FR3001219A1 - KINASE INHIBITORS - Google Patents

Abstract

The present invention relates to the indole, benzothiophene or benzofuran derivatives of formula (I) in which Y1 is chosen from an NH group, a sulfur atom or an oxygen atom, Y2 is chosen from a CH group or a Nitrogen, R9 and R10 may form a ring, as well as their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. Some of these compounds may also be useful in the treatment of cancer. It also relates to certain new corresponding compounds and their method of preparation.

Description

The present invention relates to the field of selective kinase inhibitors CLK1, DYRK IA and PIM 1 that can prevent or treat memory disorders associated with aging or Alzheimer's disease as well as other neurodegenerative diseases or treat cancer or certain viral infections, such as influenza, HIV, herpes or Herpes Simplex Virus (HSV) and influenza viruses. Thus, it relates to the use of derivatives of indoles, benzothiophene or benzofuran in the treatment of these diseases, as well as some of these derivatives as such, to their therapeutic application, especially in the treatment or prevention of diseases involving CLK1, DYRK lA and PIM 1 kinases.

More particularly, among neurodegenerative diseases, in addition to Alzheimer's disease, mention may be made of Down's syndrome, cortico-basal degeneration, Steele-Richardson-Olszwski's, Pick's, Parkinson's and Huntington's diseases. The products of the present invention cited can in particular be used for the treatment of primary tumors and / or metastases, in particular in gastric, hepatic, renal, ovarian, colon, prostate, lung (NSCLC and SCLC) cancers, glioblastomas, in thyroid, bladder, breast, melanoma, lymphoid or myeloid hematopoietic tumors, sarcomas, brain, larynx, head and neck cancers, lymphatic system, in cancers of the bones and pancreas.

The products of the invention can also be used for the treatment of benign cutaneous tumors, brain tumors and papillomas, prostate tumors and brain tumors, glioblastomas, medulloepitheliomas, medulloblastomas, neuroblastomas, embryonic origin tumors, astrocytomas , astroblastomas, ependymomas, oligodendrogliomas, plexus tumors, neuroepitheliomas, epiphyseal tumors, ependymoblastomas, malignant meningiomas, sarcomatoses, malignant melanomas and schwannomas. Among the cancers there may be mentioned hematopoietic and prostate cancers. The invention further relates to certain novel indole derivatives belonging to this family of compounds.

Alzheimer's disease is booming in developed countries due to the aging of the population. Currently, the only palliative treatments for this disease, available commercially, are either acetylcholinesterase inhibitors (galanthamine, rivastigmine, donepezil) or a noncompetitive NMDA receptor antagonist, memantine (Exibia). New therapeutic healing approaches are currently being considered. As such, the search for kinase inhibitors of the central nervous system has taken a considerable step forward because of the direct intervention of these proteins in the hyperphosphorylation of tau and their supposed influence on the secretion of Afl protein, two processes at the origin of specific links of Alzheimer's disease. In addition, the pathological action of central nervous system kinases is not confined to Alzheimer's disease and they are equally relevant targets in the treatment of other neurodegenerative diseases such as Down syndrome, corticobasal degeneration or the diseases of Steele Richardson-Olszewski, Pick, Parkinson and Huntington. Kinases are also involved in cancer. Inhibition of protein kinases has become a standard of modern clinical oncology. PIM1 belongs to a new class of serine / threonine kinases with distinct molecular and biochemical characteristics regulating different oncogenic pathways, for example the response to hypoxia, cell cycle progression and apoptosis resistance. PIM1 is overexpressed in human cancers and is associated with metastasis. In experimental models, inhibition of PIM1 suppresses cell proliferation and migration and induces apoptotic cell death. It can act in synergy with other chemotherapeutic treatments. DYRK1A kinase is involved in Down syndrome (trisomy 21) and in the development of Alzheimer's disease. The kinases of the CLK family are involved in the regulation of pre-mRNA splicing and as such are involved in many pathologies, and in particular in cancers and viral infections. The CLK target is also involved in neurodegenerative diseases such as Alzheimer's disease. C.Minot et al., "Photocyclization of stilbenes and related indole compounds: contribution to the use of the indices of reactivity", Tetrahedron Vol.36, 1980, 1209-1214, certain indole derivatives, are known. There is no mention in this article of any associated therapeutic effect.

E.Kianmehr et al., "A direct palladium-catalyzed route for the synthesis of benzo [a] carbazoles through sequential C-C bond formation and C-H bond functionalization", Eur. J. Org.Chem 2012, 256-259, a route of synthesis of benzo [a] carbazole compounds. No biological data for the synthesized compounds is described in the document. From C.Dieng et al., "Indole series study: VII (la) Synthesis of new pyridocarbazoles obtained by photocyclization of ((3-indolyl) -1 (pyridyl) -2-acrylonitriles (1b-d)" is known, J. Heterocyclic Chemistry, 1975, 12, 455-460, photocyclization of ((3-indolyl) -1 (pyridyl) -2-acrylonitriles This document is devoid of biological data relating to the compounds synthesized and described herein. and A.Shafiee et al., "Photochemical Synthesis of [1] Benzothieno [3,2-h] isoquinoline", J.Heterocyclic Chemistry, 1976, 141-144 a cyclization pathway from derivative 1- (3). benzo [b] -thienyl) -2- (3-pyridyl) acrylonitrile No biological activity is described in relation to all of the compounds described herein, and W02010 / 150211 discloses The proposed derivatives have demonstrated an inhibitory activity of MKLP-2. discloses no cyclized derivative of benzo [a] carbazole or pyrido [a] carbazole type. In contrast, a number of non-cyclized compounds are described herein without any mention of any activity on the kinases, let alone any mention of any activity on CLK1, DYRK kinases. lA and PIM 1.

There is therefore a need to find new ways to combat neurodegenerative diseases, depression, skizophrenia, viral infections and cancer. According to one of its aspects, the present invention relates to the indole, benzothiophene or benzofuran derivatives of formula (I) R10 (I) in which Y1 is chosen from an NR5 group, a sulfur atom or an oxygen atom. Y2 is selected from CH or N, R2 is hydrogen, OH, (C1-C6) alkyl or (C1-C4) alkyl, (C1-C4) alkoxy, a group -O (CH2) .Ar, a group -000 (C 1 -C 4) alkyl e, a group -000 (CH 2). (C 1 -C 4) alkoxy, a group -NHCOO (C 1 -C 4) ) alkyl e, a halogen atom, a -SH group, a thio (C1-C4) alkyl group, a -NH2 group, a -SO2 (Ci-C4) alkyl group, a -SO2NR5R6 group, a nitro group or a -CONR5R6 group, Ar represents an aryl group, such as a phenyl group, n represents an integer between 1 and 4, R9 represents a heteroaryl group which may be chosen from a thienyl, pyridyl, oxazolyl, pyrimidinyl and thiazolyl group, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazoly tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl or tetrazolyl, especially chosen from a quinolyl, isoquinolyl, pyridyl and imidazolyl group; , thienyl, pyrazolyl and pyrrolyl, said heteroaryl group being optionally substituted with one or two groups selected from (C 1 -C 4) alkyl, OH, (C 1 -C 4) alkoxy, -0 (CH2) .Ar, a -OCO (C1-C4) alkyl group, a -000 (CH2) group, (C1-C4) alkoxy group, a -NHCOO (C1-C4) alkyl group, a halogen atom, a -SH group, a thio (C1-C4) alkyl group, a -NH2 group, a -SO2 (C1-C4) alkyl group, a -SO2NR5R6 group, a nitro group and a -NHCOR5R6 group, - a R11 group, a Pyr group. H is pyridyl, -CH (CN) R11, C (CN) = NR11 or -C (CN) = CHR11, R11 is aryl, such as phenyl, or a group heteroaryl, which may be selected from thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl or tetrazolyl, especially chosen from a pyridyl group, a thienyl group, a pyrazolyl, pyrroloyl, imidazolyl group, the said phenyl or heteroaryl group being optionally substituted by one or two groups selected from a group (C 1 -C 4); C4) alkyl, (C1-C4) alkoxy, halogen, -NR5R6, -CONR5R6, CN, -OH, -SH, thio (C1-C4) ) alkyl, -NH2 group, -SO2 (C1-C4) alkyl group, -SO2NR5R6 group and a nitro group, R10 represents a hydrogen atom, a (C1-C6) alkyl or (C1-C4) alkyl group, an aryl group, such as a phenyl group or a heteroaryl group, which may be chosen from a thienyl, pyridyl or oxazo group; lyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl or tetrazolyl, especially chosen from a pyridyl group, a thienyl group, R5 and R6 independently represent a hydrogen atom or a (C1-C4) alkyl group, or else R9 and R10 together with the indolyl group carrying them form a saturated, unsaturated or partially saturated 6-membered ring, which may comprise, as the atom forming this ring, an -NH- group and / or a -CO- group, said cycle being able to be substituted by one or two group (s) chosen (s) from a -CN group and a heteroaryl group may be selected from thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3-ox adiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl or tetrazolyl, especially chosen from a pyridyl group and a thienyl group, said 6-membered ring being able to be represented in particular as follows: CN (R 9) HetAr NH (R 10) 0, where HetAr represents a heteroaryl group, or R9 and R10 together with the indolyl group carrying them a (R9) R4 group (R10) in which X1, X2, X3 and X4 represent a CH group, an atom of carbon or a nitrogen atom, it being understood that at most only one of Xl, X2, X3 and X4 is a nitrogen atom, R1 represents a hydrogen atom, a (C1-C6) alkyl group or (Ci -C4) alkyl, (C1-C4) alkoxy group, thio- (C1-C4) alkyl group, -NR5R6 group, -CONR5R6 group or CN group, -OH group, -SH group, thio (C1-C4) alkyl group, -NH2 group, -SO2 (C1-C4) alkyl group, -SO2NR5R6 group and nitro group, and R4 represents -CN group, -CONH2 group, -CH2NR5R6 group or a group -CH2NHCOCH 3, as well as their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. According to a particular embodiment, Y 1 is a group NR 5, Y 2 is a group CH with R 5 as defined above and preferably being a hydrogen atom. According to another particular embodiment, the present invention relates to the indole, benzothiophene or benzofuran derivatives of formula (Ia) X, wherein R 1 represents a single bond or no bond, the a double bond bearing the group R 4 being of configuration E when it represents an absence of bond, Y 1 is chosen from an NH group, a sulfur atom or an oxygen atom, Y 2 is chosen from a CH group or a nitrogen atom X1, X2, X3 and X4 represent a CH, a carbon atom or a nitrogen atom, it being understood that at most only one of X1, X2, X3 and X4 is a nitrogen atom, R1 represents a hydrogen atom, a (C 1 -C 6) alkyl or (C 1 -C 4) alkyl group, a (C 1 -C 4) alkoxy group, a group -NR 5 R 6, a group -CONR 5 R 6, a halogen atom, a group CN , a -OH group, -SH group, a thio (C1-C4) alkyl group, -NH2 group, -SO2 (C1-C4) alkyl group, -SO2NR5R6 group and a nitro group, R2 Y1 R2 represents hydrogen, OH, (C 1 -C 6) alkyl or (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy, -O (CH 2) AR, -000 ( C1-C4) alkyl, -000 (CH2). (C1-C4) alkoxy, -NHCOO (C1-C4) alkyl, halogen, -SH, thio (C1-C4) ) alkyl, -NH2 group, -SO2 (C1-C4) alkyl group, -SO2NR5R6 group and a nitro group, R3 represents a hydrogen atom, a (C1-C4) alkyl group, an aryl group, such as a phenyl group or a heteroaryl group, which may be chosen from a thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl or pyridazinyl group, 3-oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl and tetrazolyl, such as a thienyl group, R4 represents a -CN group, a -CONH2 group, a -CH2NR5R6 group, a C = C group - CH2NHCOCE13, a group -CC-1-1 R5 and R6 represent independently, a hydrogen atom or a (C 1 -C 4) alkyl group, Z represents a CH group or a nitrogen atom, Ar represents an aryl group, such as a phenyl group, and n represents an integer between 1 and 4, and their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections.

The compounds of formula (I) may comprise one or more asymmetric carbon atoms. They can therefore exist as enantiomers or diastereoisomers. These enantiomers, diastereoisomers, as well as their mixtures, including the racemic mixtures, form part of the invention.

The compounds of formula (I) may exist in the form of bases or addition salts with acids. Such addition salts are part of the invention. These salts are advantageously prepared with pharmaceutically acceptable acids, but the salts of other acids that are useful, for example, for the purification or the isolation of the compounds of formula (I) are also part of the invention. Pharmaceutically acceptable salts include inorganic or organic acid salts. Representative examples of acceptable inorganic acids include hydrochloric, hydrobromic, iodic and phosphoric acids. Representative examples of organic acids include formic, acetic, trichloroacetic, trifluoroacetic, propionic, benzoic, cinnamic, citric, fumaric, maleic and methanesulfonic acids. Other examples of addition salts with inorganic and organic acids include pharmaceutically acceptable salts as listed in J. Pharm. Sci. 1977, 66, 2 and in Handbook of Pharmaceutical Salts: Properties, Selection, and Use edited by P. Heinrich Stahl and Camille G. Wermuth 2002. In a particular embodiment, the salt is selected from the group consisting of the maleate, hydrochloride, hydrobromide and methanesulfonate. The compounds of general formula (I) may be in the form of hydrates or solvates, namely in the form of combinations or combinations with one or more water molecules or with a solvent. Such hydrates and solvates are also part of the invention. In the context of the present invention, the following terms are understood: - (Ct-C,) where t and z may take the values from 1 to 6, a carbon chain that may have from t to z carbon atoms, for example (C1- C3) a carbon chain which may have from 1 to 3 carbon atoms; - "halogen" an atom chosen from fluorine, chlorine, bromine and iodine, in particular from fluorine, chlorine, bromine, and even more particularly from chlorine and bromine; an alkyl group: a saturated linear or branched aliphatic group. By way of examples, mention may be made of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl and pentyl groups, and the like. The term (C1-C4) alkyl relates more particularly to the methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl groups. The term (C1-C6) alkyl relates more particularly to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl or hexyl groups; an alkoxy group: an -O-alkyl group in which the alkyl group is as previously defined. The term (C1-C4) alkoxy relates more particularly to the methoxy, ethoxy, propyloxy, isopropyloxy, tert-butyloxy, and isobutyloxy groups, a thio (C1-C4) alkyl group corresponds to an alkyl group as defined above. top bound by a -S- bond. The term thio- (C1-C4) alkyl group refers to thio-methyl, thio-ethyl, thio-propyl and thio-butyl groups. an aryl group is a mono- or biaromatic hydrocarbon ring containing from 6 to 12 carbon atoms. Said aryl group may be in particular an aryl group, a biphenyl group or a naphthyl group and in particular a phenyl group, said phenyl group possibly being substituted by one to three groups selected from a group -OH, group (Ci-C4) alkoxy a -SH group, a thio (C 1 -C 4) alkyl group, a group -NH 2, a group -SO 2 (C 1 -C 4) alkyl, a group -SO 2 NR 5 R 6, with R 5 and R 6 as defined above and a nitro group, - A heteroaryl group is an aromatic group, mono- or polycyclic comprising between 5 and 14 atoms and comprising at least one heteroatom such as nitrogen, oxygen or sulfur. Examples of such heteroaryl groups are: pyridyl, dihydroypyridyl, thiazolyl, thiophenyl, furyl, azocinyl, pyranyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, benzofuranyl, thianaphthalenyl, indolyl, indolenyl, quinolyl, isoquinolyl, benzimidazolyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, triazinyl, 6H-1,2,5-thiadiazinyl, 2H, 6H-1,5,2-dithiazinyl, thianthrenyl, isobenzofuryl, chromenyl, xanthenyl, phenoxanthinyl, 2H-pyrrolyl, isothiazolyl, isoxazolyl, pyrazinyl, pyridazinyl, indolizinyl , isoindolyl, 3H-indolyl, 1H-indazolyl, purinyl, 4H-quinolizinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, pyrimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl , furazanyl, phenoxazinyl, isochromanyl, chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, indolinyl, iso oindolinyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, benzothienyl, benzothiazolyl, isatinyl, dihydropyridyl, pyrimidinyl, pyrazinyl, s-triazinyl, oxazolyl, thiofuranyl. According to a preferred embodiment, the heteroaryl group is a thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, furyl, pyrazolyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3 group. oxadiazolyl, 1,3,4-oxadiazolyl, triazolyl or tetrazolyl, more particularly a thienyl group, a pyrridyl group, a quinolyl group, an isoquinolyl group, an imidazole group or a pyrrolyl group. Among the compounds of general formula (Ia) according to the invention, a first subgroup of compounds is constituted by the compounds for which Z is a CH group.

Among the compounds of general formula (Ia) according to the invention, a second subgroup of compounds consists of the compounds for which X2 is a nitrogen atom and X1, X3 and X4 are CH groups. Among the compounds of general formula (Ia) according to the invention, a third subgroup of compounds is constituted by the compounds for which R4 is a -CN group. Among the compounds of general formula (Ia) according to the invention, a fourth subgroup of compounds is constituted by the compounds for which is a bond, forming a tetracyclic compound. Among the compounds of general formula (Ia) according to the invention, a fifth subgroup of compounds is constituted by the compounds for which there is no binding. According to a particular embodiment, the present invention relates to the indole, benzothiophene or benzofuran derivatives of formula (I), for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections, in which the groups R9 and R10 do not form a ring. According to this same embodiment and more particularly, the present invention relates to indole benzothiophene or benzofuran derivatives of formula (I) in which Y1, Y2 and R2 are as defined above, R9 represents - a heteroaryl group chosen from a quinolyl, isoquinolyl, pyridyl group, said heteroaryl group possibly being substituted by a (C 1 -C 4) alkyl group, a -NHCO (C 1 -C 4) alkyl group, an OH group, a (C 1 -C 4) alkoxy group, a -O (CH2) .Ar group, -OCO (C1-C4) alkyl group, -000 (CH2). (C1-C4) alkoxy group, -NHCOO (C1-C4) alkyl group, an atom of halogen, -SH group, thio (C1-C4) alkyl group, -NH2 group, -SO2 (C1-C4) alkyl group, -SO2NR5R6 group, nitro group or -CONR5R6 group, or -R11 group Pyr where Pyr H is pyridyl, -CH (CN) R 11, C (CN) = NR 11 or -C (CN) = CHR 11, Ar is aryl, such as phenyl group, R11 represents a phenyl group or a heteroaryl group, selected from a pyridyl group, a thienyl group, a pyrazolyl group, an imidazolyl group, a pyrrolyl group, the said phenyl or heteroaryl group being optionally substituted by one or two groups chosen from a (C1-C4) alkyl group, a (C1-C4) alkoxy group, a halogen atom, a group -NR5R6, a group -CONR5R6 and a group CN, R10 represents a hydrogen atom, a group (Ci -C6) alkyl or (C1-C4) alkyl, a phenyl group or a heteroaryl group selected from a pyridyl group and a thienyl group, R5 and R6 independently represent a hydrogen atom or a (C 1 -C 4) alkyl group e, as well as their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. The compounds of formula (II), included in the definition of formulas (I), and (Ia) for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections, are also part of the invention. The compounds of formula (II) are defined as follows: in which R 1, R 2, R 3, R 4, Z, X 1, X 2, X 3, Y 1 and Y 2 are as defined above.

According to one particular embodiment, the present invention relates to the compounds of formula (II) in which X 1, X 2, X 3, R 3, Z, Y 1 and Y 2 are as defined above, R 1 represents a hydrogen atom, a group (C1-C4) alkyl, (C1-C4) alkoxy, -NR5R6, -CONR5R6, CN or halogen, R2 is hydrogen, OH, (C1-C4) alkoxy group, -O (CH2) .phenyl group, -OCO (C1-C4) alkyl group, -000 (CH2). (C1-C4) alkoxy group, -NHCOO (Ci -C 4) alkyl or a halogen atom, C = C 15 represents a group -CN, a group R 4 or a group CC-H and R 5 and R 6 independently represent a hydrogen atom or a group (C 1 -C 4) C4) alkyl, and their pharmaceutically acceptable salts, in the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. Among the compounds of formula (II), in accordance with the invention, a first subgroup of compounds is constituted by the compounds for which X 2 is N.

Among the compounds of formula (II), in accordance with the invention, a second subgroup of compounds is constituted by the compounds for which X 1 is N. Among the compounds of formula (II), in accordance with the invention, a third subgroup of compounds is constituted by the compounds for which none of X1, X2, X3 and X4 is N. Among the compounds of formula (II), in accordance with the invention, a fourth subgroup of compounds is constituted by the compounds for which Y1 is different from Na Among the compounds of formula (II), in accordance with the invention, a fifth subgroup of compounds is constituted by compounds for which Y2 is different from C, and in particular is N. Among the compounds of formula (II), in accordance with the invention, a sixth subgroup of compounds is constituted by the compounds for which Z is N. Among the compounds of formula (II), in accordance with the invention, a seventh subgroup of compounds is constituted by comp Examples where R 4 is different from CN and C = C 1 or especially is a group H Of the compounds of formula (II) listed below in Table I, some are novel and form part of the invention. . These compounds No. 7, 11, 16, 18, 19, 22, 25, 27, 31 and 34. According to another embodiment, the present invention also relates to a family of compounds of formula (IIa) in as such wherein R 1, Z, R 4, X 1, X 2, X 3, R 2, Y 2 and Y 1 are as previously defined, R 3 represents an aryl group, such as a phenyl group or a heteroaryl group, such as a group which may be selected from thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3-oxadiazolyl, 1,3, 4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl and tetrazolyl, in particular chosen from a pyridyl group, a thienyl group, a pyrazolyl group, the said phenyl or heteroaryl group being optionally substituted with one or two groups chosen from a (C 1 -C 4) alkyl group , a (C 1 -C 4) alkoxy group, a halogen atom, a group -NR 5R6, -CONR5R6, CN, -OH, -SH, thio (C1-C4) alkyl, -NH2, -SO2 (C1-C4) alkyl, -SO2NR5R6, and a nitro group, R5 and R6 being as defined above, and their pharmaceutically acceptable salts. Among these compounds of formula (IIa) are in particular compounds Nos. 18 and 19 of Table I below.

According to this same embodiment, the present invention may in particular relate to a compound of formula (IIa) defined above in which R1, X1, X2, X3, R2, Y2 and Y1 are as defined previously, R4 is a group -CN, Z is -CH, R3 is phenyl optionally substituted by (C1-C4) alkyl, halogen, -OH, or heteroaryl selected from thienyl and pyrrolyl, and as their pharmaceutically acceptable salts.

The compounds of formula (III), included in the definition of formula (I), and for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections, are also part of the invention. The compounds of formula (III) are defined as follows: wherein R1, R2, R4, X1, X2, X3, X4, Y1 and Y2 are as defined above. According to a particular embodiment, the present invention relates to the compounds of formula (III) in which X 1, X 2, X 3, Y 1 and Y 2 are as defined above, R 1 represents a hydrogen atom, or a group (C 1 C4) alkoxy, R2 is hydrogen, (C1-C4) alkoxy or halogen, R4 is -CN, -CONH2, -CH2NR5R6 or -CH2NHCOCH3, and R5 and R6 independently represent a hydrogen atom or a (C1-C4) alkyl group, as well as their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections.

Among the compounds of formula (III), in accordance with the invention, a first subgroup of compounds is constituted by the compounds for which Y1 = N. Among the compounds of formula (III), in accordance with the invention, a second subgroup of compounds is constituted by the compounds for which X 2 is N. Among the compounds of formula (III), in accordance with the invention, a third subgroup of compounds is constituted by the compounds for which X 1 is N. Among the compounds of formula (III), in accordance with the invention, a fourth subgroup of compounds is constituted by the compounds for which X 3 is N. the compounds of formula (III), in accordance with the invention, a fifth subgroup of compounds is constituted by the compounds for which X4 is N.

Among the compounds of formula (III), in accordance with the invention, a sixth subgroup of compounds consists of compounds for which none of Xl, X2, X3 and X4 are N. Among the compounds of formula (III ), according to the invention, a seventh subgroup of compounds is constituted by compounds for which Y2 is N.

It also relates to new compounds. Thus, the compounds of formula (III) as defined above are new with the exception of the following compounds: the compound for which Y 2 = CH, R 1 = R 2 = H, R 4 = CN, X 1 = X 3 = X 4 = CH, and X2 = N, - the compound for which Y2 = CH, R1 = R2 = H, R4 = CN, X1 = X2 = X3 = CH, and X4 = N, - the compound for which Y2 = CH, R1 = R2 = H, R4 = CN, X1 = X2 = X4 = CH, and X3 = N, - the compound for which Y2 = CH, R1 = R2 = H, R4 = CN, X1 = X2 = X3 = X4 = CH and the compound for which Y2 = CH, R1 = R2 = H, R4 = CN, X2 = X3 = X4 = CH, and X1 = N, and - the compound for which Y2 = CH, R2 = H, R4 = CN , X1 = X3 == X4 = CH, X2 = N, and R1 = CH3 positioned on X2.

The compounds of formula (Ib), included in the definition of formula (I), also form part of the invention. The subject of the present invention is therefore also the compounds of formula (Ib): R 11 (Ib) in which Y 1, Y 2, R 2 and R 11 are as defined above, as well as their pharmaceutically acceptable salts. According to a particular embodiment, the present invention relates to a compound of formula (Ib) in which Y1 is a group NR5, where R5 represents a hydrogen atom or a (C1-C4) alkyl group. According to another embodiment, Y2 is a CH group. According to another embodiment, R 11 is a heteroaryl group, this heteroaryl group possibly being chosen from a thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl or triazinyl group, pyrazinyl, pyridazinyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl or tetrazolyl, especially chosen from a pyridyl group, a thienyl group, a pyrazolyl, pyrroloyl, imidazolyl group, the said heteroaryl group; optionally substituted with one or two groups selected from (C1-C4) alkyl, (C1-C4) alkoxy, halogen, -NR5R6, -CONR5R6, CN , -OH, -SH, thio (C1-C4) alkyl, -NH2, -SO2 (C1-C4) alkyl, -SO2NR5R6 and nitro. According to this last embodiment, the heteroaryl group is in particular a pyridyl group optionally substituted with one or two groups as defined above. According to another embodiment, the present invention relates to a compound of formula (Ib) in which Y 1 is a group NR 5, R 5 being as defined above, Y 2 is a group CH and R 11 is a pyridyl group optionally substituted with a or two groups as previously defined. The compounds of formula (Ic), included in the definition of formula (I), also form part of the invention. The subject of the present invention is therefore also the compounds of formula (Ic): Y1 in which Y1 and Y2 are as defined above, and R9 represents a quinolyl or isoquinolyl group which may optionally be substituted by one or two groups chosen from (C1-C4) alkyl group, OH group, (C1-C4) alkoxy group, -O (CH2) Ar group, -OCO (C1-C4) alkyl group, -000 group ( CH 2). (C 1 -C 4) alkoxy, -NHCOO (C 1 -C 4) alkyl group, halogen atom, -SH group, thio (C 1 -C 4) alkyl group, -NH 2 group, - SO 2 (C 1 -C 4) alkyl, a group -SO 2 NR 5 R 6, a nitro group and a group -NHCOR 5 R 6, the groups R 5, R 6, Ar and n being as defined above, as well as their pharmaceutically acceptable salts.

According to a particular embodiment, the present invention relates to a compound of formula (Tc) in which Y1 is an NR5 group, R5 representing a hydrogen atom or a (C1-C4) alkyl group. According to another embodiment, Y2 is a CH group.

According to another embodiment, R 9 represents a quinolyl or isoquinolyl group which may be optionally substituted with a group chosen from a group -NN 12, a group -NHCOO (C 1 -C 4) alkyl and a group -NHCOHR 5, R 5 being a group (C - C4) alkyl e. According to another embodiment, the present invention relates to a compound of formula (Ic) in which Y 1 is an NR 5 group, R 5 being as defined above, Y 2 is a CH group and R 9 represents a quinolyl or isoquinolyl group which may be optionally substituted with a group selected from -NH2, -NHCOO (C1-C4) alkyl and -NHCOHR5, wherein R5 is (C1-C4) alkyl e.

The compounds of formula (Id), included in the definition of formula (I), also form part of the invention. The subject of the present invention is therefore also the compounds of formula (Id): R 10 (Id) in which Y 1, Y 2 and R 2 are as defined above, one of the groups R 9 and R 10 is a hydrogen atom and the another group of R 9 and R 10 groups is a heteroaryl group comprising from 6 to 8 or from 10 to 14 members, such as a pyridyl group, said heteroaryl group possibly being substituted with one or two groups chosen from a group ( C 1 -C 4) alkyl, OH, (C 1 -C 4) alkoxy, -O (CH 2) AR, -OCO (C 1 -C 4) alkyl, -000 (CH 2). -C4) alkoxy, -NHCOO (C1-C4) alkyl, halogen, -SH, thio (C1-C4) alkyl, -NH2, -SO2 (C1-C4) alkyl , a group -SO2NR5R6, a nitro group and a group -NHCOR5R6, the groups R5, R6, Ar and n being as defined above, as well as their pharmaceutically acceptable salts.

According to a particular embodiment, the present invention relates to a compound of formula (Id) in which Y 1 is a group NR 5, R 5 representing a hydrogen atom or a group (C 1 -C 4) alkyl. According to another embodiment, Y2 is a CH group.

According to another embodiment, one of the groups R9 and R10 is a hydrogen atom and the other group of R9 and R10 groups is a pyridyl group which may be optionally substituted with a group chosen from a group (Ci-C4) alkyl, OH, (C 1 -C 4) alkoxy, -NHCOO (C 1 -C 4) alkyl, halogen, -NH 2 and -NHCOR 5 R 6, with R 5, R 6 being as previously defined. According to another embodiment, the present invention relates to a compound of formula (Id) in which Y 1 is a group NR 5, R 5 being as defined above, Y 2 is a group CH and one of the groups R 9 and R 10 is one hydrogen atom and the other group of R9 and R10 groups is a pyridyl group which may be optionally substituted with a group chosen from a (C1-C4) alkyl group, an OH group and a (C1-C4) alkoxy group, a -NHCOO (Ci-C4) alkyl group, a halogen atom, a group -NH2 and a group -NHCOR5R6, the groups R5, R6 being as defined above. The compounds of formula (Ie), included in the definition of formula (I), also form part of the invention. The present invention therefore also relates to the compounds of formula (Ie) R 2 NH HetAr (Ie) in which Y1, Y2, R2 and HetAr are as defined above, as well as their pharmaceutically acceptable salts.

According to a particular embodiment, the present invention relates to a compound of formula (Ie) in which Y1 is a NR5 group, R5 representing a hydrogen atom or a (C1-C4) alkyl group. According to another embodiment, Y2 is a CH group. According to another embodiment, the HetAr group may be chosen from a thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl or pyridazinyl group. , 3-oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl or tetrazolyl, especially chosen from a pyridyl group and a thienyl group or from a pyridyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, triazinyl or pyrazinyl group, pyridazinyl, quinolyl or isoquinolyl especially a pyridyl group, more particularly from a pyridyl, pyrimidinyl, triazinyl, pyrazinyl, pyridazinyl, quinolyl or isoquinolyl group, especially a pyridyl group. According to another embodiment, the present invention relates to a compound of formula (Ie) in which Y 1 is a group NR 5, R 5 being as defined above, Y 2 is a group CH and the group HetAr may be chosen from a group thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl or tetrazolyl, in particular chosen from a pyridyl group and a thienyl group or from a pyridyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, triazinyl, pyrazinyl, pyridazinyl, quinolyl or isoquinolyl group, in particular a pyridyl group, more particularly from a group pyridyl, pyrimidinyl, triazinyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl especially a pyridyl group. Compounds (Ib), (Tc), (Id) and (Ie) may especially be useful in the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. As neurodegenerative diseases is meant in particular Alzheimer's disease. Down syndrome, basal cortical degeneration, Steele-Richardson-Olszwski, Pick, Parkinson's and Huntington's diseases, depression and schizophrenia may also be mentioned. As viral diseases include HIV, influenza, herpes or herpes simplex virus (HSV) or Influenza virus. The present invention also extends to the compounds of formula (III), (IIa), (Ib), (Ic), (Id) and (Ie) as defined above, for the treatment of cancer. The products of the present invention cited can in particular be used for the treatment of primary tumors and / or metastases, in particular in gastric, hepatic, renal, ovarian, colon, prostate, lung (NSCLC and SCLC) cancers. , glioblastomas, thyroid, bladder, breast, melanoma, lymphoid or myeloid hematopoietic tumors, sarcomas, brain, larynx, head and neck cancers, lymphatic system, cancers of the bones and pancreas. The products of the present invention cited can also be used for the treatment of benign skin tumors, brain tumors and papillomas, prostate tumors and brain tumors, glioblastomas, medulloepitheliomas, medulloblastomas, neuroblastomas, embryonic origin tumors, astrocytomas, astroblastomas, ependymomas, oligodendrogliomas, plexus tumors, neuroepitheliomas, epiphyseal tumors, ependymoblastomas, malignant meningiomas, sarcomatoses, malignant melanomas, and schwannomas In particular, hematopoietic cancer or prostate cancer may be mentioned. Among the compounds of formula (I) according to the invention, there may be mentioned the following compounds, which are new and form part of the invention: (Z) -3- (5-fluoropyridin-3-yl) -2 - (5-methoxy-1H-indol-3-yl) -acrylonitrile (Compound No. 7) - (Z) -2- (7-methoxy-1H-indol-3-yl) -3-pyridin-3-yl acrylonitrile (Compound No. 11), (Z) -2- (5-methoxy-1H-indol-3-yl) -346- (methylamino) -pyridin-3-yl] acrylonitrile (Compound No. 16), - (Z) -2- (2-phenyl-1H-indol-3-yl) -3- (pyridin-3-yl) -acrylonitrile (Compound No. 18), (Z) -3- (pyridin-3- y1) -242- (thiophen-3-yl) -1H-indol-3-yl] -acrylonitrile (Compound No. 19), - (Z) -2- (5-benzyloxy-1H-indol-3-yl) 3-pyridin-2-yl-acrylonitrile (Compound No. 22), - (Z) -2- (1H-indol-3-yl) -3- (3-methoxy-phenyl) -acrylonitrile (Compound No. 25 ), (Z) -2- (5-methoxy-1-methyl-1H-indol-3-yl) -3-pyridin-3-yl-acrylonitrile (Compound No. 27), (Z) -3- (pyridin) -3-yl) -2- (6-methoxy-1H-pyrrolo [2,3-b] pyridin-3-yl) -acrylonitrile (Compound No. 31), - (E) -5-Methoxy-3- [ 1- (pyridin-3-y1) -4- (pyridin-4 1H-α-1-en-3-yn-2-yl] -1Hindole (Compound No. 34), 1,8-dimethoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile ( compound 36), 9-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (compound 37), 9-methoxy-11H-pyrido [4,3-a] carbazole 6-carboxamide (compound 38), 9-methoxy-11H-pyrido [4,3-a] carbazole-6-methanamine (compound 39), 1,9-dimethoxy-11H-pyrido [4, 3-a] carbazole-6-carbonitrile (compound No. 40), 1,9-dimethoxy-11H-pyrido [4,3-a] carbazole-6-carboxamide (compound No. 41), - N - [( 9-methoxy-11H-pyrido [4,3-a] carbazol-6-yl) methyl] acetamide (compound no. 42), 1- (9-methoxy-11H-pyrido [4,3-a] carbazol 6-yl) -N, N-dimethylmethanamine (Compound No. 43), 10-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 44), -8-chloro 11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 45), -8-fluoro-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 46), 7-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 47), 10-methoxy-11H-pyrido [4,3-a] ca rbazole-6-carboxamide (Compound No. 48), 11H-pyrido [3 ', 2': 4,5] -9-methoxypyrrolo [2,3-f] isoquinoline-6-carbonitrile (Compound No. 49), 8-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 50), 11H-pyrido [3 ', 2': 4,5] pyrrolo [2,3-f] isoquinoline-6-carbonitrile (Compound No. 55) - 2- (5-methoxy-1H-indol-3-yl) -2- (pyridin-3-yl) -acetonitrile (Compound No. 56), - N- [ 7- (5-methoxy-1H-indol-3-yl) -isoquinolin-6-yl] -acetamide (Compound No. 57), - (Z) -2- (5-methoxy-1H-indol) -3- yl) -3- (1H-pyrrol-3-yl) -acrylonitrile (Compound No. 60), (Z) -3- (1H-imidazol-4-yl) -2- (5-methoxy-1H-indole) 3-yl) -acrylonitrile (Compound No. 61), 20-6-methoxy-2- (pyridin-4-yl) -1H-pyrrolo [2,3-b] pyridine (Compound No. 62), -6- methoxy-3- (pyridin-4-yl) -1H-pyrrolo [2,3-b] pyridine (compound 63), 6-methoxy-1-oxo-3- (pyridin-3-yl) -2 9-Dihydro-1H-pyrido [3,4-Mn-4-carbonitrile (Compound No. 64), and - their pharmaceutically acceptable salts. The preparation of the compounds of the invention is described below. The processes for synthesizing the compounds according to the invention can in particular be differentiated according to whether or not R9 and R10 form a ring. A - Synthesis of the compounds for which R9 and R10 do not form, together with the indolyl group carrying them, a ring A-1 Synthesis of compounds for which R9 or R10 represents a heteroaryl group and the other group (R9 or R10 ) represents a hydrogen atom Scheme 1 According to this scheme 1, one can proceed to obtain a compound of formula (I) and in particular of formula (Ic) and (Id) according to the invention according to Wang, X .; Gribkov, D. V .; Samples, D. JOC 2007, 72, 1476-1479 by reacting a compound of formula (IX) wherein Y1, Y2 and R2 are as defined above, with a halo heteroaryl compound or a salt thereof. The compounds for which R 9 and a heteroaryl group respectively and R 10 is a heteroaryl group can be separated for example by flash chromatography on silica gel. The compound of formula (IX) is commercially available or may be obtained according to methods well known to those skilled in the art. A-2 Synthesis of compounds for which R9 is -CH (CN) R11 HO heteroaryl heteroaryl (IX) NC R11 R11 (X) (I) wherein R10 = H and R9 = -CH (CN) R11 or lb) Diagram 2 According to this scheme 2, it is possible to proceed to obtain a nitrile compound of formula (I) according to the invention and in particular of formula (Ib) according to Soltani Rad, MN; Khalafi-Nezhad, A .; Behrouz, S .; Faghihi, M. A. TeL Lett. 2007, 48, 6779-6784 by conversion of an alcohol compound of formula (X) wherein Y1, Y2, R2 and R11 are as previously defined. The compound of formula (X) can be obtained by adding a compound of formula (IX) to a (hetero) aromatic aldehyde. A-3 Synthesis of Compounds for Which R9 represents a Pyr / 11 / R11H Group, an H Group, or Pyr represents a Pyridyl Group The compound of formula (I) in which R9 represents a R11H group can be obtained according to the method described in WO2010 / 150211, in particular in Example 58-3. The compound of formula (I) in which R 9 represents a Pyr R 11 group can be obtained from the corresponding compound of formula (I) in R 11 H by reacting it with the hydrochloride of which R 9 represents a 4-bromopyridine group according to a coupling Sonogashira (well known to those skilled in the art) with a possible protection NBoc when Y1 = N.

A-4 Synthesis of compounds for which R9 represents a group C (CN) = CHR11 The compounds of the invention of formula (I), for which R9 represents a group C (CN) = CHR11, in particular the compounds of formula ( Ia) for which no bond is present, can be prepared according to the general method described in WO2010 / 150211. These compounds can in particular be prepared according to Scheme 1 which follows. According to this scheme 3, it is possible to obtain, in order to obtain a compound according to the invention, a condensation of Knoevenagel by reacting a compound of formula (IV) in which Y1, Y2, R2 and R3 are as defined above with a compound of formula (V) in which R11 is as defined above, in the presence for example of sodium or hydride of sodium, for example in a solvent such as ethanol or DMSO, for example at a temperature ranging from RT (room temperature) to 70 ° C, for a period of time ranging from 20 minutes to several days. The compounds of formulas (IV) and (V) are commercially available or accessible to those skilled in the art by known methods. In particular, obtaining a compound of formula (IV) when R 3 is an aryl or heteroaryl group and is not bonded to the nitrogen atom, ie a precursor for the compounds of formula (IIa), may be carried out according to scheme 2 according to CN CN B (01-) 2 CN (hetero) aryl / (hetero) aryl (IV) Scheme 4 According to this scheme 4, the brominated derivative of indole-acetonitrile can be reacted with a (hetero) arylboronic acid in the presence, for example, of sodium carbonate and of a catalyst such as PdCl 2 (PPh 3) 2, for example at a temperature that may vary between 60 ° C. and 100 ° C., for example for a period that may vary from 6h to 24h. To obtain a compound in which Y 1 = NR 3, where R 3 is a (C 1 -C 4) alkyl group, alkylation can be carried out in the presence of alkyl iodide according to methods known to those skilled in the art.

Similarly obtaining compounds of formula (Ia) for which R 1 and a group NR 5 R 6 can be obtained from compounds of formula (Ia) for which R 1 is a halogen atom, according to methods known to those skilled in the art. art. Furthermore, the compounds of formula (Ia) for which R4 is not a CN group can be obtained by adding an organomagnesium or organolithium type nucleophilic reagent to a ketone of formula (VIII), in which R2 and Y2 are as previously defined, followed by a second step of dehydrating the formed alcohol adduct (by a KHSO4 treatment, for example). The final compound is obtained by deprotection of the carbamate by treatment with trifluoroacetic acid, for example according to scheme 5 below. The ketone of formula (VIII) can be obtained by reaction of anhydrides of pyridylacetic acid hydrochloride -formed in situ in the presence of acetic anhydride-with indole. The protection of the indole in carbamate form can be carried out by reaction with di-tert-butyl dicarbonate, according to scheme 6 below.

In the case where Y1 is a sulfur or oxygen atom, the reaction can be carried out without prior protection. A-5 Synthesis of compounds for which R9 represents a -C (CN) = NR11 group The compounds of the invention of formula (I), for which R9 represents a C (CN) = NR11 group, may be prepared according to the method described in WO2010 / 150211. B - Synthesis of compounds for which R9 and R10 together with the indolyl group carrying them form a ring B-1 Synthesis of compounds for which R9 and R10 together form a group X4 \ x2 X3 \ R1 These compounds, and more particularly the compounds of formula (Ia) of the invention for which a single bond is represented and R4 is a CN group, or the compounds of formula (III), may be prepared according to scheme 7 which follows 1. A C2 0 NH R 2 (C 1 -C 2 O (VIII) II) wherein R 4 = CN Scheme 7 According to this scheme 7 a solution is made to be photochemically irradiated, for example an ethanolic solution comprising a compound of formula (VI) as defined previously under air sparging, for example in the presence of diiod, at ambient temperature, for a variable period of time, for example from 10 to 50 hours. To obtain a compound of formula (III) in which R 4 is a CONH 2 group, a corresponding compound of formula (III) in which R 4 is CN can be reacted with refluxing potassium tert-butanol, for example for a period of time. may vary from 8 to 48 hours. To obtain a compound of formula (III) in which R4 is a CH2NH2 group, the CN function of a corresponding compound of formula (III) can be reduced for which R4 is a CN group, for example in the presence of NaBH4 and CoC12 in a solvent such as tetrahydrofuran, methanol or their mixture, for example at a temperature ranging from 0 ° C to room temperature, for example for a period of time which may vary from 1 to 2 hours. To obtain a compound of formula (III) in which R4 is a CH2NHCOCH3 group, a corresponding compound of formula (III) in which R4 is CH2NH2 can be reacted by acetylation, for example by treatment with acetic anhydride. in a solvent such as tetrahydrofuran, for example in the presence of triethylamine, for example at room temperature, for example for a period of time ranging from 10 to 20 hours. To obtain a compound of formula (III) wherein R4 is CH2N (CH3) 2, a corresponding compound of formula (III), wherein R4 is CH2NH2 by a reductive amination reaction, can be reacted with example by the joint action of sodium cyanoborohydride and formaldehyde in acidic medium, for example at a temperature ranging from 0 ° C to room temperature, for example for a period of time ranging from 2 to 3 hours.

More generally, to obtain a compound of formula (III) in which R4 is a CH2NR5R6 group, a corresponding compound of formula (III) in which R4 is CH2NH2 can be reacted by a reductive amination reaction. for example by the combined action of sodium cyanoborohydride and an equivalent aldehyde in an acidic medium, for example at a temperature that can vary from 0 ° C. to room temperature, for example for a duration that can vary from 2h to 3h, in order to obtain a compound of formula (III) wherein R4 is CH2NR5H. A novel reductive amination reaction with an aldehyde equivalent provides a compound of formula (III) wherein R4 is CH2NR5R6.

B-2 Synthesis of the compounds for which R9 and R10 together form a saturated, unsaturated or partially saturated 6-membered ring, which may comprise, as the atom forming this ring, an -NH- group and / or a -CO-HetAr R2 group Wherein in this scheme 8, there is prepared a compound of formula (Ie) wherein R2, HetAr and Y2 are as previously defined by reacting a compound of formula (XI) in which R2 is , Y2 and HetAr are as previously defined in a high-boiling decalin solvent at a temperature of 140 ° C to 180 ° C for a period of 6 to 10 hours.

The following examples describe the preparation of certain compounds according to the invention. These examples are not limiting and only illustrate the present invention. The numbers of the exemplified compounds refer to those given in Table I. The elemental microanalyses, the SM (mass spectrometry) analyzes, the I.R. spectra or the R.M.N. spectra. confirm the structures of the compounds obtained.

EXAMPLES Example 1: (Z) -2- (7-methoxy-1H-indol-3-yl) -3-pyridin-3-yl-acrylonitrile (Compound No. 11) H3co To a solution of sodium methanolate (218 mg , 4.0 mmol, 1.5 eq.) In anhydrous ethanol (40 mL) are added under argon atmosphere 2- (7-methoxy-1Hindol-3-yl) acetonitrile (500 mg, 2 mg). , 7 mmol, 1.0 eq.) And then, after 30 minutes of stirring, pyridine-3-carbaldehyde (504 1.1, L, 5.4 mmol, 2.0 eq.). The assembly is protected from light and the reaction medium is heated at 50 ° C. for 3 hours. After cooling to room temperature, the solvent is evaporated under reduced pressure and the residue taken up in ethyl acetate. The organic phase is then washed with water, with saturated aqueous sodium chloride solution, dried over MgSO 4 and evaporated under reduced pressure. The crude product is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / EtOH, 98/2 to 95/5) to give compound No. 11 in the form of a yellow powder (680 mg, Yield: 92% ). 1 H NMR (d 6 -DMSO, 500 MHz): b (ppm): 3.96 (3H, s, 7'-methoxy); 6.83 (1H; d; J6'-5 '= 7.7 Hz; H6'); 7.13 (1H; t; J5'-4 '= J5'-6' = 7.7 Hz; H5 '); 7.54 (1H, dd; J5 "-4" = 7.9 Hz; J5 "-6" = 4.6 Hz; H5 "); 7.66 (1H; d; J4'-5 '= 7.7 Hz; H4'); 7.68 (1H; 7.80 (1H; s; H3); 8.33 (1H; d; J4 "-5" = 7.9 Hz; H4 "); 8.59 (1H, d6-6 "= 4.6Hz, H6-); 8.98 (1H; s; H2-); 11.92 (1H, s; H indole) 13 C NMR (d 6 -DMSO, 75.5 MHz): b (ppm): 55.8 (7'-methoxy); 103.7 (C6 '); 108.5 (C2); 111.5 (C3 '); 112.6 (C4 '); 118.5 (Cl); 121.9 (C5 '); 124.2 (C5 "); 125.5 (C3a '); 126.8 (C2'); 127.8 (C3"); 131.2 (C7a '); 133.2 (C3); 135.0 (C4-); 146.9 (C7 '); 150.1 (C2 "); 150.4 (C6-) HRMS (ESI): calcd for C17H13N3ONa +: m / z = 298.0956, measured: 298.0957 IR (cm-1): 2212 (v CN) Melting point: 182 ° C Example 2: (Z) -2 - (5-Methoxy-1-methyl-1H-indol-3-yl) -3-pyridin-3-yl-acrylonitrile (Compound No. 27) To a solution of (Z) -2- (5-methoxy-1H) -indo1-3-yl) -3-pyridin-3-yl-acrylonitrile [example 4, WO2010150211A2] (200 mg, 0.7 mmol, 1.0 eq.) in anhydrous THF (30 mL) maintained at 0 ° C is added under argon, NaH (44 mg, 60%, 1.1 mmol, 1.5 eq.) And then, after 10 minutes of stirring at 0 ° C, methyl iodide (80 1.1 1.3 mmol, 1.8 eq.) The assembly is protected from light and the reaction mixture is stirred at room temperature for 3 hours and then treated with a saturated aqueous solution of ammonium chloride. extracted with ethyl acetate and the organic phase is dried over MgSO 4, filtered on celite and evaporated under reduced pressure The residue is triturated in diethyl ether than to give compound No. 27 in the form of a yellow powder (210 mg, yield: 99%). 1 H NMR (d 6 -DMSO, 300 MHz): b (ppm): 3.82 (3H, s, N-methyl); 3.83 (3H, s, 5'-methoxy); 6.96 (1H, dd; J6'-7 '= 8.9 Hz; J6'-4' = 2.4 Hz; H6 '); 7.46 (1H; d; J7'-6 '= 8.9 Hz; H7'); 7.49 (1H; d; J4'-6 '= 2.4 Hz; H4'); 7.52 (1H, dd; J5 "-4" = 8.1 Hz; J5 "-6" = 4.8 Hz; H5 "); 7.71 (1H; s; H3); 7.80 (1H; s; H2 '); 8.30 (1H; d4; -5 "= 8.1 Hz; H4"); 8.57 (1H, dd; J6 "-5" = 4.8 Hz; H6 "); 8.98 (1H; s; H2") MS: ESI: m / z: 290.2 ([M + H] +); 312.2 ([M + Na] +) HRMS (ESI): calcd for C18H16N3O +: m / z = 290.1293; measured: 296.1286 Microanalysis: Calculated for C18H15N3O, 0.2 H2O%: C, 73.80; H, 5.30; N, 15.34; 0 6.55 Measured%: C 73.63; H, 5.44; N, 14.29 Melting point: 136 ° C. Example 3: (Z) -2- (2-phenyl-1H-indol-3-yl) -3- (pyridin-3-yl) -acrylonitrile (Compound No. 18) a solution of (1H-indol-3-yl) -acetonitrile (700 mg, 4.5 mmol, 1.0 eq) in dry dichloromethane (60 mL) is added silica (400 mg, 6.7 mmol, 1.5 eq.) Then, little by little, N-bromosuccinimide (800 mg, 4.5 mmol, 1.0 eq.). The reaction medium is stirred at ambient temperature for 25 minutes, then filtered on sintered and evaporated under reduced pressure. To the 2-bromoindole derivative taken up in toluene (40 mL) are added ethanol (20 mL), PhB (OH) 2 (1.1 g, 9.0 mmol), Na2CO3 (1.4 g, 13.4 mmol) and LiCl (570 mg, 13.4 mmol). The mixture is degassed before addition of PdCl2 (PPh3) 2 (380 mg, 0.54 mmol). The reaction mixture is stirred at 80 ° C for 16 hours and then treated, after cooling to room temperature, by adding water. The mixture is extracted with ethyl acetate and the organic phase is washed with a saturated aqueous solution of sodium carbonate, dried over MgSO 4, filtered on silica gel and then evaporated. To the coupling product taken up in anhydrous NMP (100 mL) are added, under argon, NaH (188 mg, 80%, 6.3 mmol) and then pyridine-3-carbaldehyde (760 μL, 8.1 mmol). The reaction medium is stirred at ambient temperature for 2 hours and then treated by adding a saturated aqueous solution of ammonium chloride. The mixture is extracted with ethyl acetate and the organic phase is successively washed with water, with saturated aqueous sodium chloride solution and dried over MgSO 4. The solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: heptane / AcOEt, 50/50) to give, after trituration in diethyl ether, compound no. 18 in the form of a yellowish solid (440 mg, yield: 31%). NMR 111 (d 6 -DMSO, 500 MHz): b (ppm): 7.18 (1H, t; J5'-6 '= J5'-4' = 7.9 Hz; H5 '); 7.25 (1H; t; J6'-5 '= J6'-7' = 7.9 Hz; H6 '); 7.45 (1H, m; H11 '); 7.50 (1H, m; H7 '); 7.53 (2H, m; H10 'and H12'); 7.56 (1H, m; H5-); 7.62 (1H; s; H3); 7.71 (2H; d; J9'-10 '= J13'-12' = 7.6 Hz; H9 'and H13'); 7.77 (1H; J4'-5 '= 7.9 Hz; H4'); 8.34 (1H; d; J4 "-5" = 7.9 Hz; H4 "); 8.64 (1H, d6-6 "= 4.9Hz, H6-); 8.95 (1H; s; H2-); 11.96 (1H, s; H indole) MS: ESI:: 322.1 ([M + H] +) HRMS (ESI): calcd for C22H16N3 +: m / z = 322.1344; measured: 322.1352 Example 4: (Z) -3- (pyridin-3-yl) -242- (thiophen-3-yl) -1H-indol-3-yl] -acrylonitrile (Compound No. 19) The same protocol as that described in Example 3 is used except for the addition of thiophen-3-ylboronic acid (1.15 g, 8.96 mmol) instead of the PhB (OH) 2 of the example previous. Compound No. 19 is obtained in the form of a yellowish solid (320 mg, yield: 22%). NMR 111 (d 6 -DMSO, 300 MHz): b (ppm): 7.15 (1H, t; J5'-6 '= J5'-4' = 7.9 Hz; H5 '); 7.23 (1H, t; J6'-5 '= J6'-7' = 7.9 Hz; H6 '); 7.47 (1H, J7'-6 '= 7.9 Hz, H7'); 7.51 (1H, m; H9 '); 7.57 (1H, dd; J5 "-4" = 7.9 Hz; J5 "-6" = 4.9 Hz; H5 "); 7.61 (1H; s; H3); 7.71 (2H; m; H4 'and H10'); 7.91 (1H, m; H12 '); 8.37 (1H; d; J4 "-5" = 7.9 Hz; H4 "); 8.64 (1H, d6-6 "= 4.9Hz, H6-); 8.97 (1H; s; H2-); 11.89 (1H, s; H indole) MS: ESI:: 328.1 ([M + H] +) HRMS (ESI): calcd for C20H14N3S +: m / z = 328.0908; measured: 328.0906 Example 5: (Z) -2- (5-Benzyloxy-1H-indol-3-yl) -3-pyridin-2-yl-acrylonitrile (Compound No. 22) To a suspension of NaH (13 mg 80%, 0.5 mmol, 1.4 eq.) In anhydrous DMF (3 mL) is added, under an argon atmosphere, a solution of (5-benzyloxy-1H-indol-3-yl) - acetonitrile (100 mg, 0.4 mmol, 1.0 eq.) and pyridine-2-carbaldehyde (40 μL, 0.42 mmol, 1.1 eq.) in anhydrous DMF (3 mL). The assembly is protected from light and the reaction medium is stirred at ambient temperature for 20 minutes and then treated with a saturated aqueous solution of sodium chloride. The mixture is extracted with ethyl acetate and the organic phase is washed with saturated aqueous ammonium chloride solution and then dried over MgSO 4. The solvent was evaporated under reduced pressure and the product was recrystallized from dichloromethane and diethyl ether to give compound No. 22 as a yellowish crystalline powder (45 mg, yield: 34%).

111 NMR (d6-DMSO, 300 MHz): b (ppm): 5.19 (2H, s, 2H8 '); 6.99 (1H, dd; J6'-7 '= 8.6 Hz; J6'-4' = 2.1 Hz; H6 '); 7.33 (1H; t; J12'-11 '= J12'-13' = 7.3 Hz; H12 '); 7.38 (1H, m; H5-); 7.39 (2H; m; H11 'and H13'); 7.43 (1H; d; J7'-6 '= 8.6 Hz; H7'); 7.52 (2H; d; J10 '); -11 '= J14'-13' = 7.3 Hz; H10 'and H14'); 7.60 (1H; d; J4'-6 '= 2.1 Hz; H4'); 7.64 (1H; s; H3); 7.77 ( 1H; d; J3 "-4" = 7.6 Hz; H3 "); 7.81 (1H; s; H2 '); 7.91 (1H; td; J4 "-3" = J4 "-5" = 7.6 Hz; J4 "-6" = 1.5 Hz; H4 "); 8.70 (1H; d; J6" -5 "= 4.0 Hz; H6; "); 11.70 (1H; s; H indole) MS: ESI:: 352.1 ([M + H] +); 374.1 ([M + Na] +) HRMS (ESI): calcd. For C23H18N3O +: m / z = 352.1450; measured: 352.1458 IR (cm-1): 2215 (v CN); 3354 (v NH) Melting point: 195 ° C. Example 6: (Z) -2- (1H-Indol-3-yl) -3- (3-methoxy-phenyl) -acrylonitrile (Compound No. 25) freshly prepared sodium ethanolate solution (addition of sodium (125 mg, 5.85 mmol, 1.7 eq.) in 15 mL of anhydrous ethanol) was added, under argon, to the (1H-indole). 3-yl) -acetonitrile (500 mg, 3.20 mmol, 1.0 eq) and then, after stirring for 30 minutes, 3-methoxy-benzaldehyde (700 μL, 5.76 mmol, 1.1 eq. ). The assembly is protected from light and the reaction medium is stirred at room temperature for 48 hours. The solvent is evaporated off under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2, 100) to give compound No. 25 in the form of a yellow powder (580 mg, yield: 66%) . 1 H NMR (d 6 -DMSO, 300 MHz): b (ppm): 3.82 (3H, s, 3 "-methoxy), 6.99 (1H, dm, J4" -5 "= 7.8 Hz, H4"); 7.18 (1H; t; J5'-4 '= J5'-6' = 7.8 Hz; H5 '); 7.24 (1H, t; J6'5 '= J6'-7' = 7.8 Hz; H6 '); 7.41 (1H, t; J5 "-4" = J5 "-6" = 7.8 Hz; H5 "); 7.49 (2H; m; H7 'and H6"); 7.51 (1H, s; H 2 "); 7.74 (1H; s; H 3); 7.79 (1H; s; H 2 '); 8.05 (1H; d; J 4'-5' = 7.8 Hz; H 4 '); 11.72 ( 1 H; s; H indole) MS: ESI: m / z: 297.1 ([M + Na] +) HRMS (ESI): calcd. For C18H14N2ONa +: m / z = 297.1004; measured: 297.0997 Microanalysis: Calculated for C18H14N2O, 0.2 H2O %: C 77.79, H 5.22, N 10.08, 0 6.91 Measured%: C 77.77, H 5.13, N 10.23 Melting point: 103 ° C Example 7: (Z) -2- (5-methoxy-1H-indole) 1- (346- (methylamino) -pyridin-3-yl] -acrylonitrile (Compound No. 16) HN- To a mixture of the compound (Z) -3- (6-chloropyridin-3-yl) -2- 5-methoxy-1H-indol-3-yl) -acrylonitrile [Example 49, WO2010150211A2] (50 mg, 0.16 mmol, 1.0 eq) in ethanol (2.5 mL) is added a solution of methylamine in ethanol (612 1.1, L, 33%, 6.40 mmol, 40.0 eq.) The assembly is protected from light and the reaction medium is heated in a sealed tube for 40 hours. at room temperature, the solvent is evaporated Reduced pressure and the residue taken up in ethyl acetate. The organic phase is then washed with water, dried over MgSO 4 and evaporated under reduced pressure. The crude product is triturated in diethyl ether to give compound No. 16 as a yellow solid (45 mg, yield: 92%).

NMR 11I (d 6 -DMSO, 500 MHz): b (ppm): 2.84 (3H, d; J7 "-NH = 4.0 Hz, H7"); 3.81 (3H, s, 5'-methoxy); 6.57 (1H, d; J5 "-4" = 8.7 Hz; H5 "); 6.86 (1H; dd; J6'-7 '= 8.9 Hz; J6'-4' = 2.1 Hz; H6 '); 7.15 (1H; JNH 7 = 4.0 Hz; H amine); 7.36 (1H, d, J7'-6 '= 8.9 Hz, H7'); 7.38 (1H; d; J4'-6 '= 2.1 Hz; H4'); 7.48 (1H; s; H3); 7.63 (1H; s; H2 '); 8.12 (1H, dd, J4 "-5" = 8.7 Hz, J4 "-2" = 2.4 Hz, H4 "), 8.43 (1H, d, J2" -4 "= 2.4 Hz, H2"); 11.44 (1H, s; H indole) MS: ESI: m / z: 305.1 ([M + H] +) HRMS (ESI): calcd for C18H17N4O +: m / z = 305.1402; measured: 305.1396 Example 8: (E) -5-Methoxy-3- [1- (pyridin-3-yl) -4- (pyridin-4-yl) -but-1-en-3-yn-2-yl] 1Hindole (Compound No. 34) To a solution of 4-bromopyridine hydrochloride (47 mg, 0.24 mmol, 1.0 eq.) In anhydrous THF and degassed (3 mL) was added, under an atmosphere of argon, CuI (4.1 mg, 0.02 mmol, 0.09 eq.), PdCl2 (PPh3) 2 (8.4 mg, 0.01 mmol, 0.05 eq.), the compound (E) - Tert-butyl 5-methoxy-3- [1- (pyridin-3-yl) -but-1-en-3-yn-2-yl] -1H-indole-1-carboxylate [Example 58-3, WO2010150211A2] ] (90 mg, 0.24 mmol, 1.0 eq.) Followed by diisopropylamine (3 mL). The assembly is protected from light and the reaction medium is heated at 50 ° C. for 36 hours and then treated, after cooling to room temperature, by addition of a saturated aqueous solution of sodium bicarbonate. The mixture is extracted with ethyl acetate and the organic phase is washed with water, dried over MgSO4 and then evaporated under reduced pressure. The crude N-Boc product is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / EtOH, 98/2 to 96/4). The solvents are evaporated and the residue is taken up in a mixture of dichloromethane (4 mL) and TFA (4 mL). The reaction medium is stirred at ambient temperature for 2 hours and then treated by addition of a 1M aqueous sodium hydroxide solution. The mixture is extracted with ethyl acetate and the organic phase is washed with water, dried over MgSO4, then filtered through silica gel and evaporated under reduced pressure to give compound No. 34 in the form of a brown solid (40 mg, yield: 47%).

R1VIN111 (d6-DMSO, 300 MHz): b (ppm): 3.84 (3H, s, 5-methoxy); 6.86 (1H, dd, J6-7 = 8.7 Hz, J6-4 = 2.4 Hz, H6); 7.39 (1H, d, J7-6 = 8.7 Hz, H7); 7.43 (1H; s; H1 '); 7.50 (1H, dd; J5 "-4" = 7.9 Hz; J5 "-6" = 4.7 Hz; H5 "); 7.52 (1H; d; J4-6 = 2.4 Hz; H4); 7.58 (2H; d; J6'-7 '= J10'-9' = 4.5 Hz, H6 'and H10'), 7.83 (1H, m, H2), 8.48 (1H, m, H4- and H6-), 8.67 (2H, d; J7'-6 '= J9'-10' = 4.5 Hz; H7 'and H9'); 9.05 (1H; d; J2 "-4" = 1.5 Hz; H2 "); 11.45 (1H, s; H indole) MS: ESI:: 352.1 ([M + H] +) HRMS (ESI): calcd for C23H18N3O +: m / z = 352.1450; measured: 352.1442 Example 9: 7-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 47) OCH3 6 6a 5 10 10a 11 IV 3a N Na H 4a 1 N 3 2 A solution of (Z) -2- (4-methoxy-1H-indol-3-yl) -3- (pyridin-3-yl) acrylonitrile (300 mg, 1.1 mmol) in ethanol (200 mL) is irradiated under air sparging for 40 hours in a glass vessel with a halogen bulb (150 W). The solvent is evaporated under reduced pressure and the residue is triturated in diethyl ether and dichloromethane to give compound No. 47 as a yellow powder (260 mg, yield: 86%). 1 H NMR (d 6 -DMSO, 500 MHz): b (ppm): 4.03 (3H, s, 7-methoxy); 6.87 (1H, d, J89 = 7.3 Hz, H8); 7.34 (1H, d; J10-9 = 7.3 Hz; H10); 7.52 (1H, t; J9-8 = J9-10 = 7.3 Hz; H9); 8.43 (1H, d; J1-2 = 5.5 Hz; H1); 8.50 (1H; s; H5); 8.79 (1H, d, J2-1 = 5.5 Hz, H2); 9.50 (1H; s; H4); 13.00 (1H, s; carbazolic H) MS: ESI: m / z: 274.1 ([M + H] +) HRMS (ESI): calcd for C17H12N3O +: m / z = 274.0980; measured: 274.0974 IR (cm-1): 2228 (ν CN); 3276 (v NH) 9 Example 10: 8-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 50) 3 2 A solution of (Z) -2- (5-methoxy) -1H-indol-3-yl) -3- (pyridin-3-yl) acrylonitrile (500 mg, 1.8 mmol) in ethanol (80 mL) is irradiated under air sparging for 40 hours in a tank glass with a halogen bulb (150 W). The precipitate formed is filtered, washed with ethanol and with diethyl ether to give compound No. 50 in the form of an orange powder (320 mg, yield: 64%).

NMR 11I (d 6 -DMSO, 500 MHz): b (ppm): 3.87 (3H, s, 8-methoxy); 7.24 (1H, dd, J9-10 = 8.9 Hz, J9-7 = 2.2 Hz, H9); 7.68 (1H, d; J10-9 = 8.9 Hz; H10); 7.84 (1H, d, J7-9 = 2.2 Hz, H7); 8.35 (1H, d; J1-2 = 5.8 Hz; H1); 8.36 (1H, s, H5); 8.76 (1H, d, J2-1 = 5.8 Hz, H2); 9.43 (1H; s; H4); 12.80 (1H, s; carbazolic H) MS: ESI: m / z: 274.1 ([M + H] +) HRMS (ESI): calcd for C17H12N3O +: m / z = 274.0980; measured: 274.0978 Example 11: 8-fluoro-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 46) 2 A solution of (Z) -2- (5-fluoro-1H-indole) 3-yl) -3- (pyridin-3-yl) acrylonitrile (300 mg, 1.1 mmol) in ethanol (200 mL) is irradiated under air bubbling for 40 hours in a glass vessel equipped with a halogen bulb (150 W). The solvent is evaporated under reduced pressure and the residue is triturated in diethyl ether, dichloromethane and ethanol to give compound No. 46 in the form of a beige powder (270 mg, yield: 91%). NMR 11I (d 6 -DMSO, 300 MHz): b (ppm): 7.50 (1H, td, J9-10 = J9-F = 9.0 Hz, J9-7 = 2.4 Hz, H9); 7.83 (1H, dd; J10-9 = 9.0 Hz; J10-F = 4.5 Hz; H10); 8.06 (1H, dd, J7-F = 9.0 Hz, J7-9 = 2.4 Hz, H7); 8.43 (1H, d; J1-2 = 5.7 Hz; H1); 8.50 (1H; s; H5); 8.83 (1H, d; J2-1 = 5.7 Hz; H2); 9.51 (1H; s; H4); 13.14 (1 H; s; carbazol H) MS: ESI: m / z: 262.1 ([M + H] +) HRMS (ESI): calcd for C16H9N3F +: m / z = 262.0781; measured: 262.0776 Example 12: 8-Chloro-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 45) CI N 10 10a 11 3a 1 N A solution of (Z) -2- (5 chloro-1H-indol-3-yl) -3- (pyridin-3-yl) acrylonitrile (300 mg, 1.1 mmol) in ethanol (200 mL) is irradiated under air sparge for 40 hours in a glass vessel with a halogen bulb (150 W). The solvent is evaporated under reduced pressure and the residue is triturated in diethyl ether, dichloromethane and ethanol to give compound no. 45 in the form of a beige powder (270 mg, yield: 91%). NMR 11I (d 6 -DMSO, 300 MHz): b (ppm): 7.63 (1H, d, J9-10 = 8.7 Hz, H9); 7.84 (1H, d; J10-9 = 8.7 Hz; H10); 8.36 (1H; s; H7); 8.44 (1H, d; J1-2 = 5.7 Hz; H1); 8.54 (1H; s; H5); 8.84 (1H, d; J2-1 = 5.7 Hz; H2); 9.53 (1H; s; H4); 13.04 (1 H; s; carbazol H) MS: ESI: m / z: 278.1 ([M + H] +) HRMS (ESI): calcd for C16H9N335Cl +: m / z = 278.0485; EXAMPLE 13: 1,8-Dimethoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 36) H3C.

A solution of the compound (Z) -2- (5-methoxy-1H-indol-3-yl) -3- (5-methoxy-pyridin-3-yl) -acrylonitrile [Example 46, WO2010150211A2] (110 mg. 36 mmol) in ethanol (50 ml) is irradiated under air sparge for 17 hours in a glass vat equipped with a halogen bulb (150 W). The solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: AcOEt / EtOH, 95/5 to 93/7) to give compound No. 36 in the form of a beige powder ( 70 mg, Yield: 64%). 1 H NMR (d 6 -DMSO, 500 MHz): b (ppm): 3.90 (3H, s, 8-methoxy); 4.27 (3H, s, 1-methoxy); 7.29 (1H, dd, J9-10 = 8.9 Hz, J9-7 = 2.1 Hz, H9); 7.85 (1H, d; J10-9 = 8.9 Hz; H10); 7.96 (1H, d, J7-9 = 2.1 Hz, H7); 8.44 (1H; s; H5); 8.49 (1H; s; H2); 9.12 (1H; s; H4); 12.05 (1 H; s; carbazol H) MS: ESI: m / z: 304.1 ([M + H] +) HRMS (ESI): calcd for C18H14N3O2 +: m / z = 304.1086; Example 14: 9-Methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 37) H 3 C 0 2 A solution of (Z) -2- (6-methoxy) -1H-indol-3-yl) -3- (pyridin-3-yl) acrylonitrile (300 mg, 1.1 mmol) in ethanol (200 mL) is irradiated under air sparge for 10 hours in a tank glass with a halogen bulb (150 W). The solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: AcOEt / EtOH, 100/0 to 90/10) to give, after trituration in diethyl ether, compound 37 in the form of a beige powder (200 mg, Yield: 67%). NMR 111 (d 6 -DMSO, 300 MHz): b (ppm): 3.93 (3H, s, 9-methoxy); 7.03 (1H, dd, J8-7 = 8.8 Hz, J8-10 = 2.2 Hz, H8); 7.17 (1H, d, J10-8 = 2.2 Hz, H10); 8.26 (1H, d, J7-8 = 8.8 Hz, H7); 8.33 (1H, d, JI-2 = 5.7 Hz, HI); 8.39 (1H; s; H5); 8.74 (1H, d; J2-1 = 5.7 Hz; H2); 9.44 (1H; s; H4); 12.77 (1H, s; carbazol H) MS: ESI: m / z: 274.1 ([M + H] +) HRMS (ESI): calcd for C17H12N3O +: m / z = 274.0980; measured: 274.0975 ESI: m / z: 272.1 ([M-H] -) Example 15: 1,9-Dimethoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 40) 15.1. Preparation of an intermediate compound (Z) -2- (6-methoxy-1H-indol-3-yl) -3- (5-methoxy-pyridin-3-yl) -acrylonitrile OCH3 to a solution of sodium methanolate ( 87 mg, 1.6 mmol, 1.5 eq.) In anhydrous ethanol (10 mL) are added, under an argon atmosphere, 2- (6-methoxy-1H-indol-3-yl) acetonitrile 127 ( 200 mg, 1.1 mmol, 1.0 eq.) Followed by 5-methoxy-pyridine-3-carbaldehyde (265 mg, 1.9 mmol, 1.8 eq.). The reaction medium is brought to reflux temperature for 4 hours. After cooling to room temperature, the solvent is evaporated off under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / MeOH, 98/2) to obtain the expected intermediate compound in the form of a yellow powder (260 mg, yield: 80%) 15.2. Preparation of compound No. 40 H3C0 A solution of the intermediate compound prepared in step 15.1. (230 mg, 0.75 mmol) in ethanol (200 mL) is irradiated by sparging with air for 14 hours in a glass vat equipped with a halogen bulb (150 W). The solvent is evaporated off under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: AcOEt / EtOH, 95/5 to 93/7) to give compound No. 40 in the form of a beige powder ( 150 mg, yield: 66%). NMR 111 (d 6 -DMSO, 500 MHz) - b (ppm): 3.91 (3H, s, 9-methoxy); 4.25 (3H, s, 1-methoxy); 7.06 (1H, dd, J8-7 = 8.8 Hz, J8-10 = 2.2 Hz, H8); 7.41 (1H, d; J10-8 = 2.2 Hz; H10); 8.33 (1H, d, J7-8 = 8.8 Hz, H7); 8.43 (1H; s; H5); 8.44 (1H; s; H2); 9.10 (1H; s; H4); 12.03 (1H; s; H carbazole) MS: ESI: m / z: 304.1 ([M + H] +) HRMS (ESI): calcd. For C18H14N3O2 +: m / z = 304.1086; Example 16: 10-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound No. 44) 10 10 11 N 1 H 4a 9 2 A solution of (Z) -2 - (7-methoxy-1H-indol-3-yl) -3- (pyridin-3-yl) acrylonitrile (300 mg, 1.1 mmol) in ethanol (200 mL) is irradiated while bubbling with air for 40 hours in a glass vat equipped with a halogen bulb (150 W). The solvent is evaporated under reduced pressure and the residue is triturated in diethyl ether, dichloromethane and ethanol to give compound No. 44 as a yellow powder (250 mg, yield: 83%). NMR 11I (d 6 -DMSO, 500 MHz): b (ppm): 4.10 (3H, s, 10-methoxy); 7.20 (1H, d; J9-8 = 7.6 Hz; H9); 7.36 (1H, t; J8-7 = 8.2 Hz; J8-9 = 7.6 Hz; H8); 8.05 (1H, d, J7-8 = 8.2 Hz, H7); 8.50 (1H; s; H5); 8.75 (1H, d; J1-2 = 5.7 Hz; H1); 8.79 (1H, d, J2-1 = 5.7 Hz, H2); 9.50 (1H; s; H4); 13.05 (1H, s; carbazol H) MS: ESI: m / z: 274.1 ([M + H] +) HRMS (ESI): calcd for C17H12N3O +: m / z = 274.0980; measured: 274.0971 Example 17: 11H-pyrido [3 ', 2': 4,5] pyrrolo [2,3-f] isoquinoline-6-carbonitrile (Compound No. 56) A mixture of the compound (Z) -3- ( pyridin-3-yl) -2- (1H-pyrrolo [2,3-b] pyridin-3-yl) -acrylonitrile [Example 36, WO2010150211A2] (200 mg, 0.8 mmol) and diiodine (30 mg) in ethanol (60 mL) is irradiated with air for 24 hours in an open glass vessel and equipped with a halogen bulb (150 W). The diiodide is neutralized with a solution of 10% sodium thiosulfate and the solvent is partially evaporated under reduced pressure. The insoluble material is filtered and then washed with water and acetone to give Compound No. 56 in the form of a beige solid (100 mg, Yield: 51%). NMR 11I (d 6 -DMSO, 500 MHz): b (ppm): 7.45 (1H, dd, J8-7 = 7.5 Hz, J8-9 = 4.5 Hz, H8); 8.47 (1H, m; H1); 8.48 (1H; s; H5); 8.66 (2H, m; H7 and H9); 8.79 (1H, d, J2-1 = 5.8 Hz, H2); 9.47 (1H; s; H4); 13.45 (1H, s, pyrrolic H) MS: ESI: m / z: 245.1 ([M + H] +) HRMS (ESI): calcd for C15H9N4 +: m / z = 245.0820; EXAMPLE 18: (Z) -3- (pyridin-3-yl) -2- (6-methoxy-1H-pyrrolo [2,3-b] pyridin-3-yl) -acrylonitrile (Compound No. 31) ) 18.1. Preparation of an Intermediate Compound (2- (6-methoxy-1H-pyrrolo [2,3-b] pyridin-3-yl) -acetonitrile) To a mixture of 6-methoxy-1H- pyrrolo [2,3-b] pyridine (1.1 g, 7.4 mmol, 1.0 eq.) and paraformaldehyde (0.31 g, 10.4 mmol, 1.4 eq.) in isopropanol (60 mL) is added dimethylamine hydrochloride (0.85 g, 10.4 mmol, 1.4 eq). The reaction mixture is stirred at reflux temperature for 2 hours and then treated by adding a 5M aqueous sodium hydroxide solution, after cooling to room temperature. The mixture is extracted with ethyl acetate and then the organic phase is dried over MgSO 4 and evaporated under reduced pressure. The gramine residue is taken up in anhydrous dichloromethane (40 ml) and toluene (80 ml), and then the methyl iodide (0.74 ml, 11.9 mmol, 1.6 eq) is added under argon atmosphere. The reaction medium is stirred at room temperature for 36 hours, then the precipitate is filtered and washed with diethyl ether. To the powder obtained are added water (100 ml) and potassium cyanide (0.63 g, 9.7 mmol, 1.3 eq.). The mixture is stirred at reflux temperature for 40 minutes and then treated with saturated aqueous sodium carbonate solution after cooling to room temperature. The crude product is extracted with ethyl acetate and then the organic phase is dried over MgSO 4, filtered through silica gel and evaporated under reduced pressure to give the intermediate compound in the form of a beige solid (0.35 g Yield: 25%). NMR 11I (d 6 -DMSO, 300 MHz): b (ppm): 3.87 (3H, s, 6-methoxy); 4.01 (2H; s; 25 CH 2); 6.58 (1H, d, J5-4 = 8.5 Hz, H5); 7.18 (1H, s, H2); 7.92 (1H, d, J4-5 = 8.5 Hz, H4); 11.49 (1H, s, pyrrolic H) MS: ESI: m / z: 188.1 ([M + H] +) HRMS (ESI): calcd for C 10 H 30 N +: m / z = 188.0824, measured: 188.0825 18.2. Preparation of Compound No. 31 H3 OCH3 To a solution of sodium methanolate (58 mg, 1.07 mmol, 2.0 eq.) In anhydrous ethanol (16 mL) is added, under an argon atmosphere, the compound intermediate prepared in step 18.1. (100 mg, 0.53 mmol, 1.0 equiv) then, after stirring for 30 minutes, pyridine-3-carbaldehyde (201 μL, 2.14 mmol, 4.0 eq.). The assembly is protected from light and the reaction medium is heated at 50 ° C. for 4 hours. After cooling to room temperature, the solvent is partially evaporated and the mixture is extracted with ethyl acetate. The organic phase is washed with water, dried over MgSO4, then filtered on silica gel and evaporated under reduced pressure. The crude product is triturated in diethyl ether to give compound No. 31 as a yellow solid (85 mg, yield: 58%). NMR 11I (d 6 -DMSO, 300 MHz) - b (ppm): 3.91 (1H, s, 6'-methoxy); 6.71 (1H; d; J5'-4 '= 8.7 Hz; H5'); 7.54 (1H, m; H5-); 7.66 (1H; s; H?); 7.81 (1H; s; H3); 8.33 (1H; d; J4 "-5" = 7.9 Hz; H4 "); 8.44 (1H, d, J4'-5 '= 8.7 Hz, H4'); 8.59 (1H, d6-6 "= 4.8 Hz, H6-); 8.99 (1H; s; H2-); 12.14 (1H, s, pyrrolic H) MS: ESI: m / z: 277.1 ([M + H] +) HRMS (ESI): calcd for C16H13N4O +: m / z = 277.1089; measured: 277.1082 EXAMPLE 19: 11H-pyrido [3 ', 2': 4,5] -9-methoxypyrrolo [2,3-f] isoquinoline-6-carbonitrile (Compound No. 49) H3CO2 A solution of (Z) 3- (pyridin-3-yl) -2- (6-methoxy-1H-pyrrolo [2,3-b] pyridin-3-yl) -acrylonitrile (40 mg, 0.14 mmol) in ethanol ( 40 mL) is irradiated for 16 hours in a closed glass vessel and equipped with a halogen bulb (150 W). The solvent evaporated under reduced pressure and the residue is triturated in diethyl ether to give compound No. 49 as a beige powder (34 mg, yield: 86%). 1 H NMR (d 6 -DMSO, 500 MHz): b (ppm): 4.03 (3H, s, 9-methoxy); 6.93 (1H, d; J8-7 = 8.7 Hz; H8); 8.47 (1H, d; J1-2 = 5.5 Hz; H1); 8.52 (1H; s; H5); 8.59 (1H, d, J7-8 = 8.7 Hz, H7); 8.76 (1H, d, J2-1 = 5.5 Hz, H2); 9.47 (1H; s; H4); 13.54 (1H, s; pyrrolic H) MS: ESI: m / z: 275.1 ([M + H] +) HRMS (ESI): calcd for C16H11N4O +: m / z = 275.0933; measured: 275.0929 Example 20: 9-Methoxy-11H-pyrido [4,3-a] carbazole-6-carboxamide (Compound No. 38) H3CO To a solution of 9-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile 475 (70 mg, 0.26 mmol, 1.0 eq.) in t-butanol (10 mL) is added potash spray (250 mg, 4.4 mmol, 17.0 eq). The reaction medium is heated at reflux temperature in a sealed tube for 8 hours. After cooling to room temperature, the solvent is evaporated under reduced pressure and the crude solubilized in ethyl acetate. The organic phase is successively washed with water and a saturated aqueous solution of ammonium chloride and then dried over MgSO 4 and evaporated under reduced pressure. The product is triturated in ethyl acetate and diethyl ether to give compound No. 38 as a beige powder (50 mg, yield: 66%). 1 H NMR (d 6 -DMSO, 300 MHz) - b (ppm): 3.90 (3H, s, 9-methoxy); 6.89 (1H, dd, J8-7 = 8.9 Hz, J8-10 = 2.3 Hz, H8); 7.14 (1H, d; J10-8 = 2.3 Hz; H10); 7.71 (1H; s; H amide); 7.94 (1H; s; H5); 8.19 (1H; s; H amide); 8.29 (1H, d, J7-8 = 8.9 Hz, H7); 8.33 (1H, d; J1-2 = 5.8 Hz; H1); 8.65 (1H, d, J2-1 = 5.8 Hz, H2); 9.40 (1H, s, H4); 12.50 (1H, s; carbazole H) MS: ESI: m / z: 292.1 ([M + H] +) HRMS (ESI): calcd for C17H14N3O2 +: m / z = 292.1086; EXAMPLE 21: 1,9-Dimethoxy-11H-pyrido [4,3-a] carbazole-6-carboxamide (Compound No. 41) H 3 CO 7 O NH 2 6a N, N Ila 2 H 4a H 3 CO 10 At one solution of 1,9-dimethoxy-11H-pyrido4,3-acarbazole-6-carbonitrile (compound No. 40) (60 mg, 0.20 mmol, 1.0 eq.) in t-butanol (10 mL) is added potash spray (190 mg, 3.4 mmol, 17.0 eq). The reaction medium is heated at reflux temperature in a sealed tube for 16 hours. After cooling to room temperature, the solvent is evaporated under reduced pressure and the crude solubilized in ethyl acetate. The organic phase is successively washed with water and a saturated aqueous solution of ammonium chloride and then dried over MgSO 4 and evaporated under reduced pressure. The product is triturated in diethyl ether to give compound No. 41 in the form of a brown powder (45 mg, yield: 70%). 1 H NMR (d 6 -DMSO, 300 MHz): b (ppm): 3.89 (3H, s, 9-methoxy); 4.24 (3H, s, 1-methoxy); 6.87 (1H, dd, J8-7 = 8.8 Hz, J8-10 = 2.2 Hz, H8); 7.34 (1H, d; J10-8 = 2.2 Hz; H10); 7.73 (1H; s; H amide); 7.88 (1H, s, H5); 8.20 (1H; s; H amide); 8.25 (1H, d, J7-8 = 8.8 Hz, H7); 8.31 (1H; s; H2); 9.03 (1H; s; H4); 11.74 (1H; s; H carbazole) MS: ESI: m / z: 322.1 ([M + H] +) 10a 11 3a HRMS (ESI): calcd. For C18H16N3O3 +: m / z = 322.1192; measured: 322.1183 Example 22: 10-Methoxy-11H-pyrido [4,3-a] carbazole-6-carboxamide (Compound No. 48) 2 To a solution of 10-methoxy-11H-pyrido [4,3-a] carbazol-6-carbonitrile (compound No. 44) (220 mg, 0.81 mmol, 1.0 eq.) in t-butanol (20 mL) is added powdered potash (1.4 g, 24.3 mmol, 30.0 eq). The reaction medium is heated at reflux temperature in a sealed tube for 48 hours. After cooling to room temperature, the solvent is evaporated under reduced pressure and the crude solubilized in ethyl acetate. The organic phase is successively washed with water and a saturated aqueous solution of ammonium chloride and then dried over MgSO 4 and evaporated under reduced pressure. The product is triturated in ethyl acetate and diethyl ether to give compound No. 48 in the form of a beige powder (150 mg, yield: 64%). 1 H NMR (d 6 -DMSO, 500 MHz): b (ppm): 4.07 (3H, s, 10-methoxy); 7.07 (1H, d; J9-8 = 7.6 Hz; H9); 7.36 (1H, t; J8-7 = 8.2 Hz; J8-9 = 7.7 Hz; H8); 7.74 (1H; s; H amide); 7.90 (1H, s, H5); 7.94 (1H, d, J7-8 = 8.2 Hz, H7); 8.20 (1H; s; H amide); 8.65 (1H, d; J1-2 = 5.7 Hz; H1); 8.79 (1H, d, J2-1 = 5.7 Hz, H2); 9.41 (1H; s; H4); 12.65 (1H, s; carbazolic H) MS: ESI: m / z: 292.1 ([M + H] +) HRMS (ESI): calcd for C17H14N3O2 +: m / z = 292.1086; measured: 292.1080 IR (cm-1): 1644 (y C = O); EXAMPLE 23: 9-Methoxy-11H-pyrido [4,3-a] carbazole-6-methanamine (Compound No. 39) To a mixture of 9-methoxy-11H-pyrido [4.3] carboxole-6-carbonitrile 475 (90 mg, 0.33 mmol, 1.0 eq) and cobalt chloride hexahydrate (157 mg, 0.66 mmol, 2.0 eq) in methanol solution (6 mL) and THF (2.4 mL) are added at 0 ° C, sodium borohydride (125 mg, 3.30 mmol, 10.0 eq). The reaction medium is stirred at 0 ° C. for 1 h 30 and then treated by addition of a 1M aqueous hydrochloric acid solution (14 ml). The mixture is then stirred at ambient temperature for 30 minutes until the black color disappears. The pH is adjusted with an ammonia solution and the basic solution is extracted with ethyl acetate and the organic phase is then washed with an aqueous solution of sodium bicarbonate and dried over MgSO 4. The product is triturated in diethyl ether to give compound no. 39 as a beige powder (50 mg, yield: 55%). NMR 11I (d 6 -DMSO, 500 MHz): b (ppm): 3.91 (3H, s, 9-methoxy); 4.46 (2H; s; 2H12); 5.76 (2H, s, 2H amine); 6.94 (1H, dd; J8-7 = 8.9 Hz; J8-10 = 2.1 Hz; H8); 7.16 (1H, d; J10-8 = 2.1 Hz; H10); 7.81 (1H, s, H5); 8.08 (1H, d, J7-8 = 8.9 Hz, H7); 8.28 (1H, d; J1-2 = 5.5 Hz; H1); 8.57 (1H, d; J2-1 = 5.5 Hz; H2); 9.31 (1H; s; H4); 12.38 (1H, s; carbazol H) MS: ESI: m / z: 278.1 ([M + H] +) HRMS (ESI): calcd for C17H15N3O +: m / z = 278.1293; EXAMPLE 24: N - [(9-Methoxy-11H-pyrido [4,3-a] carbazol-6-yl) methyl] acetamide (Compound No. 42) 14 H 3 C H 3 CO To a mixture of 9-Methoxy-11H-pyrido [4,3-a] carbazol-6-methanamine (Compound No. 39) (20 mg, 0.07 mmol, 1.0 eq.) In anhydrous THF (3 mL) is added under argon atmosphere, triethylamine (19 [iL, 0.14 mmol, 2 eq.) and then acetic anhydride (240 [iL). The reaction medium is stirred at ambient temperature for 15 hours and then treated by adding a saturated aqueous solution of ammonium chloride. The mixture is extracted with ethyl acetate and then the organic phase is dried over MgSO 4 and evaporated under reduced pressure. The product is triturated in diethyl ether to give compound No. 42 in the form of a beige powder (17 mg, Yield: 77%).

NMR 11I (d 6 -DMSO, 300 MHz): b (ppm): 1.99 (3H, s, 3H15); 3.91 (3H, s, 9-methoxy); 4.95 (2H, d, J12-12 = 5.1 Hz, 2H12); 6.93 (1H, dd, J8-7 = 8.7 Hz, J8-10 = 1.5 Hz, H8); 7.17 (1H, d; J10-8 = 1.5 Hz; H10); 7.62 (1H, s, H5); 8.03 (1H, d; J7-8 = 8.7 Hz; H7); 8.29 (1H, d, JI-2 = 5.5 Hz, HI); 8.54 (1H, m; H13); 8.59 (1H, d, J2-1 = 5.5 Hz, H2); 9.33 (1H, s, H4); 12.47 (1H; s; carbazol H) MS: ESI: m / z: 320.1 ([M + H] +) HRMS (ESI): calcd for C19H18N3O2 +: m / z = 320.1399; Example 25: 1- (9-Methoxy-11H-pyrido [4,3-a] carbazol-6-yl) -N, N-dimethylmethanamine (Compound No. 43) H3CO2 To a mixture of 9-methoxy 11H-pyrido [4,3-a] carbazol-6-methanamine (compound No. 39) (30 mg, 0.10 mmol, 1.0 eq.), Sodium cyanoborohydride (12 mg, 0.19 mmol) 1.9 eq.) And acetic acid (26 μL, 0.28 mmol, 2.8 eq.) In ethanol (6 mL) is added, at 0 ° C., a solution of formaldehyde (25 μL). 37% in water, 0.31 mmol, 3.1 eq.) In ethanol (2 mL). The reaction mixture is stirred at ambient temperature for 2 h 30, treated by adding a saturated aqueous solution of sodium carbonate and then concentrated under reduced pressure. The mixture is extracted with ethyl acetate and then the organic phase is dried over MgSO 4, evaporated under reduced pressure and the residue purified by filtration over alumina (eluent: CH 2 Cl 2 / EtOH) to give compound No. 43 in the form a beige powder (18 mg, Yield: 57%). NMR 11I (d 6 -DMSO, 300 MHz) - b (ppm): 2.31 (6H, s, 3H14 and 3H15); 3.90 (3H, s, 9-methoxy); 3.99 (2H; s; 2H12); 6.93 (1H, dd, J8-7 = 8.5 Hz, J8-10 = 2.1 Hz, H8); 7.14 (1H, d, J10-8 = 2.1 Hz, H10); 7.66 (1H, s, H5); 8.12 (1H, d, J7-8 = 8.5 Hz, H7); 8.29 (1H, d, JI-2 = 5.8 Hz, HI); 8.58 (1H, d; J2-1 = 5.8 Hz; H2); 9.33 (1H, s, H4); 12.37 (1H, s; carbazol H) MS: ESI: m / z: 306.2 ([M + H] +) HRMS (ESI): calcd for C19H21ON3O +: m / z = 306.1606; Example 26: (Z) -3- (5-Fluoropyridin-3-yl) -2- (5-methoxy-1H-indol-3-yl) -acrylonitrile (Compound No. 7) To a solution of the compound 3- (cyanomethyl) -5-methoxy-1H-indol-1-carboxylic acid tert-butyl ester [Example 28-1, WO2010150211A2] (327 mg, 1.14 mmol, 1.0 eq.) In anhydrous THF (15). mL) is added under argon, NaH (41 mg, 80%, 1.37 mmol, 1.2 eq.). The mixture is stirred at room temperature for 2 hours and then cooled to 0 ° C. before adding a solution of 5-fluoro-pyridine-3-carbaldehyde (200 mg, 1.60 mmol, 1.4 eq. Anhydrous THF (3 mL). The assembly is protected from light and the reaction medium is stirred at 0 ° C. for 1 h 30 before adding a saturated aqueous solution of ammonium chloride. The stirring is then continued at room temperature for 1 hour. An addition of water is made and the solution is extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium chloride and dried over MgSO4. The solvent is evaporated off under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / EtOH, 98/2) to give, after trituration in diethyl ether, compound No. 7 in the form of a yellow powder (200 mg, yield: 60%). 1 H NMR (d 6 -DMSO, 500 MHz): b (ppm): 3.84 (3H, s, 5'-methoxy); 6.92 (1H, dd; = 8.5 Hz, J6'4 '= 1.5 Hz, H6'); 7.42 (1H, d; J7-6 '= 8.5 Hz; H7'); 7.48 (1H; d; 6 '= 1.5Hz; H4'); 7.77 (1H; s; H3); 7.82 (1H; s; H2 '); 8.20 (1H; d; J4 "-F = 10.1Hz; H4; "); 8.61 (1H, m; H6-); 8.90 (1H; s; H2-); 11.72 (1H, s; H indole) MS: ESI: m / z: 294.1 ([M + H] +); 316.1 ([M + Na] +); 348.1 ([M + Na + MeOH] +) HRMS (ESI): calcd for C17H13N3OF +: m / z = 294.1043; measured: 294.1048 Example 27: (Z) -2- (5-methoxy-1H-indol-3-yl) -3- (1H-pyrrol-3-yl) -acrylonitrile (Compound No. 60) To a mixture of ( 5-methoxy-1H-indol-3-yl) -acetonitrile (400 mg, 2.2 mmol, 1.0 eq.) And 1H-pyrrole-3-carbaldehyde (225 mg, 2.4 mmol, 1.1 eq.) in ethanol (10 mL) is added a methanolic solution of benzyltrimethylammonium hydroxide (40%, 540 μL, 1.3 mmol, 0.6 eq). The reaction medium is heated at 80 ° C. in a sealed tube for 5 days. After cooling to room temperature, the mixture is extracted with ethyl acetate and the organic phase is washed with a saturated aqueous solution of ammonium chloride and then dried over MgSO 4. The solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / EtOH, 100/0 to 98/2) and then by filtration on silica gel (eluent: heptane / AcOEt) to give compound No. 60 in the form of a yellow meringue (170 mg, yield: 30%). 1 H NMR (d 6 -DMSO, 500 MHz): b (ppm): 3.81 (3H, s, 5'-methoxy); 6.84 (1H, m; H4-); 6.85 (1H, dd; = 8.9Hz; J6'4 '= 2.3Hz; H6'); 6.92 (1H; s; H5 "); 7.35 (2H, m; H4 'and H7'); 7.41 (1H; s; H3); 7.54 (1H; s; H 2 '); 11.32 (1H, s; H indole) MS: ESI: m / z: 264.1 ([M + H] +); 286.1 ([M + Na] +) HRMS (ESI): calcd for C16H13N3ONa +: m / z = 286.0956; Example 28: (Z) -3- (1H-imidazol-4-yl) -2- (5-methoxy-1H-indol-3-yl) -acrylonitrile (Compound No. 61) CN To a mixture of tert-butyl 3- (cyanomethyl) -5-methoxy-1H-indol-1-carboxylate compound [Example 28-1, WO2010150211A2] 100 mg, 0.35 mmol, 1.0 eq.) and 1-imidazole-4 Caraldehyde (34 mg, 0.35 mmol, 1.0 equiv) in ethanol (3 mL) is added piperidine (31.1.1, L, 0.31 mmol, 0.9 eq). The reaction medium is heated at 90 ° C. in a sealed tube for 4 days. After cooling to room temperature, the mixture is extracted with ethyl acetate and the organic phase is washed with a saturated aqueous solution of ammonium chloride and then dried over MgSO 4. The solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / EtOH, 97/3 to 96/4) to give compound No. 61 in the form of a yellowish meringue ( 47 mg, Yield: 51%). 1 H NMR (d 6 -DMSO, 300 MHz): b (ppm): 3.81 (3H, s, 5'-methoxy); 6.87 (1H, d = 8.9 Hz, H6 '); 7.35 (1H; s; H4 '); 7.37 (1H, d; J7-6 '= 8.9 Hz; H7'); 7.51 (1H; s; H3); 7.64 (1H; s; H2 '); 7.73 (1H, s, H5-); 7.83 (1H; s; H2-); 11.41 (1H; s; indolic H); 12.46 (1H, s; H imidazole) MS: ESI: m / z: 265.1 ([M + H] +); 287.1 ([M + Na] +) HRMS (ESI): calcd for C15H13N4O +: m / z = 265.1089; EXAMPLE 29: 2- (5-Methoxy-1H-indol-3-yl) -2- (pyridin-3-yl) -acetonitrile (Compound No. 56) 29.1. Preparation of an intermediate compound (5-methoxy-1H-indol-3-yl) - (pyridin-3-yl) methanol To a solution of 5-methoxyindole (1 g, 6.8 mmol, 1.0 eq. ) in methanol (8 mL) are added, at 0 ° C, an aqueous solution of sodium hydroxide (80%, 200 1.1, L, 4.0 mmol, 0.6 eq.) and then pyridine-3-carbaldehyde (800 [iL, 8.5 mmol, 1.3 eq.). The reaction medium is stirred at 0 ° C. for 4 hours and then treated by adding a saturated aqueous ammonium chloride solution. The mixture is extracted with ethyl acetate and the organic phase is washed with a saturated aqueous solution of sodium chloride and then dried over MgSO 4. The solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / EtOH, 96/4 to 94/6) to give the intermediate compound in the form of a pink meringue (1, 3 g, yield: 75%). 1 H NMR (d 6 -DMSO, 300 MHz): δ (ppm): 3.68 (3H, s, 5'-methoxy); 5.73 (1H, d; J (ori) -1 = 4.5 Hz; H alcohol); 5.99 (1H, d; 1-140H) = 4.5 Hz; H1); 6.70 (1H, dd; = 8.7 Hz; SM: ESI: m / z: 255.1 ([M + H] +) HRMS (ESI): calcd for C151-115N2O2 +: m / z = 255.1134; measured: 255.1133 29.1 Preparation of Compound No. 56 To a solution of the intermediate compound prepared in Step 29.1 (450 mg, 1.8 mmol, 1.0 eq.) In DMSO (50 ml) was added tosylimidazole (472 mg, 2%). 1 mmol, 1.2 eq.), Triethylamine (614 μL, 4.4 mmol, 2.5 eq.), Sodium cyanide (217 mg, 4.4 mmol, 2.5 eq.) And TBAI (66 mg. 0.2 mmol, 0.1 eq.) The reaction medium is stirred at 60 ° C. for 2 hours and then treated by addition of an aqueous solution of sodium bicarbonate The mixture is extracted with sodium acetate ethyl and the organic phase is successively washed with water, saturated aqueous sodium chloride solution and then dried over MgSO.sub.4.The solvent is evaporated off under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / EtOH, 97/3) to give compound no. s the shape of a brown meringue (260 mg, yield: 56%). = 2.4 Hz; H6 '); 6.95 (1H, d; J4w = 2.4 Hz; H4 '); 7.06 (1H; s; H2 '); 7.23 (1H, d = 8.7 Hz, H7 '); 7.33 (1H, dd, 15 "4" = 7.7 Hz, 1-5 "_6" = 4.7 Hz, H5 "), 7.82 (1H, d = 7.7 Hz, H4"); 8.42 (1H, dd; 16 "_5" = 4.7 Hz, 16 "4" = 1.7 Hz, H6 "); 8.65 (1H; d; J2" -4 "= 1.9 Hz; H2"); 10.79 (1H, s; H indol) NMR 11I (d 6 -DMSO, 300 MHz): b (ppm): 3.70 (3H, s, 5'-methoxy); 6.02 (1H; s; H2); 6.89 (1H, dd; = 8.9 Hz, J6'4 '= 2.4 Hz, H6'); 6.94 (1H; d; J4'-6 '= 2.4 Hz; H4'); 7.31 (1H, d = 8.9 Hz, H7 '); 7.35 (1H; s; H2 '); 7.43 (1H, dd; J5 "-4" = 7.9 Hz; J5 "_6" = 4.9 Hz; H5 "); 7.87 (1H; d; J4" -5 "= 7.9 Hz; H4"); 8.54 (1H, dd; J6 "- 5 '= 4.9 Hz, J6" -4 "= 1.6 Hz, H6"); 8.70 (1H; d; J2 '' - 4 "= 2.4 Hz; H2"); 11.15 (1H, s; H indole) MS: ESI: m / z: 264.1 ([M + H] +); 286.1 ([M + Na] +); 318.1 ([M + Na + MeOH] +) HRMS (ESI): calcd for C16H14N3O +: m / z = 264.1137; measured: 264.1133 Example 30: N47- (5-methoxy-1H-indol-3-yl) -isoquinolin-6-yl] acetamide (Compound No. 57) 6 'To a solution of (Z) -2- (5) -methoxy-1H-indol-3-yl) -3- (4-methylpyridin-3-yl) acrylonitrile (636 mg, 2.2 mmol, 1.0 eq.) in anhydrous THF (50 mL) maintained at 0 ° C. A solution of KHMDS in toluene (31 mL, 0.5M, 15.4 mmol, 7.0 eq.) Is added under argon. The reaction is stirred at room temperature for 20 hours and then treated by addition of a saturated aqueous solution of ammonium chloride. The aqueous phase is extracted with ethyl acetate and then the organic phase is dried over MgSO4. The solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: CH 2 Cl 2 / EtOH, 96/4 to 94/6) to give compound No. 57 in the form of a beige powder ( 365 mg, yield: 50%). R1VIN111 (d6-DMSO, 300 MHz): b (ppm): 1.98 (3H; s; CH3 amide); 3.71 (3H, s, 5'-methoxy); 6.84 (1H, dd; = 8.8 Hz; J6'4 '= 2.4 Hz; H6'); 6.92 (1H; d; J4'-6 '= 2.4 Hz; H4'); 7.40 (1H, d; J7-6 '= 8.8 Hz; H7'); 7.64 (1H, m; H 2 '); 7.76 (1H, J4-3 = 5.8 Hz, H4); 8.14 (1H; s; H8); 8.41 (1H, d; J3 4 = 5.8 Hz; H3); 8.42 (1H, s, H5); 9.19 (1H; s; H1); 9.24 (1H; s; NH amide); 11.40 (1H, s; H indole) MS: ESI: m / z: 332.1 ([M + H] +) HRMS (ESI): calcd for C 20 H 18 N 3 O 2 +: m / z = 332.1399; measured: 332.1403 ESI: m / z: 330.1 ([M + EI] -) HRMS (ESI): calcd for C20H16N3O2-: m / z = 330.1243; measured: 330.1271 Melting point: 267 ° C Example 31: 6-Methoxy-1-oxo-3- (pyridin-3-yl) -2,9-dihydro-1H-pyrido [3,4-nitro-4-carbonitrile (Compound No. 64) 31.1. Preparation of the intermediate compound (E) -3-Amino-2- (5-methoxy-1H-indol-3-yl) -3- (pyridin-3-yl) -acrylonitrile CN To a solution of (5-methoxy) 1H-indol-3-yl) -acetonitrile (2 g, 10.8 mmol, 1.0 eq.) And nicotinonitrile (1.2 g, 12.9 mmol, 1.2 eq.) In THF (20 mL) maintained at 0 ° C is added under an argon atmosphere, a solution of potassium tert-butanolate in THF (21.6 mL, 1M, 21.6 mmol, 2.0 eq.). The assembly is protected from light and the reaction medium is stirred at ambient temperature for 10 hours and then treated with an aqueous solution of sodium bicarbonate. The mixture is extracted with ethyl acetate and the organic phase is successively washed with water and a saturated aqueous solution of sodium chloride and then dried over MgSO 4. The solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel (eluent: heptane / THF, 35/65 to 0/100) to give, after trituration in diethyl ether, dichloromethane and ethanol, the intermediate compound in the form of a yellow powder (2.20 g, yield: 70%). 1H NMR (d 6 -DMSO, 500 MHz): b (ppm): 3.77 (3H, s, 5'-methoxy); 6.53 (2H; s; H enamine); 6.82 (1H, dd; = 8.9 Hz, J6'4 '= 2.1 Hz, H6'); 7.06 (1H; d; J4'-6 '= 2.1 Hz; H4'); 7.34 (1H, d; J7-6 '= 8.9 Hz; H7'); 7.47 (1H; s; H 2 '); 7.55 (1H, dd; J5 "-4" = 7.6 Hz; J5 "_6" = 4.9 Hz; H5 "); 8.08 (1H; d; J4" -5 "= 7.6 Hz; H4"); 8.70 (1H, dd; J6 -5 "= 4.9 Hz; J6-4- = 1.5 Hz; H6"); 8.90 (1H; d; J2-4- = 2.3 Hz; H2 "); 11.22 (1H, s; H indole) MS: ESI: m / z: 291.1 ([M + H] +); 313.1 ([M + Na] +); 345.1 ([M + Na + MeOH] +) HRMS (ESI): calcd for C17H14N4O4 +: m / z = 313.1065; measured 313.1055 31.2. Preparation of N-tert-butyl (E) -3- (2- (tert-butoxycarbonylamino) -1-cyano-2- (pyridin-3-yl) -vinyl) -5-methoxy-1H-indole-1-carboxylate Boc H To a solution of the intermediate compound prepared in step 31.1. (1.4 g, 4.8 mmol, 1.0 eq.) And (Boc) (4.1 mL, 19.3 mmol, 4.0 eq.) In anhydrous dichloromethane (200 mL) maintained at 0 ° C. is added, under an argon atmosphere, DMAP (59 mg, 0.48 mmol, 0.1 eq.). The reaction medium is stirred at 0 ° C. for 30 minutes and then treated by addition of an aqueous solution of sodium bicarbonate. The organic phase is then washed with water, dried over MgSO 4, then filtered on silica gel and evaporated under reduced pressure. The residue is taken up in a mixture of dichloromethane (150 mL) and TFA (7.1 mL, 96.0 mmol, 20.0 eq.), And the reaction mixture is stirred at ambient temperature for 6 hours and then treated by addition of an aqueous solution of 1M soda. The mixture is extracted with ethyl acetate and the organic phase is washed with water, dried over MgSO4 and then evaporated under reduced pressure. The residue is purified by flash chromatography on silica gel (eluent: heptane / AcOEt, 50/50) to give the intermediate compound in the form of a yellow meringue (1.7 g, Yield: 72%). NMR 11I (d 6 -DMSO, 300 MHz): b (ppm): 1.47 (9H, s, Boc); 1.65 (9H, s, Boc); 3.77 (3H, s, 5-methoxy); 6.95 (1H, d; J4_6 = 2.4 Hz; H4); 7.05 (1H, dd, J6_7 = 8.9 Hz, J6-4 = 2.4 Hz, H6); 7.55 (1H, dd; J5-4- = 7.9 Hz; J5 -6 "= 4.9 Hz; H5"); 7.81 (1H; s; H2); 8.03 (2H; m; H7 and H4 "); 8.70 (1H, dd; J6 -5 "= 4.9 Hz; J6-4- = 1.5 Hz; H6"); 8.82 (1H; d; J2-4- = 1.8 Hz; H2 "); 9.56 (1H; s; NH carbamate) MS: ESI: m / z: 491.2 ([M + H] +); 513.2 ([M + Na] +) NHBoc H 3 CO NH 2 HRMS (ESI): calcd for C 27 H 31 N 4 O 5 +: m / z = 491.2294; measured: 491.2274 31.3. Preparation of compound No. 64 A suspension of the intermediate compound prepared in step 31.2. (300 mg, 0.61 mmol) in decalin (12 mL) is heated at 160 ° C for 7 hours. After cooling to room temperature, the reaction medium is diluted with ethyl acetate, and the precipitate is filtered off and then rinsed with heptane, ethanol and diethyl ether to give compound ° 64 in the form of a brown solid (110 mg, Yield: 57%). R1VIN111 (d6-DMSO, 300 MHz): b (ppm): 3.83 (3H, s, 6-methoxy); 7.21 (1H, dd; J7_8 = 8.9 Hz; J7_5 = 2.4 Hz; H7); 7.55 (1H, d, J8-7 = 8.9 Hz, H8); 7.64 (1H, dd; = 7.9 Hz, J5'_6 '= 4.7 Hz, H5'); 7.67 (1H, d; J5-7 = 2.4 Hz; H5); 8.17 (1H; d; L4'-5 '= 7.9 Hz; H4'); 8.76 (1H; d; J6 '5' = 4.9 Hz; H6 '); 8.92 (1H; s; H 2 '); 12.44 (1H; s; H indole); 12.54 (1H, s; NH amide) MS: ESI: m / z: 317.1 ([M + H] +) HRMS (ESI): calcd for C18H31N4O2 +: m / z = 317.1039; EXAMPLE 32: 6-Methoxy-2- (pyridin-4-yl) -1H-pyrrolo [2,3-b] pyridine (Compound No. 62) 4 H3CO To a mixture of 6-methoxy-1H-pyrrolo [2,3-b] pyridine (100 mg, 0.67 mmol, 1.0 equiv), Cs0Ac (363 mg, 1.89 mmol, 2.8 eq.), 4-bromopyridine hydrochloride (235 mg, 1.21 mmol, 1.8 eq.), Anhydrous diisopropylamine and degassed (266 1.1, L, 1.89 mmol, 2.8 eq.) Are added, under argon, Pd (OAc) 2 (6.1 mg. 0.027 mmol, 0.04 eq.) And anhydrous NMP (100 [tL). The reaction medium is stirred at 120 ° C. for 60 hours, then diluted with ethyl acetate and filtered through silica gel after cooling to room temperature. The organic phase is washed with a saturated aqueous solution of ammonium chloride, dried over MgSO 4 and then evaporated under reduced pressure. The residue is purified by flash chromatography on silica gel (eluent: heptane / AcOEt, 50/50 to 0/100) to give compound No. 62 (25 mg, yield: 17%), in the form of a solid Brown.

1 H NMR (d 6 -DMSO, 300 MHz): b (ppm): 3.92 (3H, s, 6-methoxy); 6.59 (1H; d; J5 4 = 8.5 Hz; H5); 7.15 (1H; s; H3); 7.83 (2H; d; J3'-2 '= J5'-6' = 4.5 Hz; H3 'and H5'); 7.92 (1H, d; J4_5 = 8.5 Hz; H4); 8.56 (2H; d; J2'-3 '= J6'-5' = 4.5 Hz; H2 'and H6'); 12.28 (1H, s; pyrrolic H) MS: ESI: m / z: 226.1 ([M + H] +) HRMS (ESI): calcd for C13H12N3O +: m / z = 226.0980, measured: 226.0981 Example 33: 6-methoxy 3- (pyridin-4-yl) -1H-pyrrolo [2,3-b] pyridine (Compound No. 63) The procedure is identical to Example 32. Compound No. 63 is obtained in a second time at the end of the chromatography column (25 mg, Yield: 17%) in the form of a brown solid. 1 H NMR (d6-DMSO, 300 MHz): b (ppm): 3.90 (3H, s, 6-methoxy); 6.67 (1H, d, J5 4 = 8.5 Hz, H5); 7.71 (2H; d; J3'-2 '= J5'-6' = 4.5 Hz; H3 'and H5'); 7.94 (1H, m; H 2); 8.33 (1H, d, J4-5 = 8.5 Hz, H4); 8.52 (2H; d; J2'-3 '= J6'-5' = 4.5 Hz; H2 'and H6'); 12.04 (1H, s; pyrrolic H) MS: ESI: m / z: 226.1 ([M + H] +) HRMS (ESI): calcd for C13H12N3O +: m / z = 226.0980, measured: 226.0981 Table I below illustrates the chemical structures and the physical properties of some examples of compounds of formula (I) according to the invention. In this table: - PF = Melting Point, in degrees Celsius (° C) - mu '= mass spectrometry (m / z), - "Bn" represents a benzyl group R 10 (I) Table IN ° Structure Characterization 1 HN 2 N / N 3 HNH 3 N H N N H N N H N N H N N N H N N H N N N N H N N H N N N N H N N ## STR5 ## - H 0% Fe 0) ----- 9 N, / N \\ - H HN 0 iOCH3 0 10 N / N \\ - H HN * 0 11 N / N Pf = 182 ° C \\ - H HN H3CO 12 N / N H H N - Cl 13 N / N H N 14 N, N N H H OCH 3 O- / N - H HN OCH 3 NHCH 3 ESI: m / z: 305.1 ([M + H] +) N "N, \ - H HN 4 OCH 3 17 N / N \ - H HN 0 0 - 1H - Y 1 N), LH 18 N / N ESI: m / z: 322.1 ([M + H] +) ν -H HN te 19 N / N ESI: m / z: 328.1 ([M + H] +) - H HN 4 N / N ## STR2 ## ## STR1 ## ## STR1 ## ## STR1 ## where ## STR2 ## NH 2 H 2 O 3 HN - * 25 N, mp = 103 ° C, OCH 3 H HN - 26 ... N CN \\ HNH 27 N / N Mp = 136 ° C, \\ HN * ocH3 28 N, / N \\ HS 29 N, / 'N \\ H 0 30 N / N % \\ - / H HN / N 31 / ESI: miz V: 277.1 ([M + H] +) \ NH HN N OCH3 32 N, / N \\ _ HN 4 33 H / N \\ - H HN OCH3 34 - ESI: miz: \ / 352.1 ([M + H] +) N H HN OCH3 HN fill NN H3CO HN N ESI: miz: H3CO II 304.1 ([M + H] + 37 H300 iNi I ESI: miz: HN 01/1 N 274.1 ([M + H] +) NN 38 H3CO. 0 NH 2 ESI: miz: HNOOI 292.1 ([M + H] +) N N H3co. HN 00 NH 2 ESI: mI: X I 278.1 ([M + H] +) N 40 H300 iNi ESI: miz: HN 0110 304.1 ([M + H] +) H300 N 41 H3CO. 0 NH 2 ESI: miz: HN OO N 322.1 ([M + H] +) H 3 CO 42 H, CO 0 ESI: m / z: NH 320.1 ([M + H] +) HN 0111 / N., N 43 H3CO N ESI: m / z: 306.2 HN 1110 ([1 + 4 + 1-1] +) N + 44 H 3 CO (+ ESI: m / z: 274.1 ([M + H] +) HN XN 45 cl HN Ni ESI: m / z: H 278.1 ([M + H] +) O11) XN 46 F HN N ESI: m / z: and 262.1 ([M + H] +) X N 47 ESI: miz: 274.1 ([M + H] +) 0 CH 3 II * HN 40 INN 48 H 3 C 0 o NH 2 ESI: in / z: HN fill N 292.1 ([M + H] +) X 49 H 3 0 0 iNi N ESI: in / z : N ------ 010 275.1 ([M + H] +) HNN 50 H 3 C 0 N ESI: miz: 274.1 ([M + H] +) 11 HNIXN 51 II HN El NX 2 II HN N 53 / i - HN N 54 II HN 0101111 Ille 55 N ESI: rniz: II 245.1 ([M + H] +) / N "" - - - - - - - 010 HN NN 56 VA ESI: rniz: 264.1 ([M + H] +); 286.1 ([M + Na] +); 318.1 ([M + Na + MeOE1] +) / - HN gleocH3 57 Mp: 267 ° C. HN OCH3 8 N / s H N OCH3 59 N, H N OCH3 60 N / NH ESI: m / z: 286.1264.1 ([M + H] +); ([M + Na] +) HN H Ob OCH3 61 H N ESI: m / z: 287.1 N = 265.1 ([M + Hr); ([M + Na] +) OCH3 62H, CO / N-ESI: m / z: 226.1 ([M + H] +) N- HN 63 H3C0 / N ESI: m / z: 226.1 ([M + H] +) N ------- HN 64 N / / N ESI: m / z: 317.1 ([M + H] +) H3CO NH 0 4111 NH The compounds according to the invention have been the subject of pharmacological tests to determine their inhibitory effect on the activity of protein kinases.

Example 34: Pharmacological Data The compounds were evaluated on the kinases CK1, CDK5, GSK3, PIM1, DYRK IA and CLK1. 1VIATERIAL AND METHODS Kinase Inhibition Tests The biological test protocol for evaluating the inhibition of compounds on the different kinases is directly derived from the experimental section of the publication "Meriolins (3- (Pyrimidin-4-yl) -7-azaindoles): Synthesis, Kinase Inhibitory Activity, Cellular Effects, and Structure of a CDK2 / Cyclin A / Meriolin Complex. Echalier, A .; Bettayeb, K .; Ferandin, Y .; Lozach, O .; Clement, M .; Valette, A .; Liger, F. o .; Marquet, B .; Morris, J. C .; Endicott, J. A .; Joseph, B. / E .; Meijer, L.J. Med. Chem. 2008, 51, 737-751. Preparation of buffers homogenization buffer: 60 mM (3-glycerophosphate, 15 mM p-nitrophenyl phosphate, 25 mM Mops (3- (N-morpholino) propanesulfonic acid) (pH 7.2), 15 mM EGTA (ethylene glycol tetraacetic acid), 15 mM MgCl2, 1 mM DTT (Dithiothreitol), 1 mM sodium vanadate, 1 mM NaF, 1 mM phenylphosphate, 10 μg / mL elepin, 1.1. g / mL aprotinin, 1.1 g / mL inhibitors from trypsin soybean sprouts, and 1001.1M benzamidine Buffer A: 10 mM MgCl 2, 1 mM EGTA, 1 mM DTT, mM Tris-HCl, pH 7.5, and 50 μg heparin / mL Buffer C: It consists of the homogenization Buffer indicated previously, except that it comprises 5 mM EGTA and not 15 mM, and that it does not include either NaF or trypsin inhibitor.

Kinase Preparation and Activity Measurements The kinase activities were assayed in Buffer A or C at 30 ° C, and a final concentration of ATP of the background was determined and subtracted from the measured values accordingly. Kinase activities are calculated in picomoles of incorporated phosphate for a 30 minute incubation. The activities are usually expressed in relation to the maximum percentage of activity, that is to say in the absence of inhibitor. Controls are carried out with appropriate dilutions of dimethyl sulfoxide. CDK5 / p25 was reconstituted by mixing equal amounts of recombinant mammalian CDK5 and p25 expressed by E. coli as a GST (glutathione-S-transferase) -associated fusion protein and purified by affinity chromatography. on agarose-gluthatione. As a reminder, p25 is a truncated form of p35, the 35 kDa CDK5 activator. Its activity was assayed in Buffer C with 1 mg / ml Histone H1, in the presence of 151 μM [γ-3311 ATP (3000 Ci / mmol, 10 mCi / ml) for a final volume of 30 minutes. incubation at 30 ° C, 25 μl aliquots of supernatants were deposited on Whatman P81 nitrocellulose filter papers, and 20 seconds later the filters were washed 5 times (for at least 5 minutes each) in a solution of 10 mL of phosphoric acid / L of water. Wet filters are then counted in the presence of ACS (Amersham). GSK-3a / (3 was purified from porcine brain by affinity chromatography on axin-1 immobilized on beads (Primot, A., Baratte, B., Gompel, M., Borgne, A. Liabeuf, S., Romette, JL, Costantini, F. and Meijer, L., 2000. Purification of GSK-3 by affinity chromatography on immobilized axin Protein Expr. & Purif 20 (3), 394-404). It was assayed in Buffer A, after a 1/100 dilution in 1 mg BSA / mL 10mM DTT, with 5! IL substrate peptide GS-1 to 4 in the presence of 15 μM [γ-3311ATP. 3000 Ci / mmol, 10 mCi / mL) for a final volume of 30 minutes of incubation at 30 ° C, 25 μL aliquots of supernatants were treated as indicated above. of porcine brain by affinity chromatography on a fragment of axin-2 immobilized on beads (Reinhardt J., Ferandin, Y. and Meijer, L., 2007. Purification CK1 by affinity chromatography on immobilized axin Protein Expr. Purify 54, 1 01-109) The assay was performed as previously indicated for CDK5 but using a CK1 specific substrate peptide. DYRK IA (recombinant, expressed by E. coli as GST fusion protein) was purified by affinity chromatography with glutathione agarose and assayed as described above for CDK5. - CLK1 (Human, recombinant, expressed by E. coli as a fusion protein with GST) was assayed in Buffer A (+ 0.15 mg BSA / ml) with an RS peptide (GRSRSRSRSRSR) (1 [tg / test ) according to the protocol described above, mutatis mutandis, for CDK5. - PIM1 (recombinant human) was assayed in Buffer C, with 1 mg Histone H1 / mL according to the protocol described above for CDK5. KB Cell Cytotoxicity Assay KB cells (human squamous cell carcinoma) were cultured in Dulbecco's Modified Eagle Minimal Essential Medium supplemented with 25 mM glucose, 10% (v / v) FCS, 100 IU penicillin , 100 μg / ml of streptomycin and 1.5 μg / ml of fungizone, then stored under 5% CO2 at 37 ° C. A 96-well plate was seeded with 500 KB cells per well in 200 μl of medium. 24 hours later, some of the compounds considered in the examples were dissolved in DMSO and then added to the wells for 72 hours at a final concentration of 10-5M in a fixed volume of DMSO (final concentration 1%). The controls received an equivalent amount of DMSO. 40 μl of MTS reagent (Promega, Madison, WI) were added per well. 2 hours later, the percent inhibition was calculated by measuring the difference in optical density at 490 nm between controls and samples. RESULTS Cytotoxicity on KB Compounds tested CK1 CDK5 GSK3 PIM1 DYRK CLK1. . % 1050 1050 1050 IC50 IC 50% min. . (IIM) (IIM) (IIM) (111M) IC50 (111M) (10-5M) minb (Jun (10-6M) 1 NT inactive inactive 1.4 5.5 NT 27 NT> 101, tM> 101, tM 2 NT inactive inactive 1.1 6.3 NT 57 NT 21 NT inactive inactive 7 inactive NT 76 NT 22 NT inactive inactive 6.5 inactive NT 24 NT 35 NT 0.8 1 0.35 0.05 NT 82 46 53 NT inactive inactive inactive inactive NT 42 NT 28 NT inactive inactive 4.8 inactive NT inactive NT 29 NT inactive inactive 1.6 inactive NT 20 NT 23 NT inactive inactive 7 inactive NT 75 NT 3 NT inactive inactive 1.7 inactive NT 22 NT 24 NT inactive 5 4 inactive NT 35 NT 4 inactive inactive inactive NT 5.5 5 78 18 inactive inactive inactive NT i nactive 10 2.3 63 NT 50 inactive 0.8 1.7 NT 0.37 0.051 76 inactive 32 inactive inactive inactive NT inactive 7.6 27 NT 52 inactive 6 2.4 NT 0.37 0.17 100 3 55 inactive inactive inactive NT 2.3 1.4 62 NT 51 inactive inactive inactive NT inactive 10 inactive inactive 23 NT 54 inactive inactive inactive NT inactive inactive 54 NT 36 inactive 0.93 4 NT 0.6 0.056 42 NT 6 inactive inactive inactive NT 1.6 1.3 87 78 37 inactive 0.44 0, 68 NT 0.025 0.023 93 64 38 inactive 4.5 9 NT 2 1.6 30 NT 39 inactive 5.6 inactive NT 0.87 0.83 100 85 40 inactive 6.4 0.14 NT 0.018 0.023 78 38 41 inactive 1 , 6 inactive NT 3.3 1.6 77 15 42 inactive 6 inactive NT 0.97 2.4 81 16 43 inactive 5.4 inactive NT 0.67 1.4 100 37 25 inactive inactive inactive NT 3.5 6, 1 89 inactive 7 inactive inactive inactive NT Inactive> 3.2 80 11 0 8 inactive inactive Inactive> 0 NT inactive 2.4 32 NT 9 inactive inactive 27 NT Inactive> i 32 NT 0 inactive inactive inactive inactive NT 9 3.7 29 NT 11 inactive inactive inactive NT 1.2 1.5 85 inactive 12 inactive inactive inactive NT 3.3 2 32 NT 13 inactive inactive inactive NT 1.8 1.7 26 NT 14 inactive inactive inactive NT 6 3 27 NT 44 inactive 0 , 46 2 NT 0.027 0.041 85 9 45 inactive inactive inactive NT 4 inactive 13 NT 46 inactive inactive inactive NT 0.31 0.23 29 NT 47 inactive inactive inactive NT 0.85 0.62 58 13 27 inactive inactive inactive NT 5, 5 5 33 NT 48 inactive 9 8.8 NT 0.6 0.57 inactive NT 15 inactive inactive inactive NT inactive 8.7 6 NT 16 inactive inactive i inactive NT active 8.2 41 NT 20 inactive inactive inactive NT inactive 6.2 69 NT 30 inactive 0.72 0.13 NT 0.021 0.016 100 29 33 inactive inactive inactive NT 9 4.2 19 NT 56 inactive 0.78 1, 8 NT 0.44 0.16 71 NT 34 inactive inactive inactive NT 5.7 1.1 94 inactive 49 inactive inactive inactive NT 0.2 0.19 29 NT 31 inactive inactive inactive NT 0.18 0.23 18 NT 26 inactive inactive inactive NT 7.3 1.6 14 NT 17 inactive inactive i nactive NT 4 0.6 10 NT> 10 nactive 18 inactive inactive inactive NT i nactive 10 1.2 93 inactive 19 inactive inactive inactive NT i nactive 10 2, 3 99 12 56 inactive 5.4 1.3 NT inactive inactive 45 NT 57 inactive 8 inactive NT 0.85 0.034 inactive inactive 58 inactive inactive inactive NT inactive 9.1 98 16 59 inactive inactive inactive NT inactive 4.3 92 47 60 inactive inactive inactive NT 5.5 6.4 31 NT 61 inactive inactive inactive NT 5.5 3.5 36 NT 62 inactive? Inactive inactive Inactive NT 2.9 inactive NT 63 inactive 7 inactive NT 5.8 0.43 inactive NT 64 inactive inactive inactive NT 4.3 0.14 2 NT "NT" not tested The compounds according to the invention can therefore be used for the preparation of medicaments, in particular medicinal products having a protein kinase inhibitory activity and in particular CLK1, DYRK lA and PIM1 kinases. Among the compounds in accordance with the invention, mention may be made in particular of the following compounds (17) , (30), (31), (35), (36), (37), (39), (40), (42), (44), (46), (47), (48), 49), (50), (57), (63) and (64). These drugs find their therapeutic use, especially in the prevention and treatment of various pathologies such as cancers, chronic neurodegenerative diseases such as Alzheimer's disease, Down syndrome, cortico-basal degeneration, Steele-Richardson diseases -Olszwski, Pick, Parkinson and Hundington. They are also used in the treatment of depression and skizophrenia and also in the treatment of viral diseases chosen in particular from HIV, influenza, herpes or Herpes Simplex Virus (HSV) or Influenza virus.

The present invention, according to one of its aspects, relates to a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa) or (III) , or (1) to (64) or a pharmaceutically acceptable salt thereof, for the treatment of neurodegenerative diseases, depression, skizophrenia and viral infections. According to another of its aspects, the present invention relates to a compound of formula (III), (IIa), (Ib), (Ic), (Id) or (Ie) or (35) to (57) and (62) (64) or a pharmaceutically acceptable salt thereof for the treatment of cancer. The present invention also relates to a pharmaceutical composition comprising at least one compound chosen from the compounds of formula (III) with the exception of the non-novel compounds listed above, the compounds of formula (IIa), (Ib), (Ic), Id) and (Ie), the novel compounds selected from compounds (7), (11), (16), (18), (19), (22), (27), (31), (34), (36) to (50), (55), (56), (57) and (60) to (64) or mixtures thereof and at least one pharmaceutically acceptable excipient. Said excipients are selected according to the pharmaceutical form and the desired mode of administration, from the usual excipients which are known to those skilled in the art. In the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal administration, the active ingredient of formula (I) above, or its Any salt, solvate or hydrate may be administered in unit dosage form, in admixture with conventional pharmaceutical excipients, to humans for the prophylaxis or treatment of the disorders or diseases mentioned above.

Suitable unit dosage forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sublingual, oral, intratracheal, intraocular, intranasal forms of administration. by inhalation, topical, transdermal, subcutaneous, intramuscular or intravenous administration forms, rectal administration forms and implants. The present invention, according to yet another of its aspects, also relates to a method for preventing and / or treating the pathologies indicated above which comprises the administration to a patient of an effective dose of a compound according to the invention, or a pharmaceutically acceptable salt thereof or hydrates or solvates thereof. The pharmaceutical compositions according to the invention may also find use in the veterinary field and also be administered to animals such as dogs and cats for the prophylaxis or treatment of the disorders or diseases mentioned above.

Claims (21)

REVENDICATIONS1. A compound of formula (I) R10 (I) wherein Y1 is selected from NR5, sulfur or oxygen, Y2 is selected from CH or N, R2 is hydrogen, an OH group, a (C 1 -C 6) alkyl or (C 1 -C 4) alkyl group, a (C 1 -C 4) alkoxy group, a -O (CH 2) n Ar group, a -000 group (C - C4) alkyl, -000 (CH2) n, (C1-C4) alkoxy, -NHC 00 (C -C4) alkyl, halogen, -SH, thio (C1-C4) ) alkyl, -NH2, -SO2 (C1-C4) alkyl, -SO2NR5R6, nitro or -CONR5R6, Ar is aryl, n is an integer of 1 to 4, R9 is - a heteroaryl group optionally substituted with one or two groups selected from a (C 1 -C 4) alkyl group, an OH group, a (C 1 -C 4) alkoxy group, a -O (CH 2) Ar group, a OCO (C 1 -C 4) alkyl, a group -000 (CH 2) '(C 1 -C 4) alkoxy, a group -NHCOO (C 1 -C 4) alkyl, a halogen atom, a group -SH, a group thio (C1-C4) alkyl, -NH2 group, -SO2 (C1-C4) alkyl group, -SO2NR5R6 group, nitro group and -NHCOR5R6 group, -H group, where Pyr represents a group pyridyl, a group -CH (CN) R11, a group C (CN) = NR11 or a group -C (CN) = CHR 1 1, R11 represents an aryl group or a heteroaryl group, said phenyl or heteroaryl group being optionally substituted by one or two groups selected from a (C 1 -C 4) alkyl group, a (C 1 -C 4) alkoxy group, a halogen atom, a group -NR 5 R 6, a group -CONR 5 R 6, a group. CN, -OH, -SH, thio (C1-C4) alkyl, -NH2, -SO2 (C1-C4) alkyl, -SO2NR5R6, and nitro, R10 represents a hydrogen, a (C 1 -C 6) alkyl or (C 1 -C 4) alkyl group, an aryl group or a heteroaryl group, R 5 and R 6 independently represent a hydrogen atom or a (C 1 -C 4) alkyl group, or R 9 and R10 together with the indolyl group carrying them, form a saturated, unsaturated or partially saturated 6-membered ring which may comprise, as the atom forming this ring, a group -NH- and / or a group -CO-, said a ring which may be substituted with one or two group (s) chosen from a -CN group and a heteroaryl group, said 6-membered ring being in particular represented as follows: CN (R 9) HetAr NH (R 10) O, where HetAr represents a heteroaryl group, R11 R11 or R9 and R10 together with the indolyl group carrying them a group in which X1, X2, X3 and X4 represent It is understood that at most one of X 1, X 2, X 3 and X 4 is a nitrogen atom, R 1 is a hydrogen atom, a group is a carbon atom, or a nitrogen atom. (C1-C6) alkyl or (C1-C4) alkyl, (C1-C4) alkoxy group, thio- (C1-C4) alkyl group, -NR5R6 group, -CONR5R6 group or CN group, a group -OH, -SH, thio (C1-C4) alkyl, -NH2, -SO2 (C1-C4) alkyl, -SO2NR5R6 and nitro, and R4 is -CN, -CONH2 group, -CH2NR5R6 group or -CH2NHCOCH3 group, as well as their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. 2. Compound according to claim 1, characterized in that Ar is an aryl group, especially a phenyl group and the heteroaryl group is chosen from a thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl and imidazolyl group. , tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl or tetrazolyl, more particularly chosen from a thienyl, pyrazolyl, pyrrolyl and imidazolyl group; , quinolyl, isoquinolyl and pyridyl. 3. Compound of formula (Ia) in which represents a single bond or no bond, the double bond - bearing the group R4 being of configuration E when it represents an absence of bond, YI is chosen from an NH group, an atom of sulfur or an oxygen atom, Y2 is chosen from a CH group or a nitrogen atom, X1, X2, X3 and X4 represent a CH group, a carbon atom or a nitrogen atom, it being understood that more than one of X1, X2, X3 and X4 is a nitrogen atom, R1 represents a hydrogen atom, a (C1-C6) alkyl or (C1-C4) alkyl group, a (C1-C4) alkoxy group a group -NR5R6, a group -CONR5R6, a halogen atom, a group CN, a group -OH, a group -SH, a thio group (C1-C4) alkyl, a group -NH2, a group -SO2 (C1-C4) alkyl, -SO2NR5R6 group and nitro group, R2 represents a hydrogen atom, an OH group, a (C1-C6) alkyl or (C1-C4) alkyl group, a (C1-C4) alkoxy group , a group -O (CH2) 'Ar, a group -000 (C1-C4) alkyl, a gro upe -000 (CH2) '(C -C4) alkoxy, -NHCOO (C1-C4) alkyl, halogen, -SH, thio (C1-C4) alkyl, -NH2 , a group -SO 2 (C 1 -C 4) alkyl, a group -SO 2 NR 5 R 6 and a nitro group, R 3 represents a hydrogen atom, a (C 1 -C 4) alkyl group, an aryl group, such as a phenyl group or a heteroaryl group , which may be selected from thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3-oxadiazolyl, 1,3, 4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl and tetrazolyl, such as a thienyl group, R4 represents a -CN group, -CONH2 group, -CH2NR5R6 group, -CH2NHCOCH3 group, or a CH5 group or CH5 group. and R6 independently represent a hydrogen atom or a (C1-C4) alkyl group, Z represents a CH group or a nitrogen atom, Ar represents an aryl group, such as a group phenyl, and n represents an integer between 1 and 4, as well as their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. 4. Compound according to the preceding claim, of formula (Ia), wherein Z is a CH group. 5. Compound of formula (Ia) according to one of claims 3 or 4, wherein X2 is a nitrogen atom and Xl, X3 and X4 are CH groups. 6. A compound of formula (Ia) according to any one of claims 3 to 5, wherein R4 is a -CN group. 7. Compound of formula (I) according to claim 1 or 2, characterized in that Y1, Y2 and R2 are as defined in one of claims 1 or 2, R9 represents - a heteroaryl group chosen from a quinolyl group, isoquinolyl, pyridyl, said heteroaryl group possibly being substituted by a (C 1 -C 4) alkyl group, a -NHCO (C 1 -C 4) alkyl group, an OH group, a (C 1 -C 4) alkoxy group, a -O group ( CH 2), 1Ar, a group -OC 0 (C -C 4) alkyl, a group -000 (CH 2) n (C 1 -C 4) alkoxy, a group -NHCOO (C 1 -C 4) alkyl, a halogen atom, a -SH group, a thio (C1-C4) alkyl group, a -NH2 group, a -SO2 (C1-C4) alkyl group, a -SO2NR5R6 group, a nitro group or a -CONR5R6 group, or H Pyr - a H group, a group, where Pyr represents a pyridyl group, a group -CH (CN) R11, a group C (CN) = NR11 or a group -C (CN) = CHR1 1, Ar represents an aryl group, such as a group phenyl, R11 represents a phenyl group or a heteroaryl group, selected from a group pyridyl, a thienyl group, a pyrazolyl group, an imidazolyl group, a pyrrolyl group, the said phenyl or heteroaryl group being optionally substituted by one or two groups selected from a (C 1 -C 4) alkyl group, a (C 1 -C 4) group; alkoxy, halogen, -NR5R6, -CONR5R6 or CN, R10 is hydrogen, (C1-C6) alkyl or (C1-C4) alkyl, phenyl or a heteroaryl group selected from a pyridyl group and a thienyl group, and R5 and R6 independently represent a hydrogen atom or a (C1-C4) alkyl group, as well as their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. A compound of formula (II) wherein R 1, R 2, R 3, R 4, Z, X 1, X 2, X 3, Y 1 and Y 2 are as defined in claim 3, as well as their pharmaceutically acceptable salts, for the treatment of diseases neurodegenerative diseases, depression, skizophrenia or viral infections. 9. Compound of formula (II) according to the preceding claim, wherein X1, X2, X3, R3, Z, Y1 and Y2 are as defined in claim 3, R1 represents a hydrogen atom, a group C4) alkyl, a (C1-C4) alkoxy group, a group -NR5R6, a group -CONR5R6, a group CN or a halogen atom, R2 represents a hydrogen atom, an OH group, a group C4) alkoxy, -O (CH2) 'phenyl, -OCO (C1-C4) alkyl, -000 (CH2), (C1-C4) alkoxy, -NHCOO (C1-C4) alkyl or a halogen atom, (> or R4 represents a group -CN, a group a CH group and R5 and R6 independently represent a hydrogen atom or a group (Ci -C4) alkyl, and their pharmaceutically salts acceptable for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. 10. Compounds of formula (I) according to claim 1, defined by the formula R2 / 1 X4 R1 (III) wherein R1, R2, R4, X1, X2, X3, X4, Y1 and Y2 are as defined in claim 3 and their pharmaceutically acceptable salts for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. 11. Compound of formula (III) according to the preceding claim, wherein X1, X2, X3, X4, Y1 and Y2 are as defined in claim 3, R1 represents a hydrogen atom, or a group (C1-C4 alkoxy, R2 is hydrogen, (C1-C4) alkoxy or halogen, R4 is -CN, -CONH2, -CH2NR5R6, -CH2NHCOCH3, and R5 and R6 independently represent a hydrogen atom or a (C 1 -C 4) alkyl group, as well as their pharmaceutically acceptable salts, for the treatment of neurodegenerative diseases, depression, skizophrenia or viral infections. 12. A compound according to any one of the preceding claims, characterized in that the neurodegenerative diseases are Alzheimer's disease, Down syndrome, cortico-basal degeneration, Steele-RichardsonOlszwski, Pick, Parkinson's diseases and Huntington's and viral infections are selected from influenza, HIV, Herpes or Herpes Simplex Virus and Influenza virus. Compounds of formula (IIa) wherein R 1, Z, R 4, X 1, X 2, X 3, R 2, Y 2 and Y 1 are as defined in claim 3, R 3 represents an aryl group, such as a phenyl group or a group heteroaryl, such as a group that may be selected from thienyl, pyridyl, oxazolyl, pyrimidinyl, thiazolyl, pyrazolyl, furyl, pyranyl, pyrrolyl, imidazolyl, tetrazolyl, benzofuranyl, pyrrolinyl, triazinyl, pyrazinyl, pyridazinyl, 1,2,3 oxadiazolyl, 1,3,4-oxadiazolyl, quinolyl, isoquinolyl, triazolyl and tetrazolyl, especially chosen from a pyridyl group, a thienyl group and a pyrazolyl group, said phenyl or heteroaryl group being optionally substituted with one or two groups chosen from ) from (C1-C4) alkyl, (C1-C4) alkoxy, halogen, -NR5R6, -CONR5R6, CN, -OH, -SH, a thio (C1-C4) alkyl group, an -NH2 group, a -SO2 (C1-C4) alkyl group, a -SO2NR5R6 group and a nitro group, R5 and R6 being as defined in claim 1, and their pharmaceutically acceptable salts. 14. Compound of formula (I1D) II in which Y1, Y2, R2 and R11 are as defined in claim 1 or 2, as well as their pharmaceutically acceptable salts. A compound of formula (Ic) Y 1 Y 2 N 1 (Ic) wherein Y 1 and Y 2 are as defined in claim 1, and R 9 represents a quinolyl or isoquinolyl group which may be optionally substituted by one or two groups selected from one of (C1-C4) alkyl group, an OH group, a (C1-C4) alkoxy group, a -O (CH2), Ar group, a -000 (C1-C4) alkyl group, a -000 (CH2) group. (C1-C4) alkoxy, -NHCOO (C1-C4) alkyl, halogen, -SH, thio (C1-C4) alkyl, -NH2, -SO2 ( C1_C4) alkyl, a group -SO2NR5R6, a nitro group and a group -NHCOR5R6, the groups R5, R6, Ar and n being as defined in claim 1, as well as their pharmaceutically acceptable salts. 16. A compound of formula (Id) R10 (Id) in which Y1, Y2 and R2 are as defined in claim 1, one of R9 and R10 is a hydrogen atom and the other group of R9 and R9 groups. R10 is a heteroaryl group comprising from 6 to 8 or 10 to 14 members, such as a pyridyl group, said heteroaryl group possibly being substituted by one or two groups chosen from (C 1 -C 4) alkyl group, an OH group, a (C1-C4) alkoxy group, a -O (CH2) Ar group, a -000 (C1-C4) alkyl group, a -000 (CH2) n (C1-C4) alkoxy group, a -NHCOO (C1-C4) alkyl group, a halogen atom, a -SH group, a thio (C1-C4) alkyl group, a -NH2 group, a -SO2 (C1_C4) alkyl group, a -SO2NR5R6 group; a nitro group and a group -NHCOR5R6, the groups R5, R6, Ar and n being as defined in claim 1, as well as their pharmaceutically acceptable salts. 17. A compound of formula (Ic) R2 HetAr (Ie) wherein Y1, Y2, R2 and HetAr are as defined in claim 1, as well as their pharmaceutically acceptable salts. 18. Compound of formula (III) as defined in one of claims 10 or 11, of formula (IIa) according to claim 13, of formula (Ib) according to claim 14, of formula (Ic) according to claim 15 , of formula (Id) according to claim 16 and of formula (Ie) according to claim 17, for the treatment of cancer, in particular gastric, hepatic, renal, ovarian, colon, prostate, lung cancers (NSCLC and SCLC), glioblastomas, thyroid, bladder, breast, melanoma, lymphoid or myeloid hematopoietic tumors, sarcomas, cancers of the brain, larynx, head and neck, lymphatic system , bone and pancreatic cancers, benign skin tumors, brain tumors and papillomas, prostate tumors and brain tumors, glioblastomas, medulloepithelio, medullo blastomas, neuroblastomas, embryonic origin tumors, astrocytomas, astroblastom es, ependymomas, oligodendrogliomas, plexus tumors, neuroepitheliomas, epiphyseal tumors, ependymoblastomas, malignant meningiomas, sarcomatoses, malignant melanomas and schwannomas, more particularly hematopoietic and prostate cancers. 19. Compound of formula (III) as defined in claim 10 or claim 11, with the exception of the following compounds: the compound for which Y2 = CH, R1 = R2 = H, R4 = CN, X1 = X3 = X4 = CH, and X2 = N, - the compound for which Y2 = CH, R1 = R2 = H, R4 = CN, X1 = X2 = X3 = CH, and X4 = N, - the compound for which Y2 = CH , R1 = R2 = H, R4 = CN, X1 = X2 = X4 = CH, and X3 = N, - the compound for which Y2 = CH, R1 = R2 = H, R4 = CN, X1 = X2 = X3 = X4 = CH and - the compound for which Y2 = CH, R1 = R2 = H, R4 = CN, X2 = X3 = X4 = CH, and X1-N, and - the compound for which Y2 = CH, R2 = H, R4 = CN, X1 = X3 = X4 = CH, X2 = N, and R1 = CH3 positioned on X2. 20. A compound selected from (Z) -3- (5-fluoropyridin-3-yl) -2- (5-methoxy-1H-indol-3-yl) -acrylonitrile (Compound No. 7), - (Z) - 2- (7-Methoxy-1H-indol-3-yl) -3-pyridin-3-yl-acrylonitrile (Compound No. 11), (Z) -2- (5-methoxy-1H-indol) -3- yl) -346- (methylamino) -pyridin-3-yl] -acrylonitrile (Compound No. 16), - (Z) -2- (2-phenyl-1H-indol-3-yl) -3- (pyridin) 3-yl) -acrylonitrile (Compound No. 18), (Z) -3- (pyridin-3-yl) -2 [2- (thiophen-3-yl) -1H-indol-3-yl] -acrylonitrile ( Compound No. 19), - (Z) -2- (5-benzyloxy-1H-indol-3-yl) -3-pyridin-2-yl-acrylo nitrile (Compound No. 22), - (Z) - 2- (1H-Indol-3-yl) -3- (3-methoxy-phenyl) -acrylonitrile (Compound No. 25), (Z) -2- (5-methoxy-1-methyl-1H-indol) -3- 1-yl) -3-pyridin-3-yl-acrylo nitril (Compound No. 27), (Z) -3- (pyridin-3-yl) -2- (6-methoxy-1H-pyrrolo [2], 3-b] pyridin-3-yl) -acrylonitrile (Compound No. 31), - (E) -5-methoxy-3- [1- (pyridin-3-yl) -4- (pyridin-4-yl) 1-but-1-en-3-yn-2-yl-1Hindole (Compound No. 34), 1,8-Dimethoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (Compound 36), 9-methoxy-11H-pyrido [4,3-a] carbazo-6-carbonitrile (compound 37), 9-methoxy-11H-pyrido [4,3-a] carbazo-6-carboxamide (compound 38), 9-methoxy-11H-pyrido [4,3-a] carbazo-6-methanamine (compound 39), 1,9-dimethoxy-11H- pyrido [4,3-a] carbazole-6-carbonitrile (compound No. 40), 1,9-dimethoxy-11H-pyrido [4,3-a] carbazo-6-carboxamide (compound No. 41), N - [(9-methoxy-11H-pyrido [4,3-a] carbazol-6-yl) methyl] acetamide (compound no. 42), 1- (9-methoxy-11H-pyrido [4, 3-a] carbazol-6-yl) -N, N-dimethylmethanamine (Compound No. 43), 10-methoxy-11H-pyrido [4,3-a] carbazol-6-carbonitrile (Compound No. 44), 8-chloro-11H-pyrido [4,3-a] carbazole-6-carbonitrile (compound 45), 8-fluoro-11H-pyrido [4,3-a] carbazole-6-carbonitrile (compound no. 46), 7-methoxy-11H-pyrido [4,3-a] carbazo-6-carbonitrile (Compound No. 47), 10-methoxy-11H-pyrido [4,3-a] carbazo 6-carboxamide (compound 48), 11H-pyrido [3 ', 2': 4,5] -9-methoxypyrrolo [2,34] isoqui n-6-carbonitrile (compound 49), 8-methoxy-11H-pyrido [4,3-a] carbazole-6-carbonitrile (compound 50), 11H-pyrido [3 ', 2': 4,5] pyrrolo [2,34] isoquino-6-carbonitrile (Compound No. 55) - 2- (5-methoxy-1H-indol-3-yl) -2- (pyridin-3-yl) - acetonitrile (Compound No. 56), N- [7- (5-methoxy-1H-indol-3-yl) -isoquinolin-6-yl] -acetamide (Compound No. 57), (Z) -2- ( 5-methoxy-1H-indol-3-yl) -3- (1H-pyrrol-3-yl) -acrylonitrile (Compound No. 60), (Z) -3- (1H-imidazol-4-yl) -2 (6-methoxy-1H-indol-3-yl) -acrylonitrile (Compound No. 61), 6-methoxy-2- (pyridin-4-yl) -1H-pyrrolo [2,3-b] pyridine ( Compound No. 62), 6-methoxy-3- (pyridin-4-yl) -1H-pyrrolo [2,3-b] pyridine (Compound No. 63), -6-methoxy-1-oxo-3- (Pyridin-3-yl) -2,9-dihydro-1H-pyrido [3,4-b] indo-4-carbonitrile (Compound No. 64), and - their pharmaceutically acceptable salts. 21. Pharmaceutical composition comprising a compound of formula of formula (III) as defined in claim 19, of formula (IIa) according to claim 13, of formula (Ib) according to claim 14, of formula (Ic) according to claim 15, of formula (Id) according to claim 16, of formula (Ie) according to claim 17, any of the compounds as defined in claim 20 or their mixture.