natural compounds (actinonin, CAPE, berberine, brutieridine, and melitidine), as well as iii) experimental compounds (oligomycin and AR-C155858, an MCT1 / 2 inhibitor), among others. Cyclin-dependent kinases (CDKs) 4 and 6 are known enzymes that promote cell mitosis and meiosis in both normal and cancer cells. These enzymes are responsible for phosphorylating and thus inactivating the retinoblastoma protein, which plays a role in cell cycle progression from the G1 to the S phase. Research has identified abnormalities in cancer cells that increase CDK activity. This increased activity results in the inactivation of several tumor suppressor genes, thereby paving the way for the rapid proliferation of cancer stem cells and tumor growth. Inhibitors have been shown MA / 14 naturally occurring CDK proteins, such as pl6 and p27, inhibit the in vitro growth of lung cancer cell lines. Certain CDK inhibitors can be useful as chemoprotective agents through their ability to inhibit cell cycle progression in normal, non-transformed cells. Targeted inhibition of these enzymes is a potential strategy for anticancer treatments and therapeutic agents, either alone or in combination with other therapies. Blocking the CDK 4 / 6 pathway prevents cells from progressing to the S phase, which leads to cell death via apoptosis. This paper describes three classes of CDK inhibitors, primarily CDK 4 and CDK 6 (CDK 4 / 6) inhibitors, which have strong efficacy as anticancer therapeutic agents. The first class of anticancer CDK 4 / 6 inhibitors consists of substituted pyrrolopyrimidine compounds with a fatty acid moiety. The formula shown below, where 'n' is an integer from 9 to 20, and more preferably from 12 to 20, illustrates some modalities within this first class of anticancer CDK 4 / 6 inhibitors. The second class comprises substituted pyridopyrimidines, which have a fatty acid moiety. The formula shown below, in which 'n' is an integer from 9 to 20, and more preferably from 12 to 20, is illustrative of modalities in the second class of anticancer CDK 4 / 6 inhibitors. The third class comprises substituted benzimidazole compounds, which have a fatty acid moiety. The formula shown below, in which 'm' is an integer from 0-4, and more preferably from 0-2, and 'n' is an integer from 9-20, and more preferably from 12-20, is illustrative of modalities in the third class of anticancer CDK 4 / 6 inhibitors. MA / 4 Compounds in either the first, second, or third class, including their salts, may be used as a pharmaceutical compound for the treatment of cancer. Demonstrative salts include succinate, trifluoroacetate, tartrate, and malate, among others, as will be appreciated by those with a standard level of experience in the field. This statement also provides pharmaceutical formulations that contain a therapeutically effective amount of a compound from either the first, second, or third class, or in some forms, one or more compounds from each class, or therapeutically acceptable salt(s) thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. All such forms are included in this statement. It should be noted that a pharmaceutically acceptable carrier, as known in the field, may be used. The compounds described herein may be used in connection with methods for treating cancer in a mammal, including humans, comprising administering to the mammal a quantity of a compound from either the first, second, or third class, or a pharmaceutically acceptable salt thereof, which is effective in treating this disorder or condition. For example, the present approach is useful for treating abnormal cell proliferation such as cancer. The compounds described herein may be used to treat disorders of abnormal cell proliferation, and in particular a cancer selected from the group consisting of cancers of the breast, ovary, cervix, prostate, testicles, esophagus, stomach, skin, lung, bone, colon, pancreas, thyroid, bile ducts, oral cavity and pharynx, lip, tongue, mouth, pharynx, small intestine, colon-rectum, large intestine, rectum, brain, and central nervous system.glioblastoma, neuroblastoma, keratoacanthoma, squamous cell carcinoma, large cell carcinoma, adenocarcinoma, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, sarcoma, bladder carcinoma, liver carcinoma, kidney carcinoma, myeloid disorders, lymphoid disorders, Hodgkin's disease, hairy cell carcinoma, and leukemia, by administering a therapeutically effective amount of a Class I, Class II, or Class III compound, or a pharmaceutically acceptable salt thereof, to a subject diagnosed with this cancer. In some modalities, the present approach may be used in combination with and / or to increase the effectiveness of other therapies. Some variations of this approach can take the form of a compound that has the general formula R1 is hydrogen, aryl, alkyl of 1 to 8 carbon atoms, alkoxy of 1 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms or heterocyclyl of 3 to 7 carbon atoms; R2 is independently selected from hydrogen, halogen, alkyl of 1 to 8 carbon atoms, acyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, alkoxy of 1 to 8 carbon atoms, alkoxyalkyl of 1 to 8 carbon atoms, haloalkyl of 1 to 8 carbon atoms, hydroxyalkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, nitrile, nitro, OR5, SR5, NR5R6, N(O)R5R6, P(O)(OR5)(OR6), (CR5R6)mNR7R8, COR5, (CR4R5)mC(O)R7, CO2R5, CONR5R6, C (O) NR5SO2R6, NR5SO2R5, C(O)NR5OR6, S(O)nR5, SO2NR5R6, P (O) (OR5) (OR6) , (CR5R6) nP (O) (OR7) (OR8) , (CR5R6) m-aryl, (CR5R6)m-heteroaryl and —CR5=CR6C (O) R7; R3 is independently, in each case, hydrogen, halogen, alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 7 carbon atoms; R5, R6, R7, and R8 are independently hydrogen, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, arylalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or heteroarylalkyl; m is from 0 to 6; and n represents an integer from 9 to 20, and preferably from 12 to 20. In some preferred embodiments, R1 is cyclopentyl and R2 is acetyl. Furthermore, in some embodiments, n is preferably 12. In some embodiments, the present approach may take the form of a pharmaceutical composition that includes a compound as described herein as the active therapeutic agent, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. For example, the composition may be, in some embodiments, a tablet having a core with between 18% and 55% by weight of the active therapeutic agent and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be, for example, microcrystalline cellulose, crospovidone type A, low-substituted hydroxypropylcellulose, magnesium stearate, and colloidal anhydrous silica. The compounds and pharmaceutical compositions described herein possess potency and selectivity toward cancer stem cells that make them suitable for various anticancer therapeutic uses. For example, this approach may take the form of methods to prevent or reduce the proliferation of at least one of the cancer cells, cancer stem cells, and circulating tumor cells, in which a pharmaceutically effective amount of a compound or pharmaceutical composition described herein is administered to a patient in need. The present approach may take the form of methods for treating cancer, in which a patient in need is administered a pharmaceutically effective amount of a compound or pharmaceutical composition as described in this document. The present approach may take the form of methods for treating or preventing metastatic diseases, in which a patient in need of them is administered a pharmaceutically effective amount of a compound or pharmaceutical composition as described in this document. The present approach may take the form of methods to treat or prevent tumor recurrence, in which a patient in need is administered a pharmaceutically effective amount of a compound or pharmaceutical composition as described in this document. The present approach may take the form of methods for reducing resistance to cancer treatment, such as resistance to chemotherapy, in which a patient in need is given a pharmaceutically effective amount of a compound or pharmaceutical composition as described in this document. The present approach may take the form of methods for treating or preventing at least one of the following: resistance to radiation therapy, resistance to chemotherapy, and resistance to hormone therapy, in which a patient in need of these treatments is administered a pharmaceutically effective amount of a compound or pharmaceutical composition as described in this document. It should be appreciated that a person with an ordinary level of experience in the field can apply common methods known in the field to determine the treatment dosage, dosage form, and dosage schedule for a particular modality. The compounds in this formulation can also be used in the manufacture of a drug for a number of therapeutic uses, such as the treatment or prevention of cancer, the treatment or prevention of metastatic disease, and the treatment or prevention of tumor recurrence. The modalities of the present approach can be recognized by those who have ordinary experience in the field, having reviewed the following detailed description. DRAWINGS Figure 1 shows dose response curves comparing Compound [1C] with its precursor compound, using the mammosphere formation assay in the MCF7 cell line. Figure 2 shows dose response curves comparing Compound [2C] with its precursor compound, using the mammosphere formation assay in the MCF7 cell line. Figure 3 is a dose-response curve for the precursor compound of Compound [3C], by means ML / 14 of the use of the mammosphere formation assay in the MCF7 cell line. Figure 4 shows dose response curves comparing Compound [1C] with its precursor compound, using the Hoechst staining assay on the MCF7 cell line. Figure 5 shows dose response curves comparing Compound [2C] with its precursor compound, using the Hoechst staining assay on the MCF7 cell line. Figure 6 is a dose-response curve comparing the precursor compound of Compound [3C], by means of the Hoechst staining assay on the MCF7 cell line. Figure 7 shows dose response curves comparing Compound [1C] with its precursor compound, using the Hoechst staining assay on the hTERT-BJl cell line. Figure 8 shows dose response curves comparing Compound [2C] with its precursor compound, using the Hoechst staining assay on the hTERT-BJl cell line. Figure 9 is a dose-response curve comparing the precursor compound of Compound [3C] , by means of the Hoechst staining assay on the hTERT-BJl cell line. DESCRIPTION The following description includes the methods currently contemplated for carrying out the exemplary embodiments of the present approach. The following description should not be taken in a limiting sense and is made solely for the purpose of illustrating the general principles of the invention. According to the present approach, compounds from three classes of CDK 4 / 6 inhibitors can be used as anticancer therapeutic agents. The first class comprises substituted pyrrolopyrimidine compounds containing a fatty acid moiety. The second class comprises substituted pyridopyrimidine compounds containing a fatty acid moiety. The third class comprises substituted benzimidazole compounds containing a fatty acid moiety. The compounds described herein have useful pharmaceutical and medicinal properties. Many of the compounds exhibit significant selective CDK 4 / 6 inhibitory activity and are therefore valuable in the treatment of a wide variety of clinical conditions in which CDK 4 / 6 kinases are abnormally elevated, or are activated or present in normal amounts and activities, but where inhibition of CDKs is not effective. MA / t / ZUZZ / UOZO I4 is desirable for treating a proliferative cell disorder. In particular, these compounds are promising as anticancer therapeutic agents. The compounds in each class are described under the following definitions, which are applicable to modalities of the present approach. As used in this document, the notation C(O) refers to a carbon-oxygen double bond. The term halo as used in this document means a halogen and includes fluorine, chlorine, bromine, or iodine, bonded as understood in the field. The term alkyl used in this document refers to saturated aliphatic groups, which include straight-chain alkyl groups (e.g., methyl, ethyl, etc.), branched-chain alkyl groups (isopropyl, tert-butyl, etc.), cycloalkyl (alicyclic) groups (cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl), alkyl-substituted cycloalkyl groups, and cycloalkyl-substituted alkyl groups. The term alkyl also includes alkenyl and alkynyl groups. The general formula may use the term alkyl-Cn, where n is an integer from, for example, 1–20, to denote a particular alkyl group (straight-chain or branched) of a particular range or number of carbons in the group. For example, the term MA / 14 C1-C3 alkyl includes, but is not limited to, methyl, ethyl, propyl, and isopropyl. Similarly, the term C3-C6 cycloalkyl includes, but is not limited to, cyclopropyl, cyclopentyl, and cyclohexyl. Alkyl groups, as well as cycloalkyl groups, can be substituted or unsubstituted. Thus, the term alkyl includes both unsubstituted and substituted alkyl, the latter referring to portions that have substituents replacing a hydrogen atom on one or more carbon atoms of the main hydrocarbon structure. The term alkenyl includes unsaturated aliphatic groups that are analogous in length and possible substitution to the alkyl groups described above, but which contain at least one double bond. Alkenyl also includes unsubstituted alkenyls and substituted alkenyls, the latter of which refers to portions that have substituents replacing a hydrogen atom on one or more carbon atoms of the main hydrocarbon structure. For example, the term alkenyl includes straight-chain alkenyl groups (e.g., ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, etc.), branched-chain alkenyl groups, and cycloalkenyl (alicyclic) groups. ML / 14 (cyclopropenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl) includes cycloalkenyl groups substituted with alkyl or alkenyl groups and alkenyl groups substituted with cycloalkyl or cycloalkenyl groups. The term alkenyl also includes alkenyl groups containing oxygen, nitrogen, sulfur, or phosphorus atoms that replace one or more carbon atoms in the main hydrocarbon structure. In certain embodiments, a straight-chain or branched-chain alkenyl group has 6 or fewer carbon atoms in its main structure (e.g., C2-Cg for straight chain, C3-C6 for branched chain). Similarly, cycloalkenyl groups may have 3-8 carbon atoms in their ring structure and more preferably have 5 or 6 carbon atoms in the ring structure. The term C2-Cg includes alkenyl groups containing 2-6 carbon atoms. The term alkynyl includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but which contain at least one triple bond. Furthermore, the term alkynyl includes both unsubstituted and substituted alkynyls, the latter referring to alkynyl portions that have substituents replacing a hydrogen atom on one or more carbons of the main hydrocarbon structure. For example, the term alkynyl includes straight-chain alkynyl groups (e.g., ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, etc.), branched-chain alkynyl groups, and alkynyl groups substituted with cycloalkyl or cycloalkenyl. The term alkynyl further includes alkynyl groups that incorporate oxygen, nitrogen, sulfur, or phosphorus atoms replacing one or more carbon atoms in the main hydrocarbon structure. In certain embodiments, a straight-chain or branched-chain alkynyl group has six or fewer carbon atoms in its main structure (e.g., C2-C6 for straight-chain, C3-C6 for branched-chain). The term C2-C6 includes alkynyl groups containing from two to six carbon atoms. The term substituted is intended to describe portions that have substituents replacing a hydrogen in one or more atoms, for example C, O or N, of a molecule.These substituents may include, for example but are not limited to, alkyl, alkoxy, alkenyl, alkynyl, halo, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxy, phosphate, phosphonate, phosphinate, amino (which includes alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (which includes alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureide), amidyne, imine, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azide, heterocyclyl, alkylaryl, morphol, phenol, benzyl, phenyl, piperizine, cyclopentane, cyclohexane, pyridine, 5H-tetrazol, triazole, piperidine or an aromatic or heteroaromatic portion, and combinations thereof. The terms amine and amino must both refer to a molecule, or a portion or functional group, as generally understood in the field, and can be primary, secondary, or tertiary. The term amine or amino includes compounds where a nitrogen atom is covalently bonded to at least one carbon, hydrogen, or heteroatom. These terms include, for example, but are not limited to, alkylamino, arylamino, diarylamino, alkylarylamino, alkylaminoaryl, arylaminoalkyl, alkaminoalkyl, amide, amido, and aminocarbonyl. The term alkylamino comprises groups and compounds where the nitrogen is bonded to at least one additional alkyl group. The term dialkylamino includes groups where the nitrogen atom is bonded to at least two additional alkyl groups. The terms arylamino and diarylamino include groups where the nitrogen is bonded to at least one or two aryl groups, respectively.The term alkylarylamino, alkylaminoaryl, or arylaminoalkyl refers to an amino group bonded to at least one alkyl group and at least one aryl group. The term alqaminoalkyl refers to an alkyl, alkenyl, or alkynyl group bonded to a nitrogen atom, which is also bonded to an alkyl group. The term amide, amido, or aminocarbonyl includes compounds or portions containing a nitrogen atom bonded to the carbon of a carbonyl or thiocarbonyl group. The term includes alkyaminocarbonyl or alkylaminocarbonyl groups, which consist of alkyl, alkenyl, aryl, or alkynyl groups bonded to an amino group, which is itself bonded to a carbonyl group. It also includes arylaminocarbonyl and arylcarbonylamino groups, which consist of aryl or heteroaryl portions bonded to an amino group, which is itself bonded to the carbon of a carbonyl or thiocarbonyl group. The terms alkylaminocarbonyl, alkenylaminocarbonyl, alkynylaminocarbonyl, arylaminocarbonyl, alkylcarbonylamino, alkenylcarbonylamino, alkynylcarbonylamino, and arylcarbonylamino are all used interchangeably. MA / 4 included in the term amide. Amides also include urea (aminocarbonylamino) and carbamate (oxycarbonylamino) groups. The term aryl includes groups, including single-ring aromatic groups of 5 and 6 members that may contain from zero to four heteroatoms, for example, phenyl, pyrrole, furan, thiophene, tlazole, isothiazol, imidazole, triazole, tetrazole, pyrazole, oxazole, isoxazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like. Additionally, the term aryl includes multicyclic aryl groups, for example, tricyclic and bicyclic groups, such as naphthalene, benzoxazole, benzodioxazole, benzothiazole, benzoimidazole, benzothiophene, methylenedioxyphenyl, quinoline, isoquinoline, anthril, phenantrile, naphthridine, indole, benzofuran, purine, benzofuran, deazapurine, and indolizine. These aryl groups that have heteroatoms in the ring structure may also be referred to as aryl heterocycles, heterocycles, heteroaryls, or heteroaromatics.The aromatic ring can be substituted in one or more ring positions by these substituents as described above, such as alkyl, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkylaminoacarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphonate, phosphinate, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureide), amidyne, imine, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azide, heterocyclyl, alkylaryl or an aromatic or heteroaromatic portion.Aryl groups can also be fused or connected to alicyclic or heterocyclic rings which are not aromatic in order to form a polycycle (e.g., tetralin). The term heteroaryl, as used herein, represents a stable monocyclic or bicyclic ring of up to 7 atoms in each ring, wherein at least one ring is aromatic and contains 1 to 4 heteroatoms selected from the group consisting of O, N, and S. Heteroaryl groups within the scope of this definition include, but are not limited to: acridinyl, carbazolyl, cinolinyl, quinoxalinyl, pyrrazolyl, indolyl, benzotriazolyl, furanyl, thienyl, benzothienyl, benzofuranyl, quinolinyl, isoquinolinyl, oxazolyl, isoxazolyl, indolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, and tetrahydroquinoline. As with the definition of heterocycle below, heteroaryl is also understood to include the N-oxide derivative of any nitrogen-containing heteroaryl.In cases where the heteroaryl substituent is bicyclic and a ring is not aromatic or does not contain heteroatoms, it is understood that the bond is via the aromatic ring or via the ring containing heteroatoms, respectively. The term heterocycle or heterocyclyl, as used herein, is understood to mean a 5- to 10-membered aromatic or non-aromatic heterocycle containing 1 to 4 heteroatoms selected from the group consisting of O, N, and S, and including bicyclic groups. Therefore, heterocyclyl includes the heteroaryls mentioned above, as well as their dihydro and tetrahydro analogues. Additional examples of heterocyclyl include, but are not limited to, the following: benzoimidazolyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyrimidiyl, pyrrolyl.quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, azetidinyl, 1,4-dioxanyl, hexahydroazepinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, dihydrobenzoimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazaolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, Dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, and tetrahydrothienyl, and N-oxides thereof. The attachment of a heterocyclyl substituent can occur via a carbon atom or via a heteroatom. The term acyl includes compounds and portions which contain the acyl radical (CH3CO—) or a carbonyl group. The term substituted acyl includes acyl groups where one or more of the hydrogen atoms are replaced, for example, by alkyl groups, alkynyl groups, halogens, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxy, phosphate, phosphonate, phosphinate, cyano, amino (which includes alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (which includes alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureide), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azide, heterocyclyl, alkylaryl or an aromatic or heteroaromatic portion. The term acylamino includes groups where an acyl group is bonded to an amino group. For example, the term includes alkylcarbonylamino, arylcarbonylamino, carbamoyl, and ureide groups. The term alkoxy includes substituted and unsubstituted alkyl, alkenyl, and alkynyl groups covalently bonded to an oxygen atom. Examples of alkoxy groups include methoxy, ethoxy, isopropyloxy, propoxy, butoxy, and pentoxy groups, and may include cyclic groups such as cyclopentoxy. Examples of substituted alkoxy groups include halogenated alkoxy groups.Alkoxy groups may be substituted by groups such as alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxy, phosphate, phosphonate, phosphinate, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureide), amidyne, imine, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azide, heterocyclyl, alkylaryl or a portion aromatic or heteroaromatic. Examples of halogen-substituted alkoxy groups include, but are not limited to, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy, trichloromethoxy, etc. The term carbonyl or carboxy includes compounds and portions containing a carbon atom double-bonded to an oxygen atom, as well as tautomeric forms thereof. Examples of portions containing a carbonyl group include aldehydes, carboxyl groups, carboxylic acids, amides, esters, and anhydrides. MA / t / ZUZZ / UOZO I4 etc. The term carboxy portion or carbonyl portion refers to groups such as alkylcarbonyl groups where an alkyl group is covalently bonded to a carbonyl group, alkenylcarbonyl groups where an alkenyl group is covalently bonded to a carbonyl group, alkynylcarbonyl groups where an alkynyl group is covalently bonded to a carbonyl group, and arylcarbonyl groups where an aryl group is covalently bonded to the carbonyl group. Additionally, the term also refers to groups where one or more heteroatoms are covalently bonded to the carbonyl portion. For example, the term includes portions such as aminocarbonyl portions (where a nitrogen atom is bonded to the carbon of the carbonyl group, e.g., an amide), and aminocarbonyloxy portions, where an oxygen atom and a nitrogen atom are both bonded to the carbon of the carbonyl group (e.g., also referred to as a carbamate).Additionally, aminocarbonylamino groups (e.g., ureas) are also included, as well as other combinations of carbonyl groups bonded to heteroatoms (e.g., nitrogen, oxygen, sulfur, etc., as well as carbon atoms). Furthermore, the heteroatom may be substituted by one or more alkyl, alkenyl, alkynyl, aryl, aralkyl, acyl, etc. groups. The term thiocarbonyl or thiocarboxyl includes compounds and portions containing a carbon atom double-bonded to a sulfur atom. The term thiocarbonyl portion includes portions analogous to carbonyl portions. For example, thiocarbonyl portions include aminothiocarbonyl, where an amino group is bonded to the carbon atom of the thiocarbonyl group. Other thiocarbonyl portions include oxythiocarbonyls (oxygen bonded to the carbon atom), aminothiocarbonylamino groups, and so on. The term ether includes compounds or portions containing an oxygen atom bonded to two different carbon atoms or heteroatoms. For example, the term includes alkoxyalkyl, which refers to an alkyl, alkenyl, or alkynyl group covalently bonded to an oxygen atom that is covalently bonded to another alkyl group. The term ester includes compounds and portions containing a carbon or a heteroatom bonded to an oxygen atom bonded to the carbon of a carbonyl group. The term ester includes alkoxycarboxyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, and so on. Alkyl, alkenyl, or alkynyl groups are ML / 14 as previously defined. The term thioether includes compounds and portions containing a sulfur atom bonded to two different carbon atoms or heteroatoms. Examples of thioethers include, but are not limited to, alkylthioalkyls, alkylthioalkenyls, and alkylthioalkynyls. The term alkylthioalkyls includes compounds with an alkyl, alkenyl, or alkynyl group bonded to a sulfur atom that is itself bonded to an alkyl group. Similarly, the terms alkylthioalkenyls and alkylthioalkynyls refer to compounds or portions in which an alkyl, alkenyl, or alkynyl group is bonded to a sulfur atom that is covalently bonded to an alkynyl group. The term hydroxy or hydroxyl includes groups with an —OH or —O- . The terms polycycline or polycyclic radical include portions with two or more rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, and / or heterocyclyls) in which two or more carbons are common to two adjacent rings; for example, the rings are fused rings. Rings that are joined through non-adjacent atoms are called connected rings.Each of the rings of the polycycle can be substituted by substituents such as those described above, for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonate, phosphinate, cyano, amino (which includes alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (which includes alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureide), amidyne, imine, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkyl, alkylaryl or an aromatic or heteroaromatic portion. The term heteroatom includes atoms of any element other than carbon or hydrogen. The preferred heteroatoms are nitrogen, oxygen, sulfur, and phosphorus. Additionally, the phrase "any combination thereof" implies that any number of the listed functional groups and molecules can be combined to create a larger molecular architecture. For example, the terms phenyl, carbonyl (or =O), —O—, —OH, and Ci-Cg (i.e., —CH3 and —CH2CH2CH2—) can be combined to form a substituent of 3-methoxy-4-propoxybenzoic acid. It should be understood that when functional groups and molecules are combined to create a larger molecular architecture, hydrogens can be removed or added as needed to satisfy the valency of each atom. The compounds described in this document include bonds between adjacent atoms and / or hydrogens as required to satisfy the valency of each atom, as would be understood by those with a standard level of experience in the field. Bonds and / or hydrogen atoms are added, if necessary, to provide the following total number of bonds for each of the following types of atoms: carbon: four bonds; nitrogen: three bonds; oxygen: two bonds; and sulfur: two to six bonds. The term salt of a compound refers to the corresponding salt prepared by means of the use of an acid selected from the group of mineral acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, metaphosphoric acid, nitric acid and sulfuric acid, and organic acids, such as tartaric acid, acetic acid, trifluoroacetic acid, citric acid, malic acid, lactic acid, fumaric acid, benzoic acid, glycolic acid, gluconic acid and succinic acid, and alkylsulfonic acids such as methanesulfonic acids, ethanesulfonic acids, ethane-1,2-disulfonic acid and 2-hydroxyethanesulfonic acid and arylsulfonic acids such as benzenesulfonic acid, 2-naphthalenesulfonic acid, p-toluenesulfonic acid and naphthalene-1,5-disulfonic acid. The phrase "pharmaceutically effective amount" as used herein indicates the amount necessary to administer to a host, or to a cell, tissue, or organ of a host, to achieve a therapeutic result, such as the regulation, modulation, or inhibition of protein kinase activity, for example, inhibition of protein kinase activity, or the treatment of cancer. A physician or veterinarian with ordinary experience in the field can readily determine and prescribe the required effective amount of the pharmaceutical composition. For example, the physician or veterinarian could start dosing the compounds of the invention employed in the pharmaceutical composition at levels lower than those required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.For example, common and well-established methods in the field can be used to determine both the maximum tolerable dose of a compound and the effective dose that provides a detectable therapeutic benefit to an individual in need. Similarly, common and well-established methods in the field can be used to determine the dose and dosing schedule for administering sufficient therapeutic agent to provide a detectable therapeutic benefit. The illustrative dosage examples presented herein do not in any way limit the potential dosages and dosing schedules that may be provided in accordance with this approach. The term "approximately" means that a value falls within an accepted standard error of the mean, as considered by a person of ordinary experience in the field. As might be expected, the meaning of "approximately" depends on the context in which it is used. Frequently, the term "approximately" can refer to ±5%, preferably +2.5%, and more preferably ±1% of the value or interval to which it refers. For example, in the context of weight fractions, the phrase "approximately 20%" can mean 20% ± 5%, preferably 20% ± 2.5%, and more preferably 20% ± 1%. The terms treat, treated, treating, and treatment include the reduction or relief of at least one symptom associated with or caused by the condition, disorder, or disease being treated, particularly cancer. In certain modalities, treatment comprises reducing and / or relieving at least one symptom associated with or caused by the cancer being treated, by the compound of the invention. For example, treatment may be the reduction of one or more symptoms of a cancer or the complete eradication of a cancer. The compounds described in this document include what this description refers to as a fatty acid portion. As used herein, a fatty acid is a carboxylic acid with an aliphatic side chain, which may be saturated or unsaturated, although saturated chains are preferred. Examples of saturated fatty acids include lauric acid (CH3(CH2)10COOH), palmitic acid (CH3(CH2)14COOH), stearic acid (CH3(CH2)18COOH), and myristic acid (CH3(CH2)12COOH). Oleic acid (CH3(CH2)7CH=CH(CH2)7COOH) is an example of a naturally occurring unsaturated fatty acid. Reference may also be made to the salt or ester of a fatty acid, as well as its fatty amide portion, but for simplicity, these are included under the meaning of the fatty acid portion as used herein. For example, myristic acid can be referred to as myristate and oleic acid can be referred to as oleate.A fatty acid moiety can also be a fatty acid carboacyl group, that is, a group formed by the loss of a hydroxyl group from a carboxylic acid. In some formulations, a fatty acid moiety can be linked to a therapeutic agent via an amide bond. For example, a myristic acid conjugate may have a fatty acid moiety CH3(CH2)12CO-NH-, where the tertiary nitrogen is linked to the therapeutic agent. EITHER CH3(CH2)n-^''N / ,zH yn is an integer from 1 to 20 and is preferably from 10 to 20. This can result when the myristate portion is conjugated through myristoylation, resulting in a tetradecanamide (or myristamide) group. Substituted pyrrolopyrimidine compounds In some embodiments of the present approach, a first class of anticancer CDK 4 / 6 inhibitors consists of substituted pyrrolopyrimidine compounds and pharmaceutically acceptable salts thereof. It should be noted that some compounds in the first class are derivatives of the precursor compound 7cyclopentyl-N,N-dimethyl-2-[(5-piperazin-l-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidin-6-carboxamide, also known as Ribociclib. Some embodiments in the first class have the chemical structure shown in the general formula [1A] below, in which a fatty acid moiety is linked to the piperazine. [1A] As used in the general formula [1A]: R4 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, substituted alkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, substituted cycloalkyl of 3 to 8 carbon atoms, aryl, substituted aryl, heteroaryl and substituted heteroaryl; Z is CRZ in which Rz is selected from the group consisting of halo, hydrogen, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, CN, C=NOH, C=NOCH3, C(O)H, C(O)-alkyl —Ci —C3, cycloalkyl of 3 to 8 carbon atoms, heterocyclyl, aryl, heteroaryl, substituted alkyl of 1 to 3 carbon atoms, substituted cycloalkyl of 3 to 8 carbon atoms, substituted heterocyclyl, substituted aryl, substituted heteroaryl, —B—NRaRb, —B—ORa, —B—C (O) Ra, —B—C (O) ORa, —B—C(O)NRaRa; wherein B is either a bond, an alkyl of 1 to 3 carbon atoms, or a branched alkyl of 1 to 3 carbon atoms; and each of Ray Rbse independently selects from the group consisting of hydrogen, 1 to 3 carbon atom alkyl, 3 to 8 carbon atom cycloalkyl, heterocyclyl, aryl, heteroaryl, substituted alkyl, substituted cycloalkyl, substituted heterocyclyl, substituted aryl, and substituted heteroaryl;and in the fatty acid portion, 'n' represents an integer from 9 to 20 and is preferably 12-20.; It should be noted that pharmaceutically acceptable salts can also be used. As mentioned earlier, salts can be prepared using an acid selected from mineral acids, organic acids, alkylsulfonic acids, ethanesulfonic acids, and arylsulfonic acids, for example. In some preferred embodiments of the present approach, a first class of anticancer CDK 4 / 6 inhibitors are compounds having the general formula [IB] shown below. In these embodiments, R4 is a 5-carbon cycloalkyl group, Z is a dimethylcarboxamide or acetyl group, and n represents an integer from 9 to 20, and more preferably from 12 to 20. The precursor compound of this general formula is Ribociclib, an EDA-approved pharmaceutical used to treat HER2-negative, HR-positive advanced or metastatic breast cancers (with an aromatase inhibitor).However, the embodiments of the present formulation according to formula 1[A] have a fatty acid moiety of 11 to 22 carbon atoms conjugated to the terminal piperazine. Preferably, the fatty acid moiety is linear and saturated. In some preferred embodiments, the fatty acid moiety is one of lauric acid, myristic acid, palmitic acid, or stearic acid. The fatty acid moiety significantly enhances cellular uptake of the compound, thereby greatly increasing its inhibition of cancer stem cell proliferation and its selectivity for tumor cells. A demonstrative formulation is shown below as Compound [1C], in which R4 is an unsubstituted 5-carbon cycloalkyl group, Z is a dimethylcarboxamide, and n is 12. As a result, this formulation has a 14-carbon fatty acid moiety (i.e., myristate). The compound shown as Compound [1C] has been synthesized and, in the mammosphere assay, showed markedly enhanced inhibition of MCF7 cells compared to the known anticancer therapeutic Ribociclib at concentrations from 1 μM to 100 μM, demonstrating the remarkable impact of the fatty acid moiety on the compound. In preliminary laboratory evaluations, this formulation effectively inhibited 100% cell proliferation at concentrations as low as 1 μM, demonstrating excellent anticancer efficacy.For example, Figure 1 shows dose-response curves for Compound [1C] and its precursor compound, illustrating the enhanced CSC inhibition resulting from the addition of the fatty acid portion. It should be appreciated that similar results are expected for other fatty acid portions ranging from as few as 11 carbons to as many as 22 carbons. In some embodiments of the present approach, a first class of anticancer CDK 4 / 6 inhibitors are substituted pyrrolopyrimidine compounds as shown below in the general formula [ID]. Compared to general formula [1A], compounds having the general formula [ID] include a fatty acid portion at Z. It should be noted that pharmaceutically acceptable salts may also be used. [ID] As used in the general formula [ID]: R4 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, substituted alkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, substituted cycloalkyl of 3 to 8 carbon atoms, aryl, substituted aryl, heteroaryl and substituted heteroaryl; R3 is selected from the group consisting of hydrogen, OH, alkyl of 1 to 8 carbon atoms, substituted alkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, C(0) alkyl-Cq-Cg, haloalkyl of 1 to 8 carbon atoms, cyanoalkyl of 1 to 8 carbon atoms, alkyl Ci-Cg-OH, SO2-alkyl of 1 to 8 carbon atoms, alkyl-Ci-Cg-cycloalkyl-Cs-Cg and alkoxy of 1 to 8 carbon atoms, which may be substituted or unsubstituted when R3 is not hydrogen; and in the fatty acid portion, 'n' represents an integer from 9 to 20 and is preferably 12-20. In preferred embodiments of the present approach, a first class of anticancer CDK 4 / 6 inhibitors are compounds having the general formula [1E] shown below. In these embodiments, R4 is a 5-carbon cycloalkyl group, R3 is hydrogen, and n represents an integer from 9 to 20, and more preferably 10⁻²⁰, and more preferably 10⁻¹⁶. The compounds having the general formula [1E] are derivatives of Ribociclib, in which a fatty acid portion replaces the dimethyl-amino group at the carboxyl group. A demonstrative embodiment is shown below in the formula of Compound [1F], in which R4 is an unsubstituted 5-carbon cycloalkyl group, R3 is hydrogen, and n is 12. As a result, this embodiment has a 14-carbon fatty acid portion (i.e., myristate). Compound [1F] is expected to show enhanced inhibition in the mammosphere assay. [1F] Table 1 below summarizes the results for several assays comparing Compound [1C] and its precursor compound (Ribociclib) and contains the in vitro biological data for both compounds. Compound [1C] showed a 7-fold improvement in potency in the 3D mammosphere assay (IC50 of approximately 0.2 vs. approximately 1.5 μM) when compared to the precursor compound, while retaining similar activity in the 2D cell viability assay (IC50 of approximately 2 μM for both compounds). This demonstrates that conjugation with a fatty acid moiety greatly improves not only potency in the 3D mammosphere assay. Comparison of mammosphere monolayer selectivity indices (SI) shows that conjugation also improves selectivity to mammospheres (SI 10 vs. 1.3).Both compounds were non-toxic in the hTERT-BJl non-tumor cell line up to a concentration of 90 μM, indicating high selectivity toward the tumor cell line. As can be seen, the compounds, according to the present approach, result in significantly improved potency and selectivity toward humoral cells. ML / 14 IC50 IC50 SI (mammosphere / IC50 SI Compound (mammosphere (monolayer of monolayer of (monolayer of (monolayer of of MCF7) MCF7) MCF7) of BJ1) BJ1 / MCF7) Ribociclib 1.5± 1.0 pM 2.0 ± 0.7 pM 1.3 > 90 pM >45 Compound 0.2 ±0.1 pM 2.0 ± 1.0 pM 10 > 90 pM >45 [1C] TABLE 1. Resulfates from the mammosphere test for the demonstrative compound in the first class. As used in the tables, IC50 (mammosphere of MCF7 refers to the semi-maximal inhibitory concentration in the 3D mammosphere assay using the ER+ breast cancer cell line, MCF7. The term IC50 (MCF7 monolayer) refers to the semi-maximal inhibitory concentration in the 2D cell viability assay using the ER+ breast cancer cell line, MCF7. The term IC50 (BJ1 monolayer) refers to the semi-maximal inhibitory concentration in the 2D cell viability assay using the immortalized non-humoral fibroblast cell line, hTERT-BJ1. The term SI (mammosphere / MCF7 monolayer) refers to the mammosphere selectivity index, a ratio between the values IC50 values ​​compare biological activity in 3D and 2D assays against MCF7. The term SI (BJ1 / MCF7 monolayer) refers to the cancer selectivity index, a ratio between IC50 values ​​that compares biological activity in cell viability assays against MCF7 and hTERT-BJ1. Substituted pyridopyrimidine compounds The second class comprises substituted pyridopyrimidines, which have a fatty acid moiety, as shown in the general formula [2A] below. It should be noted that some forms in the second class comprise derivatives of 6-acetyl-8-cyclopentyl-5-methyl-2(5-piperazin-l-yl-pyridin-2-ylamino)-8H-pyrido[2,3d]pyrimidin-7-one, also known as Palbociclib. It should also be noted that pharmaceutically acceptable salts, such as those identified above, may also be used, as would be understood by those with an ordinary level of experience in the field. Other exemplary salts include malate, tartarate, bromide, hydrogen bromide dihydrate, hydrogen chloride, sulfate dihydrate, camsylate, napsilate, napsilate dihydrate, tosylate, citrate monohydrate, maleate, and oxalate. [2A] MA / t / ZUZZ / UOZO I4 In the general formula 2[A]: R1 is hydrogen, aryl, alkyl of 1 to 8 carbon atoms, alkoxy of 1 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms or heterocyclyl of 3 to 7 carbon atoms; R2 is independently selected from hydrogen, halogen, alkyl of 1 to 8 carbon atoms, acyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, alkoxy of 1 to 8 carbon atoms, alkoxyalkyl of 1 to 8 carbon atoms, haloalkyl of 1 to 8 carbon atoms, hydroxyalkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, nitrile, nitro, OR5, SR5, NR5R6, N(O)R5R6, P (O) (OR5) (OR6), (CR5R6) mNR7R8, COR5, (CR4R5) mC (O) R7, CO2R5, CONR5R6, C (O) NR5SO2R6, NR5SO2Rs, C(O)NR5OR6, S (O) nR5, SO2NR5R6, P (O) (OR5) (OR6) , (CR5R6)nP (O) (OR7) (OR8) , (CR5R6) m-aryl, (CR5R6)m-heteroaryl and —CR5=CR6C (O) R7; R3 is independently, in each case, hydrogen, halogen, alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 7 carbon atoms; R5, R6, R7 and R8 are independently hydrogen, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, arylalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or heteroarylalkyl; m is from 0 to 6; and in the fatty acid portion, n represents an integer from 9 to 20 and preferably is 12-20. Shown below as the general formula [2B], a general formula for preferred embodiments of the second class according to the present approach is found. In the general formula [2B], R1 is an unsubstituted 5-carbon cycloalkyl, R2 is a 1-carbon acyl (acetyl), R3 is a methyl, and n represents an integer from 9 to 20 and more preferably from 12 to 20. [2B] A demonstrative embodiment of the second class is shown below in the formula of Compound [2C], in which R1 is an unsubstituted 6-carbon cycloalkyl group, R2 is a 1-carbon acyl group (acetyl), R3 is a methyl group, and n is 12. As a result, this embodiment has a 14-carbon fatty acid moiety (i.e., myristate). Compound [2C] has been synthesized and, in the mammosphere assay, showed markedly improved inhibition of MCF7 cells compared to the known anticancer therapeutic Palbociclib at concentrations from 1 μM to 100 μM. These results also show that, for the second class of compounds according to the present approach, the fatty acid moiety has a significant beneficial impact on the compound's anticancer efficacy.For example, Figure 2 shows dose-response curves for Compound [2C] and its precursor compound and illustrates the enhanced CSC inhibition resulting from the addition of the fatty acid portion. It should be appreciated that similar results are expected for other fatty acid portions ranging from as few as 11 carbons to as many as 22 carbons. The second class also comprises substituted pyridopyrimidines, which have a fatty acid portion, as shown in the general formula [2D] below. As can be seen, the fatty acid portion in formula [2D] is conjugated to pyrido[2,3d]pyrimidine, unlike piperazine as seen in formula [2A]. In the general formula 2[D]: R1 is hydrogen, aryl, alkyl of 1 to 8 carbon atoms, alkoxy of 1 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms or heterocyclyl of 3 to 7 carbon atoms; R2 is selected from hydrogen, halogen, alkyl of 1 to 8 carbon atoms, acyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, alkoxy of 1 to 8 carbon atoms, alkoxyalkyl of 1 to 8 carbon atoms, haloalkyl of 1 to 8 carbon atoms, hydroxyalkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, nitrile, nitro, OR5, SR5, NR5R6, N(O)R5R6, P(O)(OR5)(OR6), (CR5R6)mNR7R8, COR5, (CR4R5)mC(O)R7, CO2R5, CONR5R6, C(O)NR5SO2R6, NR5SO2R6, C(O)NR5OR6, S(O)nR5, SO2NR5R6, P (O) (OR5) (OR6), (CR5R6)nP (O) (OR7) (OR8), (CR5R6) m-aryl, (CR5R6)m-heteroaryl, and —CR5=CR6C (O) R7; R3 is independently, in each case, hydrogen, halogen, alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 7 carbon atoms; R5, R6, R7 and R8 are independently selected from hydrogen, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, arylalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or heteroarylalkyl; m is from 0 to 6; and in the fatty acid portion, n represents an integer from 9 to 20 and is preferably 12-20. Shown below as the general formula [2E] are examples of another preferred modality of the second class according to the present approach. In the general formula [2E], R1 is an unsubstituted 5-carbon cycloalkyl, R2 is H, R3 is methyl and n represents an integer from 9 to 20 and more preferably from 12-20. (CH2)nCH3 A demonstrative modality of the second class is shown below in the formula of Compound [2F], in which R1 is an unsubstituted 5-carbon cycloalkyl (e.g., cyclopentyl), R2 is H, R3 is methyl and n is 12. As a result, this modality has a 14-carbon fatty acid portion (i.e., myristate). (CH2)12CH3 Table 2 below summarizes the results for several assays comparing Compound [2C] and its precursor compound (Palbociclib) and contains the in vitro biological data for both compounds. The results show that Compound [2C] had reduced potency in the 3D mammosphere assay (IC50 of approximately 5.1 vs. approximately 0.2 μM) when compared to the precursor compound Palbociclib. However, Compound [2C] was non-toxic in the 2D cell viability assay up to a concentration of 30 μM, while Palbociclib showed an IC50 of approximately 0.1 μM. Furthermore, Palbociclib was not selective when comparing the 2D and 3D MCF7 assays. These results show that Compound [2C] demonstrates improved selectivity for 3D mammospheres, unlike normal cells.Thus, it should be noted that the compounds in this formulation can be used to selectively target cancer cells, and in particular, CSCs. Both compounds were non-toxic to the non-tumor cell line hTERT-BJl up to a concentration of 90 μM, representing high selectivity for the tumor cell line. Therefore, the compounds in the second class of this formulation show increased selectivity for targeting cancer stem cells. ICso IC50 SI (mammosphere / IC50 bSI Compound (mammosphere (monolayer monolayer of (monolayer (monolayer of of MCF7) of MCF7) MCF7) of BJ1) BJ1 / MCF7) Palbociclib 0.2 ± 0.2 pM 0.1 ±0.2 pM Non-selective > 90 pM > 900 Compound 5.1 ± 1.0 pM > 30 pM >5 > 90 pM [2C] TABLE 2. Results of the mammosphere test for the demonstration compound of the second class. Substituted benzimidazole compounds A third class comprises substituted benzimidazole compounds having the general formula [3A], shown below. It should also be noted that pharmaceutically acceptable salts, such as those identified above, may also be used, as would be understood by those with an ordinary level of experience in the field. It should be noted that some forms in the third class comprise derivatives of N-[5-[(4-ethylpiperazine-1-1)methyl]pyridin-2-yl]-5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazole5-yl)pyrimidin-2-amine), also known as Abemaciclib. As with the compounds in the first two classes, the compounds in the third class are also potent inhibitors of CDK 4 / 6. in R2 R3 the general formula 3A N H In R1 is a portion of acid which m is a number ML / 14 R5 / N>___ θ [3A] No fattyCH3 <CH2)nÍCH2)m ;ro de 0-4 y más preferiblemente 0-2, de tal manera que cuando m es 0 hay un enlace directo al nitrógeno en la piperazina, y n es un número entero de 9-20 y más preferiblemente de 12-20; R2 is H or alkyl of 1 to 3 carbon atoms; R3 and R4 are H or fluorine and at least one of R3 and R4 is fluorine; R5 is alkyl of 3 to 5 carbon atoms, cycloalkyl of 3 to 5 carbon atoms or cyclopropyl-methyl; R6 is H or an alkyl of 1 to 3 carbon atoms; and X is a bond, alkyl of 1 to 3 carbon atoms, O or S. Shown below as general formula [3B], a general formula for the preferred modalities of the third class is found according to the present approach. In general formula [3B], R1 is a The fatty acid portion CH3(CH2)ndCH2Úi, wherein m is an integer from 0-4 and more preferably 0-2, such that when m is 0 there is a direct bond to the nitrogen in the piperazine, yn is an integer from 9-20 and more preferably 12-20, R2 is H, R3 and R4 are fluorine, R5 is Shown below as Compound [3C], the formula for a preferred demonstrative modality of the third class is found according to the present approach. In the general Compound [3C], R1 is a The fatty acid portion CH3(CH2)n CH2^m, where m is 0 and n is 12, R2 is H, R3 and R4 are fluorine, R5 is a 3-carbon alkyl (isobutyl), and R6 is methyl. Modalities in which n is from 9 to 20 are contemplated and planned for evaluation. The modality shown as Compound [3C] is a derivative of Abemaciclib, a CDK 4 / 6 inhibitor compound approved by the EDA for the treatment of advanced and metastatic breast cancer. Compound [3C], and other compounds having the formula [3A], are anticipated to be effective in inhibiting CDK 4 / 6, making them particularly suitable for use as an anticancer therapeutic and for selectively targeting and inhibiting cells. A second demonstrative representation of the third class of compounds is shown below as formula 3D. In this example, R1 is a portion of acid. The fatty compound, in which m is 2 and n is 12, R2 is H, R3 and R4 are fluorine, R5 is a 3-carbon alkyl (isobutyl), and R6 is methyl. As with Compound [3C], this formulation is expected to be more potent than Abemaciclib with respect to CDK 4 / 6 inhibition and selectivity and to be particularly suitable for use as an anticancer therapeutic agent as described herein. [3D] Table 3 below shows the in vitro biological data for abemacib. As can be seen, the compound is already extremely potent in the 3D mammosphere assay (IC50 < 0.04 μM) prior to conjugation. Compounds with the formula [3A], which include a variety of fatty acid moieties, are being evaluated. It should be appreciated from Table 3 that abemacib is both highly specific and extremely potent for CSCs. Thus, abemacib can be used as a therapeutic agent to specifically target CSCs. Due to its selectivity, the Abemaciclib can be used to treat and / or prevent recurrence and / or metastasis of tumors and to target circulating tumor cells. IC50 IC50 SI (mammosphere / IC50 SI Composite (mammosphere (monolayer monolayer of (monolayer (monolayer of of MCF7) of MCF7) MCF7) of BJ1) BJ1 / MCF7) Abemaciclib < 0.04 pM 11 pM >250 30 ±6 2.7 TABLE 3 Results of the mammosphere assay for Abemaciclib. Figures 1–3 are dose-response curves for several compounds described in this document, obtained using the mammosphere assay. The assay was performed using the MCF7 cell line. The curves are plotted as the mean of two independent experiments, and the standard deviation for each point is represented by vertical bars. The percentage of inhibition is shown as a function of the logarithm of the concentration (μM). Figure 1 shows dose-response curves comparing Compound [1C] with its precursor compound, Ribociclib, using the mammosphere assay in the MCF7 cell line. Figure 4 shows dose-response curves comparing Compound [1C] with its precursor compound using the Hoechst staining assay in the MCF7 cell line. As can be seen, Compound [1C] is more potent against MCF7 cells at each concentration.This demonstrates that compounds with the general formula [1A], and in particular the general formula [IB], are effective as potent anticancer therapeutic agents. Figure 7 shows dose-response curves comparing Compound [1C] with its precursor compound, using the Hoechst staining assay on the hTERT-BJ1 cell line. The precursor compound was more potent at most of the tested concentrations, demonstrating that compounds with the general formula [1A], and in particular the general formula [IB], are more selective for CSCs. Similar effects are expected for compounds with the general formula [ID]. Furthermore, although the data disclosed in this document refers to the MCF7 and hTERT60 cell lines BJ1, the compounds in the present formulation are effective against other types of cancer. In previous work, the inventors demonstrated that mitochondrial biogenesis inhibitors successfully inhibited tumor-sphere formation in a wide variety of cell lines from several tumor types. Table 4 below lists cancer cell lines that have been shown to be susceptible to mitochondrial biogenesis inhibitors. Based on these results, the present formulation is effective against numerous types of cancer. Cancer Type Cell Line(s) Breast (ER+) MCF7 T47D Breast (ER-) MDA-MB-231 15 DCIS MCF10.DCIS.com (pre-malignant) SKOV3 Ovary Tov21G ES2 20 Prostate PC3 Pancreatic MIA PaCa2 Lung A549 Melanoma A375 Glioblastoma U-87 MG TABLE 4. Mitochondrial biogenesis inhibitors are effective against a wide variety of cancer types. The present formulation describes pharmaceutical compositions comprising a therapeutically effective amount of a compound of the first or second class, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. Compounds according to the present formulation may be used as anticancer therapeutic agents. Pharmaceutically effective amounts of a compound in a pharmaceutically acceptable carrier may be administered to a subject according to means known in the field. In some modalities, a compound of the present formulation may be used in conjunction with other anticancer therapies, such as, but not limited to, chemotherapeutic agents, inhibitors of mitochondrial biogenesis (e.g., mitoriboskines, mitocetoskines, repurposkines, such as antimitoskines), radiation therapy, phototherapy, and caloric restriction. It should be appreciated that a person with an ordinary level of experience in the field can use common and well-known methods to develop a formulation for a particular modality. In some modalities, the pharmaceutical composition may be in a tablet, capsule, or pill form. The pharmaceutical composition may have a dosage of the therapeutic compound ranging from 20 mg to 500 mg. In some modalities, the pharmaceutical composition may comprise a tablet containing 200 mg of the therapeutic compound, for example, a compound described above, such as Compound [1C]. A tablet may have a therapeutic compound content of at least approximately 35%, 40%, 45%, 50%, or 55%, measured as the percentage by weight of the therapeutic compound (as a free base) in the tablet core. The tablet may have a core made of microcrystalline cellulose, crospovidone type A, low-substituted hydroxypropylcellulose, magnesium stearate, and colloidal anhydrous silica. In a first demonstrative embodiment, a tablet containing 200 mg of the therapeutic compound (e.g., Compound [1C]) may include an inner core having microcrystalline cellulose (67.44 mg), hydroxypropylcellulose (48.12 mg), crospovidone (29.20 mg), colloidal silicon dioxide (anhydrous) (2.12 mg), and magnesium stearate (6.36 mg), and an outer core having crospovidone (12.84 mg), colloidal silicon dioxide (anhydrous) (1.06 mg), and magnesium stearate (8.46 mg).In a second demonstrative embodiment, a tablet may contain approximately 10% to approximately 45% (w / w) of the therapeutic compound (e.g., Compound [2C]) and preferably approximately 18% to approximately 28% of the therapeutic compound; approximately 4% to approximately 18% of water-soluble acid; approximately 20% to approximately 75% of diluent; approximately 5% to approximately 18% of disintegrant; approximately 0.2% to approximately 10% of lubricant; and, optionally, approximately 0% to approximately 5% of gluing agent and approximately 0% to approximately 15% of binding agent. It should be appreciated that the pharmaceutical compositions of the present formulation may closely resemble pharmaceutical compositions that include the precursor compound.For example, International Patent Application Publication WO 2016 / 166703, filed on April 14, 2016, describes exemplary tablet formulations for Ribociclib and is incorporated herein by reference in its entirety. As another example, International Patent Application Publication WO 2016 / 193860, filed on May 24, 2016, describes solid dosage forms of Palbociclib and is incorporated herein by reference in its entirety. The tablet may have a film coating. The film coating may include iron oxide black, iron oxide red, soy lecithin, polyvinyl alcohol (partially hydrolyzed), talc, titanium dioxide, and xanthan gum. The tablet may be coated using commercially available coating premixes, depending on the desired appearance of the final tablet. For example, OpadryMR (Colorcon, Harleysville, PA) is an HPMC (hydroxypropyl methylcellulose) coating material with the following composition: HPMC (Pharmacoat 603) 71.4%, polyethylene glycol 7.15%, talc 7.15%, and iron oxide 14.3%. The selective inhibition of CDK 4 / 6 also indicates that the compounds described herein can be used to reduce or eliminate drug and / or therapy resistance in cancers. Due to their inhibitory activity against CDKs and other kinases, the compounds in this proposal are also useful research tools for studying the mechanism of action of these kinases and can be used both in vitro and in vivo. The treatment methods described herein are preferably carried out by administering a therapeutically effective amount of a compound from either the first or second class to a subject in need of treatment. The compounds are readily synthesized using the reaction steps described below, or alternative reaction steps may be used. The alternative reaction steps would be readily recognizable by a person experienced in the field after reviewing this description and include the reaction steps described in Comprehensive Organic Synthesis, Trost, Fleming, Pergamon: 1991 and Comprehensive Organic Functional Group Transitions, Katritky, MethCohn, Rees, Pergamon: 1995. They can be administered by a variety of routes, including orally and parenterally, and have little or no toxicity. The following abbreviations may be used in the following exposition of exemplary synthesis methods: N-methylmorpholine (NMM), dichloromethane (DCM), dimethylformamide (DMF), ethyl acetate (EtOAc), sodium bicarbonate (NaHCO3), sodium sulfate (Na2SO4), methanol (MeOH). In the description that follows, [M+H]+ refers to the protonated molecule and the identified value is the mass of the protonated molecule. RT refers to the solute retention time. Analytical LC-MS: Waters SunfireMR C18 column, 30 x 4.6 mm, with a 3–97% acetonitrile / water gradient eluent containing 0.05% formic acid. Time: 0–6 minutes. Preparative HPLC: LC column: Phenomenex KinetexMR EVO C18 100, 250 x 21.2 mm, 5 pm. Gradient eluent: 40–95% acetonitrile / water containing 0.1% formic acid. In a first example of synthesis, the compound [2C] shown above, also known as 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(4-tetradecanoylpiperazin-l-yl)2-Pyridyl]amino]pyrido[2,3-d]pyrimidin-7-one was synthesized using Palbociclib (acquired from LC laboratories, Woburn, MA, USA). Tetradecanoic acid (0.104 g, 0.46 mmol) was dissolved in thionyl chloride at room temperature. The solution was refluxed for 60 minutes, concentrated under reduced pressure, and the residue was dissolved in dry DCM (2 ml) at room temperature to provide a 0.227 M stock solution of the acid chloride. The acid chloride stock solution (0.25 mL, 0.057 mmol) was added to a stirred mixture of 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-pyrido[2,3d]pyrimidin-7(8H)-one (0.024 g, 0.05 mmol) and NMM (18 μA, 0.16 mmol) in DCM (1 mL) and DMF (0.5 mL). The mixture was stirred at room temperature for 90 minutes. The solvents were evaporated under reduced pressure, and the residue was dissolved in EtOAc (30 mL), washed with saturated NaHCOa (15 mL) and brine (15 mL), and then dried over Na2SO4.The drying agent was separated by filtration, and the filtrate was concentrated under reduced pressure to generate a crude product. The crude product was ground with diethyl ether, and the resulting light brown solid was collected by filtration, washed with diethyl ether, and dried under vacuum to produce 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(4-tetradecanoylpiperazin-l-yl)-2-pyridyl]amino]pyrido[2,3d]pyrimidin-7-one (0.0145 g). LC-MS 658.2 [M+H]+, RT 4.12 minutes. In a second synthesis example, Compound [1C] shown above, also known as 7cyclopentyl-N,N-dimethyl-2-[[5-(4-tetradecanoylpiperazin-lyl)-2-pyridyl]amino]pyrrolo[2,3-d]pyrimidin-6-carboxamide, was synthesized by using the same method as in the first synthesis example, except that instead of Palbociclib, Ribociclib (acquired from LC laboratories, Woburn, MA, USA) (0.022 g, 0.05 mmol) was reacted with the acid chloride stock solution. The crude product was purified on silica gel (2-4% MeOH / DCM) to produce 7-cyclopentyl-N,N-dimethyl-2-[[5-(4-tetradecanoylpiperazin-1-yl)-2-pyridyl]amino]pyrrolo[2,3d]pyrimidin-6-carboxamide (0.0166 g) as a light brown solid. LC-MS 645.2 [M+H]+, RT 2.72 minutes. In a third example of synthesis, Compound [3C] shown above, also known as 1-[4-[[6[[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-benzimidazol-511)pyrimidin-2-yl]amino]-3-pyridyl]methyl]piperazin-1-yl]tetradecan-l-one, was synthesized from a series of intermediate compounds as follows. First, Intermediate Compound [4A], shown below and known as tert-butyl 4-tetradecanoylpiperazin-l-carboxylate, was synthesized as follows. Iso-butylchloroformate (0.65 ml, 5.0 mmol) was added to a stirred solution of tetradecanoic acid (1.26 g, 5.5 mmol) and NMM (0.73 ml, 5.5 mmol) in dry DCM (20 ml) at room temperature under a nitrogen atmosphere. After 4 hours, a solution of 1-Boc-piperazine (0.93 g, 5.0 mmol) in dry DCM (5 ml) was added to the mixture. The mixture was stirred for 16 hours. The solvent was removed under reduced pressure to yield the crude product.The crude product was dissolved in EtOAc (75 mL), washed with 2 M HCl (50 mL), saturated NaHCO3 (40 mL), and brine (30 mL), and then dried over MgSO4. After filtration, the solvent was evaporated under reduced pressure to produce 4-tetradecanoylpiperazin-l-carboxylate (1.76 g) as a white solid. LC-MS 397.2 [M+H]+, RT 4.02 mins. [4A] Secondly, the intermediate compound [4B], shown below and known as 1-piperazin-lyltetradecan-l-one, was synthesized as follows. A solution of tert-butyl 4-tetradecanoylpiperazin-l-carboxylate (0.51 g, 1.26 mmol) in a 1:1 mixture of dry DCM (10 mL) and trifluoroacetic acid, or TEA (10 mL), was stirred at room temperature under a nitrogen atmosphere for 90 minutes. The solvent was then removed under reduced pressure to generate a crude product. The crude product was dissolved in EtOAc (30 mL), washed with saturated NaHCO3 (15 mL) and brine (15 mL), and dried over MgSO4. After filtration, the solvent was evaporated under reduced pressure to produce 1-piperazin-l-yltetradecan-l-one (0.33 g) as a white, waxy solid. LC-MS 297.3 [M+H]+, RT 1.81 minutes. EITHER [4B]HN\^ Third, the intermediate compound [4C], shown below and known as 6-[[5-fluoro-4-(7fluoro-3-isopropyl-2-methyl-benzimidazol-5-yl)pyrimidin-2-yl]amino]pyridin-3-carbaldehyde, was prepared as follows. A suspension of 6-aminopyridin-3-carbaldehyde (0.076 g, 0.625 mmol), 6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-lysopropyl-2-methylbenzimidazole (0.161 g, 0.500 mmol), Xantphos (0.0276 g, 0.0476 mmol), palladium chloride (0.0056 g, 0.0315 mmol), and K₂CO₃ (0.069 g, 0.500 mmol) in 2-methyl-2-butanol (4 mL) was heated in a sealed tube at +100°C for 18 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (30 mL) and water (30 mL). The product precipitated with the aqueous phase was separated and collected by filtration. The light brown solid was washed with water (30 ml) and acetone (20 ml), and dried under vacuum to produce 6-[[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-benzimidazol-5-yl)pyrimidin-2-yl]amino]pyridin-3-carbaldehyde (0.125 g) as a light brown solid. LC-MS 409.0 [M+H]+, RT 2.07 minutes. Fourth, the intermediate compound [4D], shown below and known as 1-[4-[[6-[[5fluoro-4-(7-fluoro-3-isopropyl-2-methyl-benzimidazol-5yl)pyrimidin-2-yl]amino]-3-pyridyl]-methyl]piperazin-1yl]tetradecan-l-one, also previously known as compound [3C], was synthesized as follows. A suspension of 6-[[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-benzimidazol5-yl)pyrimidin-2-yl]amino]pyridin-3-carbaldehyde (0.050 g, 0.122 mmol), 1-piperazin-l-yltetradecan-l-one (0.030 g, 0.100 mmol), and sodium triacetoxyborohydride (0.212 g, 1.00 mmol) in DCE (20 mL) was heated in a sealed tube to +60°C for 90 minutes. The reaction mixture was cooled to room temperature, diluted with DCM (30 mL), washed with water (10 mL) and brine (10 mL), and dried over MgSO4. After filtration, the solvent was evaporated under reduced pressure to generate a crude product (0.1564 g) which was purified by preparative HPLC to produce 1-[4-[[6—[[5-fluoro-4-(7-fluoro-3-isopropyl-2methyl-benzimidazol-5-yl)pyrimidin-2-yl]amino]-3pyridi1]methyl]piperazin-l-yl]tetradecan-l-one (0.012 mg). [4D] The following paragraphs describe the materials and methods used in relation to the data and modalities presented in this document. It should be noted that those with a standard level of experience in the field may use alternative materials and methods that are generally accepted in the field, without deviating from the present approach. Regarding cell culture and reagents, the human breast adenocarcinoma (MCF-7) cell line was from the American Type Culture Collection (ATCC). The hTERT-BJl cells were from Clontech, Inc. MCF-7 and hTERT-BJl cells were grown in DMEM supplemented with 10% fetal bovine serum, GlutaMAXMR, and 1% penicillin-streptomycin and incubated at 37°C in a humidified incubator with 5% water. CO2. The medium was changed 2-3 times / week. Mammosphere formation assay: A single cell suspension was prepared using enzymatic disaggregation (Trypsin-EDTA Ix, Sigma Aldrich, cat. # T3924) and manual disaggregation (25-gauge needle). Five thousand cells were plated with mammosphere medium (DMEM-F12 / B27 / 20 ng / ml EGF / PenEstrep) under non-adherent conditions in six-well plates coated with 2-hydroxyethyl methacrylate (poly-HEMA, Sigma, cat. # P3932). Cells were grown for 5 days and maintained in a humidified incubator at 37°C at atmospheric pressure in 5% carbon dioxide / air (v / v). After 5 days, 3D spheroids with a diameter greater than 50 pm were counted using a microscope, equipped with a gridded eyepiece lens, and the percentage of cells that formed spheroids was calculated and normalized against one (1 = 100% MFE; mammosphere formation efficiency).Mammosphere tests were performed in triplicate and repeated three times independently. A Hoechst-based viability assay was used to characterize the selectivity of compounds, according to the present approach, for preferential targeting of cancer cells. In summary, MCF7 cell monolayers were treated with a compound at concentrations ranging from 1 pM to 100 pM for one day. Cell viability was assessed using Hoechst 33342, a nuclear dye that stains DNA in live cells. The viability of normal human fibroblasts (hTERT-BJl) treated with the compounds described herein was also assessed in parallel. Quantification was performed using a plate reader. The terminology used in the description of modalities in this formulation is intended to describe only particular modalities and is not intended to be exhaustive. As used in the description and accompanying claims, the singular forms *un*, *una*, *el*, and *la* are intended to include the plural forms as well, unless the context clearly indicates otherwise. This formulation encompasses numerous alternatives, modifications, and equivalents, as will become evident from the following detailed description. It is understood that although the terms first, second, third, a), b), and c), etc., may be used herein to describe various elements of the present approach, and the claims shall not be limited by these terms, these terms are used only to distinguish one element of the present approach from another. Thus, a first element subsequently stated could be referred to as an aspect of the element, and similarly, a third, without departing from the teachings of the present approach. Therefore, the terms first, second, third, a), b), and c), etc., are not intended to express a sequence or other hierarchy for the associated elements but are used solely for identification purposes. The sequence of operations (or steps) is not limited to the order presented in the claims. Unless otherwise defined, all terms (including technical and scientific terms) used in this document have the same meaning as commonly understood by a person of ordinary experience in the field. It is further understood that terms, such as those defined in commonly used dictionaries, should be interpreted in a way that is consistent with their meaning in the context of this application and the relevant technique, and should not be interpreted in an idealized or overly formal sense unless expressly defined as such in this document. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the event of a conflict in terminology, this specification shall prevail. Also, as used in this document, and / or refers to and includes any and all possible combinations of one or more of the associated listed elements, as well as the lack of combinations when interpreted alternatively (or). Unless the context indicates otherwise, the various elements of the present approach described in this document are specifically intended to be used in any combination. Furthermore, this approach also allows for the exclusion or omission of any element or combination of elements described in relation to demonstrative modalities in some cases. As used herein, the transitional phrase consisting essentially of (and grammatical variants) should be interpreted to include the cited materials or steps and those that do not materially affect the basic and novel feature(s) of the claim. Thus, the term consisting essentially of, as used herein, should not be interpreted as equivalent to including. Having thus described certain modalities of the present approach, it should be understood that the scope of the attached claims should not be limited by particular details set forth in the above description since many obvious variations of it are possible without departing from its spirit or scope as claimed later.

Claims

1. A compound, characterized in that it comprises the general formula CH3(CH2)n in which: R1 is hydrogen, aryl, alkyl of 1 to 8 carbon atoms, alkoxy of 1 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms or heterocyclyl of 3 to 7 carbon atoms; R2 is independently selected from hydrogen, halogen, alkyl of 1 to 8 carbon atoms, acyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, alkoxy of 1 to 8 carbon atoms, alkoxyalkyl of 1 to 8 carbon atoms, haloalkyl of 1 to 8 carbon atoms, hydroxyalkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkynyl of 2 to 8 carbon atoms, nitrile, nitro, OR5, SR5, NR5R6, N(O)R5R6, P(O)(OR5)(OR6), (CR5R6)mNR7R8, COR5, (CR4R5)mC(O)R7, CO2R5, CONR5R6, C(O)NR5SO2R6, NR5SO2Rs C(O)NR5OR6, S(O)nR5, SO2NR5R6, P (O) (OR5) (OR6), (CR5R6)nP (O) (OR7) (OR8), (CR5R6) m-aryl, (CR5R6) m-heteroaryl and -CR5=CR6C (O) R7;R3 is independently, in each case, hydrogen, halogen, alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 7 carbon atoms; ML / 14 R5, R6, R7 and R8, are alkyl of 1 to 8 carbon atoms, alkynyl, arylalkyl, cycloalkyl, independently hydrogen, carbon, alkenyl of 2 to 8 carbon atoms, heterocycloalkyl, aryl, heteroaryl or heteroarylalkyl; m is from 0 to 6; yn represents an integer from 9 to 20.; 2. The compound according to claim 1, characterized in that n is an integer from 12 to 20.

3. The compound according to claim 2, characterized in that R1 is cyclopentyl and R2 is acetyl.

4. The compound according to claim 1, characterized in that the compound comprises the general formula representing an integer from 9 to 20, wherein n is an integer from 12 to 20. The compound according to claim 4, characterized in that n is an integer from 12 to 20.

6. The compound according to claim 4, characterized in that n is 12.

7. A pharmaceutical composition, characterized in that it comprises a compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, characterized in that the composition is a tablet comprising a core having between 18% and 55% by weight of the compound of any of claims 1 to 6, and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition according to claim 8, characterized in that the pharmaceutically acceptable carrier comprises microcrystalline cellulose, crospovidone type A, low-substituted hydroxypropylcellulose, magnesium stearate, and colloidal anhydrous silica.

10. A method for treating cancer, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any one of claims 1 to 6 or the pharmaceutical composition according to any one of claims 7 to 9.

11. A method for treating or preventing metastatic diseases, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any of claims 1 to 6 or the pharmaceutical composition according to any of claims 7 to 9.

12. A method for treating or preventing tumor recurrence, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any of claims 1 to 6 or the pharmaceutical composition according to any of claims 7 to 9.

13. A method for reducing resistance to cancer treatment, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any of claims 1 to 6 or the pharmaceutical composition according to any of claims 7 to 9.

14. A method for treating or preventing at least one of the resistance to radiation therapy, resistance to chemotherapy, and resistance to hormone therapy, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any one of claims 1 to 6 or the pharmaceutical composition according to any one of claims 7 to 9.

15. A method for preventing or reducing the proliferation of at least one of the cancer cells, cancer stem cells, and circulating tumor cells, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any one of claims 1 to 6 or the pharmaceutical composition according to any one of claims 7 to 9.

16. The use of the compound according to any of claims 1 to 6, in the manufacture of a medicament for the treatment or prevention of cancer.

17. The use of the compound according to any of claims 1 to 6, in the manufacture of a medicament for the treatment or prevention of a metastatic disease.

18. The use of the compound in accordance with any of claims 1 to 6, in the manufacture of a medicament for the treatment or prevention of tumor recurrence.