FR2953838A1 - TRISUBSTITUTED 9H-BETA-CARBOLINE (OR 9H-PYRIDINO [3,4-B] INDOLE) DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC USE - Google Patents

Abstract

Products of the general formula (I): wherein R3 is 5- or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, S or O, optionally substituted; R5 especially represents Hal; OH ; alkoxy; -Y-alkyl (Y = S, SO, SO 2); -X-aryl or -X-heteroaryl (X = O, S, SO, SO 2); -NH2, -NH (alkyl), -N (alkyl) 2; -NH (aryl); NH (heteroaryl); -N (alkyl) (aryl); -N (alkyl) (heteroaryl); -C (O) OH; -C (O) linear alkyl; -C (O) Oaryl; -C (O) Oheteroaryl; -CONH2; -CONH (alkyl), CON (alkyl) 2; CO-heterocycloalkyl; -CON (alkyl) (aryl); -CON (alkyl) (heteroaryl); -C1-C10 linear, branched or cyclic alkyl; aryl; heteroaryl; heterocycloalkyl; -C2-C6 alkenyl; -C2-C6 alkynyl; R6 is especially H; Hal; -OH ; alkoxy; O-cycloalkyl; -Y-alkyl (Y = S, SO, SO2); -NH2; -NH (alkyl); -N (alkyl) 2; -C (O) OH; -C (O) Oalkyl; -CONH2; - CONH (alkyl); CON (alkyl) 2; C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom; aryl; all optionally mono or poly substituted; as well as the isomers and salts of said products of formula (I) and their therapeutic application for the treatment of cancer.

Description

The present invention relates to 9H-BETA-CARBOLINE (or 9H-PYRIDINOf3,4-b) INDOLE derivatives, TRISUBSTITUES, THEIR PREPARATION AND THEIR THERAPEUTIC USE. The present invention relates to 9H-beta-carboline derivatives (or 9H-pyridino [3,4] -b] indole), their preparation and their therapeutic application.

The present invention relates to compounds acting on protein kinases, these kinases being involved in the development of cancers. More particularly, the present invention relates to compounds acting on a target called Pim involved in the development of cancers.

Pim kinases, encompassing Pim-1, Pim-2 and Pim-3, form a distinct family of serine / threonine kinases, and play a functional role in cell growth, differentiation and apoptosis. One of the mechanisms by which Pim kinases can increase cancer cell survival and promote cancer progression is through the modulation of ADB activity, a key regulator of apoptosis. Pim kinases are highly homologous to each other and exhibit similar oncogenic behavior.

Clinical reports highlight the importance of the role of Pim kinases in the development of human cancers:

Pim kinases, particularly Pim-1 and Pim-2, have been found to be abnormally expressed in a large number of hematological malignancies. Amson et al. report overexpression of Pim-1 in acute myeloid leukemia and acute lymphoid leukemia, and that overexpression of Pim-1 appears to result from inappropriate activation in various leukemias (Proc Nat / Acad Sci, Vol 86 8857-8861 (1989)). Studies have demonstrated overexpression of Pim-1 in primary and metastatic CNS lymphoma, an aggressive form of non-Hodgkin lymphoma (Rubenstein et al., Blood, Vol 107, 9, 3716-3723 (2006)). ). Hüttmann et al. have also found overexpression of Pim-2 in B-cell chronic lymphocytic leukemia and suggest that upregulation of Pim-2 may be associated with a more aggressive course of the disease (Leukemia, 20, 1774-1782 (2006)). Abnormal expression of Pim-1 and Pim-2 has been linked to multiple myeloma (Claudio et al., Blood, v. 100, No. 6, 2175-2186 (2002).) Hypermutations of Pim-1 have have been identified in diffuse large cell lymphomas (Pasqualucci et al., Nature, Vol 412, 2001, pp. 341-346 (2001)) and in predominantly lymphocytic, nodular, nodular Hodgkin's lymphoma (Liso et al., Blood 108, 3, 1013-1020 (2006)).

Numerous studies have also linked abnormal expression of Pim kinases to various non-hematological human cancers (prostate, pancreas, head and neck, etc.) and their presence is often associated with a more aggressive phenotype. For example, both Pim-1 and Pim-2 have been implicated in prostate cancer (Chen et al., Mol Cancer Res, 3 (8) 443-451 (2005)). Valdman et al. have demonstrated upregulation of Pim-1 in patients with prostate carcinoma and in high-grade prostatic intraepithelial neoplasia (precancerous lesions) (The Prostate, (60) 367-371 (2004) ), while Dai et al. suggest that overexpression of Pim-2 in prostate cancer is associated with more aggressive clinical features (The Prostate, 65: 276-286 (2005)). Xie et al. found that 44 kDa Pim-1 (Pim-1L) was significantly upregulated in human prostate tumor specimens, and indicate that Pim-1 L has an anti-apoptotic effect on cancer cells of the prostate. human prostate in response to chemotherapeutic drugs (Oncogene, 25, 70-78 (2006)). Pim-2 is linked to the perineural invasion (PNI), during which cancer cells curl around the nerves, which are often found in certain cancers such as cancers of the prostate, pancreas, ducts biliary and head and neck (Ayala et al., Cancer Research, 64, 6082-6090 (2004)). According to Li et al., Pim-3 is aberrantly expressed in human and mouse hepatocarcinomas and human pancreatic cancer tissues (Cancer Res 66 (13), 6741-6747 (2006)). Aberrant expression of Pim-3 has also been observed in gastric adenoma and metastatic sites of gastric carcinoma (Zheng et al., J Cancer Res Clin Oncol, 134: 481-488 (2008)). Together, these reports suggest that Pim kinase inhibitors are useful for the treatment of cancer, including leukemias, lymphomas, myelomas, and various solid tumors, including head and neck cancers, colon cancer, prostate cancer, pancreatic cancer, liver cancer and oral cancer, for example. Since cancer remains a disease for which existing therapies are insufficient, it is clearly necessary to identify novel inhibitors of Pm kinases that are effective for the treatment of cancer. for the treatment of cancer.

The present invention relates to products of the following general formula (I): wherein R 3 represents a heteroaryl radical consisting of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O) linked to the carboline moiety; by a C being an N belonging to R3, R3 being optionally mono or poly substituted; R5 is selected from: 1. halogen; 2. -OH 3. linear or branched alkoxy whose alkyl part is optionally mono, di or tri substituted; 4-Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono-, di- or tri-substituted; 5. -X-aryl (X = O, S, SO, SO2) optionally mono, di or tri substituted; 6.-X-heteroaryl (X = O, S, SO, SO 2) with optionally mono, di or tri-substituted heteroaryl; 7. -NH 2, 8. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted; 9. -NH (aryl) whose aryl part is optionally mono, di or tri substituted; 10. -NH (heteroaryl) whose heteroaryl part (heteroaryl of 5 or 6 members with 1 to 4 heteroatoms chosen from N, S or O bonded to the nitrogen atom is a C or an N) is optionally mono , di or substituted tri; 11. -N (alkyl) (aryl) whose alkyl (linear, branched or cyclic) and aryl portions are optionally mono, di or tri substituted; 12. -N (alkyl) (heteroaryl) whose alkyl (linear, branched or cyclic) and heteroaryl (5- or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by a C or an N) are optionally mono, di or tri substituted; 13. -C (O) OH 14. -C (O) linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted; 15. -C (O) Oaryl optionally mono, di or tri substituted; 16. -C (O) Oheteroaryl (heteroaryl of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O bonded to oxygen by a C atom) optionally mono, di or tri substituted; 17. -CONH2; 18. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted; 19. -CO-heterocycloalkyl mono, di or tri substituted; 20. -CON (alkyl) (aryl), linear, branched or cyclic alkyl of which the alkyl and aryl parts are optionally mono, di or tri substituted; 21. -CON (alkyl) (heteroaryl), linear, branched or cyclic alkyl and heteroaryl of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by a C or by an N) of which the alkyl and the hetroaryl parts are optionally mono, di or tri substituted; 22. -C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom and optionally mono-, di or tri-substituted; 23. optionally mono, di or tri substituted aryl; 24. optionally mono or poly substituted heteroaryl; 25. optionally mono or poly substituted heterocycloalkyl; 26. -C2-C6 alkenyl optionally mono or poly substituted; 27. -C 2 -C6 alkynyl optionally mono or poly substituted; - R6 is chosen from: 1. H; 2. halogen; 3.OH; 4. linear or branched alkoxy whose alkyl part is optionally mono, di or tri substituted; 5. O-cycloalkyl optionally mono, di or tri substituted; 6. -Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono, di or tri substituted; 7. -NH2, 8. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted; 9. -C (O) OH; 10. -C (O) linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted; 11. -CONH2 12. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted; 13. C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom and optionally mono-, di or tri-substituted; 14. aryl optionally mono, di or tri substituted; said products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as the addition salts with mineral and organic acids or with the inorganic and organic bases of said products of formula (I).

The present invention relates in particular to compounds of the following general formula (I): as defined above in which R3 and R6 are chosen by the meanings indicated above and R5 is chosen from: 1. halogen; 2.OH; 3. linear or branched alkoxy whose alkyl part is optionally mono, di or tri substituted; 4. -NH 2, 5. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted; 6. -NH (aryl) whose aryl part is optionally mono, di or tri substituted; 7. -NH (heteroaryl) whose heteroaryl part (heteroaryl of 5 or 6 members with 1 to 4 heteroatoms chosen from N, S or O bonded to the nitrogen atom is a C or an N) is optionally mono , di or substituted tri; 8. -N (alkyl) (aryl) whose alkyl (linear, branched or cyclic) and aryl portions are optionally mono, di or tri substituted; 9. -N (alkyl) (heteroaryl), the alkyl (linear, branched or cyclic) and heteroaryl (heteroaryl) parts of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by a C or an N) are optionally mono, di or tri substituted; 10. -C (O) OH 11. -C (O) linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted; 12. -C (O) Oaryl optionally mono, di or tri substituted; 13. -C (O) Oeteroaryl (heteroaryl of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O bonded to oxygen by a C atom) optionally mono, di or tri substituted; 14. -CONH2 15. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted; 16. -CO-heterocycloalkyl mono, di or tri substituted; 17. -CON (alkyl) (aryl), linear, branched or cyclic alkyl of which the alkyl and aryl parts are optionally mono, di or tri substituted; 18. -CON (alkyl) (heteroaryl), linear, branched or cyclic alkyl and heteroaryl of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by a C or by an N) of which the alkyl and the hetroaryl parts are optionally mono, di or tri substituted; 19. -C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom and optionally mono-, di or tri-substituted; 20. aryl optionally mono, di or tri substituted; 21. optionally mono or poly substituted heteroaryl; 22. optionally mono or poly substituted heterocycloalkyl; 23. -C2-C6 alkenyl optionally mono or poly substituted; 24. -C2-C6 alkynyl optionally mono or poly substituted; said products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as the addition salts with mineral and organic acids or with the inorganic and organic bases of said products of formula (I). The present invention relates to products of general formula (I) as defined above in which the possible substituents of R3 are the groups R1a, R1b, R1c; are selected independently from each other from: 1. F; 2. Cl; 3. Br; 4. I; 5. -C, -C, o linear or branched alkyl optionally mono or poly substituted by R3a, R3b, R3c; 6. -OH; 7. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R3a, R3b, R3c; 8. -Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono, di or tri substituted by R3a, R3b, R3c; O-cycloalkyl (C3-C7) optionally mono or poly substituted with R3a, R3b, R3c; 10. -NH2 11. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R3a, R3b, R3c ; the groups R3a, R3b, R3c; either the substituents of the groups R1a, R1b, R1c, R2a, R2b and R2c; are chosen independently of each other from: 1. F, 2. Cl; 3. Br; 4. I; 5. -C, -C, o linear or branched alkyl optionally mono or poly substituted with R4a, R4b, R4c; 6. -C3-C7 cycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 7. -OH; 8. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R4a, R4b, R4c; 9. -Y-alkyl (Y = S, SO, SO2) linear or branched optionally mono, di or tri substituted by R4a, R4b, R4c; 10. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R4a, R4b, R4c; 11.-O-aryl optionally mono or poly substituted with R4a, R4b, R4c; 12. aryl optionally mono or poly substituted with R4a, R4b, R4c; 13. heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 14. heterocycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 15. -NO2; 16.-NH2; 17. -NH- (C 1 -C 10 alkyl) or C 3 -C 7 cycloalkyl or heterocycloalkyl) each optionally mono or poly substituted with R 4a, R 4b, R 4c; 18. -N (C 1 -C 10 alkyl) or C 3 -C 5 cycloalkyl) 2 each group being optionally mono or poly substituted with R 4a, R 4b, R 4c; 19. -NHaryl or NH heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 20. -NHC (O) substituted with R4a, R4b, R4c; 21. -N (C 1 -C 10 alkyl) C (O) substituted with R 4a, R 4b, R 4c; 22. -NHS (O 2) substituted with R 4a, R 4b, R 4c; -C, o) S (O2) substituted with R4a, R4b, R4c; 24. -CO2substituted by R4a, R4b, R4c; 25. -CON H2 26. -CONH (alkyl), CON (alkyl) 2 linear (s) , branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R4a, R4b, R4c; 27. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R4a, R4b, R4c 28. -S substituted with R4a, R4b, R4c; 29.-S (O2) substituted with R4a, R4b, R4c; 30. -S (O) substituted with R4a, R4b, R4c; 31. oxo (double bond O 32. -C 2 -C6 alkenyl optionally mono or poly substituted with R4a, R4b, R4c; 33. -C2-C6 alkynyl optionally mono or poly substituted with R4a, R4b, R4c;

the groups R4a, R4b, R4c; either the substituents of groups R3a, R3b and R3c; are independently selected from 1 F, 2. Cl; 3. Br; 4. I; 5. -CF3; -CHF2 6 -C1-C10 linear or branched alkyl; 7. -C3-C7 cycloalkyl; 8. -OH; 9. -O-alkyl (C, -C, O) linear or branched; Linear or branched-Y-alkyl (Y = S, SO, SO 2); 11. -O-cycloalkyl (C3-C7); 12.-O-aryl; 13. aryl; 14. heteroaryl; 15. heterocycloalkyl; 16. -NO2; 17.-NH2; 18. -NH- (C 1 -C 10 alkyl) or C 3 -C cycloalkyl or heterocycloalkyl; 19. -N (alkyl (C1-C10) or cycloalkyl (C3-C4)) 2; 20. -NHaryl or NH heteroaryl; 21. -NHS (O2) alkyl; 22. -N (alkyl (C1-C10) S (O2) alkyl; 23. -CO2alkyl; 24. -CONH2 25. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s); 26. -C (O) heterocycloalkyl; 27. S-alkyl; 28. -S (O2) alkyl; 29.-S (O) alkyl; 30. oxo (O double bond); -C6 linear or branched alkenyl; 32. -C2-C6 linear or branched alkynyl; said products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as the addition salts with acids inorganic and organic or with the inorganic and organic bases of said products of formula (I) The present invention relates to products of general formula (I) as defined above in which the possible substituents of groups R5 and R6 are R2a groups. R2b, R2c are independently selected from: 1. F; 2. C1; 3. Br; 4. I; -C1-C10 linear or branched alkyl optionally mono or poly substituted with R3a; , R3b, R3c; -C3-C7 cy cloalkyl optionally mono or poly substituted with R3a, R3b, R3c; 7. -OH; 8. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R3a, R3b, R3c; 9. -Y-alkyl (Y = S, SO, SO2) linear or branched optionally mono, di or tri substituted by R3a, R3b, R3c; 10. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R3a, R3b, R3c; 11.-O-aryl optionally mono or poly substituted with R3a, R3b, R3c; Optionally aryl mono or poly substituted with R3a, R3b, R3c; 13. heteroaryl optionally mono or poly substituted with R3a, R3b, R3c; 14. heterocycloalkyl optionally mono or poly substituted with R3a, R3b, R3c; 15. -NO2; ; 16.-NH2; 17. -NH- (C 1 -C 6 -alkyl) or C 3 -C 7 -cycloalkyl or heterocycloalkyl) each optionally mono or poly-substituted group with R 3a, R 3b, R 3c; 18. -N (C 1 -C 10 alkyl) or C 3 -C 7 cycloalkyl) 2 each group being optionally mono or poly substituted with R 3a, R 3b, R 3c; 19. -NHaryl or NH heteroaryl optionally mono or poly substituted 20. -NHC (O) substituted with R3a, R3b, R3c; 21. -N (C 1 -C 10 alkyl) C (O) substituted with R 3a, R 3b, R 3c; 22. -NHS (O 2) substituted with R 3a, R 3b, R 3c; -C, o) S (O2) substituted with R3a, R3b, R3c; 24. -CO2substituted by R3a, R3b, R3c; 25. -CONH2 26. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R3a, R3b, R3c; 27. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R3a, R3b, R3c; 28. -S substituted with R3a, R3b, R3c, 29.-S (O2) substituted with R3a, R3b, R3c; 30. -S (O) substituted with R3a, R3b, R3c; 31. oxo (O double bond) 32. -C2-C6 alkenyl optionally mono or poly substituted with R3a, R3b, R3c; 33. -C2-C6 alkynyl optionally mono or poly substituted with R3a, R3b, R3c; the groups R3a, R3b, R3c; R1a, R1b, R1c, R2a, R2b and R2c are independently selected from: 1. F, 2. Cl, 3. Br, 4. I, 5. -C, -C, linear or branched alkyl optionally mono or poly substituted with R4a, R4b, R4c; 6. -C3-C7 cycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 7. -OH; 8. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R4a, R4b, R4c; 9. -Y-alkyl (Y = S, SO, SO2) linear or branched optionally mono, di or tri substituted by R4a, R4b, R4c; 10. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R4a, R4b, R4c; 11.-O-aryl optionally mono or poly substituted with R4a, R4b, R4c; 12. aryl optionally mono or poly substituted with R4a, R4b, R4c; 13. heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 14. heterocycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 15. -NO2; 16.-NH2; 17. -NH- (C 1 -C 10 alkyl) or C 3 -C 4 cycloalkyl or heterocycloalkyl) each optionally mono or poly substituted with R 4a, R 4b, R 4c; 18. -N (C 1 -C 10 alkyl) or C 3 -C 5 cycloalkyl) 2 each group being optionally mono or poly substituted with R 4a, R 4b, R 4c; 19. -NHaryl or NH heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 20. -NHC (O) substituted with R4a, R4b, R4c; 21. -N (C 1 -C 10 alkyl) C (O) substituted with R 4a, R 4b, R 4c; 22. -NHS (O 2) substituted with R 4a, R 4b, R 4c; -C, o) S (O2) substituted with R4a, R4b, R4c; 24. -CO2substituted by R4a, R4b, R4c; 25. -CON H2 26. -CONH (alkyl), CON (alkyl) 2 linear (s) , branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R4a, R4b, R4c; 27. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R4a, R4b, R4c 28. -S substituted with R4a, R4b, R4c; 29.-S (O2) substituted with R4a, R4b, R4c; 30. -S (O) substituted with R4a, R4b, R4c; 31. oxo (double bond O 32. -C 2 -C6 alkenyl optionally mono or poly substituted with R4a, R4b, R4c; 33. -C2-C6 alkynyl optionally mono or poly substituted with R4a, R4b, R4c; R4a, R4b, R4c; substituents of R3a, R3b and R3c are independently selected from: 1. F, 2. Cl, 3. Br, 4. I, 5. -CF3, -CHF2 6. -C1-C10 linear or branched alkyl; -C3-C7 cycloalkyl Linear or branched 8-OH; 9 -O-alkyl (C 1 -C 10); Linear or branched-Y-alkyl (Y = S, SO, SO 2); 11. -O-cycloalkyl (C3-C7); 12.-O-aryl; 13. aryl; 14. heteroaryl; 15. heterocycloalkyl; 16. -NO2; 17.-NH2; 18. -NH- (C 1 -C 10 alkyl) or C 3 -C cycloalkyl or heterocycloalkyl; 19. -N (alkyl (C1-C10) or cycloalkyl (C3-C4)) 2; 20. -NHaryl or NH heteroaryl; 21. -NHS (O2) alkyl; 22. -N (alkyl (C1-C10) S (O2) alkyl; 23. -CO2alkyl; 24. -CONH2 25. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s); 26. -C (O) heterocycloalkyl; 27S-alkyl; 28. -S (O2) alkyl; 29. -S (O) alkyl; 30. oxo (O double bond); -C6 linear or branched alkenyl; 32. -C2-C6 linear or branched alkynyl; said products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as the addition salts with acids inorganic and organic or with the inorganic and organic bases of said products of formula (I) The present invention relates in particular to products of general formula (I) as defined above in which - R3 represents a heteroaryl radical consisting of 5 or 6 linkages with 1 to 4 heteroatoms selected from N, S or O bonded to the carboline moiety either by C or by N belonging to R3, R3 being optionally mono or poly substituted by R1a, R1b, R1c R5 is selected from: 1. halogen; 2. -OH 3. linear or branched alkoxy whose alkyl part is optionally mono, di or tri substituted by R2a, R2b, R2c; 4-Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono, di or tri substituted by R2a, R2b, R2c; 5. -X-aryl (X = O, S, SO, SO2) optionally mono, di or tri substituted by R2a, R2b, R2c; 6.-X-heteroaryl (X = O, S, SO, SO 2) with optionally mono, di or tri heteroaryl substituted by R2a, R2b, R2c; 7. -NH2, 8. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R2a, R2b, R 2c; 9. -NH (aryl) whose aryl part is optionally mono, di or tri substituted by R2a, R2b, R2c; 10. -NH (heteroaryl) whose heteroaryl part (heteroaryl of 5 or 6 members with 1 to 4 heteroatoms chosen from N, S or O bonded to the nitrogen atom is a C or an N) is optionally mono , di or tri substituted by R2a, R2b, R2c; 11. -N (alkyl) (aryl) whose alkyl (linear, branched or cyclic) and aryl portions are optionally mono, di or tri substituted by R2a, R2b, R2c; 12. -N (alkyl) (heteroaryl) whose alkyl (linear, branched or cyclic) and heteroaryl (5- or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by C or N) are optionally mono, di or tri substituted by R2a, R2b, R2c; 13. -C (O) OH 14. -C (O) linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted by R2a, R2b, R2c; 15. -C (O) Oaryl optionally mono, di or tri substituted by R2a, R2b, R2c; 16. -C (O) Oheteroaryl (5- or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, S or O bonded to oxygen by a C atom) optionally mono, di or tri substituted by R2a, R2b, R 2c; 17. -CONH 2 18. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R2a, R2b, R2c; 19. -CO-heterocycloalkyl mono, di or tri substituted by R2a, R2b, R2c; - CON (alkyl) (aryl), linear, branched or cyclic alkyl of which the alkyl and aryl parts are optionally mono, di or tri substituted by R2a, R2b, R2c; 20. -CON (alkyl) (heteroaryl), linear, branched or cyclic alkyl and 5 or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by a C or by an N) of which the alkyl and the hetroaryl portions are optionally mono, di or tri substituted by R2a, R2b, R2c; 21. -C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom and optionally mono, di or tri substituted by R2a, R2b, R2c; 22. aryl optionally mono, di or tri substituted by R2a, R2b, R2c; 23. heteroaryl optionally mono or poly substituted with R2a, R2b, R2c; 24. heterocycloalkyl optionally mono or poly substituted with R2a, R2b, R2c; 25. -C2-C6 alkenyl optionally mono or poly substituted by R2a, R2b, R2c; 26. -C2-C6 alkynyl optionally mono or poly substituted by R2a, R2b, R2c; - R6 is chosen from: 1. H; 2. halogen; 3. -OH 4. linear or branched alkoxy whose alkyl part is optionally mono, di or tri substituted by R2a, R2b, R2c; 5. O-cycloalkyl optionally mono, di or tri substituted by R2a, R2b, R2c, -Y-alkyl (Y = S, SO, SO2) linear or branched optionally mono, di or tri substituted by R2a, R2b, R2c; 7. -NH2, 8. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R2a, R2b, R 2c; 9. -C (O) OH 10. -C (O) O-linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted by R2a, R2b, R2c; 11. -CONH2 12. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R2a, R2b, R2c; 13. -C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom and optionally mono, di or tri substituted by R2a, R2b, R2c; 14. aryl optionally mono, di or tri substituted by R2a, R2b, R2c; the groups R1a, R1b, R1c; either the substituents of groups R3; are selected independently from each other from: 1. F; 2. Cl; 3. Br; 4. I; -C1-C10 linear or branched alkyl optionally mono or poly substituted with R3a, R3b, R3c; 6. -OH; 7. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R3a, R3b, R3c; 8. -Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono, di or tri substituted by R3a, R3b, R3c; O-cycloalkyl (C3-C7) optionally mono or poly substituted with R3a, R3b, R3c; 10. -NH2 11. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R3a, R3b, R3c ; R2a, R2b, R2c; either the substituents of groups R5 and R6; are independently selected from 1. F; 2. Cl; 3. Br; 4. I; -C1-C10 linear or branched alkyl optionally mono or poly substituted with R3a, R3b, R3c; -C3-C7 cycloalkyl optionally mono or poly substituted with R3a, R3b, R3c; 7. -OH; 8. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R3a, R3b, R3c; 9. -Y-alkyl (Y = S, SO, SO2) linear or branched optionally mono, di or tri substituted by R3a, R3b, R3c; 10. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R3a, R3b, R3c; 11.-O-aryl optionally mono or poly substituted with R3a, R3b, R3c; Optionally aryl mono or poly substituted with R3a, R3b, R3c; 13. heteroaryl optionally mono or poly substituted with R3a, R3b, R3c; 14. heterocycloalkyl optionally mono or poly substituted with R3a, R3b, R3c; 15. -NO2; 16.-NH2; 17. -NH- (C 1 -C 6 -alkyl) or C 3 -C 7 -cycloalkyl or heterocycloalkyl) each optionally mono or poly-substituted group with R 3a, R 3b, R 3c; 18. -N (C 1 -C 10 alkyl) or C 3 -C 7 cycloalkyl) 2 each group being optionally mono or poly substituted with R 3a, R 3b, R 3c; 19. -NHaryl or NH heteroaryl optionally mono or poly substituted 20. -NHC (O) substituted with R3a, R3b, R3c; 21. -N (C 1 -C 10 alkyl) C (O) substituted with R 3a, R 3b, R 3c; 22. -NHS (O 2) substituted with R 3a, R 3b, R 3c; -C, o) S (O2) substituted with R3a, R3b, R3c; 24. -CO2substituted by R3a, R3b, R3c; 25. -CON H2 26. -CONH (alkyl), CON (alkyl) 2 linear (s) , branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R3a, R3b, R3c; 27. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R3a, R3b, R3c 28. -S substituted with R3a, R3b, R3c; 29. -S (O2) substituted with R3a, R3b, R3c; 30. -S (O) substituted with R3a, R3b, R3c; 31. oxo (double bond O 32. -C2-C6 alkenyl optionally mono or poly substituted with R3a, R3b, R3c; 33. -C2-C6 alkynyl optionally mono or poly substituted with R3a, R3b, R3c; the groups R3a, R3b, R3c; substituents of groups R 1a, R 1b, R 1c, R 2a, R 2b and R 2c are independently selected from each other from: 1. F; 2. Cl; 3. Br; 4. 1; 5. -C1 -C10 linear or branched alkyl optionally mono poly substituted with R4a, R4b, R4c; 6. -C3-C7 cycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 7. -OH; 8. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R4a, R4b, R4c; 9. -Y-alkyl (Y = S, SO, SO2) linear or branched optionally mono, di or tri substituted by R4a, R4b, R4c; 10. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R4a, R4b, R4c; 11.-O-aryl optionally mono or poly substituted with R4a, R4b, R4c; 12. aryl optionally mono or poly substituted with R4a, R4b, R4c; 13. heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 14. heterocycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 15. -NO2; ; 16.-NH2; 17. -NH- (C 1 -C 10 alkyl) or C 3 -C 7 cycloalkyl or heterocycloalkyl) each optionally mono or poly substituted with R 4a, R 4b, R 4c; 18. -N (C 1 -C 10 alkyl) or C 3 -C 5 cycloalkyl) 2 each group being optionally mono or poly substituted with R 4a, R 4b, R 4c; 19. -NHaryl or NH heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 20. -NHC (O) substituted with R4a, R4b, R4c; 21. -N (C 1 -C 10 alkyl) C (O) substituted with R 4a, R 4b, R 4c; 22. -NHS (O 2) substituted with R 4a, R 4b, R 4c; -C, o) S (O2) substituted with R4a, R4b, R4c; 24. -CO2substituted by R4a, R4b, R4c; 25. -CON H2 26. -CONH (alkyl), CON (alkyl) 2 linear (s) , branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R4a, R4b, R4c; 27. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R4a, R4b, R4c 28. -S substituted with R4a, R4b, R4c; 29.-S (O2) substituted with R4a, R4b, R4c; 30. -S (O) substituted with R4a, R4b, R4c; 31. oxo (double bond O 32. -C 2 -C6 alkenyl optionally mono or poly substituted with R4a, R4b, R4c; 33. -C2-C6 alkynyl optionally mono or poly substituted with R4a, R4b, R4c; R4a, R4b, R4c; substituents of R3a, R3b and R3c are independently selected from: 1. F; 2. Cl; 3. Br; 4. I; 5. -CF3; -CHF2 6. -C1-C10 linear or branched alkyl; -C3-C7 cycloalkyl Linear or branched 8-OH; 9 -O-alkyl (C 1 -C 10); Linear or branched-Y-alkyl (Y = S, SO, SO 2); 11. -O-cycloalkyl (C3-C7); 12.-O-aryl; 13. aryl; 14. heteroaryl; 15. heterocycloalkyl; 16. -NO2; 17.-NH2; 18. -NH- (C 1 -C 10 alkyl) or C 3 -C cycloalkyl or heterocycloalkyl); 19. -N (alkyl (C1-C10) or cycloalkyl (C3-C4)) 2; 20. -NHaryl or NH heteroaryl; 21. -NHS (O2) alkyl; 22. -N (alkyl (C1-C10) S (O2) alkyl; 23. -CO2alkyl; 24. -CONH2 25. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s); 26. -C (O) heterocycloalkyl; 27S-alkyl; 28. -S (O2) alkyl; 29. -S (O) alkyl; 30. oxo (O double bond); -C6 linear or branched alkenyl; 32. -C2-C6 linear or branched alkynyl; said products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as the addition salts with acids inorganic and organic or with the inorganic and organic bases of said products of formula (I).

The present invention relates in particular to products of general formula (I) as defined above in which R 3 represents a heteroaryl radical consisting of 5 or 6 ring members with 1 to 4 heteroatoms chosen from N, S or O bonded to the carboline unit, either by a C being an N belonging to R3, R3 being optionally mono or poly substituted with R1a, R1b, R1c as indicated above, and R5 and R6 having the meanings indicated above, said products of formula (I ) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as the addition salts with the mineral and organic acids or with the inorganic and organic bases of said products of formula (I). The following terms used above or below have the following meanings: Alkyl, (C 1 -C 10) alkyl or C 1 -C 4 alkyl means all carbon chains of 1 to 10 carbons, saturated , linear or branched. C2-C6 alkenyl means all the carbon chains of 1 to 6 carbons, linear or branched, comprising at least one carbon-carbon double bond. - C2-C6 alkynyl means all carbon chains of 1 to 6 carbons, linear or branched, having at least one carbon-carbon triple bond. - Aryl means phenyl or naphthyl. - Heteroaryl means all aromatic 5- or 6-membered aromatic monocycles having at least one heteroatom (N, O, S) in particular: pyridine, pyrimidine, imidazole, pyrazole, triazole, thiophene, furan, thiazole, oxazole, isoxazole and the bicyclic systems Aromatic compounds having at least one heteroatom (N, O, S), in particular indole, benzimidazole, azaindole, benzofuran, benzothiophene, quinoloin, tetrazole - heterocycloalkyl, means all nonaromatic (spiro or non-aromatic) monocycles and bicycles having at least one heteroatom (N, O, S at different possible oxidation states) with or without unsaturation, in particular: morpholine, piperazine, piperidine, pyrrolidine, oxetane, epoxide, dioxane, imidazolone, imidazolinedione, 7-oxa-bicyclo [2.2.1] heptane, azetidine, azepine , hexahydropyrrolo [3,4-b] pyrrole, hexahydropyrrolo [2,3-b] pyrrole, hexahydropyrrolo [3,4-c] pyrrole, hexahydropyrrolo [2,3-c] pyrrole, 2,7-diazaspiro [4,4 ] nonane, 2,6-diazaspiro [4,4] nona n-3,6-diazaspiro [4,4] nonane, 3,7-diazaspiro [4,4] nonane, 3,8-diazaspiro [4,4] nonane, 3,9-diazaspiro [4,4] nonane, 4,6-diazaspiro [4.4] nonane, 4,7-diazaspiro [4.4] nonane, 4,8-diazaspiro [4,4] nonane, 4,9-diazaspiro [4.4] nonane, 1, 6-diazaspiro [4.4] nonane, 1,7-diazaspiro [4.4] nonane, 1,8-diazaspiro [4.4] nonane, 1,9-diazaspiro [4.4] nonane, octahydropyrrolo [3, 4-c] pyridine, octahydropyrrolo [3,4-d] pyridine, octahydropyrrolo [3,4-e] pyridine, octahydropyrrolo [2,3-c] pyridine, octahydropyrrolo [2,3-d] pyridine, octahydropyrrolo [2, 3-b] pyridine. - Cycloalkyl (C3-C7) means all non-aromatic rings consisting solely of carbon atoms, especially cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane; but may also carry unsaturation, for example cyclopentene, cyclohexene, cycloheptene, bicyclo [2.2.1] heptane. - C1-C10 alkylhydroxy means all carbon chains of 1 to 10 carbons, saturated, linear or branched carrying at least one hydroxyl (OH) group. - C1-C10 alkoxy means all carbon chains of 1 to 10 carbons, saturated, linear or branched in which is at least one ether function (C-O-C). - C1-C10 alkylamino means all carbon chains of 1 to 10 carbons, saturated, linear or branched in which there is at least one amine function (primary, secondary or tertiary). In the products of formula (I) as defined above, R 3 can in particular represent a pyridyl or pyrazolyl radical optionally substituted as indicated above, R 5 and R 6 having any of the values defined above, said products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as addition salts with mineral and organic acids or with the inorganic and organic bases of said products of formula (I). In particular, when C1-C10 linear or branched alkyl or O-alkyl (C1-C10) is optionally mono or poly substituted with Hal, the substituent formed can be CF3, CHF2 or OCF3, -OCHF2. The subject of the present invention is in particular Formula (I) as defined above, whose names follow: 5-Bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline-N- {4- [6-methoxy] 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanesulfonamide - N- [2- (dimethylamino) ethyl] -4- [6-methoxy-3- (pyridin-3-yl) ) -9H-beta-carbolin-5-yl] benzamide - N- [3- (dimethylamino) propyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5- Methyl-6-methoxy-5- {4- [3- (piperidine)] -benzamide-4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoate 1-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- {4- [3- (morpholin-4-yl) propoxy] phenyl} -3 - (Pyridin-3-yl) -9H-beta-carboline - 5- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl] -6-methoxy-3- ( pyridin-3-yl) -9H-b Eta-carboline - N, N-diethyl-2- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] piperazin-1-yl} ethanamine - 6- fluoro-5-methoxy-3- (pyridin-3-yl) -9H-beta-carboline-N- [2- (dimethylamino) ethyl] -4- [6-fluoro-3- (pyridin-3-yl)] - 9H-beta-carbolin-5-yl] benzamide - N- [4- (1-methylpiperidinyl)] - 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl ] benzamide - N- (2-aminoethyl) -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-fluoro-3- acid] (Pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoic acid - N - [(1S, 2S) -2-aminocyclohexyl] -4- [6-fluoro-3- (pyridin-3-yl) ) -9H-beta-carbolin-5-yl] benzamide-5-methoxy-3- (pyridin-3-yl) -9H-beta-carboline-N- [2- (dimethylamino) ethyl] -4- [3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N - [(1S, 2S) -2-aminocyclohexyl] -4- [6-methoxyethoxy-3- (1-methyl) -2- 1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxyethoxy-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1) H-pyrazol-4-yl) -9 H-beta-carbolin e-N - [(1S, 2S) -2-amin octylohexyl] -4- [6-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxy-5- {4- [3 - (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline-5-methoxy-3- (1-methyl-1H-pyrazol-4-) Yl) -9H-beta-carboline-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-betacarboline The present invention also relates to the following products of formula (I): 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N-methyl-N- (1-methylpyrrolidin-3) -yl) benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N-methyl-N- (1-methylpiperidin-4-yl) benzamide - [4- (2-Methoxyethyl) piperazin-1-yl] {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanone - 4- [6 Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2-methyl-2- (pyrrolidin-1-yl) propyl] benzamide-N- [2- ( dimethylamino) ethyl] -N-ethyl-4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-4- [6-methoxy-3- (pyridinol 3-y 1) -9H-beta-carbolin-5-yl] -N-methyl-N - [(1-methylpiperidin-2-yl) methyl] benzamide - [3- (dimethylamino) piperidin-1-yl] [4- [ 6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanone - {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta} carbolin-5-yl] phenyl} (7-methyl-2,7-diazaspiro [4.4] non-2-yl) methanone - N- [3- (dimethylamino) propyl] -4- [6-methoxy-3- ( pyridin-3-yl) -9H-beta-carbolin-5-yl] -N-methylbenzamide-4- [6-methoxy-3- (pyri-n-3-yl) -9 H -beta-carbolin) 5-yl] -N- [2- (phenylamino) ethyl] benzamide - {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} (2-yl] -N- [2- (phenylamino) ethyl] benzamide Methyloctahydro-5H-pyrrolo [3,4-c] pyridin-5-yl) methanone -1,3'-bipyrrolidin-1'-yl {4- [6-methoxy-3- (pyridin-3-yl) -9H) Beta-carbolin-5-yl] phenyl} methanone - [(3S) -3- (dimethylamino) pyrrolidin-1-yl] {4- [6-methoxy-3- (pyridin-3-yl) -9H-betacarbolin} 5-yl] phenyl} methanone - {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} [(3aS, 6aS) -5-methylhexahydropyrrolo [ 3,4-b] pyrrol-1 (2H) -yl] methanone 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (2-methylpiperidin-1-yl) ethyl] benzamide - N- [2] (1-Propan-2-ylamino) ethyl] -4- [6-methoxy-3- (pyridin-3-yl) -9 H -beta-carbolin-5-yl] benzamide-N-ethyl-4- [ 6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N - [(1-methylpyrrolidin-3-yl) methyl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N - [(3-methyl-1H-pyrazol-4-yl) methyl] benzamide - 4- [6-methoxy-3- ( pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (pyrrolidin-1-yl) propyl] benzamide-N - {[(2S) -1-ethylpyrrolidin-2-yl] Methyl-4- [6-methoxy-3- (pyridin-3-yl) -9H-benzcarbolin-5-yl] benzamide-N- [1- (dimethylamino) propan-2-yl] -4- [6- Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-N- (1H-imidazol-2-ylmethyl) -4- [6-methoxy-3- (pyridin-3) 2H-Beta-carbolin-5-yl] benzamide-N- (1-ethylpiperidin-3-yl) -4- [6-methoxy-3- (pyrid-3-yl) -9H- Beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- {2- [(methyl) lsulfonyl) amino] ethyl} benzamide - N- [2- (diethylamino) ethyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N-methylbenzamide 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [3- (2-oxopyrrolidin-1-yl) propyl] benzamide - [(3R) ) -3- (Dimethylamino) pyrrolidin-1-yl] {4- [6-methoxy-3- (pyridin-3-yl) -9H-benzarbolin-5-yl] phenyl} methanone - 4- [6-methoxy] -2- 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (1-methylpiperidin-4-yl) ethyl] benzamide - 4- [6-methoxy-3- (pyridin) 3-yl) -9H-beta-carbolin-5-yl] -N- (1H-tetrazol-5-ylmethyl) -benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H- Beta-carbolin-5-yl] -N- [2- (1-methylpyrrolidin-2-yl) ethyl] benzamide-N - [(2-hydroxypyridin-4-yl) methyl] -4- [6-methoxy-3] - (Pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- [2- (azepan-1-yl) ethyl] -4- [6-methoxy-3- (pyridin-3-) yl) -9H-beta-carbolin-5-yl] benzamide - N- [3- (dimethylamino) -2,2-dimethylpropyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H- Beta-carbolin-5-yl] benzamide - N- [2- (acetylamino) ethyl] 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta -carbolin-5-yl] -N- (1-methylazetidin-3-yl) benzamide - N- [4- (dimethylamino) butyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H) Beta-carbolin-5-yl] benzamide - N - [(1-ethylpyrrolidin-2-yl) methyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5 -yl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (pyridin-2-ylamino) ethyl] benzamide - 6 methoxy-5- [4- (propan-2-yl) piperazin-1-yl] -3- (pyridin-3-yl) -9H-beta-carboline-4- [6-methoxy-3- (pyridinyl) -2- [4- 3-yl) -9H-beta-carbolin-5-yl] -2-methylbut-3-yn-2-amine-4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin 5-yl] -2-methylbut-3-yn-2-ol - 5- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl] -6-methoxy- 3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- [4- (1-methylpiperidin-4-yl) piperazin-1-yl] -3- (pyridin-3-yl) -9H-BetaBarboline - N, N -diethyl-2- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] piperazin-1-yl} ethanamine - 6-methoxy-5- (4-methyl-1,4-diazepan-1-yl) -3- (pyridin-3-yl) -9H-beta-carboline-2- {4- [6-methoxy] -amine 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] piperazin-1-yl} ethanol-6-methoxy-5- [4- (4-methylpiperazin-1-yl) piperidin-1 yl] -3- (pyridin-3-yl) -9H-betacarboline-6-methoxy-5- [4- (morpholin-4-yl) piperidin-1-yl] -3- (pyridin-3-yl) - 9H-beta-carboline - 3- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} propanoic acid-6-methoxy-5- (4- Methylthiophen-2-yl) -3- (pyridin-3-yl) -9H-beta-carboline-5- (1 H -indol-6-yl) -6-methoxy-3- (pyridin-3-yl) 9 H-beta-carbol ne - {2- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanol - N-cyclopropyl-4- [6-methoxy 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxy-5- (4-methylthiophen-3-yl) -3- (pyridin-3-yl) -9H Beta-carboline - 3- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N, N-dimethylaniline-6-methoxy-5- (1-methyl) -methylbenzoyl; 1 H -indol-5-yl) -3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy- 5- (1-methyl-1H-pyrazol-4-yl) -3- (pyridin-3-yl) -9H-beta-carbol-N- {4- [6-methoxy-3- (pyridin)} 3-yl) -9H-beta-carbolin-5-yl] benzyl} acetamide - N- {3- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzyl} methanesulfonamide-6-methoxy-5- (2-methoxyphenyl) -3- (pyridin-3-yl) -9H-beta-carboline-5- (2-ethoxypyridin-3-yl) -6-methoxy-3- (Pyridin-3-yl) -9H-beta-carboline-4 - ({3- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} amino acid) 4-oxobutanoic acid - N- [2- (dimethylamino) ethyl] -3- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- (4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzyl} methanesulfonamide - {4- [6-methoxy-3- (pyridin-3-yl) -9 H- Beta-carbolin-5-yl] phenyl} (morpholin-4-yl) methanone-6-methoxy-5- (1-methyl-1H-pyrazol-5-yl) -3- (pyrid-3-yl) -9 H-beta-carbol-N- (2-methoxyethyl) -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - {3- [ 6-Methoxy-3- (pyridin-3-yl) -9 H -beta-carbolin-5-yl] phenyl} (morphine) olin-4-yl) methanone - {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} (4-methylpiperazin-1-yl) methanone - N - {4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} -2-methylpropanamide - N- (3-methoxypropyl) -4- [6-methoxy] 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxy-3,5-di (pyridin-3-yl) -9H-beta-carboline-N- {2} [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanesulfonamide-6-methoxy-5- (1H-pyrazol-4-yl) -3- ( pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- [3- (methylsulfonyl) phenyl] -3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- (2-Methoxypyrimidin-5-yl) -3- (pyridin-3-yl) -9H-beta-carboline-5- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5 pyridin-2-amine-2- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenoxy} -N, N-dimethylethanamine-6- Methoxy-3- (pyridin-3-yl) -5- {4- [2- (pyrrolidin-1-yl) ethoxy] phenyl} -9H-beta-carboline-3- {4- [6-methoxy-3- (pyridin-3-yl) 9H-beta-Carbolin-5-yl] phenoxy} - N, N, 2-Trimethylpropan-1-amine-6-methoxy-5- {4- [2- (morpholin-4-yl) ethoxy] phenyl} -3- (pyridin-3-yl) -9H-betaine carboline - N, N-diethyl-2- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenoxy} ethanamine - 1- {4- [6- Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenoxy} -3- (morpholin-4-yl) propan-2-ol-5- {4- [3- (morpholine) 4-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline-5- {4- [3- (piperidin-1-yl) propoxy] phenyl} -3- (pyridin) -3-yl) -9H-beta-carboline-N-ethyl-3- {4- [3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenoxy} propan-1-amine - N- [2- (dimethylamino) ethyl] -4- [3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3- (pyridin-3- yl) -9H-beta-carbolin-5-yl] -N- (pyrrolidin-3-yl) benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5- N- (pyrrolidin-2-ylmethyl) benzamide - 4- [6- (cyclobutyloxy) -3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- (pyrrolidin-2) N-(2-aminocyclohexyl) -4- [6- (oxetan-3-yloxy) -3- (pyridin-3-yl) -9H-beta-methyl) -benzamide carbolin-5-yl] benzamide - 4- [6-methoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] -N- (pyrrolidine) 2-ylmethyl) benzamide - 4- [6- (cyclopropyloxy) -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] -N- [2- (ethylamino) ) ethyl] benzamide - N- (2-aminocyclopentyl) -4- [6-methoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-betacarbolin-5-yl] benzamide-N-ethyl 3- {4- [3- (1-methyl-1H-pyrazol-4-yl) -6- (propan-2-yloxy) -9H-beta-carbolin-5-yl] phenoxy} propan-1 amine-6-methoxy-3- (1-methyl-1H-pyrazol-4-yl) -5- [4- (piperidin-3-ylmethoxy) phenyl] -9H-beta-carboline 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 comprise one or more E / Z type stereochemies on double bonds or cis / trans bonds on nonaromatic rings. These different stereoisomers and their mixtures are 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 can be prepared with pharmaceutically acceptable acids (P.Stahl, C.Wermuth, Handbook of Pharmaceutical Salts, Wiley Ed.), But salts of other acids useful, for example, for purification or isolation of compounds of formula (I) are also part of the invention.

The compounds of formula (I) may comprise one or more isotopes of the atoms described above, notably deuterium D, tritium T, 11C, 130, 140, 150, 15N, 18F, 1281, 1241 and 1351. These compounds, whatever their isotopic compositions, are part of the invention. All synthesis intermediates not described in the literature leading to the production of compounds belonging to the general formula also form part of the invention. The present invention also relates to any synthesis method known to those skilled in the art for preparing the products of formula (I) as defined above.

The present invention particularly relates to a general method of synthesis of the products of formula (I) as defined above, described below in the general scheme. The strategy is synthesis of the tricyclic nucleus is based on two coupling reactions; a carbon-carbon bond is first created by a palladium complex catalyzed coupling reaction (Suzuki or Stille type) between an An type pyridine and a Bn type aryl halide, leading to the intermediates of formula Cn After a possible reduction, the formation of an intramolecular carbon-nitrogen bond leads to the 9H-pyridino [3,4-b] indole unit (intermediate of formula Dn see general scheme below). Functional rearrangement reactions at positions 3, 5 and 6 provide access to the compounds of formula (I). 1 ~ N ^ R R1RZN An R 'Bn Coupling R1RZN (Stille, Suzuki, ...)

then reduction (case of nitro) Cn Hartwig-Buchwald or copper salt R5 R6 N H

Compounds of formula (I) in which R3, R5 and R6 are as defined above. Dn X = Br or l O <-M = -SnMe3 or -B (OH) 2 or ùB _ <O R1R2N = 02N, H2N, HPivN R = Cl, OMe, OH, OSO2CF3 or R3 as defined above R = H, OMe, OH, OSO2CF3, Br, or R5 as defined above R "= H, Br, OH or R6 as defined above

General scheme The operating conditions for obtaining the products of formula (I) as defined above, from the intermediates of formula An, Bn, Cn and Dn as defined above are described below.

For example, the process for preparing compounds having a (3'-pyridinyl) 3-position according to the invention consists in a first step in preparing 5-chloro-4- (trimethylstannanyl) -2,3'-bipyridine Al from 2- (3'-pyridyl) -5-chloropyridine (Journal of the Chemical Society, Perkin Transactions 1 2002, (16), 1847-1849). The synthesis for obtaining the compounds having the (3-methyl-1H-pyrazol-4'-yl) group at the 3-position requires the preparation of 2,5-dichloro-4- (trimethylstannanyl) -pyridine A2 by a similar method. (Scheme 1) CI ~~ LDA, THF, -78 ° C then Me3SnCl3 SnMe3 Al CI LDA, THF, -78 ° C CI ~~ then Me3SnCl

\ N ^ CI SnMe3 CI Diagram 1

Type Bn synthesis intermediates may be commercially available or prepared according to the following methods. For example, 2-bromo-4-methoxyaniline B1 is prepared by bromination of para-aniline. N- (4-fluoro-2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide B2 and N- (2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide B3 are obtained in two steps (protection of the aniline function then iodination via orthometalation). (Scheme 2) H 2 N MeOH, CH 2 Cl 2 H 2 N Bu 4 N Br 3 BI 1 °) PivCl 2 TEA CH 2 Cl 2) nBuLi, THF -78 ° C, I 2 Rp H 2 N R 2 B 2: Rp = F B 3: Rp = H

Scheme 2 For the introduction of more complex alkoxy group in the 6-position, the starting material is 3-bromo-4-nitrophenol which is alkylated by the alkyl halide (or cycloalkyl or heterocycloalkyl) to give the intermediate type B4. (Figure 3).

RBr, Bu4NI OH K2CO3, DMF O, Raid B4 Ralc = Me, and, CH2CH2OMe, cyclopropyl, cyclobutyl Scheme 3 The following step to be carried out is the coupling of Stille between the derivatives An and Bn. When Bn is carrying a nitro group, the latter is reduced to amine by the usual methods (tin dichloride or zinc-acetic acid). The intermediates before cyclization of Cn type are thus obtained. (Figure 4). An Bn Figure 4

In the next step, the tricyclic unit Dn is obtained by an intramolecular aryl amination reaction catalyzed by either a palladium complex or a copper (I) or (II) salt (Scheme 5):

Pd (OAc) 2, Josiphos tBuOK, dioxane H2N 95 ° C 1 night RR 'R "or microwave 120 ° C 1 h or Cu or Cu (acac) 2 K2CO3, DMSO 150-170 ° C Scheme 5 where Josiphos is a compound of the following formula: PtBu2 SnMe3 Brou I ~ N ^ R R1R2N R 'CI Pd (PPh3) 4 PdCl2 (dppb) Cul dioxane or CuO, DMF, R .. 95 ° C 1 night 110 ° C, 2h

If R1R2N = O2N, reduction N SnCl2, EtOH or Zn, AcOH Cn Dn In the case where the intermediate Dn bears an alkoxy in the 6-position (D1-R "= -Oalkyl or O-cycloalkyl and R '= H), the position 5 is brominated by the action of dibroma in acetic acid (Scheme 6) Where (Cyclo) Alkyl Rr Where (Cyclo) Alkyl Br 2, AcOH Scheme 6

The passage of Dn tricyclic intermediates to the products of formula (I) is carried out in several stages. For D3 compounds having a (1'-methyl-1'H-pyrazol-4'-yl) unit in position 3 according to the invention, the latter is introduced by a Suzuki reaction (Scheme 7). H D3 Pd (PPh3) 4 Cs2CO3 dioxane / microwave water 140 ° C 1 h CI Scheme 7

In cases where the intermediate Dn after cyclization carries a methoxy group at position 5 (D5 R '= OMe), the functional arrangement on this position consists of a two-step sequence comprising a demethylation reaction and the formation of a derivative. triflate D7. (Diagram 8) Diagram 8 HCl, AcOH O microwave 1 h 120 ° C-150 ° C ® LiOH, H 2 O THF, MeOH R 6 R R 6 D 2 or D 7 Pd (PPh 3) 4 C 2 CO 3 dioxane / water microwave 120-130 ° C 1 h The introduction of the phenylcarboxylic acid unit takes place by a palladium-catalyzed Suzuki coupling from a D7 triflate or D2 bromide at position 5 followed by saponification.

Figure 9

Activation of the acid function in the form of acyl chloride (action of thionyl chloride) or of activated ester (action of HATU) makes it possible to obtain the amides of formula (I). 1 °) SOCl2 reflux or HATU DMF 2 °) Amine CH2Cl2, 25 ° C Formula (I) if R = R3 as defined above R6 Scheme 10 Intermediates D2 and D7 make it possible to obtain the compounds of formula (I) in a coupling step, either by reaction of Suzuki with a boronate bearing the appropriate chain, or by another Sonogashira or Hartwig-Buchwald type coupling reaction. (Figure 11).

Pd (PPh3) 4 Cs2CO3 dioxane / microwave water 120-130 ° C 1 h O R5-B, O Scheme 11

The subject of the present invention is also, as medicaments, the products of formula (I) as defined above, as well as their prodrugs, said products of formula (I) being in all the possible isomeric forms racemic, enantiomers and diastereoiso isomers, as well as addition salts with inorganic and organic acids or with the pharmaceutically acceptable mineral and organic bases of said products of formula (I). The subject of the present invention is, in particular, as medicaments the products of formula (I) as defined above, the following names of which are: - 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H- beta-carboline - N- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanesulfonamide - N- [2- (dimethylamino) ethyl] -4 - [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- [3- (dimethylamino) propyl] -4- [6-methoxy-3- (pyridin)] 3-yl) -9H-beta-carbolin-5-yl] benzamide - methyl 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoate Methoxy-5- {4- [3- (piperidin-1-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- {4- [3 - (Morpholin-4-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline - 5- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1- 1H-1-yl] -6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline-N, N-diethyl-2- {4- [6-methoxy-3- (pyridin-3- yl) -9H-beta-carbolin-5-yl] piperazin-1-yl} ethanamine - 6-fluoro-5-methoxy-3- (pyridin-3-yl) -9H-b ta-carboline - N- [2- (dimethylamino) ethyl] -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide R3 D2 R '= Br D7 R '= OSO2CF3 or other palladium-catalyzed coupling (Sonogashira, Hartwig-Buchwald ...) formula (I) R6-N- [4- (1-methylpiperidinyl)] - 4- [6-fluoro-3- (pyridin) 3-yl) -9H-beta-carbolin-5-yl] benzamide - N- (2-aminoethyl) -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5- yl] benzamide - 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoic acid - N - [(1S, 2S) -2-aminocyclohexyl] -4 - [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-5-methoxy-3- (pyridin-3-yl) -9H-beta-carboline-N- [2- (dimethylamino) ethyl] -4- [3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N - [(1S, 2S) -2-aminocyclohexyl] - 4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxyethoxy-5- {4- [3- (ethylamino) ) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-N - [(1S, 2S) -2-aminocyclohexyl] -4- [6] -cyclobutyloxy-3- (1-methyl) 1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxy-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1) H-pyrazol-4-yl) -9H-beta-carboline-5-methoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline-5- {4- [3- The subject of the present invention is also, as medicaments, the products of formula (I) as defined herein below. above: 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N-methyl-N- (1-methylpyrrolidin-3-yl) ) benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N-methyl-N- (1-methylpiperidin-4-yl) benzamide - [4] - (2-Methoxyethyl) piperazin-1-yl] {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanone - 4- [6-methoxy 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2-methyl-2- (pyrrolidin-1-yl) propyl] benzamide - N- [2- (dimethylamino)] ethyl] -N-ethyl-4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [ 6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N-methyl-N - [(1-methylpiperidin-2-yl) methyl] benzamide - [3- (dimethylamino) ) piperidin-1-yl] {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanone - {4- [6-methoxy-3- ( pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} (7-methyl-2,7-diazaspiro [4.4] non-2-yl) methanone - N- [3- (dimethylamino) propyl] 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N-methylbenzamide - 4- [6-methoxy-3- (pyridin-3-yl) - 9H-beta-carbolin-5-yl] -N- [2- (phenylamino) ethyl] benzamide - {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl} ] phenyl (2-methyloctahydro-5H-pyrrolo [3,4-c] pyridin-5-yl) methanone-1,3'-bipyrrolidin-1-yl {4- [6-methoxy-3- (pyridinyl In-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanone - [(3S) -3- (dimethylamino) pyrrolidin-1-yl] {4- [6-methoxy-3 - ( pyridin-3-yl) -9H-betacarbolin-5-yl] phenyl} methanone - {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} [ (3aS, 6aS) -5-methylhexahydropyrrolo [3,4-b] py rrol-1 (2H) -yl] methanone 15 - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (2-methylpiperidine) 1-yl) ethyl] benzamide-N- [2- (dipropan-2-ylamino) ethyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N-ethyl-4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N - [(1-methylpyrrolidin-3-yl) methyl] benzamide 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N - [(3-methyl-1H-pyrazol-4-yl) methyl] benzamide - 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (pyrrolidin-1-yl) propyl] benzamide 25-N - {[(( 2S) -1-ethylpyrrolidin-2-yl] methyl} -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- [1- (dimethylamino)] ) propan-2-yl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- (1H-imidazol-2-ylmethyl) 4- [6-Methoxy-3- (pyridin-3-yl) -9 H -beta-carbolin-5-yl] benzamide - N- (1-ethylpiperidin-3-yl) -4- [6- Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) - 9H-beta-carbolin-5-yl] -N- {2 - [(methylsulfonyl) amino] ethyl} benzamide - N- [2- (diethylamino) ethyl] -4- [6-methoxy-3- (pyridin-3) -yl) -9H-beta-carbolin-5-yl] -N-methylbenzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [ 3- (2-Oxopyrrolidin-1-yl) propyl] benzamide - [(3R) -3- (dimethylamino) pyrrolidin-1-yl] {4- [6-methoxy-3- (pyridin-3-yl) -9H) Beta-carbolin-5-yl] phenyl} methanone - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (1-methylpiperidine) 4-yl) ethyl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- (1H-tetrazol-5-ylmethyl) benzamide 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (1-methylpyrrolidin-2-yl) ethyl] benzamide - N- [ (2-hydroxypyridin-4-yl) methyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- [2- (azepan-1 1-yl) ethyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- [3- (dimethylamino) -2,2-dimethylpropyl] 4- [6-Methoxy-3- (pyridin-3-yl) -9H-benzarbolin-5-yl] benzamide - N- [2- (acetylamino) ethyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3 - (Pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- (1-methylazetidin-3-yl) benzamide - N- [4- (dimethylamino) butyl] -4- [6-methoxy] 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-N - [(1-ethylpyrrolidin-2-yl) methyl] -4- [6-methoxy-3- (pyridinyl) -2- [(1-ethylpyrrolidin-2-yl) methyl] -4- [3- 3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- [2- (Pyridin-2-ylamino) ethyl] benzamide-6-methoxy-5- [4- (propan-2-yl) piperazin-1-yl] -3- (pyridin-3-yl) -9H-beta-carboline 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -2-methylbut-3-yn-2-amine-4- [6-methoxy-3- ( pyridin-3-yl) -9H-beta-carbolin-5-yl] -2-methylbut-3-yn-2-ol - 5- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1 -yn-1-yl] -6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- [4- (1-methylpiperidin-4-yl) piperazin-1- yl] -3- (pyridin-3-yl) -9H-beta-carboline-N, N-diethyl-2- {4- [6-methoxy-3- (pyridin-3-yl) -9} H -beta-carbolin-5-yl] piperazin-1-yl} ethanamine-6-methoxy-5- (4-methyl-1,4-diazepan-1-yl) -3- (pyridin-3-yl) 9H-beta-carboline-2- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] piperazin-1-yl} ethanol-6-methoxy-5- [4- (4-methylpiperazin-1-yl) piperidin-1-yl] -3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- [4- (morpholin-4-yl) ) piperidin-1-yl] -3- (pyridin-3-yl) -9H-beta-carboline - 3- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolinic acid 5-yl] phenyl} propanoic acid-6-methoxy-5- (4-methylthiophen-2-yl) -3- (pyridin-3-yl) -9H-beta-carbol-5- (1H-indol) 6-yl) -6-methoxy-3- (pyridin-3-yl) -9 H -beta-carbol- {2- [6-methoxy-3- (pyridin-3-yl) -9H-beta) carbolin-5-yl] phenyl} methanol-N-cyclopropyl-4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxy-5- ( 4-methylthiophen-3-yl) -3- (pyridin-3-yl) -9H-beta-carbol-3- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin) 5-yl] -N, N-dimethylaniline-6-methoxy-5- (1-methyl-1H-indol-5-yl) -3- ( pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- (1-methyl-1H-pyrazol-4-yl) -3- (pyrid-3-yl) -9H-beta- carbol - N - {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzyl} acetamide - N- {3- [6-methoxy-3- ( pyridin-3-yl) -9H-beta-carbolin-5-yl] benzyl} methanesulfonamide - 6-methoxy-5- (2-methoxyphenyl) -3- (pyrid-3-yl) -9H-beta-carbol 5- (2-Ethoxypyridin-3-yl) -6-methoxy-3- (pyridin-3-yl) -9H-beta-carbol-4 - (3- [3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl) amino) -4-oxobutanoic acid - N- [2- (dimethylamino) ethyl] -3- [6-methoxy-3- (pyridinyl) -2- [3- 3-yl) -9H-beta-carbolin-5-yl] benzamide - N- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzyl} methanesulfonamide - {4- [6-Methoxy-3- (pyridin-3-yl) -9 H -beta-carbolin-5-yl] phenyl} (morpholin-4-yl) methanone-6-methoxy-5- (1 - methyl-1H-pyrazol-5-yl) -3- (pyrid-3-yl) -9H-beta-carbol-N- (2-methoxyethyl) -4- [6-methoxy-3- (pyridin) 3-yl) -9H-beta-carbolin-5-yl] benzamide - {3- [6-methoxy-3- Yridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} (morpholin-4-yl) methanone e - {4- [6-methoxy-3- (pyridin-3-yl) -9H- Beta-carbolin-5-yl] phenyl} (4-methylpiperazin-1-yl) methan-e- N- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5} 2-Methylpropanamide - N- (3-methoxypropyl) -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxy] -yl] phenyl} -2-methylpropanamide -3,5-di (pyridin-3-yl) -9H-beta-carboline-N- {2- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanesulfonamide-6-methoxy-5- (1H-pyrazol-4-yl) -3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- [3- (methylsulfonyl) phenyl) 3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- (2-methoxypyrimidin-5-yl) -3- (pyridin-3-yl) -9H-beta-carboline - 5- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] pyridin-2-amine-2- {4- [6-methoxy-3- (pyridin-3- yl) -9H-beta-carbolin-5-yl] phenoxy} -N, N-dimethylethanamine-6-methoxy-3- (pyridin-3-yl) -5- {4- [2- (pyrrolidin-1-yl)} yl) ethoxy] phenyl} -9H-beta-carboline - 3- {4- [6-met hoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenoxy} -N, N, 2-trimethylpropan-1-amine-6-methoxy-5- {4- [2- ( morpholin-4-yl) ethoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline-N, N-diethyl-2- {4- [6-methoxy-3- (pyridin-3- yl) -9H-beta-carbolin-5-yl] phenoxy} ethanamine - 1- {4- [6-methoxy-3- (pyrid-3-yl) -9H-beta-carbolin-5-yl] phenoxy} (3-morpholin-4-yl) propan-2-ol - 5- {4- [3- (morpholin-4-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta carboline - 5- {4- [3- (piperidin-1-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline-N-ethyl-3- {4- [3- (Pyridin-3-yl) -9H-beta-carbolin-5-yl] phenoxy} propan-1-amine-N- [2- (dimethylamino) ethyl] -4- [3- (pyridin-3-yl) - 9H-beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- (pyrrolidin-3-yl) benzamide 4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- (pyrrolidin-2-ylmethyl) benzamide - 4- [6- (cyclobutyloxy) -3 - (Pyridin-3-yl) -9H-beta-carbolin-5-yl] -N- (pyrrolidin-2-ylmethyl) benzamide - N- (2-aminocyclohe) xyl) -4- [6- (Oxetan-3-yloxy) -3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3- (1- Methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] -N- (pyrrolidin-2-ylmethyl) benzamide-4- [6- (cyclopropyloxy) -3- (1- methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] -N- [2- (ethylamino) ethyl] benzamide-N- (2-aminocyclopentyl) -4- [6-methoxy- 3- (1-methyl-1H-pyrazol-4-yl) -9H-benzarbolin-5-yl] benzamide-N-ethyl-3- {4- [3- (1-methyl-1H-pyrazol-4) 2-yl] phenoxy} propan-1-amine-6-methoxy-3- (1-methyl-1H-pyrazol-4-yl) propan-2-yloxy) -9H-beta-carbolin-5-yl] phenoxy} propan-1-amine The subject of the present invention is also the pharmaceutical compositions containing, as active principle, a compound according to any one of the preceding claims. as well as at least one pharmaceutically compatible excipient. The present invention also relates to the pharmaceutical compositions according to the preceding claim used for the treatment of cancer. Thus, according to another of its aspects, the present invention relates to pharmaceutical compositions comprising, as active principle, a compound according to the invention. These pharmaceutical compositions contain an effective dose of at least one compound according to the invention, or a pharmaceutically acceptable salt, of said compound, as well as at least one pharmaceutically acceptable excipient. The said excipients are chosen 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 administration, the active ingredient of formula (I) above, or its salt, may be administered in unit dosage form. administration, in admixture with conventional pharmaceutical excipients, to animals and humans for the treatment of the above disorders or diseases.

Suitable unit dosage forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sublingual, buccal, subcutaneous, intramuscular forms of administration. or intravenous. These medicaments find use in therapy, particularly in the treatment of cancers sensitive to the deregulation of Pl M kinases. The Pim kinase inhibitors which are the subject of the present invention are useful for the treatment of cancer. Since cancer remains a disease for which existing therapies are inadequate, it is clearly necessary to identify new inhibitors of Pim kinases that are effective in the treatment of cancer. The present invention, according to another of its aspects, also relates to a method of treatment of the pathologies indicated above which comprises the administration to a patient of an effective dose of a compound according to the invention, or one of pharmaceutically acceptable salts thereof. 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 compounds exemplified refer to those given in the table below, which illustrates the chemical structures and the physical properties of some compounds according to the invention. It may be noted that the compounds of formula Dn may be synthetic intermediates making it possible to obtain products of formula (I) or may already constitute products of formula (I) making it possible to obtain other products of formula (I) by applying the methods described above or hereinafter or else usual methods known to those skilled in the art, all these products of formula (I) forming part of the present invention. The present invention also more particularly relates, as new industrial products, the synthesis intermediates of the products of formula (I) described in the schemes above. The subject of the present invention is thus, as new industrial products, the intermediates for the synthesis of formulas An as defined in the general scheme above and defined below: The object of the present invention is, for example, as products new industrial intermediates for the synthesis of the products of formula Bn described in the diagrams above. and defined below: with X = Brout R1R2N = O2N, H2N, HPivN R '= H, OMe, OH, OSO2CF3, Br, or R5 as defined above R "= H, Br, OH or R6 such that defined above 1 ~ N ^ RR = Cl, OMe, OH, OSO2CF3 or R3 as defined above An with O -M = -SnMe3 or -B (OH) 2 or ûB OR 'Bn The present invention thus has especially for object, as new industrial products, intermediates of synthesis of the products of formula Cn described in the above schemes and defined below: with R1R2N = O2N, H2N, HPivN R = C1, OMe, OH, OSO2CF3 or R3 as defined above R '= H, OMe, OH, OSO2CF3, Br, or R5 as defined above R "= H, Br, OH or R6 as defined above Cn

The subject of the present invention is therefore, as new industrial products, the synthetic intermediates of the products of formula Dn described in the above schemes and defined below: with R = Cl, OMe, OH, OSO 2 CF 3 or R 3 as defined above R '= H, OMe, OH, OSO2CF3, Br, or R5 as defined above R "= H, Br, OH or R6 as defined above DESCRIPTION OF THE EXAMPLES GENERAL: Abbreviations: 1H NMR: proton nuclear magnetic resonance DAD: wavelength scanning detector DCM: dichloromethane DME: 1,2-dimethoxyethane DMF: dimethylformamide DMSO: dimethylsulfoxide ELSD: light scattering detector HATU: O- (7 -Azabenzotriazol-1-yl) -N, N, N ', N'-tetra-methyluronium hexafluorophosphate HPLC, UPLC: high performance liquid chromatography LC: liquid chromatography LDA: lithium diisopropylamide LiTMP: lithium amide of 2.2 , 6,6-tetramethylpiperidine MS: mass spectrometry TFA: Trifluoroacetic acid Dn THF: tetrahydrofuran Tr: retention time

- All reactions are performed with anhydrous solvents from the Acros Organics AcroSeal range. The solvents used for extractions and chromatographies come from SDS. Microwave reactions are performed on a Biotage or EMC device. Purifications on silica gel are performed using commercial silica cartridges. Preparative HPLC purifications are performed on Macherey-Nagel columns (NUCLEODUR C18 phase) or other phases (Chiralcel OD-1 or OJ-H or AS-H, Chiralpak, Kromasil C18) with appropriate eluents. - LC-MS-DAD-ELSD analysis: 2 possible experimental conditions: 0 LC-MS-DAD-ELSD analysis: MS = Waters ZQ; electrospray mode +/-; mass range m / z = 100-1200; LC = Agilent HP 1100; LC column = X Bridge 18 C Waters 3.0 x 50 mm -2.5 pm; oven LC = 60 ° C; flow rate = 1.1 ml / min. Eluents: A = Water + 0.1% Formic acid B = Acetonitrile, with the following gradient: LC-MS-DAD-ELSD analysis: MS = Platform II Waters Micromass; electrospray +/-; mass range m / z = 100-1100; LC Alliance 2695 Waters; Column X Terra 18C Waters 4.6 mm x 75 mm - 2.5 μm; oven LC = 60 ° C; flow rate = 1.0 ml / min. Eluents: A = Water + 0.1% Formic acid B = Acetonitrile, with the following gradient: UPLC-MS-DAD-ELSD analysis: 2 possible experimental conditions: 44 Time A% B% 0.0 95 5 5.0 0 100 5.5 0 100 6.5 95 5 7.0 95 5 Time A% B% 0 95 5 6.0 5 95 8.0 5 95 9.0 95 5 13.0 95 5 ^ UPLC-MS-DAD-ELSD analysis: MS = Quattro Premier XE Waters; electrospray + 1-; mass range m / z = 100-1100; UPLC Waters; Acquity column UPLC BeH C18 2.1 mm x 50 mm - 1.7 μm; UPLC oven = 70 ° C; flow rate = 0.7 ml / min. Eluents: A = Water + 0.1% Formic acid B = Acetonitrile + 0, 1% Formic acid, with the gradient: Time A% B% 0 95 5 5 0 100 5.5 95 5 6.0 95 5

^ UPLC-MS-DAD-ELSD analysis: MS = SQD Waters; electrospray +/-; mass range m / z = 100-1100; Waters UPLC-; Acquity column UPLC Beh C18 2.1 mm x 50 mm - 1.7 μm; UPLC oven = 70 ° C; flow rate = 1 ml / min.

Eluents: A = Water + 0.1% Formic acid B = Acetonitrile + 0, 1% Formic acid, with the gradient: Time A% B% 0 95 5 0.8 50 50 1.2 0 100 1.85 0 100 1.95 95 5 2.00 95 5 For detection: DAD considered wavelength at = 210-400 nm ELSD: Sedere SEDEX 85; nebulization temperature = 35 ° C; nebulization pressure = 3.7 bar © UPLC-MS-DAD-ELSD analysis (4 min): MS = SQD Waters; electrospray +/-; mass range m / z = 100-1100; Waters UPLC-; Acquity column UPLC Beh C18 2.1 mm x 50 mm - 1.7 μm; UPLC oven = 70 ° C; flow rate = 1 ml / min. Eluents: A = Water + 0.1% Formic acid B = Acetonitrile + 0.1% Formic acid, with the gradient: Time A% B% 0 95 5 1.60 50 50 40 3.20 0 10030 3.85 0 100 3.95 95 5 4.00 95 5 For detection: DAD considered wavelength at = 210-400 nm ELSD: Sedere SEDEX 85; nebulization temperature = 35 ° C; nebulization pressure = 3.7 bar N.B: Depending on the structures analyzed, the dilution solvents are: dimethylsulfoxide; methanol; acetonitrile; dichloromethane. - Basic preparative HPLC Method 1 Injection 2ml of DMSO.

Preparative HPLC: Macherey-Nagel 100 * 21 mm reverse phase C18 Nucleodur 10p column; Eluent: Acetonitrile and water at 10 mM ammonium hydrogen carbonate brought to pH 9-10 with aqueous ammonia. Bearing 10% acetonitrile: 2min, gradient up to 95% acetonitrile in 23min and then bearing 95% acetonitrile 8min. Flow rate 20 ml / min Collection according to UV absorption: 254nm. Method 2 Injection 5ml of DMSO. Preparative HPLC: Macherey-Nagel column 250 * 40mm reverse phase C18 Nucleodur Gravity 10p. Eluent: Acetonitrile and water at 10 mM ammonium hydrogen carbonate brought to pH 9-10 with aqueous ammonia. Bearing 10% acetonitrile: 3min, gradient up to 95% acetonitrile in 37min and then bearing 95% acetonitrile 8min. Flow rate 70 ml / min 46 Collection according to UV254nm absorption. Preparative HPLC acid Method 3 Injection into 2 ml of DMSO. Preparative HPLC column Macherey-Nagel 100 * 21mm reverse phase C18 Nucleodur 10p. Eluent: Acetonitrile at 0.07% TFA and water at 0.07% TFA. Bearing 10% acetonitrile: 2min, gradient up to 95% acetonitrile in 23min and then bearing 95% acetonitrile 8min. Flow rate 20 ml / min Collection according to UV absorption: 254nm.

Method 4 Injection into 5 ml of DMSO. Preparative HPLC column Macherey-Nagel 250 * 40mm reverse phase C18 Nucleodur 10p. Eluent: Acetonitrile at 0.07% TFA and water at 0.07% TFA.

Bearing 10% acetonitrile: 3min, gradient up to 95% acetonitrile in 37min and then bearing 95% acetonitrile 8min. Flow rate 70 ml / min Collection according to UV254nm absorption. 3 injections of 5 ml are necessary.

EXAMPLES Example 1 Synthesis of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline Step 1: Synthesis of 5-chloro-2,3'-bipyridine To a solution of 19.6 g of 2,5-dichloropyridine and 28.5 g of 3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine in 350 ml of dioxane are added 58.8 g of cesium carbonate, 10 ml of water and 7.6 g of tetrakis (triphenylphosphine) palladium. After stirring for 8 hours under reflux (at a temperature of 91 ° C.) and returning to a temperature in the region of 20 ° C., the mixture is poured into 400 ml of water and 100 ml of a saturated hydrogen carbonate solution. of potassium. The aqueous phase is extracted with three times 500 ml of ethyl acetate and the combined organic phases are concentrated to dryness under reduced pressure.

The residue is taken up in methanol and then deposited on 70 g of SCX silica (Bond Elut VARIAN SCX cartridge) packaged in methanol. After three washes of the cartridge with 300 ml of methanol, elution with a solution of 2N ammonia in methanol. The latter is concentrated to dryness under reduced pressure and 8.32 g of 5-chloro-2,3'-bipyridine is obtained in the form of a yellow-orange solid which will be used as in the next step. LC-MS-DAD-ELSD: Tr (min) = 2.28; [M + H] +: m / z 191 Step 2: Synthesis of 5-chloro-4- (trimethylstannanyl) -2,3'-bipyridine Al Sn, Al I Cl To a solution of 5 g of diisopropylamine in 25 ml of tetrahydrofuran cooled to a temperature of -74 ° C are slowly added 30 ml of butyllithium maintaining the temperature between -74 and -70 ° C. A solution of 8.3 g of 5-chloro-2,3'-bipyridine in 50 ml of tetrahydrofuran is then added. After stirring for 2.5 hours, a solution of 9.97 g of chloro (trimethyl) stannane in 40 ml of tetrahydrofuran is poured, maintaining the temperature between -74 and -71 ° C. After stirring for one hour at this temperature, 100 ml of water are poured, allowing the mixture to return to a temperature in the region of 20 ° C. The medium is then poured into 200 ml of water and 100 ml of a saturated aqueous solution of potassium hydrogen carbonate. The aqueous phase is extracted twice with 300 ml of ethyl acetate and the combined organic phases are concentrated to dryness under reduced pressure. The residue is deposited in 30 ml of methanol over 70 g of SCX silica (70 g Bond Elut VARIAN SCX cartridge), the cartridge rinsed with 250 ml of methanol and eluted with 250 ml of a methanolic solution of ammonia (2N). The elution fractions are concentrated to dryness under reduced pressure. The residue is then fixed on 10 g of silica (Merck 40-63p) and purified by chromatography on a silica column (eluent heptane / ethyl acetate gradient from 100/0 to 50/50) and 11.89 g of 5- chloro-4- (trimethylstannanyl) -2,3'-bipyridine as a yellow-orange oil. LC-MS-DAD-ELSD: Tr (min) = 4.29; [M + H] +: m / z 355; 1H NMR (400MHz, DMSO-86) ppm: 0.45 (s, 9H) 7.52 (dd, J = 7.6, 5.1Hz, 1H) 7.94 (d, J = 1.0Hz, 1H) 8.40 (dt, J) = 7.9, 2.1 Hz, 1H) 8.63 (s, 1H) 8.64 - 8.66 (m, 1H) 9.22 (d, J = 2.4 Hz, 1H) B1 To a solution of 10 g of 4-methoxyaniline in a 320 g of tetrabutyulammonium tribromide are added to the mixture of 320 ml of dichloromethane and 160 ml of methanol. After stirring for one hour at a temperature in the region of 20 ° C., the mixture is poured onto a 0.5 M aqueous solution of thiosulphate. The aqueous phase is extracted twice with ethyl acetate, the combined organic phases are dried over anhydrous sodium sulphate, filtered and concentrated to dryness under reduced pressure. After two purifications of the residue on a silica column (eluent: heptane / ethyl acetate gradient from 9/1 to 5/5), 6 g of 2-bromo-4-methoxyaniline are obtained in the form of a brown liquid.

UPLC-MS-DAD-ELSD: Tr (min) = 0.56; [M + H] +: m / z 202 Step 3: Synthesis of 2-bromo-4-methoxyaniline BI H2N Step 4: Synthesis of 2- (5-chloro-2,3'-bipyridin-4-yl) 4-methoxyaniline Cl H2N c1 In microwaves reactors are introduced 5.49 g of 2-bromo-4-methoxyaniline, 8 g of 5-chloro-4- (trimethylstannanyl) -2,3'-bipyridine, 862 mg of copper iodide, and 6.8 g of cesium fluoride in 85 ml of dioxane. After 1 hour of microwave irradiation at a temperature of 100 ° C., the mixture is filtered on celite, the insoluble matter is rinsed with ethyl acetate, and are added to the filtrate of the water and 10 ml. of ethyl acetate. The aqueous phase is extracted twice more with ethyl acetate, the combined organic phases are dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After purification of the residue on a silica column (eluent heptane / ethyl acetate gradient from 80/20 to 0/100), 2 g of 2- (5-chloro-2,3'-bipyridin-4-yl) are obtained. -4-methoxyaniline as a brown solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.59; [M + H] +: m / z 312 Step 5: Synthesis of 6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline D1 / D1 To a solution of 1 g of 2- (5) 2-chloro-2,3'-bipyridin-4-yl) -4-methoxyaniline in 15.5 ml of dimethylformamide are added 122 mg of copper iodide and 1.3 g of potassium carbonate. After stirring overnight under argon at a temperature in the region of 160 ° C., the mixture is cooled and then poured into 100 ml of a 14% aqueous ammonia solution and 100 ml of ethyl acetate are added. After filtering the mixture on Clarcel, the aqueous phase is extracted again with 100 ml of ethyl acetate. The combined organic phases are washed with 14% aqueous ammonia and then concentrated to dryness under reduced pressure. After purification of the residue by chromatography on a column of silica (eluent dichloromethane / methanol gradient 100/0 to 95/5) 445 mg of 6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline under form of a brown solid. UPLC-MS-DAD-ELSD: Tr (min) = 2.58; [M + H] +: m / z 276 1H NMR (400 MHz, DMSO-86) ppm: 3.89 (s, 3H); 7.21 (dd, J = 2.4 and 8.8 Hz, 1H); 7.47 to 7.56 (m, 2H); 7.90 (d, J = 2.4 Hz, 1H); 8.51 (td, J = 1.9 and 8.1 Hz, 1H); 8.56 (dd, J = 1.9 and 4.6 Hz, 1H); 8.85 (s, 1H); 8.97 (s, 1H); 9.37 (d, J = 1.9 Hz, 1H); 11.52 (wide s, 1 H)

Step 6: Synthesis of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline (Example 1) o Example 1 288 mg of 6-methoxy-3- (3-pyridin) -yl) -9H-beta-carboline are dissolved in a mixture of 20 ml of acetic acid, 30 ml of tetrahydrofuran. Then 12 ml of a solution of bromine in tetrahydrofuran (0.65 ml of bromine in 60 ml of tetrahydrofuran) are added. After stirring for 30 minutes at a temperature in the region of 20 ° C., the mixture is concentrated under reduced pressure. The residue is taken up in a mixture of 25 ml of ethyl acetate and 20 ml of a 10% aqueous ammonia solution. The organic phase is washed twice with 20 ml of a 10% aqueous ammonia solution, and the combined aqueous phases are re-extracted with 60 ml of ethyl acetate. The organic phases are combined and concentrated to dryness under reduced pressure. After purification of the residue by chromatography on a column of silica (eluent dichloromethane / methanol gradient from 100/0 to 90/10), 255 mg of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H- are obtained. betacarboline in the form of a beige solid.

UPLC-MS-DAD-ELSD: Tr (min) = 3.01; [M + H] +: m / z 354; [M-H] -: m / z 352 1H NMR (400 MHz, DMSO-86) ppm: 3.94 (s, 3H); 7.49 (d, J = 8.8 Hz, 1H); 7.52 (dd, J = 4.9 and 7.8 Hz, 1H); 7.65 (d, J = 8.8 Hz, 1H); 8.46 (td, J = 1.7 and 7.8 Hz, 1H); 8.58 (dd, J = 1.7 and 4.9 Hz, 1H); 9.04 (s, 1H); 9.07 (s, 1H); 9.31 (d, J = 1.7 Hz, 1H); 11.88 (bs, 1H) Example 2: Synthesis of N- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanesulfonamide

Example 2 In a microwave reactor, to a solution of 25 mg of 5-bromo-6-25-methoxy-3- (pyridin-3-yl) -9H-beta-carboline in 0.9 ml. 62.9 mg of N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] methanesulfonamide, 46 mg of cesium carbonate, were added under argon to the dioxane solution. mg tetrakis (triphenylphosphine) palladium and 0.2 ml water. After one hour of microwave irradiation at a temperature of 130 ° C., the medium is poured into 10 ml of water and then the aqueous phase is extracted twice with 20 ml of ethyl acetate. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. After purification by chromatography on a column of silica (eluent dichloromethane / methanol gradient from 100/0 to 94/6), 22 mg of N- {4- [6-methoxy-3- (pyridin-3-yl) -9H are obtained. beta-carbolin-5-yl] phenyl} methanesulfonamide. UPLC-MS-DAD-ELSD: Tr (min) = 2.79; [M + H] +: m / z 445; [M-H] -: m / z 443 1H NMR (400 MHz, DMSO-86) ppm: 3.12 (s, 3H); 3.77 (s, 3H); 7.27 (d, J = 0.9 Hz, 1H); 7.41 (dd, J = 4.8 and 7.9 Hz, 1H); 7.44 to 7.49 (m, 5H); 7.62 (d, J = 8.8 Hz, 1H); 8.03 (td, J = 1.9 and 7.9 Hz, 1H); 8.49 (dd, J = 1.5 and 4.8 Hz, 1H); 8.88 (broad d, J = 1.9 Hz, 1H); 8.97 (d, J = 0.9 Hz, 1H); 9.96 (spread m, 1H); 11.68 (bs, 1H) Example 3: Synthesis of N - [2- (dimethylamino) ethyl] -4-[6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl) benzamide In a microwave reactor, a solution of 50 mg of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline in 1.2 ml of dioxane is added under argon 111 mg. N- [2- (dimethylamino) ethyl] -4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide, 190 mg of cesium carbonate, 13.5 mg of tetrakis (triphenylphosphine) palladium and 0.3 ml of water. After one hour of microwave irradiation at a temperature of 130 ° C., the medium is poured into 10 ml of water and then the aqueous phase is extracted twice with 20 ml of ethyl acetate. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. After purification by chromatography on a column of silica (eluent dichloromethane / methanol gradient of 96/4 to 90/10 and dichloromethane / methanol / aqueous ammonia 28-30% gradient of 90/10 / 0.5 to 85/15 / 0.5) we obtain 29 mg N- [2- (dimethylamino) ethyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide as a yellow solid. UPLC-MS-DAD-ELSD: Tr (min) = 2.19; [M + H] +: m / z 466; [M-H] -: m / z 464 NMR (400 MHz, DMSO-86) ppm: 2.23 (s, 6H); 2.48 (t, J = 6.7 Hz, 2H); 3.45 (m, 2H); 3.77 (s, 3H); 7.19 (d, J = 1.1 Hz, 1H); 7.39 (ddd, J = 0.7 and 4.8 and 7.9 Hz, 1H); 7.50 (d, J = 9.0 Hz, 1H); 7.59 (d, J = 8.6 Hz, 2H); 7.66 (d, J = 9.0 Hz, 1H); 7.97 to 8.02 (m, 1H); 8.08 (d, J = 8.6 Hz, 2H); 8.48 (dd, J = 1.7 and 4.8 Hz, 1H); 8.52 (broad t, J = 5.8 Hz, 1H); 8.79 (broad d, J = 1.7 Hz, 1H); 8.98 (d, J = 1.1 Hz, 1H); 11.73 (bs, 1H) Example 4: Synthesis of N - [3- (dimethylamino) propyl] -4 - [6 - methoxy - 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide EXAMPLE 4 The product can be prepared by the same procedure as that used for Example 3 but starting from 46 mg of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline hydrobromide (1: 2), 93 mg of N- [3- (dimethylamino) propyl] -4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide, from mg of cesium carbonate, 8 mg of tetrakis (triphenylphosphine) palladium in a mixture of 1 ml of dioxane and 0.25 ml of water. After thirty minutes of microwave irradiation at a temperature of 120 ° C. and purification by chromatography on a silica column (eluent dichloromethane / methanol gradient 95/5 to 90/10 then dichloromethane / methanol / aqueous ammonia 28-30% 85 15/0.5) gives 14 mg of N- [3- (dimethylamino) propyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide as a pale yellow solid.

UPLC-MS-DAD-ELSD: Tr (min) = 0.39; [M + H] +: m / z 480; base peak: m / z 218 [M-H] -: m / z 478 1H NMR (400 MHz, DMSO-86) ppm: 1.73 (m, 2H); 2.17 (s, 6H); 2.32 (t, J = 7.0 Hz, 2H); 3.37 (m, 2H); 3.77 (s, 3H); 7.18 (d, J = 1.0 Hz, 1H); 7.38 (dd, J = 4.8 and 8.1 Hz, 1H); 7.50 (d, J = 9.0 Hz, 1H); 7.59 (d, J = 8.5 Hz, 2H); 7.65 (d, J = 9.0 Hz, 1H); 8.01 (td, J = 2.0 and 8.1 Hz, 1H); 8.07 (d, J = 8.5 Hz, 2H); 8.47 (dd, J = 1.6 and 4.8 Hz, 1H); 8.66 (broad t, J = 5.5 Hz, 1H); 8.79 (broad d, J = 1.6 Hz, 1H); 8.98 (d, J = 1.0 Hz, 1H); 11.72 (bs, 1H) Example 5: Synthesis of methyl 4-β-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-ylbenzoate o The product can be prepared by the same procedure that used for Example 3 but starting from 73 mg of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline hydrobromide (1: 2), of 111 mg of 4- Methyl (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate, 184 mg of cesium carbonate, 13 mg of tetrakis (triphenylphosphine) palladium in a mixture of 1.6 ml of dioxane and 0.2 ml of water. After thirty minutes of microwave irradiation at a temperature of 120 ° C. and purification by chromatography on a silica column (eluent dichloromethane / methanol gradient from 95/5 to 90/10), 45 mg of 4- [6-methoxy are obtained. Methyl 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoate as a beige solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.70; [M + H] +: m / z 410; [M-H] -: m / z 408 1H NMR (400 MHz, DMSO-86) ppm: 3.77 (s, 3H); 3.96 (s, 3H); 7.22 (d, J = 1.0 Hz, 1H); 7.40 (ddd, J = 1.0 and 4.8 and 8.0 Hz, 1H); 7.51 (d, J = 9.0 Hz, 1H); 7.68 (m, 3H); 8.04 (ddd, J = 1.8 and 2.0 and 8.0 Hz, 1H); 8.21 (d, J = 8.6 Hz, 2H); 8.48 (dd, J = 1.6 and 4.8 Hz, 1H); 8.76 (broad d, J = 2.0 Hz, 1H); 8.99 (d, J = 1.0 Hz, 1H); 11.76 (s, 1H) Example 6: Synthesis of 6-methoxy-544-p- (piperidin-1-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline The product can be prepared by the same procedure as that used for Example 3 but starting from 80 mg of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline, 156 mg of 1 - {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propyl} piperidine, 244 mg of cesium carbonate, 21 mg of tetrakis (triphenylphosphine) ) palladium in a mixture of 1.6 ml of dioxane and 0.4 ml of water. After thirty minutes of microwave irradiation at a temperature of 120 ° C. and purification by chromatography on a silica column (eluent dichloromethane / methanol gradient from 100/0 to 85/15), 65 mg of 6-methoxy-5- {4- [3- (Piperidin-1-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline as a yellow solid.

UPLC-MS-DAD-ELSD: Tr (min) = 0.50; [M + H] +: m / z 493; [M + 2H] 2 +: m / z 247 (base peak); [M-H] -: m / z 491 1H NMR (400 MHz, DMSO-86) ppm: 1.35 to 1.42 (m, 2H); 1.46 to 1.54 (m, 4H); 1.96 (qd, J = 6.6 and 6.8 Hz, 2H); 2.28 to 2.41 (m, 4H); 2.46 (t, J = 7.1 Hz, 2H); 3.76 (s, 3H); 4.15 (t, J = 6.4 Hz, 2H); 7.18 (d, J = 8.8 Hz, 2H); 7.31 (bs, 1H); 7.37 to 7.43 (m, 3H); 7.45 (d, J = 9.0 Hz, 1H); 7.59 (d, J = 9.0 Hz, 1H); 8.06 (ddd, J = 1.7 and 2.0 and 8.3 Hz, 1H); 8.49 (dd, J = 1.7 and 4.6 Hz, 1H); 8.85 (broad d, J = 1.7 Hz, 1H); 8.96 (d, J = 1.0 Hz, 1H); 11.65 (bs, 1H) Example 7: Synthesis of 6-methoxy-544-β- (morpholin-4-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline Example The product can be prepared by the same procedure as that used for Example 3 but starting with 60 mg of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline, 118 mg. 4- {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propyl} morpholine, 180 mg of cesium carbonate, 15 mg of tetrakis (triphenylphosphine) palladium in a mixture of 1.2 ml of dioxane and 0.3 ml of water. After thirty minutes of microwave irradiation at a temperature of 120 ° C. and purification by chromatography on a silica column (eluent dichloromethane / methanol gradient from 100/0 to 90/10), 61 mg of 6-methoxy-5- {4- [3- (Morpholin-4-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline as a yellow solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.44; [M + H] +: m / z 495; [M + 2H] 2 +: m / z 248 (base peak) [M-H] -: m / z 493 1H NMR (400 MHz, DMSO-86) ppm: 1.98 (m, 2H); 2.41 (m, 4H); 2.47 to 2.52 (partially masked m, 2H); 3.59 (m, 4H); 3.76 (s, 3H); 4.17 (t, J = 6.4 Hz, 2H); 7.18 (d, J = 8.7 Hz, 2H); 7.30 (s wide, 1H); 7.36 to 7.43 (m, 3H); 7.45 (d, J = 9.0 Hz, 1H); 7.59 (d, J = 9.0 Hz, 1H); 8.07 (td, J = 1.9 and 7.9 Hz, 1H); 8.49 (dd, J = 1.5 and 4.6 Hz, 1H); 8.84 (broad d, J = 1.5 Hz, 1H); 8.96 (d, J = 0.7 Hz, 1H); 11.64 (s, 1H) Example 8: Synthesis of 5 - [(3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl] -6-methoxy-3- (pyri) n - In a microwave reactor 53 mg of 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline is introduced. 41 mg of 1-ethyl-4- (2-methylbut-3-yn-2-yl) piperazine, 5 mg of copper iodide, and 14 mg of bis (triphenylphosphine) dichloropalladium suspended in 1 ml of triethylamine. After purging the reactor with argon, the medium is placed under microwave irradiation for 30 minutes at a temperature of 120 ° C. Add 14 mg of bis (triphenylphosphine) dichloropalladium in 0.2 ml of dimethylformamide and place again 30 minutes under irradiation at 130 ° C. After 2 successive additions of 41 mg of 1-ethyl-4- (2-methylbut-3-yn-2-yl) piperazine and two irradiations of 30 minutes and 1 hour at a temperature of 130 ° C., the medium is filtered. on cotton, rinsed with 5 ml of ethyl acetate and concentrated to dryness under reduced pressure. After purification of the residue by chromatography on a silica column (eluent dichloromethane / methanol gradient from 100/0 to 95/05), 50 mg of 5- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1 are obtained. -yn-1-yl] -6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline as an ocher solid. UPLC-MS-DAD-ELSD: Tr (min) = 2.34; [M + H] +: m / z 454; [M-H] -: m / z 452 NMR (400 MHz, DMSO-86) ppm: 0.88 to 1.08 (m, 3H); 1.58 (s, 6H) 2.19 to 2.80 (partially masked m, 10H); 3.92 (s, 3H); 7.40 (d, J = 8.8 Hz, 1H); 7.52 (dd, J = 4.8 and 8.0 Hz, 1H); 7.62 (d, J = 8.8 Hz, 1H); 8.38 (ddd, J = 1.8 and 2.0 and 8.0 Hz, 1H); 8.58 (broad d, J = 4.8 Hz, 1H); 8.88 (brs, 1H); 9.04 (d, J = 1.0 Hz, 1H); 9.23 (brs, 1H); 11.73 (bs, 1H) Example 9: Synthesis of N, N-diethyl-2- {4- (6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] piperazin 1-yl} ethanamine Example 9 14 mg of (1E, 4E) -1,5-diphenylpenta-1,4-dien-3-one-palladium (3: 2) are introduced into a reactor for a microwave oven and 28 mg of 1,1'-binaphthalene-2,2'-diylbis (diphenylphosphane) in 0.5 ml of dioxane under argon and after five minutes of stirring at a temperature of 20 ° C are added 53 mg of 5-bromo 6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline, 36 mg sodium tertbutylate, and 139 mg N, N-diethyl-2- (piperazin-1-yl) ethanamine in 0.5 ml of dioxane. After one hour of microwave irradiation at a temperature of 140 ° C., it is again placed for 2 hours under irradiation at this same temperature. A mixture of 28 mg of (1 E, 4E) -1,5-diphenylpenta-1,4-dien-3-one-palladium (3: 2) and 56 mg of 1,1'-binaphthalene is again added. -2,2'-diylbis (diphenylphosphane) in 0.6 ml of dioxane under argon. After 5 hours of microwave irradiation at a temperature of 140 ° C, the medium is poured into 10 ml of water and extracted with three times 25 ml of ethyl acetate. The combined organic phases are dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After purification by preparative HPLC, 15 mg of N, N-diethyl-2- {4- [6-methoxy-3- (pyridine) are obtained. -3-yl) -9H-beta-carbolin-5-yl] piperazin-1-yl} ethanamine as a yellow lyophilizate. UPLC-MS-DAD-ELSD: Tr (min) = 1.89; [M + H] +: m / z 459; [M-H] -: m / z 457 1H NMR (400 MHz, DMSO-86) ppm: 1.27 (t, J = 7.3 Hz, 6H); from 3.00 to 4.50 (spread m, 12H); 3.25 (q, J = 7.3 Hz, 4H); 3.91 (s, 3H); 7.44 (d, J = 8.8 Hz, 1H); 7.49 (d, J = 8.8 Hz, 1H); 7.65 (dd, J = 4.9 and 7.8 Hz, 1H); 8.58 (broad d, J = 7.8 Hz, 1H); 8.67 (dd, J = 1.2 and 4.9 Hz, 1H); 8.85 (brs, 1H); 9.04 (s, 1H); 9.32 (broad d, J = 1.2 Hz, 1H); 11.76 (bs, 1H) Example 10: Synthesis of 6-fluoro-5-methoxy-3- (pyridin-3-yl) -9H-betacarboline Step 1: Synthesis of 4-fluoro-3-methoxyaniline NHZ To a mixture of 40 ml of water and 40 ml of ethanol are added 14 g of zinc, 5 g of 1-fluoro-2-methoxy-4-nitrobenzene and 20 ml of tetrahydrofuran. A solution of 5.7 g of ammonium chloride in 18 ml of water is added dropwise. After one hour and ten minutes of stirring the mixture at a temperature of 50 ° C, it is filtered on celite, rinsed with dichloromethane and the aqueous phase is re-extracted with twice 100 ml of dichloromethane. The combined organic phases are washed twice with 50 ml of water, dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 4.32 g of 4-fluoro-3-methoxyaniline are obtained in the form of a brown solid. LC-MS-DAD-ELSD: Tr (min) = 0.68; [M + H] +: m / z 142

Step 2: Synthesis of N- (4-fluoro-3-methoxyphenyl) -2,2-dimethylpropanamide To a solution of 12.8 g of 4-fluoro-3-methoxyaniline in 340 ml of dichloromethane is added with stirring 10.9 g of sodium chloride. 2,2-dimethylpropanoyl. At a temperature of 0 ° C., 12.6 ml of triethylamine are added dropwise. After returning to a temperature in the region of 20 ° C. and stirring for one hour at five minutes, the solution is poured into 100 ml of water. The aqueous phase is extracted with three times 50 ml of dichloromethane and the combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 19 g of N- (4-fluoro-3-methoxyphenyl) -2,2-dimethylpropanamide are obtained in the form of a pink solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.82; [M + H] +: m / z 226; [M-H] -: m / z 224

Step 3: Synthesis of N- (4-fluoro-2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide B215 B2 to a solution of 10 g of N- (4-fluoro-3-methoxyphenyl) -2,2 -dimethylpropanamide in 65 ml of tetrahydrofuran are added, at a temperature of 0 ° C, 69 ml of butyllithium (at 1.6 M in hexane) and then 60 ml of tetrahydrofuran. After stirring for four hours at a temperature of 0 ° C., the mixture is cooled to a temperature of -70 ° C. and 14 g of iodine in 25 ml of tetrahydrofuran are slowly added. After stirring for one hour at a temperature of -78 ° C. and returning to a temperature in the region of 20 ° C., the mixture is poured into 250 ml of an aqueous ammonium chloride solution and the aqueous phase is extracted with three times 100 ml of ethyl acetate. The combined organic phases are washed with 200 ml of a 0.5M aqueous sodium thiosulfate solution and then with 200 ml of a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under pressure. scaled down. The residue is purified by chromatography on a silica column (eluent dichloromethane) and 12.8 g of N- (4-fluoro-2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide are obtained in the form of orange crystals. LC-MS-DAD-ELSD: Tr (min) = 4.31; [M + H] +: m / z 352; base peak: m / z 225; [M-: m / z 350 Step 4: Synthesis of N- [2- (5-chloro-2,3'-bipyridin-4-yl) -4-fluoro-3-methoxyphenyl-2,2-dimethylpropanamide C2 C2 To a solution of 4 g of N- (4-fluoro-2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide in 40 ml of degassed dimethylformamide under argon is added 1.21 g of 5-chloro-4- (trimethylstannanyl) ) -2,3'-bipyridine, 1.7 g of cesium fluoride and 434 mg of copper iodide. Under argon with stirring are added 800 mg of bis (triphenylphosphine) dichloropalladium. After stirring for 30 minutes at a temperature of 100 ° C., 3.22 g of 5-chloro-4- (trimethylstannanyl) -2,3'-bipyridine, previously solubilized in 40 ml of dimethylformamide, are added. minutes at a temperature of 100 ° C. After cooling, the medium is poured into 150 ml of water and 100 ml of ethyl acetate, and then the aqueous phase is extracted again with twice 100 ml of ethyl acetate, and the combined organic phases are washed. with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on a silica column (eluent: dichloromethane / ethyl acetate 4/6) and 2.46 g of N- [2- (5-chloro-2,3'-bipyridin-4-yl) are obtained. 4-Fluoro-3-methoxyphenyl] -2,2-dimethylpropanamide as white crystals. UPLC-MS-DAD-ELSD: Tr (min) = 0.80; [M + H] +: m / z 414; [M-H] -: m / z 412

Step 5: Synthesis of 6-fluoro-5-methoxy-3- (pyridin-3-yl) -9H-beta-carboline (Example 10) H Example 10 In several microwave reactors are introduced in all 94 mg of palladium acetate, 267 mg of (R) - (-) - 1 - [(S) -2- (dicyclohexylphosphino) ferrocenyl] ethyldi-tert-butylphosphine in 16 ml of degassed dioxane under argon. After degassing with argon and stirring the mixture four minutes in a water bath is added a mixture of 2.49 g of N- [2- (5-chloro-2,3'-bipyridin-4-yl) -4-fluorophenol). 3-methoxyphenyl] -2,2-dimethylpropanamide and 1.15 g of sodium tertbutoxide in 46 ml of dioxane. After one hour of microwave irradiation at a temperature of 120 ° C., the contents of the various reactors are combined with additions of 50 ml of methanol and 150 ml of ethyl acetate. The organic phase is washed with a 5% aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by chromatography on a silica column (eluent: dichloromethane / methanol gradient from 100/0 to 95/5), 1.2 g of 6-fluoro-5-methoxy-3- (pyridin-3-yl) are obtained. 9H-beta-carboline as yellow crystals. UPLC-MS-DAD-ELSD: Tr (min) = 0.58; [M + H] +: m / z 294; [M-H] -: m / z 292 NMR (400 MHz, DMSO-86) ppm: 4.24 (d, J = 2.9 Hz, 3H); 7.28 (dd, J = 3.2 and 8.8 Hz, 1H); 7.45 to 7.55 (m, 2H); 8.48 (ddd, J = 1.8 and 2.0 and 7.9 Hz, 1H); 8.54 to 8.62 (m, 2H); 9.03 (d, J = 0.7 Hz, 1H); 9.33 (broad d, J = 1.8 Hz, 1H); 11.81 (bs, 1H) Example 11: Synthesis of N - [2- (dimethylamino) ethyl] -4-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide Step 1: Synthesis of 6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-ol (D6 R3 = 3'-pyridinyl, R "= F) H D6 (R3 = 3'- pyridinyl, R "= F) A solution of 615 mg of 6-fluoro-5-methoxy-3- (pyridin-3-yl) -9H-beta-carboline (Example 10) in a mixture of 15 ml of acid Acetic acid and 3 ml of concentrated hydrochloric acid is placed under microwave irradiation for eight hours at a temperature of 150 ° C. 1.5 ml of concentrated hydrochloric acid is added to the medium and after 2 hours and then one hour and thirty minutes under microwave irradiation at 150 ° C. it is concentrated to dryness several times with toluene under reduced pressure. The residue is taken up in diethyl ether and the solid is drained and dried under vacuum. 613 mg of 6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-ol is obtained in the form of a green solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.59; [M + H] +: m / z 279 NMR (400 MHz, DMSO-86) ppm: 7.08 to 7.16 (m, 1H); 7.46 to 7.56 (m, 1H); 7.86 to 8.06 (m, 1H); 8.76 to 8.89 (m, 2H); 9.02 (m, 1H); 9.10 (s, 1H); 9.47 (m, 1H); 10.91 (spread m, 1H); 12.12 (m, spread 1 H) Step 2: Synthesis of 6-fluoro-3- (pyridin-3-yl) -9H-betacarbolin-5-yl trifluoromethanesulfonate (D7 R3 = 3'-pyridinyl, R "= F ) FF D7 (R3 = 3'-pyridinyl, R "= F) To a solution of 50 mg of 6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-ol in 1.5 ml of pyridine under argon and at a temperature of 0 ° C. is added 0.09 ml of trifluoromethanesulfonic anhydride. After stirring for four hours and fifteen minutes, the mixture is poured into 50 ml of water and then the aqueous phase is extracted with three times 50 ml of ethyl acetate. The combined organic phases are washed with twice 50 ml of saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by preparative HPLC in an acid medium, 22.5 mg of 6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl trifluoromethanesulphonate are obtained in the form of a yellow lyophilisate which will be used as in the next step. UPLC-MS-DAD-ELSD: Tr (min) = 0.83; [M + H] +: m / z 412; [MH] -: m / z 410 Step 3: Synthesis of N- [2- (dimethylamino) ethyl] -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide ( Example 11) Example 11 To a solution of 46 mg of 6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl D7 trifluoromethanesulfonate and 53.8 mg of N- [2- dimethylamino) ethyl] -4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide in 1 ml of dioxane are added 4.1 mg of [1,1'-Bis (diphenylphosphino) ) -ferrocene] dichloropalladium (II) complexed with methylene chloride (1: 1) and 0.225 ml of an aqueous solution of cesium carbonate at 1.5M. After 30 minutes of microwave irradiation at a temperature of 140 ° C., the medium is poured into 50 ml of water and then extracted with three times 25 ml of ethyl acetate. The combined organic phases are washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by basic preparative HPLC, 33 mg N- [2- (dimethylamino) ethyl] -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl are obtained. ] benzamide in the form of a lyophilisate. UPLC-MS-DAD-ELSD: Tr (min) = 0.45; [M + H] +: m / z 454; [M + 2H] 2+: m / z 227.5 (base peak); [M-H] -: m / z 452 NMR (400 MHz, DMSO-86) ppm: 2.26 (s, 6H); 2.53 (partially masked m, 2H); 3.42 to 3.50 (m, 2H); 7.39 to 7.45 (m, 2H); 7.58 (dd, J = 9.0 and 9.8 Hz, 1H); 7.69 to 7.77 (m, 3H); 8.06 (td, J = 1.7 and 8.3 Hz, 1H); 8.13 (d, J = 8.5 Hz, 2H); 8.17 (s, 1H); 8.51 (dd, J = 1.7 and 4.6 Hz, 1H); 8.59 (broad t, J = 5.6 Hz, 1H); 8.84 (broad d, J = 1.7 Hz, 1H); 9.07 (d, J = 1.0 Hz, 1H); 12.03 (s large, 1 H)

Example 12 Synthesis of N - [4- (1-methylpiperidinyl)] - 4 - [6 - fluoro - 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide Step 1: Synthesis of N- [4- (1-methylpiperidinyl)] - 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide 521 mg of acid 4 are introduced into a 25 ml flask. - (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid, 200 mg of 4-amino-1-methylpiperidine, 603 mg of TOTU and 7 mL of DMF. Triethylamine (1.23 mL) is then added dropwise and the mixture is left stirring for 6 hours. The reaction is stopped by the addition of 50 ml of distilled water and this aqueous phase is extracted with 3 × 25 ml of ethyl acetate. After washing the combined organic phases with 50 ml of brine, they are dried over magnesium sulfate, filtered and evaporated under reduced pressure. 301 mg of N- [4- (1-methylpiperidinyl)] - 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide are thus obtained, usable in the step next without further purification.

Step 2: Synthesis of N- [4- (1-methylpiperidinyl) 1-4- (6-fluoro-3- (pyridin-3-yl) -9H-beta-5-carbolin-5-yl] benzamide (Example 12) H Example 12 To a solution of 80 mg of 6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl D7 trifluoromethanesulfonate and 111.6 mg of N- [4- (1-methylpiperidinyl)] - 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide in 2 ml of dioxane are added 7.1 mg of [1,1'-Bis (diphenylphosphino) ferrocene] dichloropalladium (II) complexed with methylene chloride (1: 1) and 0.389 ml of an aqueous solution of cesium carbonate at 1.5M. After 30 minutes of microwave irradiation at a temperature of 140 ° C., the medium is poured into 50 ml of water and then extracted with three times 25 ml of ethyl acetate. The combined organic phases are washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by basic preparative HPLC, there is obtained 97 mg N- [4- (1-methylpiperidinyl)] - 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5- yl] benzamide as a lyophilizate. UPLC-MS-DAD-ELSD: Tr (min) = 0.47; [M + H] +: m / z 480; [M + 2H] 2+: m / z 240 (base peak); Example 13: N- (2-aminoethyl) -4- (6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide Step 1: N- [MH] -: m / z 478 - [2- (tert-butyloxycarbonylamino) ethyl] -4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide In a 25 ml flask are charged with 500 mg of acid. 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoic acid, 387 mg of tert-butyl-N- (2-aminoethyl) carbamate, 694 mg of TOTU and 7 mL of DMF. Triethylamine (1.41 ml) is then added dropwise and the mixture is left stirring for 6 hours. The reaction is stopped by the addition of 50 ml of distilled water and this aqueous phase is extracted with 3 × 25 ml of ethyl acetate. After washing the combined organic phases with 50 ml of brine, they are dried over magnesium sulfate, filtered and evaporated under reduced pressure. 623 mg of N- [2- (tert-butyloxycarbonylamino) ethyl] -4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide are thus obtained, usable in the next step without further purification.

Step 2: Synthesis of N- (2-aminoethyl) -4- (6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl) benzamide (Example 13) ~ NH 2 to a solution of 70 mg of 6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl D7 trifluoromethanesulfonate and 130 mg of N- [2- (tert-butyloxycarbonylamino) ethyl] -4- ( 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide in 1.75 ml of dioxane are added 7 mg of [1,1'-Bis (diphenylphosphino) -ferrocene] dichloropalladium (II). ) complexed with methylene chloride (1: 1) and 0.266 ml of an aqueous solution of cesium carbonate at 1.5M. After 30 minutes of microwave irradiation at a temperature of 140 ° C., the medium is poured into 50 ml of water and then extracted with three times 25 ml of ethyl acetate. The combined organic phases are washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel to give 89 mg of N- [2- (tertbutyloxycarbonylamino) ethyl] -4- [6-fluoro-3- (pyridin-3-yl) -9 H-beta). -carbolin-5-yl] benzamide. The latter compound is dissolved in 3 mL of methanol and then 2 mL of a solution of 4M hydrochloric acid in dioxane are added. After an hour and a half, the medium is neutralized with an aqueous solution of sodium hydrogencarbonate and then extracted with 3 × 25 ml of ethyl acetate. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by basic preparative HPLC, 20 mg of N- (2-aminoethyl) -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide are obtained. . UPLC-MS-DAD-ELSD: Tr (min) = 0.44; [M + H] +: m / z 426; [M-H] -: m / z 424

Example 14 Synthesis of 4-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-ylbenzoic acid OH To a solution of 281 mg of 6-fluoro-3- trifluoromethanesulfonate ( pyridin-3-yl) -9H-beta-carbolin-5-yl D7 and 210 mg of methyl 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate 19.6 mg of [1,1'-Bis (diphenylphosphino) -ferrocene] dichloropalladium (II) complexed with methylene chloride (1: 1) and 1.072 ml of an aqueous carbonate solution are added in 7 ml of dioxane. of cesium at 1.5M. After one hour of microwave irradiation at a temperature of 120 ° C., the medium is poured into 50 ml of water and then extracted with three times 50 ml of ethyl acetate. The combined organic phases are washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel (eluent CH 2 Cl 2 / MeOH: 100/0 to 90/10), 214 mg of 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta is obtained. methylcarbolin-5-yl] benzoate. This compound is dissolved in 6 mL of THF and 4 mL of methanol, and then an aqueous solution of lithium monohydrate (210 mg in 3 mL of water) is added. After three hours, 20 ml of distilled water are added and the pH of the medium is reduced to 4 by addition of an aqueous solution of hydrochloric acid. The precipitate is filtered off, washed with distilled water, drained and then dried under vacuum at 50 ° C. in the presence of potassium hydroxide. 166 mg of 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoic acid are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 0.66; [M + H] +: m / z 384; [M-H] -: m / z 382

Example 15: N - (1S, 2S) -2-aminocyclohexyl] -4-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide Example 15 A mixture of 80 mg of 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoic acid and 1.6 ml of thionyl chloride is refluxed for 2 hours. The reaction mixture is concentrated to dryness under reduced pressure to give 89 mg of 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoyl chloride as a yellow powder. This compound is suspended in 1 ml of dichloromethane, this suspension then being added to a solution of 238 mg of (1S, 2S) - (+) - diaminocyclohexane in 1 ml of dichloromethane. This mixture is stirred at room temperature for 20 h, 1 mL of methanol and 250 mg of silica are then added, and the reaction mixture is concentrated to dryness under reduced pressure. The product is purified by chromatography on silica gel (eluent CH 2 Cl 2 / NH 3 2N in MeOH: 100/0 to 91/9). 48 mg of N - [(1S, 2S) -2-aminocyclohexyl] -4- [3-fluoro-6- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide are thus obtained.

UPLC-MS-DAD-ELSD: Tr (min) = 0.47; [M + H] +: m / z 480; [M + 2H] 2+: m / z 240 (base peak); Example 16: Synthesis of 5-methoxy-3- (pyridin-3-yl) -9H-beta-carboline Step 1: Synthesis of N- (3-methoxyphenyl) -2,2 -dimethylpropanamide HA a solution of 10 g of 3-methoxyaniline in 230 ml of dichloromethane is added 8.6 g of sodium carbonate. 10 ml of 2,2-dimethylpropanoyl chloride are introduced dropwise. After stirring for sixteen hours in the suspension at a temperature in the region of 20 ° C., 800 mg of sodium carbonate and 1 ml of 2,2-dimethylpropanoyl chloride are added again. After stirring for six hours at a temperature in the region of 20 ° C., 800 mg of sodium carbonate and 1 ml of 2,2-dimethylpropanoyl chloride are added. After stirring for 16 hours, the mixture is poured into 200 ml of water and then extracted with three times 100 ml of ethyl acetate, the combined organic phases are dried over anhydrous magnesium sulphate and filtered and concentrated to dryness under reduced pressure. . 16.6 g of N- (3-methoxyphenyl) -2,2-dimethylpropanamide are obtained in the form of a white solid which will be used as in the next step. LC-MS-DAD-ELSD: Tr (min) = 3.61; [M + H] +: m / z 208

Step 2: Synthesis of N- (2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide B3 o- B3 The product can be prepared as described in Step 3 of Example 10 but from 10 g of N- (3-methoxyphenyl) -2,2-dimethylpropanamide in 45 ml of tetrahydrofuran, 75.3 ml of butyllithium (1.6 M in hexane), and 15.3 g of iodine in 25 ml of tetrahydrofuran. After purification by chromatography on a silica column (dichloromethane eluent), 12.3 g of N- (2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide are obtained in the form of an orange-colored oil. UPLC-MS-DAD-ELSD: Tr (min) = 0.99; [M + H] +: m / z 334; [MH] -: m / z 332 Step 3: Synthesis of N- [2- (5-chloro-2,3'-bipyridin-4-yl) -3-methoxyphenyl-2,2-dimethylpropanamide C3 The product can be prepared as described in step 4 of Example 10 but in four microwaves reactors and from 3.5 g of N- (2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide in 80 ml of dimethylformamide degassed under argon, 4.12 g of 5-chloro-4- (trimethylstannanyl) -2,3'-bipyridine Al, 2.05 g of cesium fluoride and 400 mg of copper iodide. Under argon with stirring are added 736 mg of bis (triphenylphosphine) dichloropalladium. After one hour and thirty minutes of microwave irradiation at a temperature of 100 ° C., and purification by chromatography on a silica column (eluent: dichloromethane / ethyl acetate 5/5), 2.14 g of a mixture containing 50 g is obtained. % N- [2- (5-chloro-2,3'-bipyridin-4-yl) -3-methoxyphenyl] -2,2-dimethylpropanamide as an orange solid to be used as in step next. LC-MS-DAD-ELSD: Tr (min) = 3.86; [M + H] +: m / z 396

Step 4: Synthesis of 2- (5-chloro-2,3'-bipyridin-4-yl) -3-methoxyaniline C4 1 C4 A solution of 2.15 g of a mixture containing 50% N- [2- ( 5-chloro-2,3'-bipyridin-4-yl) -3-methoxyphenyl] -2,2-dimethylpropanamide in 24 ml of water and 7 ml of 4M hydrochloric acid in dioxane is refluxed. After two additions of 7 ml of 4M hydrochloric acid in dioxane, an addition of 5 ml and thirteen hours of reflux, the medium is poured into 100 ml of a saturated aqueous solution of sodium hydrogen carbonate, and then extracted three times with 100 ml. ml of ethyl acetate. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by chromatography on a silica column (eluent: dichloromethane / ethyl acetate 4/6), 621 mg of 2- (5-chloro-2,3'-bipyridin-4-yl) -3- methoxyaniline as yellow crystals.

UPLC-MS-DAD-ELSD: Tr (min) = 0.64; [M + H] +: m / z 312

Step 5: Synthesis of 5-methoxy-3- (pyridin-3-yl) -9H-beta-carboline (Example 16) 620 mg of 2- (5-chloro-2) were introduced into a reactor for a microwave oven, 3'-bipyridin-4-yl) -3-methoxyaniline, 114 mg of copper iodide, 827 mg of potassium carbonate in 19 ml of dimethylsulfoxide. After two microwave irradiations of five hours thirty each at a temperature of 160 ° C, the medium is poured into a mixture of 50 ml of aqueous ammonia solution 10% and 50 ml of ethyl acetate. The aqueous phase is extracted with twice 50 ml of ethyl acetate, and the combined organic phases are washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by chromatography on a silica column (eluent: dichloromethane, 95/5 dichloromethane / methanol then 90/10 dichloromethane / methanol), 170 mg of 5-methoxy-3- (pyridin-3-yl) -9H are obtained. beta-carboline in the form of a cream solid. LC-MS-DAD-ELSD: Tr (min) = 2.64; [M + H] +: m / z 276; [M-H] -: m / z 274 NMR (400 MHz, DMSO-86) ppm: 4.09 (s, 3H); 6.81 (d, J = 8.1 Hz, 1H); 7.20 (d, J = 8.1 Hz, 1H); 7.47 to 7.55 (m, 2H); 8.46 (td, J = 2.0 and 8.0 Hz, 1H); 8.55 to 8.59 (m, 2H); 8.98 (d, J = 1.2 Hz, 1H); 9.31 (broad d, J = 2.0 Hz, 1H); 11.75 (m, spread 1 H) Example 17: N - [2- (dimethylamino) ethyl] -4 - [(pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide Step 1: Synthesis of 3 - (pyridin-3-yl) -9H-beta-carbolin-5-ol (D6 R3 = 3'-pyridinyl, R "= H) H D6 (R3 = 3 '- pyridinyl, F A solution of 170 mg of 5-methoxy-3- (pyridin-3-yl) -9H-beta-carboline (Example 10) in a mixture of 4.2 ml of acetic acid and 0.85 ml of concentrated hydrochloric acid is placed under a micro-irradiation. After six hours at a temperature of 150 ° C., 400 μl of concentrated hydrochloric acid are added to the medium and that is placed for 7 hours under microwave irradiation at 150 ° C. The reaction medium is concentrated to dryness several times with carbon dioxide. toluene under reduced pressure The residue is taken up in diethyl ether and the solid is drained and dried under a vacuum blank to give 134 mg of 3- (pyridin-3-yl) -9H-beta-carbolin-5- ol as a red solid UPLC-MS-DAD-ELSD: Tr (min) = 0.55; [M + H] +: m / z 262 Step 2: Synthesis of 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl trifluoromethanesulfonate (D7 R3 = 3'-pyridinyl, R "= H) FF D7 (R3 = 3'-pyridinyl, R) "H) To a solution of 134 mg of 3- (pyridin-3-yl) -9H-beta-carbolin-5-ol and 12 mg of DMAP in 4 ml of pyridine under argon at a temperature of 0 ° C. 0.26 ml of trifluoromethanesulfonic anhydride is added. After four hours, 100 μl of trifluoromethanesulfonic anhydride are added again. This medium is poured into 50 ml of water and then the aqueous phase is extracted with three times 50 ml of ethyl acetate. The combined organic phases are washed with twice 50 ml of saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by preparative HPLC in an acidic medium, 77 mg of 3- (pyridin-3-yl) -9H-beta-carbolin-5-yl trifluoromethanesulphonate are obtained in the form of a yellow lyophilizate which will be used as in the next step. LC-MS-DAD-ELSD: Tr (min) = 3.47; [M + H] +: m / z 394; [MH] -: m / z 392 Step 3: Synthesis of N- [2- (dimethylamino) ethyl] -4- [3- (pyridin-3-yl) -9H-betacarbolin-5-yl) benzamide (Example 17) H Example 17 To a solution of 77 mg of 3- (pyridin-3-yl) -9H-betacarbolin-5-yl trifluoromethanesulfonate D7 (R3 = 3'-pyridinyl, R "= H) and 77 mg of N- [ 2- (dimethylamino) ethyl] -4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzamide in 1.8 ml of dioxane are added 5.5 mg of [1,1'- Bis (diphenylphosphino) -ferrocene] dichloropalladium (II) complexed with methylene chloride (1: 1) and 0.304 ml of an aqueous solution of cesium carbonate at 1.5 M. After 30 minutes of microwave irradiation at a temperature at 120 ° C., the medium is poured into 50 ml of water and then extracted with three times 25 ml of ethyl acetate.The combined organic phases are washed with saturated aqueous sodium chloride solution and dried over magnesium sulphate. anhydrous, filtered and concentrated to dryness under reduced pressure. by preparative basic HPLC, 55 mg N- [2- (dimethylamino) ethyl] -4- [3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide is obtained in the form of a lyophilisate. LC-MS-DAD-ELSD: Tr (min) = 2.27; [M + H] +: m / z 436; [MH] -: m / z 434 EXAMPLE 18: Nj (1S, 2S) -2-aminocyclohexyl] -4-f6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H Beta-carbolin-5-yl] benzamide Step 1: Synthesis of 2,5-dichloro-4-trimethylstannyl-pyridine A225 A2 A solution of 10.45 ml (74.32 mmol) of diisopropylamine in 1000 ml of tetrahydrofuran is stirred under argon atmosphere at -78 ° C. 28.6 ml (74.32 mmol) of a solution of butyllithium (2.5 M) in hexane are added slowly keeping the temperature below -70 ° C. After stirring for 30 minutes at -78 ° C., a solution of 10 g (67.57 mmol) of 2,5-dichloropyridine in 200 ml of tetrahydrofuran is added over 25 minutes. After stirring for 1 hour at -78 ° C., 17.5 g (87.84 mmol) of trimethyltin chloride and 100 ml of tetrahydrofuran are added dropwise. The reaction mixture is stirred for 14 hours at ambient temperature and then hydrolysed with 400 ml of saturated ammonium chloride solution and 350 ml of water. The suspension is extracted with 3 times 500 ml of ethyl acetate. The organic solution is decanted, dried over magnesium sulphate and then concentrated to dryness on a rotary evaporator to give 27 g of a mobile oil which is purified by chromatography on silica (200 g), eluent: cyclohexane / ethyl acetate = 97.5 / 2.5 by volume. 12.46 g (59%) of a white powder are obtained. LC-MS-DAD-ELSD: Tr (min) = 5.09; [M + H] +: m / z 309 (isotopic profile corresponding to a tin derivative)

Step 2: Synthesis of 2-bromo-4- (methoxyethoxy) -1-nitrobenzene (B4, Ralc = CH 2 CH 2 O) 8 g of 3-bromo-4-nitrophenol, 5.07 g of potassium carbonate and 6.77 g of Tetrabutylammonium iodide is introduced into a dry 250 mL monocolon and under argon, 160 mL of anhydrous DMF and 5.17 mL of 2-bromoethyl methyl ether are then introduced and the mixture is heated at 100 ° C for one hour with stirring. The reaction medium is concentrated under reduced pressure, the residue is taken up in a mixture of water and ethyl acetate and stirred vigorously After separation of the phases, the organic phase is dried over magnesium sulfate, filtered and concentrated. The crude product is purified by chromatography on silica gel (400 g SiO 2, eluent CH 2 Cl 2 / Heptane: 1/1), 9.1 g of 2-bromo-4- (methoxyethoxy) -1-nitrobenzene are thus obtained. -MS-DAD-ELSD: Tr (min) = 0.99 In a tricolor (dry and under argon) of 500 mL equipped with a ref 3.1 g of 2-bromo-4- (methoxyethoxy) -1-nitrobenzene B4 (Ralc = CH2CH2OMe), 995 mg of dichloro [1,4-bis (diphenylphosphino) butane] palladium and 4.7 g of copper (II) are introduced and dissolved in 200 mL of anhydrous DMF. The mixture is returned under an argon atmosphere and then heated to 100 ° C. with stirring. After 5 minutes, a solution of 15.36 g of 2,5-dichloro-4-trimethylstannyl-pyridine A2 in 60 ml of anhydrous DMF is added and the mixture is heated for two hours at 110 ° C. After cooling, the reaction medium is filtered through Celite, the solid is rinsed several times with ethyl acetate and the filtrate is concentrated under reduced pressure. The product is purified by chromatography on silica gel (400 g SiO 2, Heptane / AcOEt eluent: 3/1). 6.2 g of 2- (2,5-dichloropyridin-4-yl) -3-methoxyethoxy-1-nitrobenzene are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 1.10; [M + H] +: m / z 343 and 345 (isotopic profile corresponding to a dichlorinated compound) Step 3: Synthesis of 2- (2,5-dichloropyridin-4-yl) -4-methoxyethoxy-1-nitrobenzene O 2 Step 4: Synthesis of 2- (2,5-dichloropyridin-4-yl) -4-methoxyethoxyaniline H 2 Cl 2 In a 500 ml flask, 7.3 g of 2- (2,5-dichloropyridin-4-yl) 3-methoxyethoxy-1-nitrobenene are dissolved in 200 mL of acetic acid. 19.4 g of powdered zinc are then introduced gradually (control of the exotherm by cooling the flask with an ice bath). The medium is then left stirring for 30 minutes at room temperature. The reaction mixture is filtered on celite, the solid is rinsed several times with ethyl acetate and the filtrate is concentrated under reduced pressure. The residue is taken up in ethyl acetate and then washed with a 28% aqueous ammonia solution until the pH is maintained at 8-9. The organic phase is dried over magnesium sulphate, filtered and evaporated. The product is then purified by chromatography on silica gel (340 g SiO 2, heptane / AcOEt eluent: 3/1). 3 g of 2- (2,5-dichloropyridin-4-yl) -4-methoxyethoxyaniline are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 0.91; [M + H] +: m / z 313 and 315 (isotopic profile corresponding to a dichlorinated compound) Step 5: Synthesis of 3-chloro-6-methoxyethoxy-9H-beta-carboline o / 3 g of 2- (2) , 5-dichloropyridin-4-yl) -4-methoxyethoxyaniline, 2.65 g of potassium carbonate and 2.5 g of copper acetoacetonate (II) are introduced into a 250 ml three-necked flask. 100 ml of DMSO are then added and the mixture is heated for one hour at 150 ° C. After cooling, the reaction medium is poured into a mixture of 800 ml of an aqueous solution of ammonium chloride and ethyl acetate with vigorous stirring. The aqueous phase is again extracted and the combined organic phases are washed successively with a 14% ammonia solution, water and brine. The organic phase is dried over magnesium sulphate, filtered and evaporated. The product is then purified by chromatography on silica gel (200 g SiO 2, heptane / AcOEt eluent: 3/2). 2.2 g of 3-chloro-6-methoxyethoxy-9H-beta-carboline are thus obtained.

UPLC-MS-DAD-ELSD: Tr (min) = 0.80; [M + H] +: m / z 277; [MH] -: m / z 275 Step 5: Synthesis of 3- (1-methyl-1H-pyrazol-4-yl) -6-methoxyethoxy-9H-betacarboline In a 35 mL microwave reactor, 1.1 g of 3-chloro-6-methoxyethoxy-9H-beta-carboline, 145 mg of [1,1'-bis- (diphenylphosphino) -ferrocene] -dichloropalladium (II), 1.24 g of 1-methyl-4 are placed therein. - (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole, 8 ml of an aqueous solution of cesium carbonate at 1.5M and 23 ml of 1, 4-dioxane. The tube is sealed and then subjected to microwave irradiation at 150 ° C for 2 hours. 145 mg of [1,1'-bis- (diphenylphosphino) -ferrocene] -dichloropalladium (II) and 413 mg of 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan) -2-yl) -1H-pyrazole are added then the tube is again subjected to microwave irradiation at 150 ° C for 1 hour. If the reaction is still not complete (UPLC / MS monitoring), this operation can be repeated once. The reaction mixture is diluted with 150 ml of ethyl acetate and washed with 150 ml of water. After decantation, the aqueous phase is extracted with 100 ml of ethyl acetate and the organic phases are combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by chromatography on a silica column (150 g SiO 2, eluent: CH 2 Cl 2 / MeOH 100/0 to 95/5). 2.3 g of 3- (1-methyl-1H-pyrazol-4-yl) -6-methoxyethoxy-9H-beta-carboline are obtained in the form of a solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.51; [M + H] +: m / z 323; [M-H] -: m / z 321

Step 6: Synthesis of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-methoxyethoxy-9H-beta-carboline 2.3 g of 3- (1-methyl-1H-pyrazol) 4-yl) -6-methoxyethoxy-9H-beta-carboline are dissolved in 500 ml of acetic acid. A solution of bromine in acetic acid (0.731 ml of bromine in 10 ml of acetic acid) is added dropwise. After stirring for two hours at room temperature, 5 ml of the same bromine / acetic acid solution are added to complete the reaction. After 6 hours, the reaction medium is concentrated under reduced pressure. The residue is taken up in a mixture of dichloromethane and water, stirred is neutralized by addition of an aqueous solution of sodium hydrogencarbonate. The organic phase is washed with an aqueous solution of sodium thiosulfate. The organic phase is dried, filtered and then concentrated to dryness under reduced pressure. 2.8 g of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-methoxyethoxy-9H-beta-carboline are obtained, usable in the next step without further purification. UPLC-MS-DAD-ELSD (4 min): Tr (min) = 1.18; [M + H] +: m / z 401 and 403 Step 7: Synthesis of 446-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5- acid In a microwavable tube, 1.0 g of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-methoxyethoxy-9H-beta-carboline, 1.96 g of 4- (Methyl 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate, 288 mg of tetrakis (triphenylphosphine) palladium and 4.06 g of cesium carbonate are dissolved in 20 ml of dioxane and 5 mL of water. After one hour of microwave irradiation at a temperature of 130 ° C., the medium is poured into 50 ml of water and then extracted with three times 50 ml of ethyl acetate. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel (eluent CH 2 Cl 2 / MeOH: 100/0 to 96/4), 270 mg of 4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4) are obtained. methyl-9H-beta-carbolin-5-yl] benzoate. This compound is dissolved in 29 mL of THF and 10 mL of methanol, and then an aqueous solution of lithium monohydrate (500 mg in 20 mL of water) is added. After two hours, the pH of the medium is reduced to 4 by adding an aqueous hydrochloric acid solution, and then extracted with 4 × 50 mL of ethyl acetate / THF (8/2). The organic phases are combined, dried over magnesium sulfate, filtered and concentrated in vacuo. 288 mg of 4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzoic acid are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 0.56; [M + H] +: m / z 443; [MH] -: m / z 441 Step 8: Synthesis of N - [(1S, 2S) -2-aminocyclohexyll-4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) Example 18 A mixture of 100 mg of 4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -acid-9H-beta-carbolin-5-ylbenzamide (Example 18) 9H-beta-carbolin-5-yl] benzoic acid and 1.8 ml of thionyl chloride is refluxed for 2 hours. The reaction mixture is concentrated to dryness under reduced pressure to give 104 mg of 4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5- chloride yl] benzoyl. This compound is suspended in 2.5 ml of dichloromethane, this suspension then being added to a solution of 257 mg of (1S, 2S) - (+) - diaminocyclohexane in 2.5 ml of dichloromethane. This mixture is stirred at ambient temperature for 20 h, then 1 mL of methanol and 450 mg of silica are then added. The reaction mixture is concentrated to dryness under reduced pressure. The product is purified by chromatography on silica gel (eluent CH 2 Cl 2 / NH 3 2N in MeOH: 100/0 to 91/9). 65 mg of N - [(1S, 2S) -2-aminocyclohexyl] -4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin) 5-yl] benzamide are thus obtained. LC-MS-DAD-ELSD: Tr (min) = 2.41; [M + H] +: m / z 539; Example 19: Synthesis of 6-methoxyethoxy-544-β- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H- [MH] -: m / z betacarboline

Step 1: Synthesis of 1- {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxylpropyl} ethylamino N ~ \ m, o- <e In a microwavable tube, 1.2 g of 2- [4- (3-bromopropoxy) phenyl] -4,4,5,5-tetramethyl-1,3,2-dioxaborolane and 4.7 g of cesium carbonate are suspended in 11 mL of THF. 4.5 mL of a 2M ethylamine solution in THF are then added. The tube is subjected to microwave irradiation for one hour at 150 ° C. The reaction medium is filtered and the filtrate is concentrated under reduced pressure. The residue is dissolved in ethyl acetate and this organic phase is washed with water. The organic phase is dried, filtered and then concentrated to dryness under reduced pressure. 2 g of 1- {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propyl} ethylamine are obtained in the form of a brown oil, usable in the next step without further purification.

Step 2: Synthesis of 6-methoxyethoxy-5- {4- [3- (ethylamino) propoxylphenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline (Example 19) The product can be prepared by the same procedure as used for Example 6 but starting from 110 mg of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-methoxyethoxy. 9H-beta-carboline (step 6 of example 18), 252 mg of 1- {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) ) phenoxy] propyl} ethylamine, 32 mg of tetrakis (triphenylphosphine) palladium in 1.8 ml of dioxane and 0.36 ml of an aqueous 1.5M cesium carbonate solution. After forty five minutes of microwave irradiation at a temperature of 150 ° C. and purification by chromatography on a silica column [eluent dichloromethane / 2M NH3 in methanol gradient from 100/0 to 80/20], 40 mg of methoxyethoxy-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline. UPLC-MS-DAD-ELSD: Tr (min) = 0.46; [M + H] +: m / z 500; [M-H] -: m / z 498

Example 20 Synthesis of N - [(1S, 2S) -2-aminocyclohexyl] -4-β-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbol 5-yl] benzamide Step 1: Synthesis of 2-bromo-4- (cyclobutyloxy) -1-nitrobenzene (B4, Ralc = cyclobutyl) 5 g of 3-bromo-4-nitrophenol, 6.33 g of potassium carbonate and 4.23 g tetrabutylammonium iodide is introduced into a 250 mL dry monocolon under argon. 100 ml of anhydrous DMF and 3.24 ml of bromocyclobutane are then introduced and the mixture is heated at 100 ° C. for one hour with stirring. 3.24 mL of bromocyclobutane are again introduced. After cooling, the reaction medium is concentrated under reduced pressure, the residue is taken up in a mixture of water and ethyl acetate and stirred vigorously. After separation of the phases, the organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product is purified by chromatography on silica gel (eluent CH 2 Cl 2 / Heptane: 1/4). 4.6 g of 2-bromo-4- (cyclobutyloxy) -1-nitrobenzene are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 1.1515 In a three-necked (dry and argon) 250 mL equipped with a water cooler, 4.6 g of 2-bromo-4- (cyclobutyloxy) -1- nitrobenzene B4 (Ralc = cyclobutyl), 511 mg of dichloro [1,4-bis (diphenylphosphino) butane] palladium and 2.42 g of copper (II) oxide are introduced and dissolved in 115 mL of anhydrous DMF. The mixture is put under an argon atmosphere and then heated at 100 ° C. with stirring. After 5 minutes, a solution of 7.88 g of 2,5-dichloro-4-trimethylstannyl-pyridine A2 in 35 mL of anhydrous DMF is added, and the mixture is then heated for two hours at 110 ° C.

After cooling, the reaction mixture is filtered on celite, the solid is rinsed several times with ethyl acetate and the filtrate is concentrated under reduced pressure. The product is purified by chromatography on silica gel (400 g SiO 2, eluent Heptane / AcOEt: 9/1). 3.2 g of 2- (2,5-dichloropyridin-4-yl) -3-cyclobutyloxy-1-nitrobenzene are thus obtained.

UPLC-MS-DAD-ELSD: Tr (min) = 1.18; [M + H] +: m / z 339 and 341 (isotopic profile corresponding to a dichlorinated compound) In a 250 ml flask, 3.2 g of 2- (2,5-dichloropyridin-4-yl) -3-cyclobutyloxy- 1-nitrobenene are dissolved in 150 mL of acetic acid. 8.63 g of powdered zinc are then introduced gradually (control of the exotherm by cooling the flask with an ice bath). The medium is then left stirring for 30 minutes at room temperature. The reaction mixture is filtered on celite, the solid is rinsed several times with ethyl acetate and the filtrate is concentrated under reduced pressure. The residue is taken up in ethyl acetate and then washed with a 28% aqueous ammonia solution until the pH is maintained at 8-9. The organic phase is dried over magnesium sulphate, filtered and evaporated. The product is Step 2: Synthesis of 2- (2,5-dichloropyridin-4-yl) -4-cyclobutyloxy-1-nitrobenzene O 2 N CI Step 3: Synthesis of 2- (2,5-dichloropyridin-4-yl) 4-cyclobutyloxyaniline H 2 NC then purified by chromatography on silica gel (200 g SiO 2, heptane / AcOEt eluent: 4/1). 1.70 g of 2- (2,5-dichloropyridin-4-yl) -4-cyclobutyloxyaniline are thus obtained. LC-MS-DAD-ELSD: Tr (min) = 4.54; [M + H] +: m / z 309 and 311 (isotopic profile corresponding to a dichlorinated compound)

Step 4: Synthesis of 3-chloro-6-cyclobutyloxy-9H-beta-carboline H 1.7 g 2- (2,5-dichloropyridin-4-yl) -4-cyclobutyloxyaniline, 1.52 g potassium carbonate and 1.44 g g of copper acetoacetonate (II) are introduced into a 150 ml flask. 60 mL of DMSO are then added and the mixture is heated for one hour at 150 ° C. After cooling, the reaction medium is poured onto a mixture of an aqueous solution of ammonium chloride and ethyl acetate with vigorous stirring. The aqueous phase is again extracted and the combined organic phases are washed successively with a 14% ammonia solution, water and brine. The organic phase is dried over magnesium sulphate, filtered and evaporated. The product is then purified by chromatography on silica gel (200 g SiO 2, heptane / AcOEt eluent: 7/3). 1 g of 3-chloro-6-cyclobutyloxy-9H-beta-carboline are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 1.07; [M + H] +: 273 m / z; [M-H] -: m / z 271

Step 5: Synthesis of 3- (1-methyl-1H-pyrazol-4-yl) -6-cyclobutyloxy-9H-beta-carboline In a 35 mL microwave reactor, 1.0 g of 6-cyclobutyloxy-9H-beta-carboline, 268 mg of [1,1'-bis- (diphenylphosphino) -ferrocene] -dichloropalladium (II), 915 mg of 1-methyl-4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole, 7.3 ml of a 1.5M aqueous solution of cesium carbonate and 20 ml of 1,4-dioxane. The tube is sealed and then subjected to microwave irradiation at 150 ° C for 1 hour. 134 mg of [1,1'-bis- (diphenylphosphino) -ferrocene] -dichloropalladium (II) and 915 mg of 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan) -2-yl) -1H-pyrazole are added then the tube is again subjected to microwave irradiation at 150 ° C for 1 hour. If the reaction is still not complete (UPLC / MS monitoring), this operation can be repeated once. The reaction mixture is diluted with 150 ml of ethyl acetate and washed with 150 ml of water. After decantation, the aqueous phase is extracted with 100 ml of ethyl acetate and the organic phases are combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by chromatography on a silica column (150 g SiO 2, eluent: CH 2 Cl 2 / MeOH 100/0 to 95/5). 530 mg of 3- (1-methyl-1H-pyrazol-4-yl) -6-cyclobutyloxy-9H-beta-carboline are obtained in the form of a solid.

UPLC-MS-DAD-ELSD (4 min): Tr (min) = 1.31; [M + H] +: m / z 319

Step 6: Synthesis of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-cyclobutyloxy-9H-beta-carboline 530 mg of 3- (1-methyl-1H-pyrazol) 4-yl) -6-cyclobutyloxy-9H-beta-carboline are dissolved in 125 ml of acetic acid. A solution of bromine in acetic acid (0.17 ml of bromine in 5 ml of acetic acid) is added dropwise. After stirring for two hours at room temperature, 5 ml of the same bromine / acetic acid solution are added to complete the reaction and the mixture is left stirring for two hours. If the reaction is still not complete (UPLC / MS monitoring), this operation can be repeated once. The reaction medium is then concentrated under reduced pressure. The residue is taken up in a mixture of dichloromethane and water, stirred is neutralized by addition of an aqueous solution of sodium hydrogencarbonate. The organic phase is washed with an aqueous solution of sodium thiosulfate. The organic phase is dried, filtered and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a silica column (70 g SiO 2, eluent: CH 2 Cl 2 / MeOH 100/0 to 95/5). 242 mg of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-cyclobutyloxy-9H-beta-carboline are obtained, usable in the next step without further purification. UPLC-MS-DAD-ELSD (4 min): Tr (min) = 1.53; [M + H] +: m / z 397 and 399 Step 7: Synthesis of 446-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5- acid In a microwavable tube 0.3 g of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-cyclobutyloxy-9H-beta-carboline, 594 mg of 4- Methyl 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate, 88 mg of tetrakis (triphenylphosphine) palladium and 1.23 g of cesium carbonate are dissolved in 6 ml of dioxane. and 1.5 mL of water. After one hour of microwave irradiation at a temperature of 130 ° C., the medium is poured into 50 ml of water and then extracted with three times 50 ml of ethyl acetate. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel (eluent CH 2 Cl 2 / MeOH: 100/0 to 95/5), 162 mg of 4- [6-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4) is obtained. methyl-9H-beta-carbolin-5-yl] benzoate. This compound is dissolved in 9 mL of THF and 3 mL of methanol, and then an aqueous solution of lithium monohydrate (151 mg in 6 mL of water) is added. After one hour, the pH of the medium is reduced to 4 by adding an aqueous hydrochloric acid solution, and then extracted with 4 × 50 mL of ethyl acetate / THF (8/2). The organic phases are combined, dried over magnesium sulfate, filtered and concentrated in vacuo. 162 mg of 4- [6-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzoic acid are thus obtained.

UPLC-MS-DAD-ELSD (4 min): Tr (min) = 1.40; [M + H] +: m / z 439; [M-H] -: m / z 437

Step 8: Synthesis of N - [(1S, 2S) -2-aminocyclohexyll-4-β-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5- yl] benzamide (Example 20) A mixture of 162 mg of 4- [6-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzoic acid and 2.8 ml of thionyl chloride is refluxed for 2 hours. The reaction mixture is concentrated to dryness under reduced pressure to give 165 mg of 4- [6-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5- chloride yl] benzoyl. This compound is suspended in 4 ml of dichloromethane, this suspension then being added to a solution of 412 mg of (1S, 2S) - (+) - diaminocyclohexane in 4 ml of dichloromethane. This mixture is stirred at room temperature for 20 h, then 1 mL of methanol and 600 mg of silica are added. The reaction mixture is concentrated to dryness under reduced pressure. The product is purified by chromatography on silica gel (eluent CH 2 Cl 2 / NH 3 2N in MeOH: 100/0 to 90/10). 86 mg of N - [(1S, 2S) -2-aminocyclohexyl] -4- [6-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl ] benzamide are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 0.59; [M + H] +: m / z 535; [M + 2H] 2+: m / z 268 (base peak); Example 21: Synthesis of 6-methoxy-544-β- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9 Step 1: Synthesis of 2- (2,5-dichloropyridin-4-yl) -4-methoxy-1-nitrobenzene In a tricolor (dry and under argon) 500 mL equipped with water. 5.44 g of 2-bromo-4-methoxy-1-nitrobenzene, 2.71 g of tetrakis (triphenylphosphine) palladium and 893 mg of copper iodide (I) are introduced and dissolved in 70 ml of anhydrous DMF. . A solution of 8.01 g of dichloro-4-trimethylstannanyl-pyridine A2 in 24 mL of anhydrous DMF is added and the mixture is heated for one hour at 110 ° C. After cooling, the reaction medium is diluted with ethyl acetate, and this organic phase is washed with water. The organic phase is dried over magnesium sulphate, filtered and evaporated. 4.15 g of 2- (2,5-dichloropyridin-4-yl) -3-methoxy-1-nitrobenzene are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 1.50; [M + H] +: m / z 299 and 301 (isotopic profile corresponding to a dichlorinated compound) In a 250-mL flask, 8.51 g of 2- (2,5-dichloropyridin-4-yl) -3-methoxy- 1-nitrobenzene and 32.1 g of tin dichloride (II) dihydrate are dissolved in 45 ml of 37% hydrochloric acid. The medium is then heated at 75 ° C. with stirring for one hour. After cooling the ethyl acetate and water are added, and the medium is neutralized with 21% sodium hydroxide solution. After decantation, the organic phase is dried over magnesium sulfate, filtered and evaporated. The product is then crystallized by trituration in dichloromethane. After filtration and spinning 3.97 g of 2- (2,5-dichloropyridin-4-yl) -4-methoxyaniline are obtained. UPLC-MS-DAD-ELSD: Tr (min) = 0.83; [M + H] +: m / z 269 and 271 (isotopic profile corresponding to a dichlorinated compound)

Step 3: Synthesis of 3-chloro-6-methoxy-9H-beta-carboline Step 2: Synthesis of 2- (2,5-dichloropyridin-4-yl) -4-methoxyaniline H 2 CN15 538 mg of 2- ( 2,5-dichloropyridin-4-yl) -4-methoxyaniline, 553 mg of potassium carbonate and 524 mg of copper acetoacetonate (II) are introduced into a microwave tube. 20 ml of DMSO are then added and the mixture is heated for two hours at 140 ° C. After cooling, the reaction medium is poured into a mixture of an aqueous solution of 7% ammonia and ethyl acetate with vigorous stirring. This mixture is filtered on celite and the filtrate is placed in a separating funnel. The aqueous phase is again extracted with ethyl acetate, and then the combined organic phases are washed successively with a 14% ammonia solution, water and brine. The organic phase is dried over magnesium sulphate, filtered and evaporated. 256 mg of 3-chloro-6-methoxy-9H-beta-carboline are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 0.85; [M + H] +: m / z 233 Step 4: Synthesis of 3- (1-methyl-1H-pyrazol-4-yl) -6-methoxy-9H-beta-carboline 1, NN 2 in a reactor for microwave, are placed 250 mg of 3-chloro-6-methoxy-9H-beta-carboline, 47 mg of [1,1'-bis (diphenylphosphino) ferrocene] -dichloropalladium (II), 447 mg of 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole, 2 ml of an aqueous solution of cesium carbonate at 1.5M and 5 ml of 1,4-dioxane. The tube is sealed and then subjected to microwave irradiation at 150 ° C for one hour. 12 mg of [1,1'-bis- (diphenylphosphino) -ferrocene] -dichloropalladium (II) and 112 mg of 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan) -2-yl) -1H-pyrazole are added and the tube is again subjected to microwave irradiation at 150 ° C for 1 hour. The reaction mixture is diluted with 50 ml of ethyl acetate and washed with 50 ml of water. After decantation, the aqueous phase is extracted with 50 ml of ethyl acetate and the organic phases are combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by chromatography on a silica column (eluent: CH 2 Cl 2 / MeOH 100/0 to 90/10). 132 mg of 3- (1-methyl-1H-pyrazol-4-yl) -6-methoxy-9H-beta-carboline are obtained as a brown solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.49; [M + H] +: m / z 279; [MH] -: m / z 277 Step 5: Synthesis of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-methoxy-9H-betacarboline 102 mg of 3- (1- Methyl-1H-pyrazol-4-yl) -6-methoxy-9H-beta-carboline are dissolved in a mixture of 10 ml of acetic acid and 5 ml of tetrahydrofuran. Then 5 ml of a bromine solution in tetrahydrofuran (0.51 ml of bromine in 50 ml of tetrahydrofuran) are added dropwise. After stirring for two hours at room temperature, 2.5 ml of the same bromine solution in THF are added to complete the reaction. This latter operation can be renewed depending on the progress of the reaction (followed by UPLC / MS). After 6 hours, the reaction medium is concentrated under reduced pressure. The residue is taken up in a mixture of dichloromethane and water, stirred is neutralized by addition of an aqueous solution of sodium hydrogencarbonate. The organic phase is washed with an aqueous solution of sodium thiosulfate. The organic phase is dried, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on a silica column (eluent: CH 2 Cl 2 / MeOH 100/0 to 90/10). 88 mg of 5-bromo-3- (1-methyl-1H-pyrazol-4-yl) -6-methoxy-9H-beta-carboline are obtained as a green solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.60; [M + H] +: m / z 357 and 359; [MH] -355 and 357 Step 6: Synthesis of 6-methoxy-5- {4- [3- (ethylamino) propoxylphenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H- Example 21 The product can be prepared by the same procedure as used for Example 6 but from 85 mg of 5-bromo-3- (1-methyl-1H-pyrazol). 4-yl) -6-methoxy-9H-betacarboline (step 6 of example 18), 218 mg of 1- {3- [4- (4,4,5,5-tetramethyl) -3, 2-dioxaborolan-2-yl) phenoxy] propyl} ethylamine (step 1 of example 19), 28 mg of tetrakis (triphenylphosphine) palladium and 233 mg of cesium carbonate dissolved in 2.4 ml of dioxane and 0.6 ml of water. After one hour of microwave irradiation at a temperature of 130 ° C. and purification by chromatography on a silica column [2M dichloromethane / NH 3 eluent in methanol gradient from 100/0 to 80/20], it is necessary to repurify the fractions containing 6-methoxy-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline by acidic HPLC. The pure fractions are passed on a SCX Bond Elut column of 3 g, and the expected product is recovered by elution of 2N ammonia methanol. 29 mg of 6-methoxy-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 0.49; [M + H] +: m / z 456; [M + 2H] 2+: m / z 228 (base peak); [MH] -: m / z 454 Example 22: Synthesis of 5-methoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-betacarboline Step 1: Synthesis of N- [2- ( The product can be prepared as described in Step 4 of Example 10 but in four microwavable reactors and in one of the following four microwavable reactors. from 7 g of N- (2-iodo-3-methoxyphenyl) -2,2-dimethylpropanamide in 75 ml of degassed dimethylformamide under argon, 7.84 g of 2,5-dichloro-4- (trimethylstannanyl) pyridine A2, 3.2 g of cesium fluoride and 800 mg of copper iodide. Under argon with stirring are added 736 mg of bis (triphenylphosphine) dichloropalladium. The medium is heated with stirring for two hours at a temperature of 130 ° C. Purification by chromatography on a silica column (eluent: heptane / ethyl acetate 4/1) gives 3.19 g of N- [2- (2,5-dichloropyridin-4-yl) -3-methoxyphenyl] - 2,2-dimethylpropanamide. LC-MS-DAD-ELSD: Tr (min) = 3.67 Step 2: Synthesis of N- {2- (5-chloro-2- (1-methyl-1H-pyrazol-4-yl) pyridin-4-yl) 3-methoxyphenyl) -2,2-dimethylpropanamide 7.3 g of N- [2- (2,5-dichloropyridin-4-yl) -3-methoxyphenyl] -2,2-dimethylpropanamide are placed in a 250 ml flask. mg of [1,1'-bis- (diphenylphosphino) -ferrocene] -dichloropalladium (II), 4.34 g of 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan) 2-yl) -1H-pyrazole, 44.5 ml of a 1.5M aqueous solution of cesium carbonate and 110 ml of 1,4-dioxane. The mixture is heated with stirring at 100 ° C for 1 hour. The reaction mixture is diluted with 300 ml of ethyl acetate and washed with 300 ml of water. After decantation, the aqueous phase is extracted with 300 ml of ethyl acetate and the organic phases are combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by chromatography on a silica column (600 g SiO 2, eluent: Heptane / ethyl acetate: 50/50 0/100). 6.62 g of N- {2- [5-chloro-2- (1-methyl-1H-pyrazol-4-yl) pyridin-4-yl] -3-methoxyphenyl} -2,2-dimethylpropanamide are obtained in the form of of solid. UPLC-MS-DAD-ELSD: Tr (min) = 0.84; [M + H] +: m / z 399; [MH] -: m / z 397 Step 3: Synthesis of 5-methoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline (Example 22) NH Example 22 In flask 39.4 mg of palladium acetate and 111 mg of (R) - (-) - 1 - [(S) -2- (dicyclohexylphosphino) ferrocenyl] ethylditert-butylphosphine, 8 ml of dioxane are introduced under dry conditions and under an argon atmosphere. degassed under argon are then added. This mixture is stirred for four minutes in a water bath at 40 ° C. 1 g of N- {2- [5-chloro-2- (1-methyl-1H-pyrazol-4-yl) pyridin-4-yl] -3-methoxyphenyl} are introduced into a reactor for a microwave oven. -2,2-dimethylpropanamide and 482 mg of sodium terbutoxide in 8 ml of dioxane. The catalyst solution is added via a syringe into the microwave tube and this tube is irradiated at a temperature of 140 ° C for one hour. After cooling, 5 ml of methanol and 50 ml of ethyl acetate are added. The organic phase is washed with a 5% aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by chromatography on a silica column (dichloromethane / methanol gradient from 100/0 to 95/5), 670 mg of 5-methoxy-3- (1-methyl-1H-pyrazol-4-yl are obtained. ) -9H-beta-carboline as yellow crystals. UPLC-MS-DAD-ELSD: Tr (min) = 0.53; [M + H] +: m / z 279; Example 23: 544-N- (ethylamino) propoxy] phenyl) -3- (1-methyl-1H-pyrazol-4-yl) -25H-beta-carboline Step 1: [MH] -: m / z Synthesis of 3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-ol (D6 R3 = 3'-pyridinyl, R "= H) A solution of 4.08 g of 5- methoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline (Example 10) in a mixture of 61 ml of acetic acid and 49 ml of concentrated hydrochloric acid is placed in a After closing, the medium is heated for two hours at a temperature of 160 ° C. under a pressure of 20. The reaction medium is concentrated to dryness several times with toluene under reduced pressure. ethyl acetate and an aqueous solution of sodium hydrogencarbonate The organic phase is dried, filtered and then concentrated to dryness under reduced pressure to give 3,008 g of 3- (1-methyl-1H-pyrazol-4- yl) -9H-beta-carbolin-5-ol UPLC-MS-DAD-ELSD: Tr (min) = 0.40, [M + H] +: m / z 265 [MH] -: m / z 263 Step 2: Synthesis of 3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl trifluoromethanesulfonate (D7 R3 = 3'- pyridinyl, R "= H) FFA a solution of 150 mg of 3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-ol and 12 mg of DMAP in 4 ml of pyridine under argon at a temperature of 0 ° C. is added 0.145 ml of trifluoromethanesulfonic anhydride. After four hours, 100 μl of trifluoromethanesulfonic anhydride are added again. The medium is poured into 50 ml of water and then the aqueous phase is extracted with three times 50 ml of ethyl acetate. The combined organic phases are washed with twice 50 ml of saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After purification of the residue by preparative HPLC in an acidic medium, 224 mg of 3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl trifluoromethanesulphonate are obtained in the form of a solid. brown.

UPLC-MS-DAD-ELSD: Tr (min) = 0.75; [M + H] +: m / z 397; [MH] -: m / z 395 Step 3: Synthesis of 5- {443- (ethylamino) propoxylphenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline (Example 23 )

EXAMPLE 23 The product can be prepared by the same procedure as that used for Example 6 but starting from 111 mg of 3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-trifluoromethanesulphonate. carbol-5-yl, 256 mg of 1- {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propyl} ethylamine (step 1 of Example 19), 32 mg of tetrakis (triphenylphosphine) palladium and 0.36 ml of an aqueous 1.5M cesium carbonate solution and 1.8 ml of 1,4-dioxane. After one hour of microwave irradiation at a temperature of 130 ° C. and purification by chromatography on a silica column (eluent dichloromethane / 2M NH3 in methanol gradient from 100/0 to 80/20) it is necessary to repurify the fractions containing 5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline by acidic HPLC. The pure fractions are passed through a SCX Bond Elut column of 2 g, and the expected product is recovered by elution of 2N ammonia methanol. 9 mg of 5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline are thus obtained. UPLC-MS-DAD-ELSD: Tr (min) = 0.50; [M + H] +: m / z 426; [M + 2H] 2+: m / z 213 (base peak); [M-H] -: m / z 424

The preparations of the pharmaceutical compositions as defined above could be carried out with any of the products of formula (I) according to the present invention: such pharmaceutical compositions form part of the present invention.

Vitro Biochemical Assay Procedures The pharmacological properties of the compounds of the invention can be confirmed by a number of pharmacological assays. The following examples of pharmacological assays were carried out with compounds according to the invention.

Example 1 TR-FRET Assay In order to determine the inhibition of Pim kinase activity, the compounds of the invention are tested in accordance with a TR-FRET assay ("Time Resolved-Fluorescence Resonance Energy Transfer"). in vitro resonance fluorescence) in vitro used routinely. The TR-FRET assay is based on the detection of phosphorylation of the Ser112 specific residue in the Bad protein, which has been shown to be a natural substrate of Pim kinases in cells. For the assay, the following reagents are used: Hisim-tagged recombinant full-length human Pim-protein, Pim-1, Pim-2, or Pim-3 (prepared according to J. Mol., Biol. (2005) 348, 183- 193); Bad - His6-tagged recombinant full-length human Bad Protein (prepared according to J. Mol Biol (2005) 348, 183-193); a-His6-APC-SureLight ™ allophycocyanin-conjugated mouse monoclonal antibody directed against the His6 tag (Perkin Elmer, No. AD0059H, Waltham, Mass., USA); a-P-Bad-Eu - mouse monoclonal antibody (Cell Signaling Technology # 9296B, Danvers, Massachusetts, USA) directed against phosphoBad (Ser112) (7E11) labeled at the request by Perkin Elmer with LANCETM reagent Eu-W1024. The assay is based on PerkinElmer's LANCETM technology: the Eu-labeled antibody binds to phospho-Ser112 and generates a TR-FRET signal by interaction with the PCA-labeled His6 antibody bound to the His6 tag of Bad. The TR-FRET signal is detected using a SpectraMax M5 plate reader (Molecular Devices) with the following settings: tex = 340 nm, ~ em1 = 615 nm, Xem2 = 665 nm. The fluorescence signal ratio at 665 nm on a fluorescence signal at 615 nm is used as the signal reading for the C150 (calculations based on the 4-parameter logistic model). The assay is carried out in a 384-well format; liquid handling is carried out using a Beckman 3000 liquid handling station. The compounds under test are tested at 10 concentration points in duplicate; the highest compound concentration is typically 30 μM. The concentration of ATP is 40 μM.

Example 2 Cell Viability Assay The representative compounds of the invention are also screened for their effects on cell proliferation and viability using a variety of tumor cell lines from humans representative of various pathological indications. These cell lines include: Models of hematologic malignancies: TF-1 (acute myelogenous leukemia, AML M6 at the time of diagnosis); KG-1 (AML, erythroleukemia evolving in AML); KG-1α (AML, subclone derived from immature KG-1); EOL-1 (AML, eosinophilic leukemia); PL-21 (AML; M3); ML-2 (AML, T-NHL evolving into T-ALL evolving in AML M4); HL-60 (AML, M3); Kasumi-1 (AML); GDM-1 (AML); K-562 (CML - chronic myelogenous leukemia, blast crisis); JURL-MK1 (CML blast crisis); DND-41 (T-ALL - acute T cell lymphoblastic leukemia); Jurkat (T-ALL); NALM-6 (B-ALL to B-cell); CEM (ALL, ALL lymphosarcoma); Jeko-1 (B-NHL-non-Hodgkin's B-cell lymphoma, mantle cell lymphoma derived from large-cell variant leukemia transformation); WSU-DLCL2 (B-NHL, diffuse large B-cell lymphoma); RL (B-NHL; undifferentiated diffuse); OCI-Ly10 (B-NHL); DoHH-2 (B-NHL); RPMI-8226 (MM-multiple myeloma); JVM-2 (B-CLL - B-cell chronic lymphocytic leukemia); and JVM-3 (B-CLL) KSM-12-BM (MM).

Solid tumor models: HCT-116 (colon cancer); HT-29 (colon cancer); HC-15 (colon cancer); H460 (lung cancer, non-small cell lung cancer); A375 (melanoma); B16F10 (melanoma); MDA-A1 (breast cancer); MDA-MB231 (breast cancer); MDA-MB231 adr (breast cancer); PANC-1 (pancreatic cancer); and PC-3 (prostate cancer).

In order to measure viability, the tumor cells are incubated in a 96-well or 384-well format for 48, 72 or 96 hours, preferably 72 hours, with a compound of the invention at 3-fold dilutions with in general, nine doses in total, the highest dose being 10 μM or 30 μM. Cell viability is assessed by the addition of CeIlTiter-Blue® (Promega, Madison, Wisconsin, USA) for 4 hours and endpoint readings are performed using a SpectraMax Genmini EM plate reader (Molecular Devices, Sunnyvale , California, United States). The CeIlTiter-Blue® cell viability assay measures the ability of cells in culture to effect resorurine reduction of resazurin, the fluorescence signal intensity being directly proportional to the number of living cells. EC 50 represents the concentration of compound that leads to a 50% reduction in proliferative cell viability / expansion.

EXAMPLE 3 The activity of the molecules is evaluated on the JEKO or DND-41 cell line by measuring the level of phosphorylation of Bad and the total Bad rate, and this, by the Elisa technique. The JEKO or DND-41 cells are resuspended at a concentration of 500,000 cells per ml. The cells are then diluted in RPMI-1640 medium containing 20% fetal calf serum. 225 μl of cells are placed in a plate. The serial dilutions of the molecules are then carried out (8 points, dilution to 1/3, start of range to 10 mM). Each dilution point is then diluted 1/100 in medium. Then, 25 μl of each of the concentrations are added to the cells and then incubated for 3 hours at 37 ° C. 100 μl of the cells are transferred to a poly-D-Lysine treated plate. The plate is then incubated for 5-10 minutes at 37 ° C. and then centrifuged for 5 minutes at 1500 rpm. A volume of 100 μl of 8% fixing solution (formaldehyde solution in PBS buffer) is added to each of the wells. After being covered with a self-adhesive film and a lid, the plate is incubated for 20 minutes at room temperature and then stored at 4 ° C overnight. Then, the liquid is removed and two successive washes are carried out with washing buffer. 100 μl of quenching buffer are added and incubated for 15 minutes at room temperature. After washing, 100 μl of stop buffer is added followed by incubation for 1 hour at room temperature. After washing, 50 μl of the primary antibody diluted to 1/250 for pBAD (Cell Signaling Cat # 5284) and 1/500 for Bad (MBL Cat # 591) are added to each of the plates. Each of the plates is incubated for 2 hours at room temperature. After two washes, 50 μl of the secondary antibody (diluted 1/16) are added to the Pbad plate (tebu-bio ref: FE-021) and 50 μl of the HRP-conjugated secondary antibody IgG (Santa Cruz Cat # SC-2004, diluted 1/1000) are added to the Bad plate. An incubation of 1 hour at room temperature is performed. 4 washes with the washing solution are carried out followed by 3 washes with PBS. Finally, 100 μl of the revealing solution is added followed by a 10 minute incubation. Finally, 100 μl of the stop solution is added before reading at 450 nm. BIOCHEMICAL RESULTS The biochemical results are expressed according to the following classification:

Class A: IC50 less than 100 nM Class B: IC50 between 100 nM and 1000 nM (or 1 μM) Class C: IC50 between 1 μM and 5 μM Class D: IC50 greater than 5 μM Example IC50 Pim1 IC50 Pim2 IC50 Pim3 IC50 CDK1 IC50 PLK1 # 1 BDC 2 ABADD 3 AAADD 4 ABADDBCBDD 6 AB 7 AB 8 AD 9 ABBDCDD 11 BCBDD 12 ACB 13 ABAABA 16 CDDDD 17 ABA 18 ABADD 99 2953838 100 AAA 21 AAA CELLULAR RESULTS The cell proliferation results are expressed as the following classification:

Class A: EC50 or IC50 less than 100 nM 10 Class B: EC50 or IC50 between 100 nM and 1000 nM (or 1 μM) Class C: EC50 or IC50 between 1 μM and 5 μM Exem I EC50 EOL-1 EC50 IC50 pM MV4-11 phosphoBAD in ° (lymphoma) pM (DND-41) (ym elo me) 2 BB 3 CCB 4 BC 6 BCB 7 BC 5 15 20

Claims (99)

CLAIMS 1-Products of general formula (I): R 3 H in which - R 3 represents a heteroaryl radical consisting of 5 or 6 members with 1 to 4 heteroatoms chosen from N, S or O, this heteroaryl being linked to the carboline unit or by a C or by an N belonging to R3, R3 being optionally mono or poly substituted; R5 is chosen from: 1 halogen; 2 -OH linear or branched alkoxy whose alkyl part is optionally mono, di or tri substituted; 4-Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono, di or tri substituted; 5 -X-aryl (X = O, S, SO, SO 2) optionally mono-, di- or tri-substituted; 6-X-heteroaryl (X = O, S, SO, SO 2) with optionally mono, di or tri-substituted heteroaryl; -NH 2, 8 -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted; 9 -NH (aryl), the aryl part of which is optionally mono, di or tri substituted; -NH (heteroaryl) whose heteroaryl part (heteroaryl of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom is a C or an N) is optionally mono, di or tri substituted; 11 -N (alkyl) (aryl) of which the alkyl (linear, branched or cyclic) and aryl portions are optionally mono, di or tri substituted; 2 12 -N (alkyl) (heteroaryl) whose alkyl parts (linear, branched or cyclic) and heteroaryl (heteroaryl of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by a C or an N) are optionally mono, di or tri substituted; -C (O) OH 14 -C (O) linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted; -C (O) Oaryl optionally mono, di or tri substituted; -C (O) 0-Oeteroaryl (5- or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, O-bonded oxygen-bound oxygen) optionally mono-, di- or tri-substituted; -CONH 2 -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted; -CO-heterocycloalkyl mono, di or tri substituted; -CON (alkyl) (aryl), linear, branched or cyclic alkyl of which the alkyl and aryl parts are optionally mono, di or tri substituted; -CON (alkyl) (heteroaryl), linear, branched or cyclic alkyl and 5- or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by C or by an N) of which the alkyl and the hetroaryl parts are optionally mono, di or tri substituted; -C1-C10 linear, branched or cyclic alkyl optionally containing a heteroatom and optionally mono-, di or tri-substituted; Aryl optionally mono-, di- or tri-substituted; Optionally mono or poly substituted heteroaryl; Optionally mono or poly substituted heterocycloalkyl; -C2-C6 alkenyl optionally mono or poly substituted; -C2-C6 alkynyl optionally mono or poly substituted; - R6 is chosen from: 1. H; 2. halogen; 3. -OH 2953838 103 4. linear or branched alkoxy whose alkyl part is optionally mono, di or tri substituted; 5. O-cycloalkyl optionally mono, di or tri substituted; 6. -Y-alkyl (Y = S, SO, SO 2) linear or branched, optionally mono-, di- or tri-substituted; 7. -NH2, 8. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted; 9. -C (0) OH 10 10. -C (O) linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted; 11. -CONH2 12. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted; 15 13. C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom and optionally mono-, di or tri-substituted; 14. aryl optionally mono, di or tri substituted; said products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as addition salts with mineral and organic acids or with the inorganic and organic bases of said products of formula (I) . 2- products of general formula (I) as defined in claim 1 wherein the possible substituents of R3 is R1 groups a, R1 b, R1 c; are independently selected from 1. F; 2. Cl; 3. Br; 4. I; 5. -C1-C10 linear or branched alkyl optionally mono or poly substituted with R3a, R3b, R3c; 6. -OH; 7. linear or branched, optionally mono or poly substituted with linear R3a, R3b, R3c; 4 8.-Y-alkyl (Y = S, SO, SO2) linear or branched, optionally mono, , di or tri substituted by R3a, R3b, R3c; O-cycloalkyl (C3-C7) optionally mono or poly substituted with R3a, R3b, R3c; 10. -NH2 11. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R3a, R3b, R3c ; the groups R3a, R3b, R3c; either the substituents of the groups R1a, R1b, R1c, R2a, R2b and R2c; being chosen independently of each other from: 1 F, 2. Cl; 3. Br; 4. I; -C1-C10 linear or branched alkyl optionally mono or poly substituted with R4a, R4b, R4c; 6. -C3-C7 cycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 7. -OH; 8. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R4a, R4b, R4c; 9. -Y-alkyl (Y = S, SO, SO2) linear or branched optionally mono, di or tri substituted by R4a, R4b, R4c; 10. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R4a, R4b, R4c; 11.-O-aryl optionally mono or poly substituted with R4a, R4b, R4c; 12. aryl optionally mono or poly substituted with R4a, R4b, R4c; 13. heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 14. heterocycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 15. -NO2; ; 16.-NH2; 17. -NH- (C 1 -C 10 alkyl) or C 3 -C 4 cycloalkyl or heterocycloalkyl) each optionally mono or poly substituted with R 4a, R 4b, R 4c; 5 10 15 20 25 30 2953838 105 18. -N (C 1 -C 10 alkyl) or C 3 -C 7 cycloalkyl) 2 each group being optionally mono or poly substituted with R 4a, R 4b, R 4c; 19. -NHaryl or NH heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 20. -NHC (O) substituted with R4a, R4b, R4c; 21. -N (C 1 -C 10 alkyl) C (O) substituted with R 4a, R 4b, R 4c; 22. -NHS (O2) substituted with R4a, R4b, R4c; 23. -N (C 1 -C 10 alkyl) S (O 2) substituted with R 4a, R 4b, R 4c; 24. -CO2substituted by R4a, R4b, R4c; 25. -CON H2 26. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R4a, R4b, R4c; 27. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R4a, R4b, R4c; 28. -S substituted with R4a, R4b, R4c; 29. -S (O2) substituted with R4a, R4b, R4c; 30. -S (O) substituted with R4a, R4b, R4c; 31. oxo (double bond O); 32. -C2-C6 alkenyl optionally mono or poly substituted with R4a, R4b, R4c; 33. -C2-C6 alkynyl optionally mono or poly substituted with R4a, R4b, R4c; the groups R4a, R4b, R4c; either the substituents of groups R3a, R3b and R3c; are selected independently from each other from: 1. F; 2. Cl; 3. Br; 4. I; 5. -CF3; -CHF2 6 -C1-C10 linear or branched alkyl; 7. -C3-C7 cycloalkyl; 8. -OH; 6 9. -O-alkyl (C, -C, O) linear or branched; Linear or branched-Y-alkyl (Y = S, SO, SO 2); 11. -O-cycloalkyl (C3-C7); 12.-O-aryl; 13. aryl; 14. heteroaryl; 15. heterocycloalkyl; 16. -NO2; 17.-NH2; 18. -NH- (C 1 -C 10 alkyl) or C 3 -C cycloalkyl or heterocycloalkyl); 19. -N (alkyl (C1-C10) or cycloalkyl (C3-C4)) 2; 20. -NHaryl or NH heteroaryl; 21. -NHS (O2) alkyl; 22. -N (alkyl (C1-C10) S (O2) alkyl; 23. -CO2alkyl; 24. -CONH2 25. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s); 26. -C (O) heterocycloalkyl; 27S-alkyl; 28. -S (O2) alkyl; 29. -S (O) alkyl; 30. oxo (O double bond); -C6 linear or branched alkenyl; 32. -C2-C6 linear or branched alkynyl; said products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as the addition salts with acids inorganic and organic or with the inorganic and organic bases of said products of formula (I) 3 - Products of general formula (I) as defined in claim 1 in which the possible substituents of groups R5 and R6 are the groups R2a, R2b , R2c; are independently selected from each other from: 1. F; 2. Cl; 2953838 107 3. Br; 4. I; -C1-C10 linear or branched alkyl optionally mono or poly substituted with R3a , R3b, R3c; -C3-C7 cycloalkyl optionally mono or poly substituted with R3a, R3b, R3c; 7. -OH; 8. O-linear or branched (C, -C, O) alkyl optionally mono or poly substituted with R3a, R3b, R3c; 9. linear or branched, optionally mono, di or tri-substituted Y-alkyl (Y = S, SO, SO 2), R 3a, R 3b, R 3c; 10. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R3a, R3b, R3c; 11.-O-aryl optionally mono or poly substituted with R3a, R3b, R3c; Optionally aryl mono or poly substituted with R3a, R3b, R3c; 13. heteroaryl optionally mono or poly substituted with R3a, R3b, R3c; 14. heterocycloalkyl optionally mono or poly substituted with R3a, R3b, R3c; 15. -NO2; ; 16.-NH2; 17. -NH- (C 1 -C 6 -alkyl) or C 3 -C -cycloalkyl or heterocycloalkyl) each optionally mono or poly-substituted group with R 3a, R 3b, R 3c; 18. -N (C 1 -C 10 alkyl) or C 3 -C 5 cycloalkyl) 2 each group being optionally mono or poly substituted with R 3a, R 3b, R 3c; 19. -NHaryl or NH heteroaryl optionally mono or poly substituted 20. -NHC (O) substituted with R3a, R3b, R3c; 21. -N (C 1 -C 10 alkyl) C (O) substituted with R 3a, R 3b, R 3c; 22. -NHS (O 2) substituted with R 3a, R 3b, R 3c; -C, o) S (O2) substituted with R3a, R3b, R3c; 24. -CO2substituted by R3a, R3b, R3c; 25. -CON H2 26. -CONH (alkyl), CON (alkyl) 2 linear (s) ), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R3a, R3b, R3c; 8 27. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R3a, R3b , R3c; 28. -S substituted with R3a, R3b, R3c; 29. -S (O2) substituted with R3a, R3b, R3c; 30. -S (O) substituted with R3a, R3b, R3c; 31. oxo (double O); -C 2 -C 6 alkenyl linkage optionally mono or poly substituted with R 3a, R 3b, R 3c; -C 2 -C 6 alkynyl optionally mono or poly substituted with R 3a, R 3b, R 3c; R 3a, R 3b, R 3c; either the substituents of the groups R1a, R1b, R1c, R2a, R2b and R2c being chosen independently of one another from: 34. F; 35. Cl; 36. Br; 37.1; 38. -C, -C, o linear or branched alkyl optionally mono or poly substituted with R4a, R4b, R4c; 39. -C3-C7 cycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 40. -OH; 41. -O-alkyl (C, -C, O) linear or branched optionally mono or poly substituted with R4a, R4b, R4c; 42.-Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono, di or tri substituted by R4a, R4b, R4c; 43. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R4a, R4b, R4c; 44.-O-aryl optionally mono or poly substituted with R4a, R4b, R4c; 45. aryl optionally mono or poly substituted with R4a, R4b, R4c; 46. optionally mono or poly substituted heteroaryl by R4a, R4b, R4c; 47. heterocycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 48. -NO2; 49. -NH2; 9 50. -NH- (C 1 -C 10 alkyl) or C 3 -C 7 cycloalkyl or heterocycloalkyl) each optionally mono or poly substituted with R 4a, R 4b, R 4c; 51. -N (C 1 -C 10 alkyl) or C 3 -C 7 cycloalkyl) 2 each group being optionally mono or poly substituted with R 4a, R 4b, R 4c; 52. -NHaryl or NH heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 53. -NHC (O) substituted with R4a, R4b, R4c; 54. -N (C 1 -C 10 alkyl) C (O) substituted with R 4a, R 4b, R 4c; 55. -NHS (O2) substituted with R4a, R4b, R4c; 56. -N (C 1 -C 10 alkyl) S (O 2) substituted with R 4a, R 4b, R 4c; 57. -CO2substituted by R4a, R4b, R4c; 58. -CONH2 59. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R4a, R4b, R4c; 60. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R4a, R4b, R4c; 61. -S substituted with R4a, R4b, R4c; 62. -S (O2) substituted with R4a, R4b, R4c; 63. -S (O) substituted with R4a, R4b, R4c; 64. oxo (double bond O); 65. -C2-C6 alkenyl optionally mono or poly substituted with R4a, R4b, R4c; 66. -C2-C6 alkynyl optionally mono or poly substituted with R4a, R4b, R4c; the groups R4a, R4b, R4c; either the substituents of groups R3a, R3b and R3c; are chosen independently of one another from: 33. F; 34. C1; 35. Br; 36.1; 37. -CF3; -CHF2 38. -C1-C10 linear or branched alkyl; 0 39. -C3-C7 cycloalkyl; 40. -OH; 41. -O-alkyl (C, -C, O) linear or branched; 42.-Y-alkyl (Y = S, SO, SO 2) linear or branched; 43. -O-cycloalkyl (C3-C7); 44.-O-aryl; 45. aryl; 46. heteroaryl; 47. heterocycloalkyl; 48. -NO2; 49. -NH2; 50. -NH- (C 1 -C 10 alkyl) or C 3 -C cycloalkyl or heterocycloalkyl); 51. -N (alkyl (C1-C10) or cycloalkyl (C3-C4)) 2; 52. -NHaryl or NH heteroaryl; 53.-NHS (O2) alkyl; 54. -N (alkyl (C1-C10) S (O2) alkyl; 55. -CO2alkyl; 56. -CONH2 57. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (S); 58. -C (O) heterocycloalkyl; 59. ûS-alkyl; 60.-S (O2) alkyl; 61.-S (O) alkyl; 62. oxo (O double bond); 63. -C2 -C6 linear or branched alkenyl; 64. -C2-C6 alkynyl linear or branched, said products of formula (I) being in all possible isomeric forms racemic, enantiomers and diastereoisomers, as well as the addition salts with acids inorganic and organic or with the inorganic and organic bases of said products of formula (I) .4 - Products of formula (I) as defined in any one of the preceding claims wherein R3 represents a radical, a heteroaryl (5), or 6-membered with 1 to 4 heteroatoms selected from N, S or O) linked to the carboline moiety either by C or by N belonging to R3, R3 being optionally mono or poly substituted by R1a, R1b, R1c; R5 is selected from: 1. halogen; 2.-OH 3. linear or branched alkoxy wherein the alkyl moiety is optionally mono, di or tri substituted by R2a, R2b, R2c; 4-Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono, di or tri substituted by R2a, R2b, R2c; 5. -X-aryl (X = O, S, SO, SO2) optionally mono, di or tri substituted by R2a, R2b, R2c; 6.-X-heteroaryl (X = O, S, SO, SO2) with the optionally mono, di or tri-substituted heteroaryl substituted by R2a, R2b, R2c; 7. -NH2, 8. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R2a, R2b, R 2c; 9. -NH (aryl), the aryl portion of which is optionally mono, di or tri substituted by R2a, R2b, R2c; 10. -NH (heteroaryl) whose heteroaryl part (heteroaryl of 5 or 6 members with 1 to 4 heteroatoms chosen from N, S or O bonded to the nitrogen atom is a C or an N) is optionally mono , di or tri substituted by R2a, R2b, R2c; 11. -N (alkyl) (aryl) whose alkyl (linear, branched or cyclic) and aryl portions are optionally mono, di or tri substituted by R2a, R2b, R2c; 12. -N (alkyl) (heteroaryl) whose alkyl (linear, branched or cyclic) and heteroaryl (heteroaryl) parts of 5 or 6 members with 1 to 4 heteroatoms selected from N, S or O bonded to the atom nitrogen either by a C or an N) are optionally mono, di or tri substituted by R2a, R2b, R2c; 13. -C (O) OH 14. -C (O) O-linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted by R2a, R2b, R2c; 2 15. -C (O) Oaryl optionally mono, di or tri substituted with R2a, R2b, R2c; 16. -C (O) Oheteroaryl (5- or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, S or O bonded to oxygen by a C atom) optionally mono, di or tri substituted by R2a, R2b, R 2c; 17. -CONH 2 18. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R2a, R2b, R2c; 19. -CO-heterocycloalkyl mono, di or tri substituted by R2a, R2b, R2c; - CON (alkyl) (aryl), linear, branched or cyclic alkyl of which the alkyl and aryl parts are optionally mono, di or tri substituted by R2a, R2b, R2c; 20. -CON (alkyl) (heteroaryl), linear, branched or cyclic alkyl and 5 or 6-membered heteroaryl with 1 to 4 heteroatoms selected from N, S or O bonded to the nitrogen atom either by a C or by an N) of which the alkyl and the hetroaryl portions are optionally mono, di or tri substituted by R2a, R2b, R2c; 21. -C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom and optionally mono, di or tri substituted by R2a, R2b, R2c; 22. aryl optionally mono, di or tri substituted by R2a, R2b, R2c; 23. heteroaryl optionally mono or poly substituted with R2a, R2b, R2c; 24. heterocycloalkyl optionally mono or poly substituted with R2a, R2b, R2c; 25. -C2-C6 alkenyl optionally mono or poly substituted by R2a, R2b, R2c; 26. -C2-C6 alkynyl optionally mono or poly substituted by R2a, R2b, R2c; - R6 is chosen from: 1. H; 2. halogen; 3. -OH3 4. linear or branched alkoxy whose alkyl part is optionally mono, di or tri substituted by R2a, R2b, R2c; 5. O-cycloalkyl optionally mono, di or tri substituted by R2a, R2b, R2c, -Y-alkyl (Y = S, SO, SO2) linear or branched optionally mono, di or tri substituted by R2a, R2b, R2c; 7. -NH2, 8. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R2a, R2b, R 2c; 9. -C (O) OH 10. -C (O) O-linear, branched or cyclic alkyl optionally mono-, di- or tri-substituted by R2a, R2b, R2c; 11. -CONH2 12. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R2a, R2b, R2c; 13. -C1-C10 linear, branched or cyclic alkyl optionally comprising a heteroatom and optionally mono, di or tri substituted by R2a, R2b, R2c; 14. aryl optionally mono, di or tri substituted by R2a, R2b, R2c; R1a, R1b, R1c; either the substituents of groups R3; are independently selected from 12. F; 13. Cl; 14. Br; 15.1; 16. -C1-C10 linear or branched alkyl optionally mono or poly substituted with R3a, R3b, R3c; 17.-OH; 18. Linear or branched, optionally mono or poly substituted with R3a, R3b, R3c; 19.-Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono-, di- or tri-substituted by R 3a, R 3b, R 3c; 4-20-cycloalkyl (C 3 -C 7) optionally mono or poly substituted with R 3a, R 3b , R3c; 21. -NH2 22. -NH (alkyl), -N (alkyl) 2 linear (s), branched (s) or cyclic (s) of which the alkyl part is optionally mono, di or tri substituted by R3a, R3b, R3c ; R2a, R2b, R2c; either the substituents of groups R5 and R6; are chosen independently of one another from: 34. F; 35. C1; 36. Br; 37.1; 38. -C1-C10 linear or branched alkyl optionally mono or poly substituted with R3a, R3b, R3c; 39. -C3-C7 cycloalkyl optionally mono or poly substituted with R3a, R3b, R3c; 40. -OH; 41. -O-alkyl (C, -C, O) linear or branched optionally mono or poly substituted with R3a, R3b, R3c; 42.-Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono, di or tri substituted by R3a, R3b, R3c; 43. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R3a, R3b, R3c; 44.-O-aryl optionally mono or poly substituted with R3a, R3b, R3c; 45. aryl optionally mono or poly substituted with R3a, R3b, R3c; 46. heteroaryl optionally mono or poly substituted with R3a, R3b, R3c; 47. heterocycloalkyl optionally mono or poly substituted with R3a, R3b, R3c; 48. -NO2; 49. -NH2; 50. -NH- (C 1 -C 4 -alkyl) or (C 3 -C 4) -cycloalkyl or heterocycloalkyl) each optionally mono or poly-substituted group with R 3a, R 3b, R 3c; 51. -N (C 1 -C 10 alkyl) or C 3 -C 5 cycloalkyl) 2 each group being optionally mono- or poly-substituted with R 3a, R 3b, R 3c, 52. -NHaryl or NH heteroaryl optionally mono or substituted poly 53. -NHC (O) substituted with R3a, R3b, R3c; 54. -N (C 1 -C 10 alkyl) C (O) substituted with R 3a, R 3b, R 3c; 55. -NHS (O 2) substituted with R 3a, R 3b, R 3c; 56. -N (C -C, o) S (O2) substituted with R3a, R3b, R3c; 57. -CO2substituted by R3a, R3b, R3c; 58. -CONH2 59. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R3a, R3b, R3c; 60. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R3a, R3b, R3c; 61.-S substituted with R3a, R3b, R3c; 62. -S (O2) substituted with R3a, R3b, R3c; 63. -S (O) substituted with R3a, R3b, R3c; 64. oxo (O double bond) 65. -C2-C6 alkenyl optionally mono or poly substituted with R3a, R3b, R3c; 66. -C2-C6 alkynyl optionally mono or poly substituted with R3a, R3b, R3c; R3a, R3b, R3c; R1a, R1b, R1c, R2a, R2b and R2c are independently selected from: 67. F; 68. Cl; 69. Br; 70.1; 71. -C, -C, o linear or branched alkyl optionally mono or poly substituted with R4a, R4b, R4c; 72. -C3-C7 cycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 73. -OH; 74. -O-alkyl (C, -C, O) linear or branched optionally mono or poly substituted with R4a, R4b, R4c; 75.-Y-alkyl (Y = S, SO, SO 2) linear or branched optionally mono-, di- or tri-substituted by R4a, R4b, R4c; 76. -O-cycloalkyl (C3-C7) optionally mono or poly substituted with R4a, R4b, R4c; 77. -O-aryl optionally mono or poly substituted with R4a, R4b, R4c; 78. aryl optionally mono or poly substituted with R4a, R4b, R4c; 79. optionally mono or poly substituted heteroaryl by R4a, R4b, R4c; 80. heterocycloalkyl optionally mono or poly substituted with R4a, R4b, R4c; 81. -NO2; 82. -NH2; 83. -NH- (C 1 -C 10 alkyl) or C 3 -C 8 cycloalkyl or heterocycloalkyl) each optionally mono or poly substituted with R 4a, R 4b, R 4c; 84. -N (C 1 -C 10 alkyl) or C 3 -C 4 cycloalkyl) 2 each group being optionally mono or poly substituted with R 4a, R 4b, R 4c; 85. -NHaryl or NH heteroaryl optionally mono or poly substituted with R4a, R4b, R4c; 86. -NHC (O) substituted with R4a, R4b, R4c; 87. -N (C 1 -C 10 alkyl) C (O) substituted with R 4a, R 4b, R 4c; 88. -NHS (O2) substituted with R4a, R4b, R4c; 89. -N (C 1 -C 10 alkyl) S (O 2) substituted with R 4a, R 4b, R 4c; 90. -CO2substituted by R4a, R4b, R4c; 91. -CONH2 92. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s) whose alkyl part is optionally mono, di or tri substituted by R4a, R4b, R4c; 93. -C (O) heterocycloalkyl optionally mono, di or tri substituted by R4a, R4b, R4c; 94. -S substituted with R4a, R4b, R4c; 95. -S (O2) substituted with R4a, R4b, R4c; 96.-S (O) substituted with R4a, R4b, R4c; 97. oxo (double bond O); 98. -C2-C6 alkenyl optionally mono or poly substituted with R4a, R4b, R4c; 99. -C2-C6 alkynyl optionally mono or poly substituted with R4a, R4b, R4c; R4a, R4b, R4c; either the substituents of groups R3a, R3b and R3c; are independently selected from: 65. F; 66. C1; 67. Br; 68.1; 69. -CF3; -CHF2 70. -C, -C, o linear or branched alkyl; 71. -C3-C7 cycloalkyl; 72. -OH; 73. -O-alkyl (C, -C, O) linear or branched; 74.-Y-alkyl (Y = S, SO, SO 2) linear or branched; 75. -O-cycloalkyl (C3-C7); 76. -O-aryl; 77. aryl; 78. heteroaryl; 79. heterocycloalkyl; 80. -NO2; 81. -NH2; 82. -NH- (C 1 -C 10 alkyl) or C 3 -C 8 cycloalkyl or heterocycloalkyl); 83. -N (alkyl (C1-C10) or cycloalkyl (C3-C)) 2; 84. -NHaryl or NH heteroaryl; 85.-NHS (O2) alkyl; 86. -N (alkyl (C1-C10) S (O2) alkyl; 87. -CO2alkyl; 88. -CONH2 89. -CONH (alkyl), CON (alkyl) 2 linear (s), branched (s) or cyclic (s); 90. -C (O) heterocycloalkyl; 91. -Si-alkyl; 92.-S (O2) alkyl; 93.-S (O) alkyl; 94. oxo (O double bond); 95. -C2 -C6 linear or branched alkenyl; -C2-C6 straight or branched alkynyl; -C products of formula (I) being in all isomeric forms possible racemic, enantiomers and diastereoisomers, as well as the addition salts with the inorganic and organic acids or with the inorganic and organic bases of said products of formula (I) 5- Products of formula (I) as defined in any one of the preceding claims whose names follow: - 5-bromide 6-Methoxy-3- (pyridin-3-yl) -9H-beta-carboline 10-N- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl} ] phenyl} methanesulfonamide - N- [2- (dimethylamino) ethyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- [3-] (dimethylamino) propyl] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide 15 - 4- [6-methoxy-3- (pyridin-3-) Methyl-6-methoxy-5- {4- [3- (piperidin-1-yl) propoxy] phenyl} -3- (pyridin-3-yl) methyl (9 H) -beta-carbolin-5-yl] benzoate -9H-beta-carboline-6-methoxy-5- {4- [3- (morpholin-4-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-betacarboline-5- [3- (4-Ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl] -6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline-N, N-diethyl- 2- {4- [6-Methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] piperazin-1-yl} ethanamine; 6-fluoro-5-methoxy 3- (pyri di n -3-yl) -9 H-beta-ca rbo fine - N- [2- (dimethylamino) ethyl] -4- [6-fluoro-3- (pyridin-3-yl) - 9H-beta-carbolin-5-yl] benzamide - N- [4- (1-methylpiperidinyl)] - 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5- yl] benzamide - N- (2-aminoethyl) -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-fluoro-3-acid - (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoic acid - N - [(1S, 2S) - 2-aminocyclohexyl] -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-5-methoxy-3- (pyridin-3-yl) -9H- beta-carboline - N- [2- (dimethylamino) ethyl] -4- [3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N - [(1S, 2S) - 2-aminocyclohexyl] -4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzamide 109 - 6-methoxyethoxy-5- { 4- [3- (Ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-N - [(1S, 2S) -2 aminocyclohexyl] -4- [6-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzamide-6-methoxy-5- {4- [ 3- (Ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline-5-methoxy-3- (1-methyl-1H-pyrazol-4) -yl) -9H-beta-carboline-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-betacarboline 6- Process of preparation of the products of formula (I) as defined in the preceding claims, characterized by the following general scheme: ~ N ^ R R1R2N An + Bn Coupling R1R2N (Stille, Suzuki, ...) Cn Hartwig-Buchwald or copper salt R5 R6 NH Compounds of formula (I) in which R3, R5 and R6 are as defined below Dn 15 X = Broul o -M = -SnMe3 or -B (OH) 2 or O 'R1R2N = O2N, H2N, HPivN R = Cl, OMe, OH, OSO2CF3 or R3 as defined below R' = H, OMe, OH , OSO2CF3, Br, or R5 as defined below R "= H. Br. OH or R6 as defined hereinafter General scheme in which the substituents R3, R5 and R6 have the meanings indicated for the products of formula ( I) according to any one of the preceding claims 2953838 120 7 of drugs, the products of formula (I) as defined in claims 1 to 5 and their prodrugs, said products of formula (I) being in any form racemic isomers, enantiomers and diastereoisomers, as well as addition salts with inorganic and organic acids or with inorganic and organic bases pharmaceutically. t acceptable of said products of formula (I). As medicaments, the products of formula (I) as defined in any one of claims 1 to 4, whose names follow: 5-bromo-6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline - N- {4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] phenyl} methanesulfonamide - N- [2- (dimethylamino) ethyl] ] -4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- [3- (dimethylamino) propyl] -4- [6-methoxy-3] - (Pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-methoxy-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoate methyl-6-methoxy-5- {4- [3- (piperidin-1-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-beta-carboline-6-methoxy-5- {4 - [3- (Morpholin-4-yl) propoxy] phenyl} -3- (pyridin-3-yl) -9H-betacarboline - 5- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1 1-yl-1-yl] -6-methoxy-3- (pyridin-3-yl) -9H-beta-carboline-N, N-diethyl-2- {4- [6-methoxy-3- (pyridin-3 -yl) -9H-beta-carbolin-5-yl] piperazin-1-yl} ethanamine - 6-fluoro-5-methoxy-3- (pyridin-3-yl) -9H-beta-carb oline - N- [2- (dimethylamino) ethyl] -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- [4- (1- methylpiperidinyl)] - 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - N- (2-aminoethyl) -4- [6-fluoro-3- (Pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide - 4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzoic acid - N - [(1S, 2S) -2-aminocyclohexyl] -4- [6-fluoro-3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide-5-methoxy-3- (Pyridin-3-yl) -9H-beta-carboline-N- [2- (dimethylamino) ethyl] -4- [3- (pyridin-3-yl) -9H-beta-carbolin-5-yl] benzamide 1 - N - [(1S, 2S) -2-aminocyclohexyl] -4- [6-methoxyethoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzamide - 6-methoxyethoxy-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-caproline - N- [(1S, 2S) -2-Aminocyclohexyl] -4- [6-cyclobutyloxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carbolin-5-yl] benzamide - 6 Methoxy-5- {4- [3- (ethylamino) propoxy] phenyl} -3- (1-methyl-1H-pyr) azol-4-yl) -9H-beta-carboline-5-methoxy-3- (1-methyl-1H-pyrazol-4-yl) -9H-beta-carboline-5- {4- [3- (ethylamino) ) propoxy] phenyl} -3- (1-methyl-1H-pyrazol-4-yl) -9H-betacarboline and their prodrugs, said products of formula (I) being in any isomeric form possible racemic, enantiomeric and diastereo isomers, as well as addition salts with inorganic and organic acids or with the pharmaceutically acceptable mineral and organic bases of said products of formula (I). 9- Pharmaceutical compositions containing as active ingredient, a compound according to any one of the preceding claims and at least one pharmaceutically compatible excipient. 10- Pharmaceutical compositions according to the preceding claim used for the treatment of cancer. 11-As new industrial products, the synthesis intermediates of formulas An, Bn, Cn and Dn as defined in the general scheme of claim 10 and as defined below: 1 ~ N ^ RR = Cl, OMe , OH, OSO2CF3 or R3 as defined above An with -M = -SnMe3 or -B (OH) 2 or ùB. ## STR2 ## with X = Brout R1R2N = O2N, H2N, HPivN R '= H, OMe, OH, OSO2CF3, Br, or R5 as defined above R "= H, Br, OH or R6 as defined above with R 1 R 2 N = O 2 N, H 2 N, HPivN R = Cl, OMe, OH, OSO 2 CF 3 or R 3 as defined above R '= H, OMe, OH, OSO 2 CF 3, Br or R 5 as defined above R "= H, Br, OH or R6 as defined above with R = Cl, OMe, OH, OSO2CF3 or R3 as defined above R '= H, OMe, OH, OSO2CF3, Br, or R5 such that defined above R "= H, Br, OH or R6 as defined above Dn