Diamine-derivative mitochondial activity inhibitors for use in the treatment of cancer

Abstract

The present invention applies to the therapeutic field of cancer. In particular, the invention relates to a compound derived from an aliphatic diamine comprising at least one pyridine or pyrimidine unit, for use as an anticancer agent, to a therapeutic composition comprising said compound, to a product comprising such a compound and another active agent, as well as to such a compound.

Description

[0001]Novel anticancer compounds The present invention applies to the therapeutic field of cancer. In particular, the invention relates to a compound derived from an aliphatic diamine comprising at least one pyridine or pyrimidine unit, for its use as an anticancer agent, to a therapeutic composition comprising said compound, to a product comprising such a compound and another active ingredient, as well as to such a compound. Cancer represents one of the most important causes of death in the world. Treatments to combat cancer are varied and include surgery, radiotherapy, chemotherapy, hormone therapy, immunotherapy, and targeted therapy. Basic research data show that the plasticity of tumor cells allows them to develop resistance mechanisms in order to escape these treatments.In this context, faced with the relatively low efficacy of a large majority of conventional anticancer drugs in the treatment of cancers in which therapeutic failure has occurred after first-line treatment or not, such as T-cell lymphomas, pancreatic adenocarcinomas, or certain pediatric brain tumors, research is moving towards new therapeutic strategies. Indeed, successfully circumventing the resistance problems encountered in this type of disease represents a real public health issue and a challenge for research. The reconfiguration of energy metabolism is one of the key steps involved in tumor development, particularly in cases of treatment resistance. In particular, tumor cells adapt to the conditions of their microenvironment and to the selective pressure exerted by chemotherapeutic treatments by adjusting their metabolism.The development of new molecules targeting cellular metabolism thus constitutes a major therapeutic challenge. Mitochondria are organelles that play a key role in cellular metabolism by centralizing the production of ATP from numerous substrates via oxidative phosphorylation (OXPHOS). The enzymatic reactions involved in this process regulate cell proliferation, differentiation, activation, and self-renewal. Numerous recent studies have shown a correlation between OXPHOS activity (i.e., the activation of mitochondrial metabolism) and chemoresistance and / or tumor progression. In particular, mitochondria are cellular organelles capable of integrating and relaying multiple signals and contributing not only to the production of energy in the form of ATP but also to the synthesis of macromolecules essential for tumor proliferation.Adaptation towards increased OXPHOS activity is a characteristic often acquired during tumor progression, particularly during resistance to chemotherapy. Molecules targeting OXPHOS metabolism through various processes have been developed and are being tested in various clinical trials; for example, those blocking the mitochondrial ribosome and indirectly the synthesis of respiratory chain complexes (e.g., the antibiotic tigecycline), or those directly inhibiting complex I (e.g., metformin) or complex III (e.g., antimycin A) of the respiratory chain. They exert a synergistic cytotoxic effect with standard treatments. Other pharmacological approaches aimed at blocking β-oxidation of fatty acids in the mitochondria, or increasing oxidative stress in OXPHOS-prone malignant cells, have also been proposed. More recently, other OXPHOS inhibitors have been described.In particular, a complex I inhibitor known as "IACS-010759" is currently undergoing clinical trials, particularly in the field of hematological cancers:. . Furthermore, international application WO2020 / 109506 describes compounds corresponding to the following formula: , in which X 1 and X 2 , identical or different, are NR 5 or a sulfur atom, Y is a C1-C10 alkanediyl group, Ar 1 and Ar 2 , identical or different, are an optionally substituted aryl group, and R 5is a hydrogen atom or a C1-C6 alkyl group, or a pharmaceutically acceptable salt and / or solvate thereof, for use in the treatment of cancer. These compounds are described as inhibitors of oxygen consumption by mitochondria, and would notably allow the treatment of certain cancers having an “OXPHOS” mechanism. In order to meet the growing needs in the context of personalized medicine, depending on the individual properties of each tumor, there is however a persistent need to develop other anticancer agents effective on tumor cells, in particular those targeting the mitochondrial respiratory chain, and consequently having an inhibitory effect on the energy charge of the cells.In particular, there is a need to develop molecules with other physicochemical characteristics, acting on other intracellular targets compared to the limited number of OXPHOS inhibitors already developed. These new molecules should be easy to prepare, and have improved cytotoxicity properties while ensuring good pharmacokinetic properties such as good ADMET properties (Absorption of the molecule, Distribution in the body, Elimination including biotransformation or Metabolism, and excretion, and Toxicity), in particular in silico. Thus, the aim of the present invention is to overcome the drawbacks of the aforementioned prior art and to provide an anticancer agent with good performance in terms of anticancer activity, easy to prepare, and having low toxicity on non-tumor cells while ensuring good ADMET properties.The object of the invention is achieved by the compounds which will be described below. The present invention has as its first object a compound chosen from the compounds corresponding to formula (I), their pharmaceutically acceptable salts, and their pharmaceutically acceptable solvates, said formula (I) having the following structure:. in which: * R 1 , R 2 , and R 3 represent, independently of each other, a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN (cyano or carbonitrile), -CF3, -CHO (aldehyde), -NH-NH2 (hydrazine), -CO2H, -CH2OH, - CH2NH2, an alkoxy group -OR 7 , a -NR group 8 R 9 , a -SR group 10 , a -C(O)R group 11 , a -CH2OR group 12 , and a -CH2NR group 13 R 14 , with R 7 , R 8 , R 10 , R 11 , R12 , and R 13 representing, independently of each other, an alkyl or cycloalkyl radical, and R 9 and R 14 representing, independently of one another, a hydrogen atom, or an alkyl or cycloalkyl radical, * X 1 represents a nitrogen atom or a CR group 15 , with R 15 being a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, -CF3, -CHO, -NH- NH2, -CO2H, -CH2OH, -CH2NH2, an alkoxy group -OR 7 , a -NR group 8 R 9 , a -SR group 10 , a -C(O)R group 11 , a -CH2OR group 12 , and a group - CH2NR 13 R 14 , * n is an integer ranging from 1 to 20, * R 4 represents a hydrogen atom, an alkyl radical, or a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected, * R5 represents a hydrogen atom, an alkyl radical, or a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 5 is connected, * Y 1 represents -CH2-, -NH-, or -O- when the R group 4 represents a hydrogen atom, or an alkyl radical; and represents -CH- or -N- when the group R 4 represents a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected, * Y 2 represents -CH2-, -NH-, or -O- when the R group 5 represents a hydrogen atom, or an alkyl radical; and represents -CH- or -N- when the group R 5 represents a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 4 is connected, and * R 6 represents one of the following two groups (IIa) and (IIb): in which, R' 1 , R' 2 , and R' 3represent, independently of each other, a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, - CF3, -CHO, -NH-NH2, -CO2H, -CH2OH, -CH2NH2, an alkoxy group -OR' 7 , a -NR' group 8 R' 9 , a -SR' group 10 , a -C(O)R' group 11 , a -CH2OR' group 12 , and a group -CH2NR' 13 R' 14 , with R' 7 , R' 8 , R' 10 , R' 11 , R' 12 , and R' 13 representing, independently of each other, an alkyl or cycloalkyl radical, and R' 9 and R' 14 representing, independently of each other, a hydrogen atom, or an alkyl or cycloalkyl radical, and X 2 represents a nitrogen atom or a CR' group 15 , with R' 15being a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, -CF3, -CHO, -NH- NH2, -CO2H, -CH2OH, -CH2NH2, an alkoxy group -OR' 7 , a -NR' group 8 R' 9 , a -SR' group 10 , a -C(O)R' group 11 , a -CH2OR' group 12 , and a group - CH2NR' 13 R' 14, for its use in the treatment of cancer. The compounds (I) of the invention are derivatives of an aliphatic diamine comprising at least one pyridine or pyrimidine unit. The inventors have discovered that such compounds exhibit significant anticancer activity. Furthermore, these compounds are easy to prepare, have low toxicity for healthy cells, and good ADMET properties, particularly in silico. The term "cancer" means all malignant neoplastic formations, regardless of their histological nature (adult and pediatric). There are two main categories of solid tumors: carcinomas, of epithelial origin, and sarcomas, of connective tissue origin.Solid tumors are formed from atypical, invasive or disseminative cells, generally characterized by the ability to grow independently, imprecise delimitation, the ability to invade neighboring tissues and vessels, and a tendency to spread through the production of metastases. These include cancers of the breast, prostate, lung, esophagus, skin, bladder, stomach, liver, uterus, colon, and rectum. Other examples include endocrine and exocrine pancreatic cancers, and pediatric tumors such as rhabdomyosarcomas and brainstem infiltrating gliomas (DIPG). The other category of tumors includes the various types of malignant hematological diseases.The second subject of the invention is a compound as defined in the first subject of the invention, for targeted use in the treatment of cancers having an altered metabolism, in particular in the treatment of cancers with an OXPHOS metabolism. A cancer with an OXPHOS metabolism corresponds to a cancer which comprises or consists of cancer cells relying predominantly on oxidative phosphorylation (OXPHOS) for biosynthetic and / or bioenergetic processes. Among such cancers with an OXPHOS metabolism, there are hematological cancers, lung cancers, cervical cancers, prostate cancers, neuroendocrine tumors, glial tumors and skin and eye cancers.According to a preferred embodiment of the invention, the compound as defined in the first subject of the invention is used in the treatment of lymphomas, in particular adult or pediatric B and T lymphomas; solid tumors such as sarcomas, in particular pediatric sarcomas (e.g., rhabdomyosarcoma type); and certain tumors recurring following chemotherapy treatments. The compound as defined in the first subject of the invention exerts antitumor activity in one or more preclinical models. By "lymphoma" is meant any tumor, generally malignant, due to a proliferation of lymphoid tissue cells, developing in the spleen or lymph nodes, but also in many other organs or tissues. The compound as defined in the first subject of the invention thus has the potential properties of a new anticancer drug targeting cellular metabolism.It acts in particular as an inhibitor of the mitochondrial respiratory chain and inhibits oxygen consumption. It can thus be considered as an OXPHOS inhibitor. Furthermore, it has: - an in vitro cytotoxic activity, competitive with OXPHOS inhibitors already in clinical trials, in particular with "IACS-010759", and - a specificity of action linked to the cellular phenotype. In the compound as defined in the first subject of the invention, the alkyl radical may be linear or branched, and it is preferably linear. In the compound as defined in the first subject of the invention, the cycloalkyl radical may be linear or branched, and it is preferably linear. For the purposes of the present invention, a halogen is chosen from F, Cl, Br and I, and particularly preferably from F and Cl. Definition of R. 1 , R 2 , R 3 R 1 , R 2 , and R 3represent, independently of each other, a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN (carbonitrile or cyano), -CF3, -CO2H, -CH2OH, -CH2NH2, -CHO (aldehyde), -NH-NH2 (hydrazine), an alkoxy group -OR 7 , a -NR group 8 R 9 , a -SR group 10 , a -C(O)R group 11 , a -CH2OR group 12 , and a -CH2NR group 13 R 14 , with R 7 , R 8 , R 10 , R 11 , R 12 , and R 13 representing, independently of each other, an alkyl or cycloalkyl radical, and R 9 and R 14 representing, independently of each other, a hydrogen atom, or an alkyl or cycloalkyl radical. The alkyl radical as a group R 1 , R 2 or R 3is preferably a C1-C5 alkyl radical, and particularly preferably a methyl, ethyl, propyl, isopropyl, butyl or tertbutyl radical. The cycloalkyl radical as group R 1 , R 2 or R 3 is preferably a C3-C6 cycloalkyl radical, particularly preferably a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical, and more particularly preferably a cyclopropyl radical. The aryl radical as group R 1 , R 2 or R 3 is preferably a C aryl radical 5 -C 15 , particularly preferably a phenyl, 2- or 3-thienyl, 2- or 3-furyl radical, and more particularly preferably a phenyl radical. Definition of R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 The alkyl radical as the R group 7 , R 8 , R 9 , R10 , R 11 , R 12 , R 13 or R 14 is preferably a C1-C5 alkyl radical, and particularly preferably a methyl, ethyl, propyl, isopropyl, butyl or tertbutyl radical. The cycloalkyl radical as group R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 or R 14 is preferably a C3-C6 cycloalkyl radical, particularly preferably a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical, and more particularly preferably a cyclopropyl radical. The -SR group 10 is preferably a thiomethyl group. The group -NR 8 R 9 is preferably a methylamine or dimethylamine group. The alkoxy group -OR 7 is preferably a methoxy or ethoxy group. According to a particularly preferred embodiment of the invention, R 1is a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an alkoxy group -OR 7 , a -SR group 10 , a -CN group, a -CF3 group, a -NR group 8 R 9 , a -NH-NH2 group, a -CO2H group, or a -CHO group. According to a particularly preferred embodiment of the invention, R 2 is a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an alkoxy group -OR 7 , a -SR group 10 , a -CN group, a -CF3 group, a -NR group 8 R 9 , a -NH-NH2 group, a -CO2H group, or a -CHO group. According to a particularly preferred embodiment of the invention, R 3 is a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an alkoxy group -OR 7 , a -SR group 10 , a -CN group, a -CF3 group, a -NR group 8 R 9, a -NH-NH2 group, a -CO2H group, or a -CHO group. Advantageously, R 1 , R 2 and R 3 are hydrogen atoms. Definition of X 1 X 1 represents a nitrogen atom or a CR group 15 , with R 15 being a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, -CF3, -CO2H, - CH2OH, -CH2NH2, an alkoxy group -OR 7 , a -NR group 8 R 9 , a -SR group 10 , a -C(O)R group 11 , a -CH2OR group 12 , and a -CH2NR group 13 R 14 . The R groups 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are as defined in the invention. According to a particularly preferred embodiment of the invention, R 15is a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an alkoxy group -OR 7 , a -SR group 10 , a -CN group, a -CF3 group, a -NR group 8 R 9 , a -NH-NH2 group, a -CO2H group, or a -CHO group. Advantageously, X 1 represents a nitrogen atom or a CH group. Definition of R 4 and R 5 R 4 represents a hydrogen atom, an alkyl radical, or a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected. The alkyl radical as the R group 4 is preferably a C1-C5 alkyl radical, and particularly preferably a methyl or ethyl radical. The divalent alkylene radical forming a cycle with Y 1 and the nitrogen atom to which R 4 is connected as group R 4is preferably an alkylene radical -(CH2)2- or -(CH2)3-, and particularly preferably an alkylene radical -(CH2)2-. Preferably, R 4 represents a hydrogen atom or a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected. R 5 represents a hydrogen atom, an alkyl radical, or a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 5 is connected. The alkyl radical as the R group 5 is preferably a C1-C5 alkyl radical, and particularly preferably a methyl, ethyl, propyl or butyl radical. The divalent alkylene radical forming a ring with Y 2 and the nitrogen atom to which R 2 is connected as group R 2 is preferably an alkylene radical -(CH2)2- or -(CH 2 ) 3 -, and particularly preferably an alkylene radical -(CH 2 ) 2-. Preferably, R 5 represents a hydrogen atom or a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 5 is connected. According to a particularly preferred embodiment of the invention, R 4 represents a hydrogen atom or a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected: and R 5 represents a hydrogen atom or a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 5 is connected. According to a particularly preferred embodiment of the invention, R 4 and R 5 are identical. Definition of Y 1 and Y 2 Y 1 represents -CH2-, -NH-, or -O- when the R group 4 represents a hydrogen atom, or an alkyl radical; and represents -CH- or -N- when the group R 4represents a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected. Preferably, Y 1 represents -CH2- when the R group 4 represents a hydrogen atom, or an alkyl radical; and represents -N- when the group R 4 represents a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected. Y 2 represents -CH2-, -NH-, or -O- when the R group 5 represents a hydrogen atom, or an alkyl radical; and represents -CH- or -N- when the group R 5 represents a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 5 is connected. Preferably, Y 2 represents -CH2- when the R group 5 represents a hydrogen atom, or an alkyl radical; and represents -N- when the group R 5 represents a divalent alkylene group forming a ring with Y2 and the nitrogen atom to which R 5 is connected. According to a particularly preferred embodiment of the invention, Y 1 represents -CH2- when the R group 4 represents a hydrogen atom, or an alkyl radical; and represents -N- when the group R 4 represents a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected; and Y 2 represents -CH2- when the R group 5 represents a hydrogen atom, or an alkyl radical; and represents -N- when the group R 5 represents a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 5 is connected. According to a particularly preferred embodiment of the invention, Y 1 and Y 2 are identical. Definition of nn is an integer ranging from 1 to 20, and preferably ranging from 1 to 14. Definition of Y 1 , Y 2in relation to n According to a preferred embodiment of the invention: - when Y 1 (respectively Y 2 ) represents -CH2-, n preferably ranges from 2 to 10, and particularly preferably from 3 to 9, - when Y 1 (respectively Y 2 ) represents -N-, -NH-, -CH- or -O-, n preferably ranges from 6 to 18, and particularly preferably from 7 to 14. This embodiment is particularly suitable when R 6 is a group of formula (IIa). When Y 1 and Y 2 represent -CH-, and R 6 is a group of formula (IIa), then n is preferably such that n ≥ 5 and / or R 1 , R' 1 , R 2 , R' 2 , R 3 , and R' 3 are preferably different from -NH2. When Y 1 and Y 2 represent -N-, and R 6is a group of formula (IIa), then n is preferably such that n ≥ 7. According to a preferred embodiment of the invention, when Y 1 and Y 2 represent -CH-, and R 6 is a group of formula (IIa), then n is such that n ≥ 5 and / or R 1 , R' 1 , R 2 , R' 2 , R 3 , and R' 3 are different from -NH2; and when Y 1 and Y 2 represent -N-, and R 6 is a group of formula (IIa), then n is such that n ≥ 7. Definition of R 6 R 6 represents one of the following two groups (IIa) and (IIb): in which, R' 1 , R' 2 , and R' 3 represent, independently of each other, a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, - CF3, -CHO, -NH-NH2, -CO2H, -CH2OH, -CH2NH2, an alkoxy group -OR' 7 , a -NR' group8 R' 9 , a -SR' group 10 , a -C(O)R' group 11 , a -CH2OR' group 12 , and a group -CH2NR' 13 R' 14 , with R' 7 , R' 8 , R' 10 , R' 11 , R' 12 , and R' 13 representing, independently of each other, an alkyl or cycloalkyl radical, and R' 9 and R' 14 representing, independently of each other, a hydrogen atom, or an alkyl or cycloalkyl radical, and X 2 represents a nitrogen atom or a CR' group 15 , with R' 15 being a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, -CF3, -CO2H, - CH2OH, -CH2NH2, an alkoxy group -OR' 7 , a -NR' group 8 R' 9 , a -SR' group 10 , a -C(O)R' group 11 , a -CH2OR' group 12 , and a group -CH2NR' 13 R'14 . R 6 is preferably a group of formula (IIb). Definition of R' 1 , R' 2 , R' 3 The alkyl radical as the R' group 1 , R' 2 or R' 3 is preferably a C1-C5 alkyl radical, and particularly preferably a methyl, ethyl, propyl, isopropyl, butyl or tertbutyl radical. The cycloalkyl radical as the R' group 1 , R' 2 or R' 3 is preferably a C3-C6 cycloalkyl radical, and particularly preferably a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical, and more particularly preferably a cyclopropyl radical. The aryl radical as group R' 1 , R' 2 or R' 3 is preferably a C5-C15 aryl radical, and particularly preferably a phenyl, 2- or 3-thienyl, 2- or 3-furyl radical, and more particularly preferably a phenyl radical. Definition of R'7 , R' 8 , R' 9 , R' 10 , R' 11 , R' 12 , R' 13 and R' 14 The alkyl radical as the R' group 7 , R' 8 , R' 9 , R' 10 , R' 11 , R' 12 , R' 13 or R' 14 is preferably a C1-C5 alkyl radical, and particularly preferably a methyl, ethyl, propyl, isopropyl, butyl or tertbutyl radical. The cycloalkyl radical as the R' group 7 , R' 8 , R' 9 , R' 10 , R' 11 , R' 12 , R' 13 or R' 14 is preferably a C3-C6 cycloalkyl radical, and particularly preferably a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical, and more particularly preferably a cyclopropyl radical. The group -SR' 10 is preferably a thiomethyl group. The -NR' group 8 R' 9is preferably a methylamine or dimethylamine group. The alkoxy group -OR' 7 is preferably a methoxy or ethoxy group. According to a particularly preferred embodiment of the invention, R' 1 is a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an alkoxy group -OR 7 , a -SR group 10 , a -CN group, a -CF3 group, a -NR group 8 R 9 , a -NH-NH2 group, a -CO2H group, or a -CHO group. According to a particularly preferred embodiment of the invention, R' 2 is a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an alkoxy group -OR 7 , a -SR group 10 , a -CN group, a -CF group 3 , a -NR group 8 R 9 , a -NH-NH group 2 , a -CO group 2 H, or a group - CHO. According to a particularly preferred embodiment of the invention, R' 3is a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an alkoxy group -OR 7 , a -SR group 10 , a -CN group, a -CF3 group, a -NR group 8 R 9 , a -NH-NH2 group, a -CO2H group, or a -CHO group. Advantageously, R' 1 , R' 2 and R' 3 are hydrogen atoms. Definition of X 2 X 2 represents a nitrogen atom or a CR' group 15 , with R' 15 being a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, -CF3, -CO2H, - CH2OH, -CH2NH2, an alkoxy group -OR' 7 , a -NR' group 8 R' 9 , a -SR' group 10 , a -C(O)R' group 11 , a -CH2OR' group 12 , and a group -CH2NR' 13 R' 14 . The R' groups 7 , R' 8 , R' 9 , R' 10 , R'11 , R' 12 , R' 13 and R' 14 are as defined in the invention. According to a particularly preferred embodiment of the invention, R' 15 is a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an alkoxy group -OR 7 , a -SR group 10 , a -CN group, a -CF3 group, a -NR group 8 R 9 , a -NH-NH2 group, a -CO2H group, or a -CHO group. Advantageously, X 2 represents a nitrogen atom or a CH group. According to a preferred embodiment of the invention, the compound of formula (I) is chosen from the following compounds: The term "pharmaceutically acceptable" means that is useful for the preparation of a pharmaceutical composition, and is generally safe and non-toxic, for pharmaceutical use. A pharmaceutically acceptable salt or solvate of a compound means a salt or solvate that is pharmaceutically acceptable as defined above, and that possesses the pharmacological activity of said compound. Pharmaceutically acceptable salts include: - acid addition salts formed with inorganic acids such as hydrobromic acid, hydrochloric acid, sulfuric acid, nitric acid, or phosphoric acid; or formed with organic acids such as formic acid, acetic acid, benzenesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, hydroxynaphthoic acid, 2-hydroxyethanesulfonic acid, maleic acid, malic acid, mandelic acid,methanesulfonic acid, propionic acid, succinic acid, muconic acid, 2-naphthalenesulfonic acid, tartaric acid, dibenzoyl L-tartaric acid, paratoluenesulfonic acid, trimethylacetic acid, trifluoroacetic acid, benzoic acid, citric acid, ethanesulfonic acid, lactic acid, mucic acid, pamoic acid, or pantothenic acid, - salts formed when an acid proton present in the compound is either replaced by a metal ion, such as an alkali metal ion, an alkaline earth metal ion, or an aluminum ion; or coordinated with an inorganic or organic base. Acceptable organic bases include diethanolamine, ethanolamine, N-methylglucamine, triethanolamine, and tromethamine. Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide,sodium carbonate and sodium hydroxide. Acceptable solvates for the therapeutic use of the compounds of the invention include conventional solvates such as those formed during the last step of preparation of these compounds due to the presence of solvents. Mention may be made of solvates linked to the presence of water (these solvates are also called hydrates) or ethanol. Due to their anticancer activity, the compounds as defined in the first subject of the invention are useful in therapy. The third subject of the invention is a pharmaceutical composition comprising a compound as defined in the first subject of the invention and at least one suitable pharmaceutical vehicle. The suitable pharmaceutical vehicle may be a pharmaceutically acceptable excipient for use in the treatment of cancer, and in particular in the treatment of cancers with an altered metabolism,and preferably cancers with OXPHOS metabolism. The pharmaceutical composition may be a solid composition or a liquid composition. The solid composition may be in the form of tablets, capsules, powders, or granules. The tablets may comprise the compound as defined in the first subject of the invention in admixture with a pharmaceutical vehicle such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic, or the like. The resulting mixture may in particular be compressed. The tablets may be coated with sucrose, sucrose,or other suitable materials or may be treated in such a way that they have prolonged or delayed activity and continuously release a predetermined amount of compound. The powders or granules may be dispersible in water. They may contain the compound as defined in the first subject of the invention in admixture with dispersing agents, wetting agents, or suspending agents, in particular with flavor correctors or sweeteners. The capsules may comprise the compound as defined in the first subject of the invention in admixture with a diluent. The capsules may be soft or hard capsules. The liquid composition may be in the form of an aqueous suspension or solution, a syrup, or an elixir. It may in particular comprise the compound as defined in the first subject of the invention in a solvent such as water, as well as optionally a sweetener, a flavoring agent,and / or a suitable colorant. The liquid composition may in particular be obtained by dissolving or suspending a powder or granules as mentioned above in a liquid such as water, fruit juice, milk, etc. The pharmaceutical composition is preferably sterile. It may be in the form of an isotonic solution (in particular compared to blood). The compound as defined in the first subject of the invention or the pharmaceutical composition in accordance with the third subject of the invention may thus be used in a method of therapeutic treatment of cancer,said method comprising administering to an individual an effective amount of said compound as defined in the first subject of the invention (or a pharmaceutically acceptable salt or solvate of said compound) or administering an effective amount of said pharmaceutical composition in accordance with the third subject of the invention. The individual is the patient requiring treatment, such as a mammal, in particular humans. The compound or pharmaceutical composition may be administered to mammals, including humans, by nasal, enteral (e.g. oral) or parenteral (e.g. intravenous) route. The dosage varies depending on the treatment and the condition in question. Suitable unit dosage forms include oral forms such as tablets, capsules, powders, granules and oral solutions or suspensions, sublingual and buccal administration forms, subcutaneous, intramuscular administration forms,intravenous, intranasal or intraocular and rectal administration forms. The compound as defined in the first subject of the invention may be used in therapy alone, or in combination with at least one other active agent. The present invention thus relates to a method of treating cancer in a patient in need thereof, comprising administering to the patient a compound as defined in the first subject of the invention (or a pharmaceutically acceptable salt or solvate of said compound) or a pharmaceutical composition in accordance with the third subject of the invention. The cancer is as defined in the first subject of the invention. The present invention also relates to a method of treating a cancer having an altered metabolism, in particular a cancer with an OXPHOS metabolism, in a patient in need thereof,comprising administering to the patient a compound as defined in the first subject of the invention (or a pharmaceutically acceptable salt or solvate of said compound) or a pharmaceutical composition in accordance with the third subject of the invention. Cancer having an altered metabolism, in particular cancer with OXPHOS metabolism are as defined in the first subject of the invention. The present invention also relates to the use of a compound as defined in the first subject of the invention (or a pharmaceutically acceptable salt or solvate of said compound) or a pharmaceutical composition in accordance with the third subject of the invention, for the manufacture of a medicament intended for the treatment of cancer or cancer having an altered metabolism, in particular cancer with OXPHOS metabolism,in a subject in need thereof. The present invention also relates to the use of a compound as defined in the first subject of the invention (or a pharmaceutically acceptable salt or solvate of said compound) or a pharmaceutical composition in accordance with the third subject of the invention, for treating cancer or cancer with altered metabolism, in particular cancer with OXPHOS metabolism, in a subject in need thereof. The term "patient" refers to an animal, generally a warm-blooded animal, preferably a mammal. The term "mammal" herein refers to any mammal, including humans, domestic and farm animals, as well as zoo, sport or companion animals, such as dogs, cats, cattle, horses, sheep, pigs, goats, rabbits, etc. Preferably, the mammal is a primate,and more particularly a human being. The term "human" designates a male or female human subject at any stage of development, including newborn, infant, juvenile, adolescent and adult. The fourth subject of the invention is a product comprising a compound as defined in the first subject of the invention and another active agent. The compound as defined in the first subject of the invention and the other active agent are then used in combination, in particular for simultaneous, separate, or time-spread use in therapy. These other active agents are in particular chosen from active agents suitable for the treatment of cancers. They may be adjuvants making it possible to improve the activity of the compounds according to the invention, or other active agents known for their use in the treatment of said conditions. Such active agents are well known to those skilled in the art,commercially available or described in reference works such as Le Dictionnaire Vidal, published with updates each year, in particular the active agents grouped under the pharmacotherapeutic families “Cancerology Hematology”. Certain compounds as defined in the first subject of the invention are new in themselves and represent the fifth subject of the invention: these compounds are chosen from the compounds corresponding to formula (I'), their pharmaceutically acceptable salts, and their pharmaceutically acceptable solvates, said formula (I') having the following structure:, in which: * R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X 1 , Y 1 , Y 2 , and n are as defined in the first subject of the invention for formula (I), it being understood that: * when Y 1 and Y 2 represent -CH-, and R 6is a radical of formula (IIa), then n ≥ 5 and / or R 1 , R' 1 , R 2 , R' 2 , R 3 , and R' 3 are different from -NH2, and * when Y 1 and Y 2 represent -N-, and R 6is a radical of formula (IIa), then n ≥ 7. Other characteristics, variants and advantages of the compound, its use, or the pharmaceutical composition according to the invention will become more apparent on reading the following exemplary embodiments, given by way of illustration and not limitation of the invention. Brief description of the drawings The appended drawings illustrate the invention. Figure 1 shows the oxygen consumption after treatment of cells of a human B lymphoma line with compounds in accordance with the invention and compounds of the prior art. Figure 2 shows the effect on cell growth of the treatment of human tumor cells, of a B lymphoma line with compounds in accordance with the invention and compounds of the prior art.Figure 3 shows the effect on cell growth of treating human tumor cells of a wide range of B and T lymphoma lines with a compound according to the invention and a compound of the prior art. Figure 4 shows the antitumor efficacy of a compound of the invention in an in ovo model. Figure 5 shows the effect on cell growth of treating human cells of two pediatric sarcoma lines with compounds of the invention. Figure 6 shows the effect on cell growth of treating human tumor cells of a B lymphoma line with compounds according to the invention. Figure 7 shows the effect on cell growth of treating human tumor cells of a pediatric sarcoma line with compounds of the invention. Example 1: Synthesis of Compound Ia Examples Flash column chromatography was performed on silica gel 60 (0.063-200 mm).Nuclear magnetic resonance (NMR) spectra. and NMR 13 C) were recorded at 25°C with a spectrometer (Bruker Avance III) (NMR at 400 MHz, NMR 13 C at 100 MHz) using CD3OD as the solvent referenced to residual CH3OH (δH = 3.31 ppm, δC = 49.00 ±0.01 ppm) and DMSO- d6 as the solvent referenced to residual DMSO (δH =2.50 ppm, δC = 39.52 ±0.06 ppm). Chemical shifts are given in ppm and coupling constants (J) in Hertz. Data for NMR spectra are reported as follows: chemical shift ppm (s = singlet, d = doublet, t = triplet, q = quadruplet, dd = doublet of doublets, td = triplet of doublets, ddd = doublet of doublets of doublets, m = multiplet, coupling constants, integration). Example 1: Synthesis of Compound Ia Compound Ia was prepared according to the steps illustrated in the following scheme: . First step: synthesis of the derivative N'-pyrimidin-2-yldodecane-1,12-diamine. To a solution of 1 g (4.99 mmol) of 1,12-dodecanediamine in 30 ml of dioxane are added 0.8 equivalents (3.99 mmol; 457.2 mg) of 2-chloropyrimidine and 5 equivalents (24.95 mmol; 3.45 g) of potassium carbonate. The reaction mixture is heated to reflux of the dioxane for 16 h. After cooling, the dioxane is concentrated under reduced pressure. The residue obtained is taken up in 50 ml of ethyl acetate, washed once with a saturated solution of sodium chloride, dried over magnesium sulfate, and evaporated under reduced pressure. The derivative obtained is purified by chromatography on silica gel with as eluent: ethyl acetate / methanol / triethylamine according to a gradient (98 / 0 / 2; 60 / 10 / 10; 70 / 20 / 10; 60 / 30 / 10). The expected compound is obtained with a yield of 53% and appears in the form of a yellow solid.It has the following characteristics: Melting point = 86°C Molar mass = C16H30N4: 278.43 g / mol NMR. 1 H (CD3OD): 8.26 (d; J = 4.8 Hz; 2H); 6.59 (t; J = 4.9 Hz; 1H); 3.38-3.34 (m; 2H); 2.84-2.76 (m; 2H); 1.66-1.53 ​​(m; 4H); 1.41-1.33 (m; 16H). NMR 13C (CD3OD): 162.1; 157.9 (2C); 109.6; 40.8; 40.1; 29.3; 29.3; 29.3; 29.3; 29.2; 29.1; 29.1; 29.0; 26.6; 26.3. Second step: synthesis of the derivative N'-(4,5-dihydro-1H-imidazol-2-yl)-N-pyrimidin-2-yl-dodecane-1,12-diamine To a solution of 100 mg (0.36 mmol) of N'-pyrimidin-2-yldodecane-1,12-diamine as prepared in the previous step in an ethanol / triethylamine mixture (12 mm / 0.1 mm) is added 1.05 equivalents (0.38 mmol) of 1-(4,5-dihydro-1H-imidazol-2-yl)-3,5-dimethyl-1H-pyrazole hydrobromide. The reaction medium is heated to reflux of ethanol for 3 days. After cooling, the reaction mixture is filtered and the filtrate is concentrated under vacuum. The derivative obtained is purified by chromatography on silica gel with dichloromethane / methanol (92 / 8) as eluent. The expected compound is obtained with a yield of 40% and appears in the form of a yellow solid.It has the following characteristics: Melting point = 90 °C Molar mass = C19H34N6: 346.51 g / mol NMR. 1 H (CD3OD): 8.14 (d; J = 4.9 Hz; 2H); 6.47 (t; J = 4.8 Hz; 1H); 3.61 (s; 4H); 3.25 – 3.22 (m; 2H); 3.14 – 3.06 (m; 2H); 1.53 – 1.45 (m; 4H); 1.31 – 1.18 (m; 16H). NMR 13 C (CD3OD): 162.1; 159.9; 157.8 (2C); 109.6; 42.6; 42.5; 40.8; 40.5; 29.3; 29.2; 29.2; 29.2; 29.1; 29.1; 28.9; 28.8; 26.6; 26.3. Example 2: Synthesis of Compound Ib Compound Ib was prepared according to the steps illustrated in the following scheme: First step: synthesis of the derivative 2-[4-[12-(4-pyrimidin-2-ylpiperazin-1-yl)dodecyl]piperazin-1-yl]pyrimidine To a solution of 700 mg (2.13 mmol) of 1,12-dibromododecane in 30 ml of dioxane are added 2 equivalents (4.26 mmol; 700.5 mg) of 2-piperazin-1-ylpyrimidine and 7 equivalents (14.94 mmol; 2.1 g) of potassium carbonate. The reaction mixture is heated to reflux of the dioxane for 20 h. After cooling, the dioxane is concentrated under reduced pressure. The residue obtained is taken up in 50 ml of ethyl acetate, washed once with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure. The derivative obtained is purified by chromatography on silica gel with ethyl acetate / methanol / triethylamine (99 / 0.5 / 0.5) as eluent. The expected compound is obtained with a yield of 64% and appears in the form of a white solid.It has the following characteristics: Melting point = 106°C Molar mass = C28H46N8: 494.72 g / mol NMR. 1 H (CD3OD): 8.23 ​​(d; J = 4.7 Hz; 4H); 6.40 (t; J = 4.7 Hz; 2H); 3.84 – 3.67 (m; 8H); 2.49 – 2.35 (m; 8H); 2.35 – 2.21 (m; 4H); 1.54 – 1.37 (m; 4H); 1.32 – 1.11 (m; 16H). NMR 13C (CD3OD): 161.7 (2C); 157.7 (4C); 109.8 (2C); 59.0 (2C); 53.2 (4C); 43.7 (4C); 29.6 (6C); 27.6 (2C); 26.9 (2C). Second step: synthesis of the derivative 2-[4-[12-(4-pyrimidin-2-ylpiperazin-1-yl)dodecyl]piperazin-1-yl]pyrimidine dihydrochloride 150 mg (0.30 mmol) of 2-[4-[12-(4-pyrimidin-2-ylpiperazin-1-yl)dodecyl]piperazin-1-yl]pyrimidine are dissolved in 5-10 ml of ethanol. Hydrochloric acid gas is bubbled for 5 minutes in the reaction medium. After stirring, the precipitate is collected by filtration, washed with diethyl ether and dried. The expected compound is obtained with a yield of 87% and is in the form of a white solid. It has the following characteristics: Melting point = 252°C Molar mass = C28H46N8. 2HCl: 567.64 g / mol NMR 1H (DMSO-d6) : 11,49 (s ; 2H) ; 8,44 (d ; J = 4,8 Hz ; 4H) ; 6,76 (t ; J = 4,8 Hz ; 2H) ; 4,67 (d ; J = 14,1 Hz ; 4H) ; 3,52 (d ; J = 12,4 Hz ; 8H) ; 3,07 - 2,99 (m ; 8H) ; 1,79 - 1,73 (m ; 4H) ; 1,35 - 1,30 (m ; 16H). RMN 13 C (DMSO-d 6): 161.2 (2C); 158.5 (4C); 111.7 (2C); 56.2 (2C); 50.9 (4C); 40.8 (4C); 29.3 (2C); 29.1 (2C); 28.9 (2C); 26.6 (2C); 23.4 (2C). Example 3: Synthesis of Compound Ic Compound Ic was prepared according to the steps illustrated in the following scheme: First step: Synthesis of the derivative 1-(2-pyridyl)-4-[12-[4-(2-pyridyl)piperazin-1-yl]dodecyl]piperazine To a solution of 700 mg (2.13 mmol) of 1,12-dibromododecane in 30 ml of dioxane are added 2 equivalents (4.26 mmol; 696.3 mg) of 1-(2-pyridyl)piperazine and 7 equivalents (14.94 mmol; 2.1 g) of potassium carbonate. The reaction mixture is heated to reflux of the dioxane for 20 h. After cooling, the dioxane is concentrated under reduced pressure. The residue obtained is taken up in 50 ml of ethyl acetate, washed once with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure.The derivative obtained is purified by chromatography on silica gel with ethyl acetate / methanol / triethylamine (99 / 0.5 / 0.5) as eluent. The expected compound is obtained with a yield of 48% and is in the form of a white solid. It has the following characteristics: Melting point = 100°C Molar mass = C30H48N6: 492.74 g / mol NMR (CD3OD): 8.12 (ddd; J = 4.9; 2.0; 0.9 Hz; 2H); 7.40 (ddd; J = 8.9; 7.1; 2.0 Hz; 2H); 6.60 – 6.51 (m; 4H); 3.48 (dd; J = 6.2; 4.1 Hz; 8H); 2.54 – 2.42 (m; 8H); 2.34 – 2.25 (m; 4H); 1.52 – 1.38 (m; 4H); 1.30 – 1.14 (m; 16H). NMR. 13C (CD3OD): 159.6 (2C); 148.0 (2C); 137.1 (2C); 113.2 (2C); 107.0 (2C); 59.0 (2C); 53.2 (4C); 45.2 (4C); 29.6 (6C); 27.6 (2C); 26.9 (2C). Second step: synthesis of the derivative 1-(2-pyridyl)-4-[12-[4-(2-pyridyl)piperazin-1-yl]dodecyl]piperazine dihydrochloride 150 mg (0.30 mmol) of 1-(2-pyridyl)-4-[12-[4-(2-pyridyl)piperazin-1- yl]dodecyl]piperazine are dissolved in 5-10 ml of ethanol. Hydrochloric acid gas is bubbled for 5 minutes in the reaction medium. After stirring, the precipitate is collected by filtration, washed with diethyl ether and dried. The expected compound is obtained with a yield of 91% and appears as a white solid. It has the following characteristics: Melting point = 200°C Molar mass = C30H48N6. 2HCl: 565.66 g / mol NMR 1H (DMSO-d6): 11.41 (s; 2H); 8.13 (dd; J = 5.8; 1.8 Hz; 2H); 7.94 (t; J = 8.2 Hz; 2H); 7.30 (d; J = 9.0 Hz; 2H); 6.96 (t; J = 6.4 Hz; 2H); 4.48 (d; J = 8.2 Hz; 4H); 3.63 - 3.57 (m; 8H); 3.05 -3.17 (m; 8H); 1.82 - 1.68 (m; 4H); 1.31 - 1.28 (m; 16H). NMR 13 C (DMSO-d6): 155.3 (2C); 142.7 (2C); 141.7 (2C); 114.4 (2C); 110.9 (2C); 56.1 (2C); 50.5 (4C); 43.2 (4C); 29.3 (2C); 29.1 (2C); 28.9 (2C); 26.6 (2C); 23.4 (2C). Example 4 of the use of compounds (Ia), (Ib), and (Ic) as cancer agents 4.1 Seahorse consumer technology treatment of cells from a line of B human with the The analyzer known as “Seahorse” allows real-time assessment of mitochondrial respiration by measuring oxygen consumption (also known as OCR for “oxygen consumption rate”). The experiments were performed following the supplier’s recommendations (“Agilent_Seahorse XFe96”). To do this, 150,000 cells per well of a human B lymphoma cell line (“RL line, CVCL_1660”) were seeded in 180 µl of “Agilent_Seahorse XF RPMI” medium (supplemented with pyruvate and glucose) on a dedicated “Agilent_Seahorse 96-well” plate, previously treated with a “CellTak” solution according to the supplier’s recommendations (Corning).After 30 min of incubation in a CO2-free incubator, the plate was analyzed with the “Seahorse” using a protocol allowing the injection (shown by arrows in Figure 1) of increasing amounts of compound to obtain a final cumulative concentration of 1.2 µM, 2.5 µM, 5 µM and 10 µM, followed each time by a reading of the OCR (in pmol / min) for 10 min. Data normalization was performed by cell counting, using the device known as “Cytation 1 / 5 Cell Imaging Multi-Mode reader” (BioTek Instruments, Inc) coupled with the “Seahorse”.Figure 1 shows the effect on mitochondrial respiration of several compounds: a reference inhibitor Rotenone (Figure 1 a, ROT, curve with inverted empty triangles), the inhibitor known as “IACS-010759” currently being evaluated in clinical trials (Figure 1 a, IACS, curve with filled diamonds), compound (Ia) (Figure 1 b, curve with inverted filled triangles), compound (Ib) (Figure 1 b, curve with empty circles) and compound (Ic) (Figure 1 b, curve with filled circles). A control is used (DMSO, curve with filled squares) in each figure and corresponds to the medium studied without addition of compound (addition only of the DMSO diluent of the molecule stocks). In Figure 1a, the injection of a concentration of 1.2 µM induces an instantaneous and almost total inhibition of the OCR, in a similar manner for the two comparative compounds not in accordance with the invention: Rotenone and “IACS-010759”.Furthermore, the injection of increasing concentrations of compounds according to the invention induces a progressive inhibition of the OCR, similarly and stepwise for compounds (Ib) and (Ic), and progressively for compound (Ia). The almost total inhibition of the OCR is obtained with a concentration of 10 µM. In Figure 1, the standard deviation is indicated (SD). In conclusion, compounds (Ia), (Ib) and (Ic) behave as inhibitors of mitochondrial respiration (= also known as OXPHOS inhibitors), with a moderate and progressive effect compared to rotenone or “IACS-010759”. Equivalent results are obtained for the various lines tested. 4.2 Analysis of the effect on cell growth of treatment of human tumor cells of a B lymphoma cell line with compounds (Ia), (Ib) and (Ic) Cells of a human B lymphoma cell line (“Karpas422, CVCL_1325”) were seeded at a density of 100,000 cells per well, in a 96-well plate in the presence of a concentration of 10 µM of compound, in a volume of 100 µl of medium. After 48 hours of treatment, analyses of the effect on cell growth were carried out, either by counting live cells in flow cytometry (Figure 2 a), or using a biochemical fluorescence detection kit for live cells (Figure 2 b).Figure 2 shows the effect on cell growth of the treatment of cells in a conventional medium “Gibco RPMI1640 / 10% FCS” (denoted RPMI), with compounds (Ia), (Ib), and (Ic) in accordance with the invention (figure 2 a); and in a medium “Gibco Human Like Plasma Medium” (Gibco HPLM_Thermo Fisher Scientific) (denoted HLPM), mimicking the metabolic conditions of human plasma, with compounds (Ia), (Ib), and (Ic) in accordance with the invention and with four comparative compounds not in accordance with the invention: “IACS-010759” (denoted IACS), an inhibitor known under the reference “IM156” currently in clinical trials, Rotenone (denoted ROT), and an apoptosis inducer staurosporine (denoted STS) (figure 2 b). In the classic “Gibco RPMI1640 / 10% FCS” medium, the number of living cells was determined after double AnnexinV / PI labeling, and analysis with a flow cytometer known as “ATTUNE” (Thermo Fisher Scientific).In the medium "Gibco Human Like Plasma Medium", the number of living cells was evaluated using the "CellTiterFluor" kit and after measuring the relative fluorescence units (RFU) according to the supplier's recommendations (Promega). The term noted DMSO in Figure 2 corresponds to the control, i.e. identical medium without addition of compound. In Figure 2, the standard deviation (SD) is indicated. According to Figure 2, compounds (Ia), (Ib), and (Ic) inhibit cell growth by reducing the number of living tumor cells after 48 hours of treatment, even in culture medium conditions mimicking human plasma. The efficacy is similar to that obtained with the inhibitor "IACS-010759" or rotenone. This effect is lineage dependent (see Figure 3). 4.3 Analysis of the effect on cell growth of the treatment of human tumor cells from a large series of B and T lymphoma lines with the. Analyses of the effect on cell growth of the compound (Ia) in accordance with the invention compared to the compound "IACS-010769" (denoted IACS) not in accordance with the invention were carried out on a large series of 31 human B and T lymphoma lines, after AnnexinV / PI labeling and analysis with the "ATTUNE" cytometer (Thermo Fisher Scientific). This technology allows, in parallel with the number of living cells represented in Figure 2a, to evaluate the % of cells undergoing apoptosis. The results were represented in Figure 3 in the form of a heat map known as "HeatMap", with a black and white gradient, black representing the highest % of cells undergoing apoptosis. According to Figure 3, the toxicity of compounds (Ia) and "IACS-010759" varies depending on the lymphoma lines analyzed. In particular, the toxicity of compound (Ia) is increased compared to that of “IACS-010759” for a subgroup of 8 lines boxed on the diagram.These data confirm that these 2 compounds have a different metabolic targeting and mode of action. 4.4 Analysis of the antitumor efficacy of compound (Ia) in an in ovo model Preclinical evaluation analyses of the antitumor efficacy of compound (Ia) were conducted using the xenograft model on the chorioallantoic membrane (CAM) of the chick embryo. Figure 4 shows the implantation of human tumor cells of a B-cell lymphoma line (“SUDHL-4, CVCL_0539”) on the upper CAM of an embryo at day E9 (Figure 4 a), as well as the indication of the presence or absence of a tumor mass (Figure 4 b), and the relative amount of metastases (Figure 4 c). Treatments were carried out at days E11, E13, E15, E17.At day E18, the upper CAM portions containing the tumors were removed and weighed, and the lower CAM fragments were used to evaluate by RT-qPCR (polymerase chain reaction from an RNA sample) the presence of human cells revealing metastases. Doxorubucin (DOXO) at 0.0097 mg / kg was used as a positive control for treatment efficacy, compound (Ia) was used at 3 different doses [1]: 0.05 mg / kg, [2]: 0.15 mg / kg, and [3]: 0.45 mg / kg, and “IACS-010759” was used at 2 different doses [1]: 0.05 mg / kg, and [2]: 0.45 mg / kg. The negative control (denoted DMSO) represents the treatment with the diluent of the DMSO molecules. Figure 4b shows the effect of treatment on tumor volume directly. Doxorubucin treatment induces a 90% regression of the primary tumor volume.Comparatively, treatment with "IACS-010759" (denoted IACS) induced a regression of 44% [1] and 82% [2] and treatment with compound (Ia) induced a regression of 48% [1], 73% [2], and 70% [3]. In Figure 4 c, the effect of treatment on the relative quantity of metastases is directly observed. Treatment with doxorubucin induced a regression of 99% of the number of metastases. Comparatively, treatment with "IACS-010759" (denoted IACS) induced a regression of 69% [1] and 73% [2], and treatment with compound (Ia) induced a regression of 45% [1], 70% [2], and 72% [3]. In Figure 4, the standard deviation is indicated (SD). In conclusion, compound (Ia), which is chemically different and acts differently on the OCR, has an antitumor efficacy comparable to that of the molecule “IACS-010759”, in the preclinical model used in this example. Compound (Ia) also inhibits tumor dissemination. 4.5 Analysis of the effect on cell growth of the treatment of human cells of two sarcoma lines with compounds (Ia), (Ib) and (Ic) Human tumor cells of two lines of pediatric rhabdomyosarcoma-like sarcomas (“RD136, CVCL_1649”, Figure 5 a and “RH30, CVCL_0041”, Figure 5 b) were seeded in 96-well plates in the presence of a concentration of 10 µM of compound, in a volume of 100 µl of “Gibco Human Like Plasma Medium” (Gibco HPLM_Thermo Fisher Scientific). The effect of compounds (Ia), (Ib) and (Ic) was compared with that of the inhibitors "IACS-010759" (denoted IACS) and "IM156" (analogue of the metformin molecule) currently in clinical trials, Rotenone (denoted ROT), and the apoptosis inducer staurosporine (denoted STS). After 48 hours of treatment, the effect on the number of living cells was evaluated using the "CellTiterFluor" kit from Promega, in a manner identical to Figure 2 b.Figure 5 a shows the effect of treatment with the compounds on the number of live cells of the RD136 line (in HLPM medium as defined above) and Figure 5 b the effect on the number of live cells of the RH30 line (in HLPM medium as defined above), represented in % of relative fluorescence units (RFU) compared to the effect of the diluent of the compounds (DMSO). In Figure 5, the standard deviation is indicated (SD). In conclusion, compounds (Ia), (Ib) and (Ic) inhibit the cell growth of the RD136 and RH30 lines by reducing the number of live cells after 48 h of treatment. Their effect is similar to that obtained with the inhibitor “IACS-010759” or rotenone. The scope of application for these compounds can therefore be extended beyond hematological cancers such as lymphomas, for example to solid tumors such as pediatric human sarcomas exemplified here. 4.6 Analysis of the IC50 of a compound (Ia) in accordance with the invention compared to that of a compound of the prior art The IC50 of compound (Ia) was compared to that of a compound as described in WO2020 / 109506 corresponding to the following formula: The results showed an IC50 of 1.5 µM for compound (Ia) and 15.1 µM for the compound as described in WO2020 / 109506. This shows the improved performance of compound (Ia) compared to the compound of the prior art. These experiments were carried out using cells of a human B lymphoma line (“Karpas422, CVCL_1325”) which were seeded in “RPMI 1640” medium (11 mM glucose) supplemented with 10% serum, in the presence of increasing concentrations of compounds.After 48 h of treatment, analyses of the effect on cell growth were carried out using the live cell detection kit, as in Figure 2 b “CellTiter-Fluor Cell Viability Assay” (Promega), and following the supplier’s instructions. Example 5: Synthesis of compound Id. To a solution of 700 mg (3.49 mmol) of 1,12-dodecanediamine in 30 ml of dioxane are added 2.2 equivalents (7.69 mmol; 880 mg) of 2-chloropyrimidine and 5 equivalents (17.47 mmol; 2.4 g) of potassium carbonate. The reaction mixture is heated at reflux of dioxane for 20 h. After cooling, the dioxane is concentrated under reduced pressure. The residue obtained is taken up in 50 ml of ethyl acetate, washed once with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure. The derivative obtained is purified by chromatography on silica gel with as eluent: ethyl acetate / cyclohexane (90 / 10). The expected compound is obtained with a yield of 26% and appears in the form of a white solid. It has the following characteristics: melting point Mp = 105°C, C20H32N6 = 356.50 g / mol. NMR 1H (CDCl3): 8.20 (d; J = 4.8 Hz; 4H); 6.43 (t; J = 4.8 Hz; 2H); 5.11 (bs; 2H); 3.32 (td; J = 7.1; 5.7 Hz; 4H); 1.57–1.50 (m, 4H); 1.35 – 1.18 (m; 16H). NMR 13 C (CDCl3): 162.4 (2C); 158.0 (4C); 110.3 (2C); 41.5 (2C); 29.6 (2C); 29.5 (2C); 29.5 (2C); 29.4 (2C); 27.0 (2C). Example 6: synthesis of compound Ie To a solution of 800 mg (3.10 mmol) of 1,7-dibromoheptane in 30 ml of dioxane are added 2 equivalents (6.20 mmol; 1.0 g) of 2-piperazin-1-ylpyrimidine and 7 equivalents (21.70 mmol; 3.0 g) of potassium carbonate. The reaction mixture is heated to reflux of the dioxane for 20 h. After cooling, the dioxane is concentrated under reduced pressure. The residue obtained is taken up in 50 ml of dichloromethane, washed once with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure. The derivative obtained is purified by chromatography on silica gel with as eluent: dichloromethane / methanol / triethylamine (98 / 1 / 1). The expected compound is obtained with a yield of 30% and appears in the form of a white solid. It has the following characteristics: melting point Mp = 86°C, C23H36N8 = 424.58 g / mol. NMR 1H (CDCl3) : 8,23 (d ; J = 4,7 Hz ; 4H) ; 6,40 (t ; J = 4,7 Hz ; 2H), 3,78 – 3,75 (m ; 8H) ; 2,44 – 2,41 (m ; 8H) ; 2,31 – 2,27 (m ; 4H) ; 1,50 – 1,43 (m ; 4H) ; 1,28 – 1,24 (m ; 6H). RMN 13 C (CDCl3) : 161,7 (2C) ; 157,7 (4C) ; 109,8 (2C) ; 58,9 (2C) ; 53,2 (4C) ; 46,2 (2C) ; 43,7 (2C) ; 29,5 ; 27,6 (2C) ; 26,9 (2C). Exemple 7 : synthèse du composé If To a solution of 800 mg (3.10 mmol) of 1,7-dibromoheptane in 30 ml of dioxane are added 2 equivalents (6.20 mmol; 1.0 g) of 1-(2-pyridyl)piperazine and 7 equivalents (21.70 mmol; 3.0 g) of potassium carbonate. The reaction mixture is heated to reflux of the dioxane for 20 h. After cooling, the dioxane is concentrated under reduced pressure. The residue obtained is taken up in 50 ml of dichloromethane, washed once with a saturated solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure. The derivative obtained is purified by chromatography on silica gel with as eluent: dichloromethane / methanol / triethylamine (98 / 1 / 1). 150 mg (0.354 mmol) of 1-(2-pyridyl)-4-[7-[4-(2-pyridyl)piperazin-1-yl]heptyl]piperazine are dissolved in 5-10 ml of ethanol. Hydrochloric acid gas is bubbled for 2 minutes into the reaction medium.After stirring, the precipitate is collected by filtration, washed with diethyl ether and dried. The expected compound is obtained with a total yield of 82% and appears as a white solid. It has the following characteristics: melting point Mp = 210 °C, C25H38N6. 2HCl = 495.53 g / mol. NMR. 1 H (D2O): 8.06 (m; 2H); 7.93 (d; J=6.3Hz; 2H); 7.30 (d; J=9.2Hz; 2H); 7.06 (t; J=6.7Hz; 2H); 4.28 (d; J=14.5Hz; 4H); 3.73 (d; J=12.8Hz; 4H); 3.59 (t; J=13.5Hz; 4H); 3.30-3.13 (m; 8H); 1.71 (m; 4H); 1.34 (m; 6H). NMR 13C (D2O): 152.1 (2C); 145.6 (2C); 136.6 (2C); 115.0 (2C); 113.3 (2C); 57.1 (2C); 50.5 (4C); 43.2 (4C); 27.7; 25.5 (2C); 23.3 (2C). Example 8 of use of compounds (Id), (Ie), and (If) as cancer agents Cells of the human B lymphoma line (“RL, CVCL_1660”) were seeded at a density of 100,000 cells per well, in a 96-well plate in the presence of a concentration of 5 µM or 10 µM of compound, in a volume of 100 µl of RPMI medium. After 48 hours of treatment, analyses of the effect on cell growth were carried out by counting live cells in flow cytometry as in Figure 2 a. Figure 6 shows the inhibitory effect on cell growth of the treatment of cells in a conventional “Gibco RPMI1640 / 10% FCS” medium (denoted RPMI), with compounds (Ia), and (Id) in accordance with the invention. In Figure 6, the standard deviation is indicated (SD).Human tumor cells of the pediatric rhabdomyosarcoma sarcoma line (“RH30, CVCL_0041”) were seeded in 96-well plates in the presence of a concentration of 10 µM or 25 µM of compound, in a volume of 100 µl of “Gibco Human Like Plasma Medium” (Gibco HPLM_Thermo Fisher Scientific). After 48 h of treatment, the effect of compounds (Ia), (Ie) and (If) on cell growth was evaluated using the “CellTiterFluor” kit from Promega as in Figure 2 b. Figure 7 shows the effect of compound treatment on the growth of the RH30 line (in HLPM medium as defined above), represented in % of relative fluorescence units (RFU) relative to the effect of the compound diluent (DMSO). In Figure 7, the standard deviation is indicated (SD). In conclusion, compounds (Ia), (Ie) and (If) inhibit the cell growth of the RH30 line by reducing the number of living cells after 48 h of treatment.The scope of application for these compounds can therefore be extended beyond hematological cancers such as lymphomas, for example to solid tumors such as pediatric human sarcomas exemplified here.

Claims

Claims 1. A compound selected from the compounds conforming to formula (I), their pharmaceutically acceptable salts, and their pharmaceutically acceptable solvates, said formula (I) having the following structure: , in which: * R 1 , R 2 , and R 3 independently represent a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, -CF3, -CHO, -NH-NH2, -CO2H, -CH2OH, -CH2NH2, an alkoxy group -OR 7 , a group -NR 8 R 9 , a group -SR 10 , a group -C(O)R 11 , a group -CH2OR 12 , and a group - CH2NR 13 R 14 , with R 7 , R 8 , R 10 , R 11 , R 12 , and R 13 representing, independently of each other, an alkyl or cycloalkyl radical, and R 9 and R 14representing, independently of each other, a hydrogen atom, or an alkyl or cycloalkyl radical, * X 1 represents a nitrogen atom or a CR group 15 , with R 15 being a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group selected from -OH, -NH2, -SH, -CN, -CF3, -CHO, -NH-NH2, -CO2H, -CH2OH, -CH2NH2, an alkoxy group -OR 7 , a group -NR 8 R 9 , a group -SR 10 , a group -C(O)R 11 , a group -CH2OR 12 , and a group - CH2NR 13 R 14 *n is an integer ranging from 1 to 20, * R 4 represents a hydrogen atom, an alkyl radical, or a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected, * R 5 represents a hydrogen atom, an alkyl radical, or a divalent alkylene group forming a ring with Y 2and the nitrogen atom to which R 5 is connected, * Y 1 represents -CH2-, -NH-, or -O- when the group R 4 represents a hydrogen atom, or an alkyl radical; and represents -CH- or -N- when the R group 4 represents a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected, * Y 2 represents -CH2-, -NH-, or -O- when the group R 5 represents a hydrogen atom, or an alkyl radical; and represents -CH- or -N- when the R group 5 represents a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 4 is connected, and * R 6 represents one of the following two groups (IIa) and (IIb): , in which, R' 1 , R' 2 , and R' 3independently represent a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, an aryl radical, or a group chosen from -OH, -NH2, -SH, -CN, -CF3, -CHO, -NH-NH2, -CO2H, -CH2OH, -CH2NH2, an alkoxy group -OR' 7 , a group -NR' 8 R' 9 , a group -SR' 10 , a group -C(O)R' 11 , a group -CH2OR' 12 , and a -CH2NR' group 13 R' 14 , with R' 7 , R' 8 , R' 10 , R' 11 , R' 12 , and R' 13 representing, independently of each other, an alkyl or cycloalkyl radical, and R' 9 and R' 14 representing, independently of each other, a hydrogen atom, or an alkyl or cycloalkyl radical, and X 2 represents a nitrogen atom or a CR' group 15 , with R' 15 being a hydrogen atom, a halogen atom, an alkyl radical, a cycloalkyl radical, a aryl radical, or a group selected from -OH, -NH2, -SH, -CN, -CF3, -CHO, -NH-NH2, -CO2H, -CH2OH, -CH2NH2, an alkoxy group -OR' 7 , a group -NR' 8 R' 9 , a group -SR' 10 , a group -C(O)R' 11 , a group -CH2OR' 12 , and a group - CH2NR' 13 R' 14 1. A compound as defined in claim 1, for use in the treatment of cancers with altered metabolism, in particular in the treatment of cancers with OXPHOS metabolism.

2. A compound as defined in claim 1, for use in the treatment of lymphomas; solid tumors; and certain tumors that recur following chemotherapy.

3. A compound for use according to any one of the preceding claims, characterized in that X 1represents a nitrogen atom or a CH group.

5. Compound for use according to any one of the preceding claims, characterized in that R 4 represents a hydrogen atom or a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected, and R 5 represents a hydrogen atom or a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 5 is connected.

6. Compound for use according to any one of the preceding claims, characterized in that Y 1 represents -CH 4 2- when the R group represents a hydrogen atom, or an alkyl radical; and represents -N- when the R group 4 represents a divalent alkylene group forming a ring with Y 1 and the nitrogen atom to which R 4 is connected; and Y 2 represents -CH 2 - when the group R 5represents a hydrogen atom, or an alkyl radical; and represents -N- when the R group 5 represents a divalent alkylene group forming a ring with Y 2 and the nitrogen atom to which R 5 is connected.

7. Compound for use according to any one of the preceding claims, characterized in that Y 1 and Y 2 are identical.

8. A compound for use according to any one of the preceding claims, characterized in that: - when Y 1 represents -CH2-, n goes from 2 to 10, - when Y 2 represents -CH2-, n goes from 2 to 10, - when Y 1 represents -N-, -NH-, -CH- or -O-, n ranges from 6 to 18, - when Y 2 represents -N-, -NH-, -CH- or -O-, n ranges from 6 to 18.

9. Compound for use according to any one of the preceding claims, characterized in that when Y 1 and Y 2 represent -CH-, and R 6is a group of formula (IIa), then n is such that n ≥ 5 and / or R 1 , R' 1 , R 2 , R' 2 , R 3 , and R' 3 are different from -NH2; and when Y 1 and Y 2 represent -N-, and R 6 is a group of formula (IIa), then n is such that n ≥ 7.

10. Compound for use according to any one of the preceding claims, characterized in that R 6 is a group of formula (IIb).

11. Compound for use according to any one of the preceding claims, characterized in that the compound of formula (I) is selected from the following compounds:

12. Pharmaceutical composition comprising a compound as defined in any one of claims 1 and 4 to 11, and at least one suitable pharmaceutical vehicle.

13. Product comprising a compound as defined in any one of claims 1 and 4 to 11 and another active agent.

14. Compound selected from compounds conforming to formula (I'), their pharmaceutically acceptable salts, and their pharmaceutically acceptable solvates, said formula (I') having the following structure: in which: * R 1 , R 2 , R 3 , R 4 , R 5 , R 6 X 1 , Y 1 , Y 2 , and n are such as defined in claim 1, it being understood that: * when Y 1 and Y 2 represent -CH-, and R 6 is a radical of formula (IIa), then n ≥ 5 and / or R 1 , R' 1 , R 2 , R' 2 , R 3 , and R' 3are different from -NH2, and * when Y 1 and Y 2 represent -N-, and R 6 is a radical of formula (IIa), then n ≥ 7.

15. Compound according to claim 14, characterized in that R 6 is a group of formula (IIb).

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