Antileukemic compounds based on nitrogen-containing heterocycles

Abstract

The present invention provides heterocyclic compounds of formula I. These compounds are useful in the treatment of tumor diseases. The disclosure describes also methods for preparation of these compounds, and pharmaceutical preparations containing these compounds.

Description

[0001] Antileukemic compounds based on nitrogen-containing heterocycles, use thereof as drugs, and pharmaceutical preparations

[0002] Field of Art

[0003] The invention relates to new derivatives of nitrogen-containing heterocyclic compounds, use thereof as drugs, and to pharmaceutical preparations containing these compounds, in particular for therapy of acute myeloid leukemia. Methods for preparing these compounds are also described.

[0004] Background Art

[0005] Acute myeloid leukemia (AML) is one of the most unfavorable diagnoses a patient can receive in an oncology clinic. As a malignant clonal disorder of hematopoietic stem cells (HSC), AML is also the most common blood cancer. It is characterized by abnormal proliferation or accumulation of immature progenitor cells with disruption of normal hematopoiesis in the peripheral blood, bone marrow and other tissues. The consequences are usually manifested by severe infections, anemia and hemorrhage. The estimated five-year overall survival rate for patients diagnosed with AML is approximately 30%.

[0006] AML disease biology, phenotype, response to treatment and subsequent risk of relapse can be characterized by multiple recurrent mutations. Interestingly, AML genomes typically contain far fewer mutations than other cancers, with an average of 5 mutations in the AML genome. At least one driver mutation has been identified in 96% of patients and two or more driver mutations in 86% of patients. Among the genes with the most frequent mutations is Fms-like tyrosine kinase 3 (FLT3), which plays a critical role in HSC survival, proliferation and differentiation [1], Defining the specific genetic abnormality is a fundamental step in classifying patients diagnosed with AML [2], Mutations in the FLT3 gene occur in approximately 30% of AML cases and include internal tandem duplications (FLT3-ITD) and mutations in the activation loop of the tyrosine kinase domain (FLT3-TKD). While FLT3-ITD accounts for 20-25% of all AML cases and is associated with a high leukemic burden and poor prognosis in patients, FLT3-TKD accounts for approximately 5-10% of all cases with a controversial prognostic status [1, 3, 4], Both mutations promote ligand-independent constitutive activation of FLT3, which initiates downstream pathways, stimulates proliferation and anti-apoptotic signals, and further leads to the development of the disease [5, 6],

[0007] There are several ways to limit FLT3 signaling, including either reversible or irreversible inhibition. Reversible inhibitors can be further divided into three categories. While type I inhibitors bind to the ATP -binding site when the enzyme is activated, type II inhibitors tend to interact with a hydrophobic pocket adjacent to the ATP-binding site. This enzyme site is accessible when the enzyme is in its inactive form. In addition, due to their binding mode to a less conserved region than the ubiquitous ATP-binding site, these type II inhibitors tend to be more selective. The least abundant type III inhibitors bind with an allosteric binding mode outside the ATP-binding site. For example, irreversible inhibitors are able to form a long-lasting covalent bond with a cysteine residue (C695) of the FLT3 protein. The most frequently cited FLT3 inhibitors include midostaurin, lestaurtinib, crenolanib and gilteritinib, which belong to type I, while quizartinib and sorafenib are type II inhibitors. Currently, EMA and FDA have registered and used in clinical practice mainly midostaurin, and in relapsed resistant patients gilteritinib. Quizartinib is currently being introduced into clinical practice. In post-transplantation therapeutic intervention, sorafenib also has its place in patients with FLT3 mutations, with relatively high efficacy, but at the same time a high incidence of adverse effects requiring discontinuation of therapy. From this perspective, emphasis is still placed on the search for new structures inhibiting FLT3 kinase, which could expand the therapeutic portfolio with a substance with higher selectivity and efficacy of action while ensuring the safety of therapy.

[0008] References

[0009] [1] DA VER, Naval, Richard F. SCHLENK, Nigel H. RUSSELL a Mark J. LEVIS. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia [online]. 2019, 33(2), 299-312. ISSN 1476-5551. Available from: doi:10.1038 / s41375-018-0357-9

[0010] [2] SHIMONY, Shai, Maximilian STAHL a Richard M. STONE. Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. American Journal of Hematology [online], 2023, 98(3), 502-526. ISSN 1096-8652. Available from: doi: 10.1002 / ajh.26822

[0011] [3] SHORT, Nicholas J., Michael E. RYTTING a Jorge E. CORTES. Acute myeloid leukaemia.

[0012] Lancet (London, England) [online]. 2018, 392(10147), 593-606. ISSN 1474-547X. Available from: doi: 10.1016 / S0140-6736(18)31041-9

[0013] [4] LI, Shuping, Na LI, Yun CHEN, Zhihua ZHENG a Yao GUO. FLT3-TKD in the prognosis of patients with acute myeloid leukemia: A meta-analysis. Frontiers in Oncology [online]. 2023, 13, 1086846. ISSN 2234-943X. Available from: doi: 10.3389 / fonc.2023.1086846

[0014] [5] KAZI, Julhash U. a Lars RONNSTRAND. FMS-like Tyrosine Kinase 3 / FLT3: From Basic Science to Clinical Implications. Physiological Reviews [online]. 2019, 99(3), 1433-1466. ISSN 0031-9333, 1522-1210. Available from: doi: 10.1152 / physrev.00029.2018

[0015] [6] LARRO SA-GARCIA, Maria a Maria R. BAER. FLT3 Inhibitors in Acute Myeloid Leukemia:

[0016] Current Status and Future Directions. Molecular Cancer Therapeutics [online]. 2017, 16(6), 991— 1001. ISSN 1538-8514. Available from: doi: 10.1158 / 1535-7163. MCT-16-0876 Summary of the Invention

[0017] Object of the present invention are nitrogen-containing heterocyclic compound derivatives of general formula I

[0018] NHR2

[0019]

[0020] wherein

[0021] - m = 0, i.e. L1is not present, and R2is H; or

[0022] m = 1 and L1together with R2form a moiety -C(=CH-)-, wherein the group =CH- is bound by a single bond to the nitrogen atom (NH); or

[0023] m = 1 and L1together with R2form a moiety -CH=C<, wherein the quarternary carbon is bound to the nitrogen atom and to the bridging methylene;

[0024] - the moiety

[0025]

[0026] is an alifatic ring having 4 to 7 members, of which one or two members are nitrogen atoms, wherein one nitrogen atom is bound to the bridging methylene;

[0027] - n = 0 or 1 or 2;

[0028] - R1is selected from the group containing C1-C4 alkyl; 4- to 6-membered alifatic ring containing 1 to 2 heteroatoms selected from the group O, N, optionally further substituted by C1-C3 alkyl, (C1-C2 alkyl)-SO2-(Cl-C3 alkylene)-, (C1-C2 alkyl)-SO2-NH-(Cl-C3 alkylene)-; -NR4R5, wherein R4is selected from H, C1-C3 alkyl, R5is selected from C1-C3 alkyl, (C1-C2 alkyl)-SO2-(Cl-C3 alkylene)-, (C1-C2 alkyl)-SO2-NH-(Cl-C3 alkylene)-, phenyl-(Cl-C3 alkylene)-; or

[0029] two R1substituents bound to the same carbon atom or to mutually adjacent (neighboring) carbon atoms form a 4- to 6-membered alifatic ring containing 1 to 2 heteroatoms selected from the group O, N;

[0030] and pharmaceutically acceptable salts thereof with alkali metals or amines, or acid addition salts thereof.

[0031] (C1-C2 alkyl)-SO2-(Cl-C3 alkylene)- is preferably methyl-SO2-ethylene- or ethyl-SO2-ethylene. (C1-C2 alkyl)-SO2-NH-(Cl-C3 alkylene)- is preferably methyl-SO2-NH-ethylene- or ethyl-SO2-NH-ethylene-.

[0032] Phenyl-(C1-C3 alkylene)- is preferably benzyl- or phenylethylene-. The pyrrolopyridine group is preferably atached to the pyridine group in the meta or para position to the nitrogen.

[0033]

[0034] Acid addition salts include, in particular, hydrochlorides, hydrobromides, hydrofluorides, hydroiodides, nitrates, nitrites, sulfates, bisulfates, borates, citrates, fumarates, lactates, malates, maleates, mesylates, tosylates, oxalates, tartrates, acetates, formates, salicylates, aspartates, adipates, benzoates, palmitates, stearates, besylates, phosphates, carbonates, bicarbonates.

[0035] The structure of the compounds of the invention consists of three key fragments that are necessary for optimal orientation of the ligand towards the target kinase. 7-Azaindole provides the NH group of the conjugated pyrrole, which primarily serves as a hydrogen bond donor, while the conjugated pyridine moiety contains a weak basic center that also functions as a hydrogen bond acceptor. This 7-azaindole moiety is atached at the 5-position to the central heterocycle that forms the 2-aminopyridine or the pyridine conjugated to the pyrrole forming the second 7-azaindole unit. On this central pyridine, the terminal 7-azaindole moiety can be atached at either the 4- or 5-position. This central heterocycle similarly contains a weak basic center and a hydrogen bond donor. The saturated heterocycle, attached via the methylene bridge, provides a strong basic center that improves the solubility of the compound and allows interaction with negatively charged amino acids, such as glutamic and aspartic acids, in the active pocket of the kinase. A total of 27 new derivatives were synthesized, which were divided into two series based on the structure of the central heterocyclic ring. These derivatives represent particularly preferred embodiments of the invention. Compounds containing the central 7-azaindole:

[0036] compound

[0037] structural formula compound name

[0038] No.

[0039] 1 -ethyl-4- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - 1 H-pyrrolo [2,3 - 1

[0040] p b]pyridin-3 -yl)methyl]piperazine

[0041] 0 1 1 -(oxetan-3 -yl)-4- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - 1H- 2 JLX /

[0042] 0 pyrrolo [2,3 -b]pyridin-3 -yl)methyl]piperazine

[0043] 1 -methyl-4- { 1 - [(5 - { IH-pyrrolo [2,3 -b]pyridin-5-yl } - 1H- 3

[0044] pyrrolo 12.3 -b | pyridin-3 -yl [methyl | pi pcridin-4-yl } piperazine M NJ_, HN

[0045] 1 -ethyl-4- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - 1 H-pyrrolo [2,3 - 4...... 'J*-..

[0046] ~ir Q_ b]pyridin-2-yl)methyl]piperazine

[0047] r%-NH0

[0048] 1 -methyl-4- { 1 - [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl } - 1H- 5

[0049] pyrrolo [2,3 -b]pyridin-2-yl)methyl]piperidin-4-yl }piperazine ( c Q

[0050] £ TZA 1 - [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - IH-pyrrolo [2,3 - 6

[0051] HN AJ O b]pyridin-2-yl)methyl]piperidine

[0052] 1 -ethyl-4- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - 1 H-pyrrolo [2,3 - 7

[0053] b]pyridin-2-yl)methyl] - 1,4-diazepane

[0054] 2-methyl-6- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - 1H- 8N^xxX

[0055] HN / X / U C7 pyrrolo[2,3-b]pyridin-2-yl)methyl]-2,6-diazaspiro[3.3]heptane

[0056] 1'- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl } - IH-pyrrolo [2,3 - 9

[0057] b]pyridin-2-yl)methyl] - 1,4'-bipiperidine

[0058] JVJV-dimethyl- 1 - [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - 1H- 10

[0059] pyrrolo[2,3-b]pyridin-2-yl)methyl]piperidine-4-amine

[0060]

[0061] A'-mcthy 1 - 1 - [(5 - { 177-pyrrolo [2,3 -b]pyridin-5 -yl } - 177- 11

[0062] pyrrolo[2,3-b]pyridin-2-yl)methyl]piperidine-4-amine z z JV-(2-methansulfonylethyl)-JV-methyl- 1 - [(5 - { IH-pyrrolo [2,3 - Oz=\

[0063] 12 Oz=\ b]pyridin-5 -yl } - 177-pyrrolo [2,3 -b]pyridin-2-zH

[0064] OZIyl)methyl]piperidine-4-amine

[0065] ZZNS N- { 2- [methyl( { 1 - [(5 - { 177-pyrrolo [2,3 -b] pyridin-5 -yl } - 177- 13 O0M= pyrrolo[2,3-b]pyridin-2-yl)methyl]piperidin-4- A yl } )amino] ethyl } methanesulfonamide

[0066] 2-( {octahydropyrrolo [3,4-c]pyrrol-2-yl }methyl)-5 - { 177- 14

[0067] pyrrolo [2,3 -b]pyridin-5 -yl} - 177-py rrolo [2,3 -b]pyridine _N N

[0068] 1 -(oxetan-3 -yl)-4- [(4- { 177-pyrrolo [2,3 -b]pyridin-5 -yl} - 177- 15 X O

[0069] pyrrolo[2,3-b]pyridin-2-yl)methyl]piperazine

[0070] 9> b

[0071] 1 -ethyl-4- [(4- { 177-pyrrolo [2,3 -b]pyridin-5 -yl} - 177-pyrrolo [2,3 - 16

[0072] b]pyridin-2-yl)methyl]piperazine

[0073]

[0074] r^J

[0075] % 12 - *

[0076] Compounds containing central 2-aminopyridine:

[0077] compound

[0078] structural formula compound name

[0079] No.

[0080] 3 - [(4-ethyl- 1,4-diazepan- 1 -yl)methyl] -5 - { 177-pyrrolo [2,3 - 17

[0081] b]pyridin-5 -yl }pyridine-2-amine

[0082] 3 - { [4-(4-methylpiperazin- 1 -yl)piperidin- 1 -yl] methyl } -5 - { 177- 18 A n

[0083] pyrrolo[2,3-b]pyridin-5-yl}pyridine-2-amine

[0084] 3 -( { [ 1,4'-bipiperidin] - 1 '-yl }methyl)-5 - { 177-pyrrolo [2,3 - 19

[0085] b]pyridin-5 -yl }pyridine-2-amine

[0086] 3 - { [4-(dimethylamino)piperidin- 1 -yl] methyl} - 5- { 177- 20

[0087] pyrrolo[2,3-b]pyridin-5-yl}pyridine-2-amine

[0088]

[0089] 3 - { [4-(methylamino)piperidin- 1 -yl]methyl } -5 - { IH-pyrrolo [2,3 - 21

[0090] b]pyridin-5 -yl }pyridine-2-amine

[0091] 3 -( {4- [(2-methanesulfonylethyl)(methyl)amino]piperidin- 1 - 22

[0092] y yl }methyl)-5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl }pyridine-2-amine TV- [2-({ l-[(2-amino-5-{ 1 / / -py rrolo [ 2.3 -b | py ridin-5 -y 1 }py ridin- if Y YY

[0093] 23 3 -yl)methyl] piperidin-4- yl } (methyl)amino)ethyl]methanesulfonamide

[0094] 3-({4-[methyl(2-phenylethyl)amino]piperidin-l-yl}methyl)-5- 24

[0095] { lH-pyrrolo[2,3-b]pyridin-5-yl}pyridine-2-amine

[0096] NNH2

[0097] 3 -( {octahydropyrrolo [3,4-c]pyrrol-2-yl }methyl)-5 - { 1H- 25 ii J

[0098] NH y pyrrolo[2,3-b]pyridin-5-yl}pyridine-2-amine

[0099] 3-{[5-(2-methansulfonylethyl)-octahydropyrrolo[3,4-c]pyrrol-2- 26

[0100] yl]methyl } -5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl }pyridine-2-amine JV-(2-{5-[(2-amino-5-{lH-pyrrolo[2,3-b]pyridin-5-yl}pyridin-3- r *r rvj

[0101] 27 yl)methyl] -octahydropyrrolo [3, 4-c]pyrrol-2- yl } ethyl)methane sulfonamide

[0102]

[0103] The invention further provides nitrogen-containing heterocyclic compound derivatives of general formula I for use as medicaments, in particular for the treatment of cancer.

[0104] Preferably, the compounds of general formula are particularly suitable for the treatment of leukemia, in particular acute myeloid leukemia, in patients with a FLT3 gene mutation.

[0105] The drugs of general formula I can be administered in particular for the purpose of stopping the progression of tumor growth, or for the purpose of reducing the number of tumor cells.

[0106] The term "treatment" refers to the administration of a drug that can serve to reduce the symptomatic manifestations of the disease. This effect may relate to slowing the progression of the disease, or improving the health of the patient in any direction. This includes reducing or stopping the proliferation of tumor cells, preventing or suppressing invasion and metastasis, promoting genomic instability and mutagenicity, preventing resistance to cell death, avoiding replicative immortality or promoting tumor suppressors. The invention further provides a pharmaceutical composition comprising at least one nitrogencontaining heterocyclic compound of the general formula I according to the invention and at least one pharmaceutically acceptable excipient. Pharmaceutically acceptable excipients may include carriers, fdlers, binders, solvents, and others, as known to the person skilled in the art of pharmaceutical formulations.

[0107] Example methods of administration and dosage of the novel compounds

[0108] The compounds of the general formula I can be administered to patients in various forms of pharmaceutical compositions, adapted to the specific needs and preferences of the patients, as well as the nature of the treatment. Compounds or their respective formulations can be administered orally, parenterally, intramuscularly, subcutaneously or intravenously. Each of these methods has its specific advantages and can be chosen depending on the specific clinical situation.

[0109] Oral administration - Pharmaceutical preparations for oral administration include tablets, capsules, granules, powders, gels and syrups. These forms are designed to ensure maximum bioavailability of the active ingredient. Tablets may be coated, with controlled release or soluble to optimize absorption and minimize possible gastrointestinal side effects. Capsules may contain the active ingredient in a solid or liquid form, providing rapid or sustained release.

[0110] Example of tablet formulation: The active ingredient (a compound of general formula I) is mixed with suitable excipients such as fdlers, binders, lubricants, and then compressed into tablet form. Tablets may be enteric-coated to prevent degradation of the active ingredient in the acidic environment of the stomach.

[0111] Parenteral administration - Pharmaceutical preparations for parenteral administration include injection and infusion solutions, which may be prepared as solutions or suspensions in sterile aqueous or oily media. These forms of administration provide a rapid onset of action, which is particularly important in acute cancer conditions or in patients unable to take oral administration forms.

[0112] Example of an injection formulation: The active ingredient is dissolved in a sterile aqueous medium, for example in isotonic sodium chloride solution or Ringer's solution. The solution may contain excipients such as preservatives (e.g. benzyl alcohol, methylparaben), solubilizers (e.g. polyethylene glycol) and stabilizers (e.g. human serum albumin) to ensure the stability and sterility of the preparation.

[0113] Dosage - The dosage of the compounds of general formula I will depend on several factors, including the type and stage of the cancer, the general health state of the patient, their response to treatment and any side effects. The usual dose for oral administration may be in the range of 10-500 mg per day, administered once or twice a day. For parenteral administration, the dose may be adjusted based on the weight of the patient, for example 0.1-10 mg / kg body weight. Methods for the preparation of heterocyclic compounds of general formula I

[0114] The chemical synthesis procedure consists of two main steps, namely reductive amination and Suzuki- Miyaura coupling reactions. While some heteroaromatic carbaldehydes may be commercially available (for example, compounds 30 and 31 in the following scheme), some (for example, aldehyde 29) must be prepared by a simple two-step procedure. Reduction of the ester group 28 to the corresponding primary alcohol is followed by oxidation to the aldehyde 29 using manganese dioxide.

[0115] The heteroaromatic aldehydes can then undergo reductive amination using either sodium cyanoborohydride or sodium triacetoxyborohydride to give the desired tertiary amines.

[0116] Various boronic acids or their pinacol esters can be used for the subsequent Suzuki-Miyaura reaction. Various palladium catalysts can be advantageously used for this reaction, such as [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane and / or bis(triphenylphosphine)palladium(II) dichloride. The reaction can be advantageously carried out in a microwave reactor, which significantly reduces the reaction time to only 30 minutes. Compounds 14, 21 and 25 were obtained as Boc-protected forms, which can be advantageously used in subsequent reactions. First, the Boc deprotection provides secondary amines 14, 21 and 25, which can be used either as final products or undergo subsequent V- alkylation. This V-alkylation can be advantageously carried out under standard conditions using an excess of the base W-diisopropylcthylaminc (DIPEA) to obtain products, for example 12, 13, 22-24, 26 and 27.

[0117] B

[0118] 5-Br, 3-methylene linked saturated heterocyclic amine 28 5-Br, 2-methylester 29 5-Br, 2-carbaldehyde 5-Br, 2-methylene linked saturated heterocyclic amine 30 5-Br, 3-carbaldehyde 4-Br, 2-methylene linked saturated heterocyclic amine 45-46 31 4-Br, 2-carbaldehyde

[0119] c); or d) with selected saturated heterocyclic amine

[0120] e); f) and g) for 12, and 13

[0121] 5-Br, 3-methylene linked saturated heterocyclic amine 5-Br, 3-methylene linked saturated heterocyclic amine 33-35 1-3

[0122] 5-Br, 2-methylene linked saturated heterocyclic amine 5-Br, 2-methylene linked saturated heterocyclic amine 36-44 4-14

[0123] 4-Br, 2-methylene linked saturated heterocyclic amine 4-Br, 2-methylene linked saturated heterocyclic amine 45-46 15-16

[0124]

[0125] 47-52 Scheme 1 Preparation of compounds of general formula I derived from 7-azaindole substituted at position 5 by another 7-azaindole, and at position 2 or 3 via the methylene bridge by a suitable saturated heterocycle containing a basic center; and of compounds of general formula I derived from 2-aminopyridine substituted at position 5 by 7-azaindole, and at position 3 via the methylene bridge by a suitable saturated heterocycle containing a basic center. Reaction conditions: a) LiAlH4, anhydrous THF, 0 °C - room temperature (RT), Ar, 16 hours; b) MnO2, anhydrous DCM / THF (1:1), RT, Ar, 24 hours; c) selected saturated heterocycle with secondary amine, AcOH, NaCNBH-,. anhydrous MeOH / THF (1:1), RT Ar, 16 hours; d) selected saturated heterocycle with secondary amine, NaBH(0Ac)3, anhydrous DCM or DCM / THF, RT Ar, 16 hours; e) d) Pd(dppf)C12. DCM or Pd(PPh3)2Cl2, Na2CO3, dioxane, H2O, MW irradiation (100 W, dynamic curve), 80 °C, 30 minutes; f) 1.

[0126] 10% HC1, MeOH 70 °C, 2 hours, 2. NaOH, H2O, RT, 10 minutes; g) appropriate alkyl bromide, DIPEA, anhydrous DCM (in some cases anhydrous MeOH added as co-solvent), RT, 24-168 hours.

[0127] Examples of carrying out the invention

[0128] The invention is described in the following examples, which should not be construed as limiting the scope of the invention.

[0129] Example 1 - Chemical synthesis of compounds of general formula I derived from 7-azaindole substituted in position 5 by another 7-azaindole, and in position 2 or 3 via the methylene bridge by a saturated heterocycle containing a basic center, and of compounds of general formula I derived from 2-aminopyridine substituted in position 5 by 7-azaindole, and in position 3 via the methylene bridge by a saturated heterocycle containing a basic center.

[0130] General chemical methods

[0131] Thin layer chromatography was performed on aluminum plates coated with silica gel 60 F254 (Merck, Prague, Czech Republic). Column chromatography was performed at atmospheric pressure on silica gel 100 (particle size 0.063 - 0.200 mm, 70 - 230 mesh ASTM, Fluka, Prague, Czech Republic). The chemicals necessary for the synthesis were purchased from Sigma Aldrich Co. LLC (Prague, Czech Republic) and were used without further purification. A CEM Explorer SP 12 S Class instrument was used for reactions carried out under microwave activation conditions. A Dionex Ultimate 3000 LC-MS analytical system coupled to an Orbitrap Q Exactive Plus spectrometer (Thermo Fisher Scientific, Bremen, Germany) was used for mass spectrometry measurements. The LC-MS system consists of a HHG-3400RS binary pump connected to a vacuum degasser, a TCC-3000 heated column compartment, a WTS-3000 autosampler and a VWD-3000 ultraviolet detector. The quadrupole mass spectrometer was equipped with an electron spray ionization source and data were recorded in positive mode with the following parameters: spray voltage was 3.2 kV, capillary temperature was 350 °C, gas temperature was 300 °C. ’H-NMR and13C-NMR spectra were measured using a Bruker Avance Neo 500 spectrometer (500 and 126 MHz) in CDCl3-d1 (CHCl3-d1; 7.26 (D), 77.16 (C) ppm), in hexadeuteriodimethylsulfoxide (DMSO-d6: 2.50 (D), 39.7 (C) ppm) or CD3OD-d4 (CH3OH-d4: 3.35, 4.78 (D), 49.3 (C) ppm). The characters of the individual signals were as follows: s (singlet), d (doublet), (dd) (doublet of doublet), t (triplet), p (pentet) or m (multiplet). Chemical shifts are given in ppm (parts per million, 5) relative to the internal residual solvent standard. The assignment of chemical shifts is based on standard NMR experiments (’LL13C).

[0132] General procedure A: preparation of carbaldehydes from the corresponding esters or alcohols A: A 2M solution of lithium aluminum hydride (LiAlH4) in tetrahydrofuran (THF) (1.1 equiv) was added dropwise to a stirred solution of ester 28 (1.0 equiv) under Ar at 0 °C. The reaction mixture was stirred at room temperature overnight. After complete consumption of the starting material, the reaction mixture was carefully treated with 1 mL of ethyl acetate, followed by 1 mL of 10% NaOH. The resulting mixture was diluted with water (70 mL) and extracted three times with 50 mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to give the corresponding primary alcohol, which was used directly in the next reaction.

[0133] B: Manganese dioxide (MnO2; 10.0 eq) was added to a stirred solution of primary alcohol (1.0 eq) in a 1: 1 mixture of anhydrous dichloromethane (DCM) and anhydrous THF under Ar. The mixture was stirred at room temperature for 4 h. After complete consumption of the starting material, the reaction mixture was diluted with additional DCM and THF and filtered through a CELITE pad. The filtrate was concentrated to give the corresponding Aldehydes, which were directly used in the next reaction, reductive amination.

[0134]

[0135] 5-Bromo-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (29): Prepared according to general procedure A. A: methyl ester compound 28 (1.15 g; 4.5 mmol); 2M LiAlH4 (4.5 mL; 9.0 mmol) in 40 mL THF; B: corresponding alcohol (1.02 g; 4.5 mmol); MnO2 (3.91 g; 45.0 mmol) in 60 mL DCM. The resulting heterocyclic carbaldehyde 29 was directly used in the next reaction, reductive amination. Yield 58% aftertwo steps. ‘HNMR (500 MHz, DMSO) 5 12.78 (s, 1H), 9.91 (s, 1H), 8.52 (d, J = 2.3 Hz, 1H), 8.49 (d, J = 2.3 Hz, 1H), 7.37 (d, J = 1.6 Hz, 1H).13C NMR (126 MHz, DMSO) 5 184.28, 148.74, 148.29, 137.70, 134.11, 121.22, 112.37, 112.03.

[0136] General Procedure B: Reductive Amination with NaCNBH3

[0137] The appropriate saturated heterocycle with a secondary amine (1.0 eq) and acetic acid (AcOH; 3.0 eq) were added to a stirred solution of heterocyclic carbaldehyde 29-32 (1.0 eq) in a 1:1 mixture of anhydrous THF and anhydrous methanol (MeOH) under Ar. The mixture was stirred at room temperature (RT) for 1 h, then sodium cyanoborohydride (NaCNBH3; 3.0 eq) was added and the reaction mixture was allowed to stir overnight (16 h) until the reaction was complete, as monitored by TLC. THF and MeOH were removed by rotary evaporation. The crude residue was diluted with saturated sodium bicarbonate (NaHCO3; 30 mL) and extracted with ethyl acetate (EA; 3 × 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and fdtered. The fdtrate was concentrated under reduced pressure and purified by column chromatography to obtain the reductive amination products.

[0138] General Procedure C: Reductive amination with NaBH(OAc)3

[0139] The appropriate saturated heterocycle with a secondary amine (1.2 equiv) was added to a stirred solution of the heterocyclic carbaldehyde 29-32 (1.0 equiv) in anhydrous DCM or a mixture of anhydrous DCM and anhydrous THF under Ar. The mixture was stirred at room temperature (RT) for 1 h, then sodium triacetoxyborohydride (NaBH(OAc)3; 3.0 equiv) was added and the reaction mixture was allowed to stir overnight (16 h) until the reaction was complete, as monitored by TLC. NaBH(OAc)3 was preferred as the reducing agent in the later stages of the study to avoid the formation of a primary alcohol by-product. The solvents were removed by rotary evaporation. The crude residue was diluted with saturated sodium bicarbonate (NaHCO3; 30 mL) and extracted with ethyl acetate (EA; 3 × 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the reductive amination products.

[0140] N'

[0141]

[0142] 1-({5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl}methyl)-4-ethylpiperazine (33): Prepared according to general procedure B. Aldehyde 30 (151 mg; 0.67 mmol); 1 -ethylpiperazine (85 pL; 0.67 mmol); AcOH (115 pL; 2.0 mmol) and NaCNBH3 (126 mg; 2.0 mmol) in 5 mL anhydrous THF a 5 mL anhydrous MeOH. The extraction residue was purified using column chromatography with the mobile phase DCM / MeOH / NH4OH (25 % aqueous solution) (20:1:0,1), to obtain a pure product 33 as light orange solid. Yield 75 %. ‘HNMR (500 MHz, DMSO-d₆) 5 11,82 - 11,62 (m, 1H), 8,23 (d, J = 2,3 Hz, 1H), 8,20 (d, J = 2,3 Hz, 1H), 7,41 (d, J = 2,4 Hz, 1H), 3,57 (s, 2H), 2,48 - 2,30 (m, 8H), 2,27 (q, J = 7,2 Hz, 2H), 0,95 (t, J = 7,2 Hz, 3H).13C NMR (126 MHz, DMSO) 5 147,23, 142,55, 129,41, 126,98, 121,75, 110,46, 110,11, 53,10, 52,65, 51,74, 12,22. HRMS (ESI+): [M+H]+: calculated for Ci4H20BrN4+(m / z): 323,08659; found: 323,0694. LC-MS purity 99 %.

[0143]

[0144] l-({5-bromo-l / / -pyrrolo[2,3- / >|pyridin-3-yl}methyl)-4-(oxetan-3-yl)piperazine (34): Prepared according to general procedure B. Aldehyde 30 (830 mg; 3,7 mmol); l-oxetan-3-yl-piperazine (480 pL; 3,7 mmol); AcOH (635 pL; 11,1 mmol) and NaCNBH3 (695 mg; 11,1 mmol) in 20 mL anhydrous THF and 20 mL anhydrous MeOH. The extraction residue was purified using column chromatography with the mobile phase CHCl3 / MeOH (9:1), to obtain a pure product 34 as light orange solid. Yield 43 %. 'H NMR (500 MHz, CDCh) 5 10,29 (s, 1H), 8,33 (d, J = 2,1 Hz, 1H), 8,18 (d, J = 2,1 Hz, 1H), 7,29 (s, 1H), 4,65 (t, J = 6,6 Hz, 2H), 4,60 (t, J = 6,2 Hz, 2H), 3,70 (s, 2H), 3,51 (p, J = 6,5 Hz, 1H), 2,48 (d, J = 93,1 Hz, 8H).13C NMR (126 MHz, CDCl3) δ 147,27, 143,46, 130,37, 125,79, 122,08, 111,56, 75,51, 59,14, 53,56, 52,43, 49,47.

[0145]

[0146] 1-[1-({5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl}methyl)piperidin-4-yl]-4-methylpiperazine (35):

[0147] Prepared according to general procedure B. Aldehyde 30 (1,5 g; 6,67 mmol); 1 -methyl -4-piperidin-4-yl-piperazine (1,26 mg; 6,67 mmol); AcOH (1,2 mL; 20,0 mmol) and NaCNBH3 (1,26 mg; 20,0 mmol) in 20 mL anhydrous THF and 20 mL anhydrous MeOH. The extraction residue was purified by column chromatography, using the mobile phase DCM / MeOH / NH4OH (25 % aqueous solution) (5:1:0,1), to obtain the pure product 35 as light orange solid. Yield 50 %. 'H NMR (500 MHz, DMSO) 5 11,76 -11,69 (m, 1H), 8,24 (d, J = 2,2 Hz, 1H), 8,20 (d, J = 2,3 Hz, 1H), 7,42 (d, J = 2,5 Hz, 1H), 3,59 (s, 2H), 2,92 - 2,84 (m, 2H), 2,48 - 2,21 (m, 8H), 2,13 (s, 3H), 2,11 - 2,05 (m, 1H), 1,95 - 1,85 (m, 2H), 1,72 -1,64 (m, 2H), 1,41 - 1,28 (m, 2H).13C NMR (126 MHz, DMSO) 5 147,50, 142,88, 129,70, 127,45, 122,11, 110,84, 61,55, 55,51, 53,19, 52,68, 48,95, 46,10, 28,40.

[0148]

[0149] 1-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)-4-ethylpiperazine (36): Prepared according to general procedure B. Aldehyde 29 (510 mg; 2,27 mmol); 1 -ethylpiperazine (288 pL; 2,27 mmol); AcOH (389 pL; 6,8 mmol) and NaCNBH3 (427 mg; 6,8 mmol) in anhydrous THF (10 mL) and anhydrous MeOH (10 mL). Extraction residues were purified by column chromatography using the mobile phase CHCl3 / MeOH (9:1) to obtain the pure product 36 as light orange solid. Yield 73 %. The compound was not characterized by NMR. HRMS (ESI+): [M+H]+: calculated for C14H20BrN4+(m / z): 323,08659; found: 323,0649. LC-MS purity 99 %.

[0150]

[0151] 1-[1-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)piperidin-4-yl]-4-methylpiperazine (37):

[0152] Prepared according to general procedure B. Aldehyde 29 (833 mg; 3,7 mmol); 1 -methyl -4-piperidin-4-yl-piperazine (678 mg; 3,7 mmol); AcOH (635 pL; 11,1 mmol) and NaCNBH3 (700 mg; 11,1 mmol) in anhydrous THF 20 mL and anhydrous MeOH 20 mL. Extraction residues were purified by column chromatography using the mobile phase DCM / MeOH / NH4OH (25 % aqueous solution) (5:1:0,1) to obtain the pure product 37 as light orange solid. Yield 70 %. 'H NMR (500 MHz, DMSO+TFA) 58,35 (d, J = 2,3 Hz, 1H), 8,30 (d, J = 2,2 Hz, 1H), 6,68 (s, 1H), 4,49 (s, 2H), 3,63 - 2,93 (m, 13H), 2,81 (s, 3H), 2,20 - 2,08 (m, 2H), 1,85 - 1,67 (m, 2H).13C NMR (126 MHz, DMSO+TFA) 5 147,48, 144,48, 131,32, 129,82, 121,97, 111,76, 104,54, 58,45, 52,06, 51,63, 50,72, 46,11, 42,46, 25,05.

[0153]

[0154] 1-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)-4-ethyl-1,4-diazepane (38): Prepared according to general procedure B. Aldehyde 29 (220 mg; 0,98 mmol); 1 -ethylhomopiperazine (140 pL; 0,98 mmol); AcOH (166 pL; 2,9 mmol) and NaCNBH3 (182 mg; 2,9 mmol) in anhydrous THF 10 mL and anhydrous MeOH 10 mL. Extraction residues were purified by column chromatography using the mobile phase CHCl3 / MeOH / NH4OH (25 % aqueous solution) (5:1:0,1) to obtain the pure product 38 as light orange solid. Yield 74 %. ‘HNMR (500 MHz, DMSO) 5 11,79 (s, 1H), 8,19 (d, J = 2,2 Hz, 1H), 8,08 (d, J = 2,2 Hz, 1H), 6,30 (s, 1H), 3,76 (s, 2H), 2,72 - 2,64 (m, 8H), 1,83 - 1,75 (m, 2H), 1,11 (t, J = 7,1 Hz, 3H).13C NMR (126 MHz, DMSO) 5 147,53, 144,54, 130,01, 129,56, 121,88, 111,38, 104,72, 55,96, 53,49, 51,70, 45,77, 43,28, 12,26.

[0155]

[0156] 2-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)-6-methyl-2,6-diazaspiro[3.3]heptane (39):

[0157] Prepared according to general procedure B. Aldehyde 29 (175 mg; 0,78 mmol); 2-methyl-2,6-diazaspiro[3.3]heptane dihydrochloride (144 mg; 0,78 mmol); AcOH (133 pL; 2,33 mmol) and NaCNBH3 (147 mg; 2,33 mmol) in anhydrous THF 10 mL and anhydrous MeOH 10 mL. The exatraction residue was purified by column chromatography using the mobile phase DCM / MeOH / NH4OH (25 % aqueous solution) (5:1:0,1) to obtain the pure product 39 as light orange solid. Yield 56 %. ’H NMR (500 MHz, DMSO) 5 11,78 (s, 1H), 8,17 (d, J = 2,3 Hz, 1H), 8,06 (d, J = 2,3 Hz, 1H), 6,28 - 6,18 (m, 1H), 3,61 (s, 2H), 3,27 (s, 4H), 3,23 (s, 4H), 2,21 (s, 3H).13C NMR (126 MHz, DMSO) 5 147,04, 141,66, 139,44, 129,19, 122,05, 110,52, 97,99, 65,39, 63,49, 55,29, 44,92, 33,98.

[0158]

[0159] 1-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)-N,N-dimethylpiperidine-4-amine (40):

[0160] Prepared according to general procedure B. Aldehyde 29 (255 mg; 1,13 mmol); 4-(dimethylamino)piperidine (145 mg; 1,13 mmol); AcOH (194 pL; 3,39 mmol) and NaCNBH3 (213 mg; 3,39 mmol) in anhydrous THF 10 mL and anhydrous MeOH 10 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (9:1) to obtain the pure product 40 as light orange solid. Yield 68 %. ’H NMR (500 MHz, DMSO-d6) 5 11,81 (s, 1H), 8,19 (d, J = 2,3 Hz, 1H), 8,09 (d, J = 2,3 Hz, 1H), 6,32 - 6,18 (m, 1H), 3,60 (s, 2H), 2,91 - 2,81 (m, 2H), 2,17 (s, 6H), 2,07 - 1,91 (m, 3H), 1,76 - 1,65 (m, 2H), 1,45 - 1,32 (m, 2H).13C NMR (126 MHz, DMSO) 5 147,49, 142,11, 140,06, 129,64, 122,55, 111,03, 99,21, 61,98, 55,41, 52,85, 41,94, 28,42.

[0161]

[0162] 1-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)piperidine (41): Prepared according to general procedure B. Aldehyde 29 (240 mg; 1,07 mmol); piperidin (106 pL; 1,07 mmol); AcOH (183 pL; 3,2 mmol) and NaCNBH3 (201 mg; 3,2 mmol) in anhydrous THF 10 mL and anhydrous MeOH 10 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (20:1) to obtain the pure product 41 as light orange solid. Yield 47 %.1H NMR (500 MHz, DMSO-d6) 5 11,80 (s, 1H), 8,19 (d, J = 2,3 Hz, 1H), 8,08 (d, J = 2,3 Hz, 1H), 6,29 (s, 1H), 3,59 (s, 2H), 2,44 - 2,31 (m, 4H), 1,51 (p, J = 5,6 Hz, 4H), 1,42 - 1,33 (m, 2H).13C NMR (126 MHz, DMSO) 5 147,48, 142,10, 129,62, 122,55, 111,02, 99,30, 97,19, 56,09, 54,31, 25,92, 24,31.

[0163]

[0164] Bob'

[0165] tert-butyl N-[1-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)piperidin-4-yl]-N-methylcarbamate (42): Prepared according to general procedure C. Aldehyde 29 (719 mg; 3,19 mmol); tert-butyl methyl(piperidin-4-yl)carbamate (822 mg; 3,83 mmol); and NaBH(OAc)3 (2,03 g; 9,57 mmol) in anhydrous DCM 10 mL and anhydrous THF 10 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (20:1) to obtain the pure product 42 as pale orange solid. Yield 71 %. ’H NMR (500 MHz, Chloroform-d) 5 11,03 (s, 1H), 8,38 (d, J = 2,1 Hz, 1H), 7,96 (d, J = 2,1 Hz, 1H), 6,26 (d, J = 1,9 Hz, 1H), 4,19 - 3,93 (m, 1H), 3,72 (s, 2H), 3,07 - 2,95 (m, 2H), 2,25 - 2,10 (m, 2H), 1,86 - 1,73 (m, 2H), 1,68 - 1,60 (m, 2H), 1,45 (s, 9H).13C NMR (126 MHz, CDCh) 5 155,67, 147,34, 142,67, 130,16, 122,71, 111,41, 99,08, 79,47, 55,87, 53,37, 28,50.

[0166]

[0167] 1'-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)-1,4'-bipiperidine (43): Prepared according to general procedure C. Aldehyde 29 (200 mg; 0,89 mmol); 4-piperidinopiperidine (180 mg; 1,07 mmol); and NaBH(OAc)3 (282 mg; 2,67 mmol) in anhydrous DCM 20 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH / NH4OH (25 % aqueous solution) (20:1:0,1) to obtain the pure product 43 as pale orange solid. Yield 52 %. 'H NMR (500 MHz, DMSO-d6) 5 11,80 (s, 1H), 8,20 (s, 1H), 8,09 (s, 1H), 6,29 (s, 1H), 3,60 (s, 2H), 2,95 - 2,84 (m, 2H), 2,45 - 2,38 (m, 4H), 2,19 - 2,11 (m, 1H), 2,02 - 1,90 (m, 2H), 1,72 - 1,61 (m, 2H), 1,53 - 1,33 (m, 8H).13CNMR (126 MHz, DMSO) 5 147,48, 142,12, 140,06, 129,64, 122,56, 111,03, 99,24, 62,35, 55,44, 53,34, 50,20, 27,94, 26,58, 25,08. N HN

[0168] Br

[0169]

[0170] 'Boc

[0171] tert-butyl 5-({5-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)-octahydropyrrolo[3,4-c]pyrrole-2-carboxylate 44: Prepared according to general procedure C. Aldehyde 29 (507 mg; 2,25 mmol); tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (574 mg; 2,7 mmol); and NaBH(OAc)3 (1,43 g; 6,75 mmol) in anhydrous DCM 20 mL and anhydrous THF 20 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (20:1) to obtain the pure product 44 as pale brown solid. Yield 72 %. ‘H NMR (500 MHz, CDC13) 5 10,27 (s, 1H), 8,29 (d, J = 2,2 Hz, 1H), 7,94 (d, J = 2,1 Hz, 1H), 6,30 - 6,17 (m, 1H), 3,82 (s, 2H), 3,51 (s, 2H), 3,29 (s, 2H), 2,89 - 2,73 (m, 4H), 2,50 (s, 2H), 1,46 (s, 9H).13C NMR (126 MHz, CDCl3) δ 154,59, 147,17, 142,93, 130,13, 122,48, 111,63, 98,48, 79,49, 60,19, 52,42, 51,45, 28,53, 28,49, 28,47.

[0172]

[0173] 1-({4-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)-4-ethylpiperazine (45): Prepared according to general procedure B. Aldehyde 31 (388 mg; 1,7 mmol); 1 -ethylpiperazine (216 pL; 1,7 mmol); AcOH (296 pL; 5,17 mmol); and NaCNBH3 (325 mg; 5,17 mmol) in anhydrous THF 10 mL and anhydrous MeOH 10 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (9:1) to obtain the pure product 45 as pale orange solid. Yield 78 %. ‘HNMR (500 MHz, DMSO) 5 11,98 (s, 1H), 8,01 (d, J = 5,2 Hz, 1H), 7,28 (d, J = 5,2 Hz, 1H), 6,26 (d, J = 1,8 Hz, 1H), 3,62 (s, 2H), 2,47 - 2,22 (m, 10H), 0,96 (t, J = 7,2 Hz, 3H).13C NMR (126 MHz, DMSO) 5 148,85, 142,88, 138,95, 123,04, 121,72, 118,72, 99,15, 55,29, 53,13, 52,76, 52,05, 12,50.

[0174]

[0175] 1-({4-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl}methyl)-4-(oxetan-3-yl)piperazine (46): Prepared according to general procedure C. Aldehyde 31 (292 mg; 1,3 mmol); l-oxetan-3-yl -piperazine (200 pL; 1,56 mmol); and NaBH(OAc)3(827 mg; 3,9 mmol) in anhydrous DCM 10 mL and anhydrous THF 10 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (20: 1) to obtain the pure product 46 as white solid. Yield 88 %. 'H NMR (500 MHz, CDCh) 5 10,95 (s, 1H), 8,04 (d, J = 5,2 Hz, 1H), 7,25 - 7,13 (m, 1H), 6,32 (d, J = 2,1 Hz, 1H), 4,58 (t, J = 6,6 Hz, 2H), 4,53 (t, J = 6,2 Hz, 2H), 3,67 (s, 2H), 3,42 (p, J = 6,5 Hz, 1H), 2,59 - 2,19 (m, 8H).13C NMR (126 MHz, CDCh) 5 148,57, 142,29, 137,71, 124,43, 122,68, 118,99, 99,71, 75,47, 59,18, 55,88, 52,82, 49,55.

[0176]

[0177] 5-bromo-3-[(4-ethyl-l,4-diazepan-l-yl)methyl]pyridine-2-amine (47): Prepared according to general procedure B. Aldehyde 32 (800 mg; 4,0 mmol); 1 -ethylhomopiperazine (565 pL; 4,0 mmol); AcOH (683 pL; 12,0 mmol); and NaCNBH3(750 mg; 12,0 mmol) in anhydrous THF 15 mL and anhydrous MeOH 10 mL. Extraction residue was purified by column chromatography using the mobile phase DCM / Me0H / NH40H (25 % aqueous solution) (20:1:0,1) to obtain the pure product 47 as pale orange solid. Yield 43 %. 'H NMR (500 MHz, DMSO) 57,93 (d, J = 2,4 Hz, 1H), 7,48 (d, J = 2,4 Hz, 1H), 6,32 (bs, 2H), 3,46 (s, 2H), 2,63 - 2,54 (m, 8H), 2,46 (q, J = 7,1 Hz, 2H), 1,79 - 1,63 (m, 2H), 0,97 (t, J = 7,1 Hz, 3H).13C NMR (126 MHz, DMSO) 5 158,15, 146,91, 139,10, 119,69, 105,77, 59,55, 55,06, 54,65, 53,77, 53,66, 51,98, 27,64, 13,06.

[0178]

[0179] 5-bromo-3-{[4-(4-methylpiperazin-l-yl)piperidin-l-yl]methyl}pyridine-2-amine (48): Prepared according to general procedure B. Aldehyde 32 (800 mg; 4,0 mmol); 1 -methyl -4-piperidin-4-yl-piperazine (730 mg; 4,0 mmol); AcOH (683 pL; 12,0 mmol); and NaCNBH3(750 mg; 12,0 mmol) in anhydrous THF 15 mL and anhydrous MeOH 15 mL. Extraction residue was purified by column chromatography using the mobile phase DCM / MeOH / NH4OH (25 % aqueous solution) (20:1:0,1) to obtain the pure product 48 as pale orange solid. Yield 37 %. 'H NMR (500 MHz, DMSO-de) 57,91 (s, 1H), 7,45 (s, 1H), 6,24 (bs, 2H), 3,31 (s, 2H), 2,81 - 2,72 (m, 2H), 2,48 - 2,19 (m, 8H), 2,16 - 2,08 (m, 4H), 1,94 - 1,87 (m, 2H), 1,75 - 1,68 (m, 2H), 1,42 - 1,31 (m, 2H).13C NMR (126 MHz, DMSO) 5 158,04, 146,95, 139,17, 119,05, 105,72, 61,36, 59,41, 55,66, 52,68, 49,04, 46,24, 28,49.

[0180]

[0181] 5-bromo-3-{[4-(dimethylamino)piperidin-l-yl]methyl}pyridine-2-amine (49): Prepared according to general procedure C. Aldehyde 32 (644 mg; 3,2 mmol); 4-(dimethylamino)piperidine (464 pL; 3,84 mmol); and NaBH(OAc)3(2,034 g; 9,6 mmol) in anhydrous DCM 30 mL. Extraction residue was purified by column chromatography using gradient mobile phase from CHCl3 / MeOH (9:1) to CHCl3 / MeOH / NH4OH (25 % aqueous solution) (5: 1:0,1) to obtain the pure product 49 as yellow oil. Yield 82 %. 'H NMR (500 MHz, DMSO-ds) 5 7,93 (d, J = 2,4 Hz, 1H), 7,46 (d, J = 2,5 Hz, 1H), 6,26 (s, 2H), 3,33 (s, 2H), 2,81 - 2,74 (m, 2H), 2,16 (s, 6H), 2,09 - 2,00 (m, 1H), 1,98 - 1,86 (m, 2H), 1,77 - 1,68 (m, 2H), 1,41 - 1,30 (m, 2H).13C NMR (126 MHz, DMSO) 5 158,03, 146,94, 139,16, 119,06, 105,72, 61,92, 59,43, 52,54, 42,01, 28,59.

[0182]

[0183] tert-butyl JV-{l-[(2-amino-5-bromopyridin-3-yl)methyl]piperidin-4-yl}-JV-methylcarbamate (50):

[0184] Prepared according to general procedure C. Aldehyde 32 (641 mg; 3,19 mmol); tert-butyl methyl(piperidin-4-yl)carbamate (822 mg; 3,83 mmol); and NaBH(OAc)3(2,03 g; 9,57 mmol) in anhydrous DCM 30 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (20:1) to obtain the pure product 50 as pale orange solid. Yield 71 %. 'H NMR (500 MHz, CDCh) 5 8,02 (d, J = 2,3 Hz, 1H), 7,33 (d, J = 2,4 Hz, 1H), 5,73 (bs, 2H), 4,04 - 4,00 (m, 1H), 3,43 (s, 2H), 2,96 - 2,86 (m, 2H), 2,72 (s, 3H), 2,15 - 2,02 (m, 2H), 1,77 - 1,59 (m, 4H), 1,45 (s, 9H).13C NMR (126 MHz, CDCh) 5 157,23, 155,60, 147,38, 140,06, 107,24, 79,58, 60,36, 52,81, 28,49.

[0185]

[0186] 3-({[l,4'-bipiperidin]-l'-yl}methyl)-5-bromopyridine-2-amine (51): Prepared according to general procedure C. Aldehyde 32 (300 mg; 1,49 mmol); 4-piperidinopiperidine (301 mg; 1,8 mmol); and NaBH(OAc)3(950 mg; 4,48 mmol) in anhydrous DCM 20 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / MeOH / NH4OH (25% aqueous solution) (20:1:0,1) to obtain the pure product 51 as yellow crystalline foam. Yield 79 %. 'H NMR (500 MHz, DMSO-ds) 5 7,93 (d, J = 2,4 Hz, 1H), 7,46 (d, J = 2,4 Hz, 1H), 6,25 (s, 2H), 3,32 (s, 2H), 2,82 - 2,75 (m, 2H), 2,42 (t, J = 5,1 Hz, 4H), 2,22 - 2,13 (m, 1H), 1,95 - 1,87 (m, 2H), 1,71 - 1,64 (m, 2H), 1,51 -1,32 (m, 8H).13C NMR (126 MHz, DMSO) 5 158,04, 146,94, 139,16, 119,08, 105,72, 62,26, 59,45, 53,00, 50,22, 28,09, 26,57, 25,05.

[0187]

[0188] tert-butyl 5-[(2-amino-5-bromopyridin-3-yl)methyl]-octahydropyrrolo[3,4-c]pyrrole-2-carboxylate (52): Prepared according to general procedure C. Aldehyde 32 (635 mg; 3,16 mmol); tertbutyl hexahydropyrrolo[3,4-c]pyrrole-2(H7)-carboxylate (805 mg; 3,8 mmol); and NaBH(OAc)3(2,01 g; 9,48 mmol) in anhydrous DCM 30 mL. Extraction residue was purified by column chromatography using the mobile phase CHCl3 / EA (1:1) to obtain the pure product 52 as pale yellow solid. Yield 84 %. 'H NMR (500 MHz, Chloroform-d) 5 8,02 (d, J = 2,3 Hz, 1H), 7,34 (d, J = 2,4 Hz, 1H), 5,65 (s, 2H), 3,58 - 3,47 (m, 4H), 3,29 - 3,15 (m, 2H), 2,86 - 2,77 (m, 2H), 2,62 - 2,54 (m, 2H), 2,50 (s, 2H), 1,45 (s, 9H).13C NMR (126 MHz, CDC13) 5 157,05, 154,24, 147,26, 139,27, 118,91, 107,16, 79,50, 59,90, 57,28, 51,86, 28,51.

[0189] General procedure D: MW assisted Suzuki-Miyaura coupling reaction

[0190] To a solution of reduction deamination product 33-52 (1.0 eq) in anhydrous dioxane, 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (1.5 eq) was added under Ar. Sodium carbonate (Na2CO3; 10.0 eq), argon-treated water and Pd(dppf)2Cl2.DCM or Pd(PPh3)2Cl2 (0.05 eq) were then added. The mixture was subjected to microwave (MW) radiation (100 W, dynamic curve, maximum pressure 300 PSI) treatment at 80 °C for 30 minutes. After cooling, the mixture was diluted with water (30 mL) and extracted by ethyl acetate (EA) (3 × 30 mL). Organic fractions were collected, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under vacuum and purified by column chromatography to obtain the desired products.

[0191]

[0192] 1-ethyl-4-[(5-{1H-pyrrolo[2,3-b]pyridin-5-yl}-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]piperazine (1): Compound 33 (65 mg; 0,20 mmol); 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (73 mg; 0,30 mmol), 10 mL anhydrous 1,4-dioxane, Na2CO3(213 mg; 2,0 mmol), 2 mL H2O and Pd(dppf)Cl2.DCM (2 mg; 0,002 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase DCM / MeOH / NH4OH (25 % aqueous solution) (15:1:0,1), to obtain a pure product 1 as pale orange solid. Yield 78 %. 'H NMR (500 MHz, DMSO-ds) 5 11,71 (s, 1H), 11,53 (d, J = 2,5 Hz, 1H), 8,54 - 8,48 (m, 2H), 8,27 (d, J = 2,2 Hz, 1H), 8,22 (d, J = 2,1 Hz, 1H), 7,52 (t, J = 2,9 Hz, 1H), 7,38 (d, J = 2,3 Hz, 1H), 6,55 - 6,49 (m, 1H), 3,66 (s, 2H), 2,48 - 2,28 (m, 8H), 2,25 (q, J = 7,2 Hz, 2H), 0,94 (t, J = 7,1 Hz, 3H).13C NMR (126 MHz, DMSO) 5 148,25, 147,99, 141,85, 127,34, 127,04, 126,85, 126,44, 125,88, 125,66, 120,09, 119,94, 110,37, 100,19, 53,27, 52,72, 52,69, 51,75, 12,21. HRMS (ESI+): [M+2H]2+: calculated for C21H26N62+(m / z): 181,11040; detected: 181,11075. LC-MS purity 98 %.

[0193]

[0194] 1-(oxetan-3-yl)-4-[(5-{1H-pyrrolo[2,3-b]pyridin-5-yl}-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]piperazine (2): Compound 34 (100 mg; 0,285 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3-6]pyridine (104 mg; 0,427 mmol), 10 mL anhydrous 1,4- dioxane, Na₂CO₃ (302 mg; 2,85 mmol), 2 mL H2O and Pd(dppf)C12. DCM (3 mg; 0,003 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase DCM / McOH / NH₄OH (25 % aqueous solution) (15:1:0,1) to obtain the pure product 2 as light orange solid. Yield 56 %.1HNMR(500 MHz, DMSO) 5 11,67 (s, 1H), 11,52 (s, 1H), 8,56 - 8,45 (m, 2H), 8,35 - 8,19 (m, 2H), 7,56 - 7,45 (m, 1H), 7,39 (d, J = 2,5 Hz, 1H), 6,57 - 6,46 (m, 1H), 4,46 (t, J = 6,5 Hz, 2H), 4,36 (t, J = 6,1 Hz, 2H), 3,68 (s, 2H), 3,32 (p, J = 6,3 Hz, 1H), 2,33 (d, J = 109,5 Hz, 8H).13C NMR (126 MHz, DMSO) 5 148,43, 148,21, 142,10, 127,60, 127,37, 127,19, 126,85, 126,44, 125,99, 120,47, 120,30, 110,36, 100,58, 74,90, 58,88, 53,30, 52,41, 49,53, 49,07. HRMS (ESI+): [M+2H]2+: calculated for C₂₂H₂₆N₆O²⁺ (m / z): 195,10786; detected: 195,10796. LC-MS purity 95 %.

[0195]

[0196] l-methyl-4-{l- [(5-{LH-pyrrolo [2,3-Z>]pyridin-5-yl}-LH-pyrrolo [2,3-Z>] pyridin-3-yl)methyl]piperidin-4-yl}piperazin (3): Compound 35 (100 mg; 0,25 mmol); 5-(4,4,5,5-tetramethyl-| l.3.2|dioxaborolan-2-yl)-l / / -pyrrolo|2.3- / ?|pyridinc (93 mg; 0,38 mmol), 10 mL anhydrous 1,4-dioxane, Na₂CO₃ (265 mg; 2,5 mmol), 2 mL H2O and Pd(PPh3)2CL> (2 mg; 0,0025 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl₃ / MeOH / NH₄OH (25 % aqueous solution) (5:1:0,1), to obtain a pure product 35 as pale orange solid. Yield 51 %. 'H NMR (500 MHz, MeOD) 58,57 - 8,45 (m, 2H), 8,40 (d, J = 2,2 Hz, 1H), 8,27 (d, J = 2,2 Hz, 1H), 7,53 (s, 1H), 7,49 - 7,40 (m, 1H), 6,57 (d, J = 3,5 Hz, 1H), 4,03 (s, 2H), 3,28 - 3,23 (m, 2H), 2,68 - 2,50 (m, 8H), 2,49 - 2,28 (m, 8H), 2,01 - 1,90 (m, 2H), 1,68 - 1,56 (m, 2H).13C NMR (126 MHz, MeOD) 5 147,47, 147,37, 141,73, 141,08, 128,73, 128,64, 127,93, 127,81, 127,52, 127,43, 126,56, 126,33, 121,04, 120,72, 60,38, 54,28, 51,85, 51,63, 44,25, 26,77. HRMS (ESI+): [M+2H]2+: calculated for C₂₅H₃₃N₇²⁺ (m / z): 215,63932; detected: 215,63899. LC-MS purity 97 %.

[0197]

[0198] l-ethyl-4-[(5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-LH-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]piperazine (4): Compound 36 (101 mg; 0,312 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3- / ?]pyridine (153 mg; 0,624 mmol), 10 mL anhydrous 1,4-dioxane, Na₂CO₃ (331 mg; 3,12 mmol), 2 mL H2O and Pd(dppf)Cl₂·DCM (5 mg; 0,0065 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl₃ / MeOH / NH₄OH (25 % aqueous solution) (15:1:0,1) to obtain a pure product 4 as pale orange solid. Yield 52 %. 'H NMR (500 MHz, DMSO) 5 11,69 (s, 1H), 11,62 (d, J = 2,0 Hz, 1H), 8,51 (d, J = 2,2 Hz, 1H), 8,46 (s, OH), 8,20 (d, J = 2,1 Hz, 1H), 8,12 (d, J = 2,1 Hz, 1H), 7,55 - 7,44 (m, 1H), 6,56 - 6,44 (m, 1H), 6,41 - 6,32 (m, 1H), 3,63 (s, 2H), 2,48 - 2,27 (m, 10H), 0,97 (t, J = 7,2 Hz, 3H).13C NMR (126 MHz, DMSO) 5 148,52, 148,27, 142,15, 141,51, 138,33, 127,65, 127,50, 127,31, 126,70, 126,06, 120,74, 120,23, 100,49, 99,88, 55,54, 53,04, 52,75, 52,04, 12,42. HRMS (ESI+): [M+2H]2+: calculated for C₂₁H₂₆N₆²⁺ (m / z): 181,11040; detected: 181,10994. LC-MS purity 99 %.

[0199]

[0200] l-methyl-4-{l- [(5-{LH-pyrrolo [2,3-Z>]pyridin-5-yl}-LH-pyrrolo [2,3-Z>] pyridin-2-yl)methyl]piperidin-4-yl}piperazine (5): Compound 38 (110 mg; 0,28 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3- / ?]pyridine (103 mg; 0,42 mmol), 10 mL anhydrous 1,4-dioxane, Na2CO3(297 mg; 2,8 mmol), 2 mL H2O and Pd(PPh3)2C12 (3 mg; 0,003 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl₃ / MeOH / NH₄OH (25 % aqueous solution) (5:1:0,1) to obtain the pure product 4 as pale orange solid. Yield 32 %. ’H NMR (500 MHz, DMSO+TFA) 5 12,80 (s, 1H), 12,52 (s, 1H), 8,88 (d, J = 1,8 Hz, 1H), 8,85 - 8,74 (m, 1H), 8,62 (d, J = 2,1 Hz, 1H), 7,77 - 7,70 (m, 1H), 6,90 (s, 1H), 6,82 - 6,77 (m, 1H), 4,62 - 4,46 (m, 2H), 3,79 - 3,24 (m, 11H), 3,11 - 2,98 (m, 2H), 2,87 (s, 3H), 2,38 - 2,27 (m, 2H), 1,99 - 1,82 (m, 2H).13C NMR (126 MHz, DMSO+TFA) 5 146,15, 141,06, 140,49, 134,31, 134,28, 130,54, 126,82, 125,87, 125,20, 121,82, 111,65, 106,00, 102,63, 59,33, 50,19, 48,72, 46,20, 42,24, 24,41. HRMS (ESI+): [M+H]+: calculated for C25H32N7+(m / z): 430,27137; found: 430,27094. LC-MS purity 98 %.

[0201]

[0202] l-[(5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-LH-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]piperidine (6):

[0203] Compound 41 (100 mg; 0,34 mmol); 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (124 mg; 0,51 mmol), 10 mL anhydrous 1,4-dioxane, Na2CO3(360 mg; 3,4 mmol), 2 mL H2O and Pd(PPh3)2Cl2(3 mg; 0,0034 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCT / McOH (20: 1) to obtain the pure product 6 as pale orange solid. Yield 41 %.1H NMR (500 MHz, DMSO-d6 + TFA) 5 12,06 – 11,97 (m, 1H), 11,82 (s, 1H), 8,65 (d, J = 2,1 Hz, 1H), 8,57 (d, J = 2,2 Hz, 1H), 8,34 (d, J = 2,2 Hz, 1H), 8,30 (d, J = 2,2 Hz, 1H), 7,60 -7,51 (m, 1H), 6,79 - 6,72 (m, 1H), 6,61 - 6,48 (m, 1H), 4,50 (s, 2H), 3,49 - 3,42 (m, 2H), 2,99 - 2,87 (m, 2H), 1,85 (d, J = 13,9 Hz, 2H), 1,75 - 1,62 (m, 3H).13C NMR (126 MHz, DMSO + TFA) 5 148,33, 147,85, 143,53, 141,64, 129,01, 128,20, 127,69, 127,59, 127,32, 127,15, 120,57, 120,37, 104,93, 100,67, 52,71, 52,40, 22,99, 21,53. HRMS (ESI+): [M+H]2+: calculated for C20H23N52+(m / z): 166,59713; found: 166,59700. LC-MS purity 93 %.

[0204]

[0205] l-ethyl-4-[(5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-LH-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]-l,4-diazepan (7): Compound 38 (190 mg; 0,56 mmol); 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (205 mg; 0,84 mmol), 10 mL anhydrous 1,4-dioxane, Na2CO3(593 mg; 5,6 mmol), 2 mL H2O and Pd(PPh3)2Cl2(5 mg; 0,0056 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (4: 1) to obtain the pure product 7 as pale orange solid. Yield 46 %. ’H NMR (500 MHz, DMSO-d₆) 5 11,73 (s, 1H), 11,67 (d, J = 2,0 Hz, 1H), 8,52 (s, 1H), 8,47 (d, J = 2,2 Hz, 1H), 8,21 (d, J = 2,1 Hz, 1H), 8,14 (d, J = 2,1 Hz, 1H), 7,56 - 7,46 (m, 1H), 6,54 - 6,45 (m, 1H), 6,43 - 6,34 (m, 1H), 3,85 (s, 2H), 3,25 - 3,06 (m, 4H), 3,05 - 2,92 (m, 2H), 2,88 (t, J = 5,0 Hz, 2H), 2,74 (t, J = 6,0 Hz, 2H), 2,00 - 1,92 (m, 2H), 1,20 (t, J = 7,1 Hz, 3H).13C NMR (126 MHz, DMSO) 5 148,58, 148,25, 142,13, 141,57, 138,94, 127,61, 127,57, 127,34, 126,70, 126,13, 120,79, 120,22, 100,46, 99,64, 55,10, 53,76, 53,69, 52,29, 51,77, 10,36. HRMS (ESI+):

[0206] [M+2H]2+: calculated for C22H28N62+(m / z): 188,11822; found: 188,11806. LC-MS purity 97 %.

[0207]

[0208] 2-methyl-6-[(5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-LH-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]-2,6-diazaspiro[3.3]heptane (8): Compound 39 (115 mg; 0,36 mmol); 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (131 mg; 0,54 mmol), 10 mL anhydrous 1,4-dioxane, Na2CO3(379 mg; 3,6 mmol), 2 mL H2O and Pd(PPh3)2Cl2(4 mg; 0,0036 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl₃ / MeOH / NH₄OH (25 % aqueous solution) (5:1:0,1) to obtain the pure product 8 as pale orange solid. Yield 64 %. ’H NMR (500 MHz, chloroform-d) 5 10,95 (s, 1H), 10,87 (s, 1H), 8,56 (d, J = 2,1 Hz, 1H), 8,49 (d, J = 2,1 Hz, 1H), 8,10 (d, J = 2,1 Hz, 1H), 8,00 (d, J = 2,1 Hz, 1H), 7,37 - 7,32 (m, 1H), 6,51 (d, J = 3,4 Hz, 1H), 6,29 (s, 1H), 3,74 (s, 2H), 3,33 (s, 4H), 3,24 (s, 4H), 2,19 (s, 3H).13C NMR (126 MHz, CDC13) 5 142,76, 142,08, 138,97, 128,49, 128,19, 126,90, 126,87, 126,25, 121,30, 120,67, 100,72, 99,12, 66,05, 64,20, 56,51, 45,40, 34,60. HRMS (ESI+): [M+H]+: calculated for C₂₁H₂₃N₆⁺ (m / z): 359,19787; found: 359,19717. LC-MS purity 95 %.

[0209]

[0210] l'-[(5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-LH-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]-l,4'-bipiperidine (9): Compound 43 (160 mg; 0,424 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3-6]pyridine (155 mg; 0,636 mmol), 8 mL anhydrous 1,4-dioxane, Na2CO3(450 mg; 4,24 mmol), 2 mL H2O and Pd(PPh3)2Cl2(15 mg; 0,02 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl3 / MeOH / NPfiOH (25 % aqueous solution) (9: 1:0,1) to obtain the pure product 9 as pale violet solid. Yield 52 %. ’H NMR (500 MHz, AcOD-t / ft 5 8,69 (d, J = 2,1 Hz, 1H), 8,61 (d, J = 2,1 Hz, 1H), 8,52 (d, J = 2,0 Hz, 1H), 8,47 (d, J = 2,0 Hz, 1H), 7,64 (d, J = 3,5 Hz, 1H), 6,92 (s, 1H), 6,71 (d, J = 3,5 Hz, 1H), 4,67 (s, 2H), 3,88 - 3,78 (m, 2H), 3,77 - 3,66 (m, 1H), 3,59 (s, 2H), 3,29 - 3,18 (m, 2H), 3,04 - 2,90 (m, 2H), 2,42 - 2,28 (m, 4H), 1,96 - 1,71 (m, 6H).13C NMR (126 MHz, AcOD) 5 146,25, 144,14, 140,88, 136,88, 131,04, 130,37, 129,07, 128,56, 127,53, 126,71, 123,48, 122,08, 106,15, 101,32, 60,16, 52,16, 50,36, 50,06, 48,67, 23,35, 22,97, 21,52. HRMS (ESI+): [M+H]+: calculated for C₂₅H₃₁N₆⁺ (m / z): 415,26047; found: 415,26016. LC-MS purity 95 %.

[0211]

[0212] /

[0213] / V, A-dimethyl-l-[(5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-LH-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]piperidine-4-amine (10): Compound 40 (136 mg; 0,4 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3-6]pyridine (148 mg; 0,6 mmol), 10 mL anhydrous 1,4-dioxane, Na2CO3(424 mg; 4,0 mmol), 2 mL H2O and Pd(PPh3)2Cl2(3 mg; 0,004 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl₃ / MeOH / NH₄OH (25 % aqueous solution) (9:1:0,1) to obtain the pure product 10 as pale orange solid. Yield 67 %. ’H NMR (500 MHz, DMSO-d6 + TLA) 5 11,99 - 11,57 (m, 2H), 8,62 - 8,43 (m, 2H), 8,30 - 8,10 (m, 2H), 7,58 - 7,43 (m, 1H), 6,65 - 6,33 (m, 1H), 4,20 - 3,68 (m, 2H), 3,52 - 3,06 (m, 5H), 2,74 (d, J = 4,8 Hz, 6H), 2,15 - 1,95 (m, 2H), 1,83 - 1,64 (m, 2H). ¹³C NMR (126 MHz, DMSO + TFA) 5 148,48, 148,31, 142,14, 127,41, 126,75, 120,57, 120,24, 118,83, 116,45, 100,50, 50,96, 49,07, 31,62, 30,30, 29,46. HRMS (ESI+): [M+H]+: calculated for C22H27N6+(m / z): 375,22917; found: 375,22971. LC-MS purity 99 %.

[0214]

[0215] / V-methyl-1 - [(5-jl / / -pyrrolo [2,3- / >]pyridin-5-yl}-l / / -pyrrolo [2,3-Z>] pyridin-2-yl)methyl]piperidine-4-amine (11): Compound 42 (850 mg; 2,0 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-l / / -pyrrolo[2,3- / ?]pyridine (732 mg; 3,0 mmol), 16 mL anhydrous 1,4-dioxane, Na₂CO₃ (2,12 g; 20,0 mmol), 4 mL H2O and Pd(PPh3)2Cl2(70 mg; 0,01 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl₃ / MeOH (20:1) to obtain pure Boc-protected product as pale yellow solid. Yield 48 %. The Boc-protected compound (425 mg; 0,92 mmol) was dissolved in MeOH (10 mL) and a concentrated 33 % HC1 solution (1 mL) was added. The mixture was kept at 70 °C for 2 hours. After cooling, the residue was concentrated, diluted with H2O and washed with DCM (2 x 30 mL). Aqueous phase was then alkalized to pH > 12, the resulting precipitate was filtered and purified by column chromatography using the mobile phase CHCl₃ / MeOH / NH₄OH (25 % aqueous solution) (9:1:0,1) to obtain the pure product 11 as white solid. Yield 86 %. ’H NMR (500 MHz, CDCW+AcOD-a^) 5 8,45 - 8,37 (m, 1H), 8,36 - 8,26 (m, 1H), 8,18 - 8,09 (m, 1H), 8,09 - 8,02 (m, 1H), 7,40 - 7,31 (m, 1H), 6,59 - 6,39 (m, 2H), 4,20 (d, J = 6,6 Hz, 2H), 3,42 - 3,28 (m, 3H), 2,84 - 2,65 (m, 2H), 2,63 - 2,52 (m, 3H), 2,19 - 1,98 (m, 4H).13C NMR (126 MHz, CDCh+AcOD) 5 147,22, 146,47, 141,46, 139,15, 130,95, 129,16, 128,73, 127,99, 127,19, 127,12, 121,92, 121,41, 103,96, 100,82, 53,49, 53,13, 49,85, 29,77, 25,50. HRMS (ESI+):

[0216] [M+H]+: calculated for C₂₁H₂₆N₆⁺ (m / z): 361,21352; found: 361,21356. LC-MS purity 99 %.

[0217]

[0218] 2-({octahydropyrrolo[3,4-c]pyrrol-2-yl}methyl)-5-{l / / -pyrrolo[2,3-Z>]pyridin-5-yl}-l / / -pyrrolo [2, 3-b] pyridine (14): Compound 44 (580 mg; 1,38 mmol); 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (504 mg; 2,06 mmol), 12 mL anhydrous 1,4-dioxane, Na₂CO₃ (1,46 g; 13,8 mmol), 3 mL H2O and Pd(PPh₃)₂Cl₂ (50 mg; 0,07 mmol). After the reaction, the residue was purified by column chromatography using the gradient mobile phase from CHCl₃ / MeOH (20:1) to CHCl₃ / MeOH / NH₄OH (25 % aqueous solution) (9:1:0,1) to obtain pure Boc-protected product as pale yellow solid. Yield 31 %. The Boc-protected compound (100 mg; 0,22 mmol) was dissolved in MeOH (10 mL) and a concentrated 33 % HC1 solution (1 mL) was added. The mixture was kept at 70 °C for 2 hours. After cooling, the residue was concentrated, diluted with water and washed with DCM (2 x 30 mL). Aqueous phase was then alkalized using NaOH to pH > 12, the obtained precipitate was filtered and purified by column chromatography using the mobile phase CHCU / MeOH / NHiOH (25 % aqueous solution) (5: 1:0,1) to obtain the pure product 14 as white solid. Yield 67 %. ’H NMR (500 MHz, DMSO-d6) 5 11,69 (s, 1H), 11,63 (s, 1H), 8,51 (d, J = 2,2 Hz, 1H), 8,45 (d, J = 2, 1 Hz, 1H), 8,20 (d, J = 2,3 Hz, 1H), 8, 11 (d, J = 2,2 Hz, 1H), 7,51 (d, J = 3,4 Hz, 1H), 6,53 - 6,45 (m, 1H), 6,32 (s, 1H), 3,67 (s, 2H), 2,82 - 2,72 (m, 2H), 2,66 - 2,53 (m, 6H), 2,41 - 2,33 (m, 2H). ¹³C NMR (126 MHz, DMSO) 5 148,58, 148,26, 142,14, 141,37, 139,62, 127,68, 127,45, 127,30, 126,68, 126,01, 120,79, 120,22, 100,48, 98,84, 60,54, 55,39, 54,01, 52,50, 43,61. HRMS (ESI+):

[0219] [M+H]+: calculated for C₂₁H₂₃N₆⁺ (m / z): 359,19787; found: 359,19772. LC-MS purity 98 %.

[0220]

[0221] l-ethyl-4-[(4-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-LH-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]piperazine (15): Compound 45 (140 mg; 0,43 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3- / ?]pyridine (158 mg; 0,65 mmol), 10 mL anhydrous 1,4-dioxane, Na2CO3(456 mg; 4,3 mmol), 2 mL H2O and Pd(PPh3)2Cl2(3 mg; 0,004 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl3 / MeOH (9: 1) to obtain the pure product 15 as pale orange solid. Yield 45 %. ’H NMR (500 MHz, Pyr) 5 13,27 (d, J = 29,0 Hz, 2H), 9,18 (d, J = 2,1 Hz, 1H), 8,67 (d, J = 4,9 Hz, 1H), 8,61 (d, J = 2,1 Hz, 1H), 7,79 (t, J = 2,9 Hz, 1H), 7,44 (d, J = 4,9 Hz, 1H), 6,88 (d, J = 1,8 Hz, 1H), 6,80 (dd, J = 3,4, 1,8 Hz, 1H), 3,80 (s, 2H), 2,57 (d, J = 74,3 Hz, 8H), 2,35 (q, J = 7,2 Hz, 2H), 1,02 (t, J = 7,2 Hz, 3H).13CNMR(126 MHz, Pyr) 5 150,97, 143,54, 143,23, 139,52, 138,28, 128,15, 127,56, 127,19, 120,60, 119,22, 115,02, 101,02, 99,42, 56,24, 53,18, 52,70, 52,10, 11,92. HRMS (ESI+): [M+2H]2+: calculated for C2IH26N62+(m / z): 181,11040; found: 181,11015. LC-MS purity 99 %.

[0222]

[0223] l-(oxetan-3-yl)-4-[(4-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-l / 7-pyrrolo[2,3-Z>]pyridin-2-yl)methyl] piperazine (16): Compound 46 (122 mg; 0,35 mmol); 5-(4,4,5,5-tetramethyl- [1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (127 mg; 0,52 mmol), 8 mL anhydrous 1,4-dioxanu, Na2CC>3 (371 mg; 3,5 mmol), 2 mL H2O and Pd(PPh3)2Cl2(14 mg; 0,018 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCL / McOH (20: 1) to obtain the pure product 16 as pale violet solid. Yield 69 %. NMR (500 MHz, Pyridine-t / 5) 5 13,26 (d, J = 22,9 Hz, 2H), 9,19 (d, J = 2,2 Hz, 1H), 8,68 (d, J = 4,9 Hz, 1H), 8,61 (d, J = 2,1 Hz, 1H), 7,83 - 7,77 (m, 1H), 7,44 (d, J = 5,0 Hz, 1H), 6,89 (d, J = 2,0 Hz, 1H), 6,83 - 6,78 (m, 1H), 4,66 - 4,56 (m, 4H), 3,82 (s, 2H), 3,33 (p, J = 6,3 Hz, 1H), 2,73 - 2,14 (m, 8H).13C NMR (126 MHz, Pyr) 5 150,96, 143,54, 143,25, 139,54, 138,16, 128,14, 127,56, 127,20, 120,60, 119,23, 115,04, 101,02, 99,44, 75,21, 59,23, 56,22, 52,96, 49,47.

[0224]

[0225] 3-[(4-ethyl-l,4-diazepan-l-yl)methyl]-5-{l / 7-pyrrolo[2,3-Z>]pyridin-5-yl}pyridine-2-amine (17):

[0226] Compound 47 (113 mg; 0,361 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3-6]pyridine (132 mg; 0,541 mmol), 10 mL anhydrous 1,4-dioxane, Na2CC>3 (382 mg; 0,361 mmol), 2 mL H2O and Pd(PPh3)2Cl2(3 mg; 0,0036 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCL / McOH (9: 1) to obtain the pure product 17 as pale orange solid. Yield 39 %. *HNMR (500 MHz, DMSO-d₆) 5 11,65 (t, J = 2,3 Hz, 1H), 8,44 (d, J = 2,1 Hz, 1H), 8,25 (d, J = 2,4 Hz, 1H), 8,11 (d, J = 2,2 Hz, 1H), 7,69 (d, J = 2,5 Hz, 1H), 7,55 - 7,43 (m, 1H), 6,50 - 6,42 (m, 1H), 6,11 (bs, 2H), 3,60 (s, 2H), 3,12 - 2,96 (m, 3H), 2,97 - 2,85 (m, 2H), 2,77 (t, J = 4,9 Hz, 2H), 2,68 (t, J = 5,9 Hz, 2H), 1,90 (p, J = 5,5 Hz, 2H), 1,14 (t, J = 7,2 Hz, 3H).13C NMR (126 MHz, DMSO) 5 158,22, 148,12, 145,07, 141,21, 136,52, 127,22, 126,44, 125,40, 123,95, 120,18, 116,66, 100,36, 59,75, 53,85, 52,80, 52,00, 49,07, 10,97. HRMS (ESI+): [M+H]+: calculated for C20H27N7+(m / z): 351,22917; found: 351,22742. LC-MS purity 92 %

[0227]

[0228] 3-{[4-(4-methylpiperazin-l-yl)piperidin-l-yl]methyl}-5-{l / 7-pyrrolo[2,3-Z>]pyridin-5-yl}pyridine-2-amine (18): Compound 49 (113 mg; 0,308 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)- lH-pyrrolo[2,3-6]pyridine (113 mg; 0,46 mmol), 10 mL anhydrous 1,4-dioxane, Na₂CO₃ (326 mg; 3,08 mmol), 2 mL H2O and Pd(PPh3)2Cl2(3 mg; 0,003 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCL / McOH / NlLOH (25 % aqueous solution) (9: 1:0,1) to obtain the pure product 18 as pale orange solid. Yield 41 %.

[0229]

[0230] NMR (500 MHz, DMSO-d6) 5 11,68 - 11,56 (m, 1H), 8,41 (d, J = 2,2 Hz, 1H), 8,22 (d, J = 2,4 Hz, 1H), 8,09 (d, J = 2,1 Hz, 1H), 7,63 (d, J = 2,5 Hz, 1H), 7,52 - 7,42 (m, 1H), 6,50 - 6,40 (m, 1H), 6,12 (s, 2H), 3,43 (s, 2H), 2,90 - 2,80 (m, 2H), 2,43 - 2,23 (m, 8H), 2,21 - 2,15 (m, 4H), 1,99 - 1,89 (m, 2H), 1,78 - 1,68 (m, 2H), 1,46 - 1,33 (m, 2H).13C NMR (126 MHz, DMSO) 5 158,23, 148,12, 144,87, 141,20, 136,24, 127,18, 126,49, 125,39, 123,92, 120,18, 116,64, 100,37, 61,44, 60,27, 55,36, 52,70, 48,79, 45,90, 28,44. HRMS (ESI+):

[0231] [M+H]+: calculated for C23H32N7+(m / z): 406,27137; found: 406,26971. LC-MS purity 96 %

[0232]

[0233] 3-({[l,4'-bipiperidin]-l'-yl}methyl)-5-{l / 7-pyrrolo[2,3-Z>]pyridin-5-yl}pyridine-2-amine (19):

[0234] Compound 51 (146 mg; 0,41 mmol); 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (151 mg; 0,62 mmol), 8 mb anhydrous 1,4-dioxane, Na2CC>3 (434 mg; 4,1 mmol), 2 mb H2O, and Pd(PPh3)2Cl2(16 mg; 0,021 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCft / MeOH / NHiOH (25 % aqueous solution) (15:1:0,1) to obtain the pure product 19 as light violet solid. Yield 64 %. ¹H NMR (500 MHz, CDCl₃-d) 5 10,58 (bs, 1H), 8,47 (d, J = 2,1 Hz, 1H), 8,27 (d, J = 2,3 Hz, 1H), 8,03 (d, J = 2,1 Hz, 1H), 7,49 (d, J = 2,4 Hz, 1H), 7,42 - 7,34 (m, 1H), 6,57 - 6,49 (m, 1H), 5,78 (s, 2H), 3,51 (s, 2H), 3,00 - 2,92 (m, 2H), 2,62 - 2,51 (m, 4H), 2,39 - 2,28 (m, 1H), 2,03 - 1,94 (m, 2H), 1,93 - 1,85 (m, 2H), 1,69 - 1,53 (m, 6H), 1,49 - 1,41 (m, 2H). ¹³C NMR (126 MHz, CDCl₃) 5157,88, 148,03, 145,17, 141,52, 136,66, 127,03, 126,53, 125,87, 125,30, 120,39, 117,13, 100,92, 62,71, 61,24, 52,93, 50,33, 28,04, 25,89, 24,48. HRMS (ESI+):

[0235] [M+H]+: calculated for C₂₃H₃₁N₆⁺ (m / z): 391,26047; detected: 391,26028. LC-MS purity 99 %

[0236]

[0237] 3-{[4-(dimethylamino)piperidin-l-yl]methyl}-5-{l / 7-pyrrolo[2,3-Z>]pyridin-5-yl}pyridine-2-amine (20): Compound 49 (113 mg; 0,36 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3- / ?]pyridine (132 mg; 0,54 mmol), 8 mL anhydrous 1,4-dioxane, Na2CO3(381 mg; 3,6 mmol), 2 mL H2O and Pd(PPh3)2Cl2(14 mg; 0,018 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCl₃ / MeOH (20:1) to obtain the pure product 20 as pale purple solid. Yield 66 %. ’H NMR (500 MHz, CDCl3-d) 5 10,49 (bs, 1H), 8,46 (d, J = 2,1 Hz, 1H), 8,27 (d, J = 2,3 Hz, 1H), 8,03 (d, J = 2,1 Hz, 1H), 7,49 (d, J = 2,4 Hz, 1H), 7,41 - 7,35 (m, 1H), 6,53 (d, J = 3,4 Hz, 1H), 5,76 (s, 2H), 3,52 (s, 2H), 2,99 - 2,91 (m, 2H), 2,33 (s, 6H), 2,28 - 2,19 (m, 1H), 2,04 - 1,96 (m, 2H), 1,92 - 1,84 (m, 3H), 1,59 - 1,48 (m, 2H).13C NMR (126 MHz, CDC13) 5 157,85, 148,01, 145,19, 141,54, 136,69, 127,02, 126,51, 125,87, 125,32, 120,37, 117,08, 100,93, 62,31, 61,22, 52,55, 41,59, 28,45. HRMS (ESI+): [M+H]+: calculated for C2oH27N6+(m / z): 351,22917; found: 351,22906. LC-MS purity 99 %

[0238]

[0239] 3-{[4-(methylamino)piperidin-l-yl]methyl}-5-{l / 7-pyrrolo[2,3-Z>]pyridin-5-yl}pyridine-2-amine (21): Compound 50 (620 mg; 1,55 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3- / ?]pyridine (568 mg; 2,33 mmol), 16 mL anhydrous 1,4-dioxane, Na2CO3(1,64 g; 15,5 mmol), 4 mL H2O, and Pd(PPh3)2Cl2(55 mg; 0,08 mmol). After the reaction, the residue was purified by column chromatography using the gradient mobile phase from CHCl3 / MeOH (20:1) to CHCl₃ / MeOH / NH₄OH (25 % aqueous solution) (9:1:0,1) to obtain a pure Boc-protected product as light yellow solid. Yield 63 %. The Boc-protected compound (320 mg; 0,73 mmol) was dissolved in MeOH (10 mL) and a concentrated 33 % HC1 solution (1 mL) was added. The mixture was kept at 70 °C for 2 hours. After cooling, the resulting residue was concentrated, diluted with water and washed with DCM (2 x 30 mL). The aqueous phase was then alkalized using NaOH to pH > 12, the obtained precipitate was filtered and purified by column chromatography using the mobile phase CHCl3 / MeOH / NHiOH (25 % aqueous solution) (5:1:0, 1) to obtain the pure product 21 as white solid. Yield 79 %. ’H NMR (500 MHz, CDCl3- +MeOD-< ) 58,31 (d, J = 2,2 Hz, 1H), 8,14 (d, J = 2,5 Hz, 1H), 7,99 (d, J = 2,2 Hz, 1H), 7,45 (d, J = 2,5 Hz, 1H), 7,31 (d, J = 3,5 Hz, 1H), 6,47 (s, 1H), 3,48 (s, 2H), 2,89 - 2,80 (m, 2H), 2,45 - 2,35 (m, 4H), 2,06 - 1,95 (m, 2H), 1,93 - 1,83 (m, 2H), 1,41 - 1,30 (m, 2H).13C NMR (126 MHz, CDCl3+MeOD) 5 157,64, 147,24, 144,54, 140,90, 136,94, 126,83, 126,66, 126,15, 125,09, 120,69, 117,37, 100,72, 61,09, 56,32, 51,96, 32,69, 31,66. HRMS (ESI+): [M+H]+: calculated for C₁₉H₂₅N₆⁺ (m / z): 337,21352; detected: 337,21579. LC-MS purity 98 %.

[0240] N NH2

[0241]

[0242] 3-({octahydropyrrolo[3,4-c]pyrrol-2-yl}methyl)-5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}pyridine-2-amine (25): Compound 52 (865 mg; 2,18 mmol); 5-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-pyrrolo[2,3- / ?]pyridine (798 mg; 3,27 mmol), 16 mL anhydrous 1,4-dioxane, Na2CO3(2,31 g; 21,8 mmol), 4 mL H2O, and Pd(PPh3)2Cl2(80 mg; 0,12 mmol). After the reaction, the residue was purified by column chromatography using the mobile phase CHCL / McOH (20: 1) to obtain a pure Boc-protected product as light yellow foam. Yield 86 %. The Boc-protected compound (809 mg; 1,86 mmol) was dissolved in MeOH (10 mL) and a concentrated 33 % HC1 solution was added (1 mL). The mixture was kept at 70 °C for 2 hours. After cooling, the residue was concentrated, diluted with water and washed with DCM (2 x 30 mL). Aqueous phase was then alkalized using NaOH to pH > 12, the obtained precipitate was filtered and purified by column chromatography using the mobile phase CHCl₃ / MeOH / NH₄OH (25% aqueous solution) (5:1:0,1) to obtain the pure product 25 as white solid. Yield 77 %. ‘H NMR (500 MHz, CDCl3-d) 5 10,57 (bs, 1H), 8,47 (d, J = 2,2 Hz, 1H), 8,27 (d, J = 2,4 Hz, 1H), 8,04 (d, J = 2,1 Hz, 1H), 7,51 (d, J = 2,4 Hz, 1H), 7,39 (d, J = 3,5 Hz, 1H), 6,54 (d, J = 3,5 Hz, 1H), 5,69 (bs, 2H), 3,59 (s, 2H), 3,08 - 3,02 (m, 2H), 2,73 - 2,62 (m, 4H), 2,54 - 2,42 (m, 4H), 2,13 (bs, 1H).13C NMR (126 MHz, CDC13) 5 157,62, 148,03, 145,16, 141,56, 136,00, 127,07, 126,54, 125,86, 125,35, 120,38, 117,90, 100,93, 59,83, 58,23, 54,43, 43,71, 31,60, 22,66. HRMS (ESI+):

[0243] [M+H]+: calculated for C₁₉H₂₃N₆⁺ (m / z): 335,19787; detected: 335,19766. LC-MS purity 98 %.

[0244] General procedure E: / V-alkylation

[0245] DIPEA (5.0 eq) was added to a stirred solution of the starting compound 11, 21, or 25 (1.0 eq) in anhydrous DCM (10 mL) at RT. Corresponding alkyl bromide (2.0 eq) was then added. To improve the solubility of the mixture, 1 mL MeOH was added as a co-solvent in some cases. The reaction mixture was stirred until total exhaustion of the starting compound, monitored by TLC (24 hours for sulfonyls and 168 hours for sulfonamides). The obtained residues were concentrated and triturated with MeOH and hexane to obtain the desired products, or transferred for further processing. The residues were diluted with sodium hydrogencarbonate (NaHCO3; 30 mL) and extracted by ethyl acetate (EA; 3 x 30 mL). Organic phases were collected, dried over anhydrous Na₂SO₄ and filtered. The filtrate was concentrated under vacuum and purified by column chromatography to obtain the desired products.

[0246]

[0247] 2V-(2-methanesulfonylethyl)-2V-methyl-l-[(5-{l / 7-pyrrolo[2,3-Z>]pyridin-5-yl}-LH-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]piperidine-4-amine (12): DIPEA (166 pL; 0,95 mmol), compound 11 (70 mg; 0,19 mmol) in anhydrous DCM (10 mL) and anhydrous MeOH (1 mL) at RT. 2-methylsulfonylethyl bromide (73 mg; 0,39 mmol) was added. The obtained residue was concentrated and triturated with MeOH and hexane to obtain the pure product 12 as white solid. Yield 52 %. ’H NMR (500 MHz, Pyridine- d5) 5 8,98 (d, J = 2,2 Hz, 1H), 8,94 (d, J = 2,2 Hz, 1H), 8,38 (d, J = 2,1 Hz, 1H), 8,31 (d, J = 2,2 Hz, 1H), 7,72 (d, J = 3,4 Hz, 1H), 6,74 (d, J = 3,4 Hz, 1H), 6,59 (s, 1H), 3,75 (s, 2H), 3,42 (t, J = 6,4 Hz, 2H), 3,21 (s, 3H), 3,04 - 2,93 (m, 4H), 2,39 - 2,29 (m, 1H), 2,18 (s, 3H), 2,00 - 1,92 (m, 2H), 1,67 - 1,60 (m, 2H), 1,58 - 1,48 (m, 2H).13CNMR(126 MHz, Pyr) 5 148,90, 142,71, 142,08, 139,06, 128,45, 128,21, 126,96, 126,75, 126,28, 122,90, 121,26, 120,70, 100,70, 99,87, 61,20, 56,14, 53,17, 52,85, 47,92, 42,20, 36,88, 27,88. HRMS (ESI+): [M+H]+: calculated for C24H31N6O2S+(m / z): 467,22237; detected: 467,22266. LC-MS purity 96 %.

[0248]

[0249] JV-{2-[methyl({l-[(5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}-l / 7-pyrrolo[2,3-Z>]pyridin-2-yl)methyl]piperidin-4-yl})amino]ethyl}methanseulfonamide (13): DIPEA (166 pL; 0.95 mmol), compound 11 (70 mg; 0,19 mmol) in anhydrous DCM (5 mL) and anhydrous MeOH (1 mL) at RT. N-(2-bromoethyl)methanesulfonamide (79 mg; 0.39 mmol) was added. The obtained residue was concentrated, diluted with sodium hydrogencarbonate (NaHCOv 30 mL) and extracted by ethyl acetate (EA; 3 x 30 mL). The organic phases were collected, dried over anhydrous Na2SO4and fdtered. The fdtrate was concentrated under vacuum and purified by column chromatography using the mobile phase CHCL / McOH / NH4OH (25 % aqueous solution) (9: 1:0.1) to obtain the pure product 13 as white solid. Yield 57 %. *HNMR (500 MHz, CDCl3-+MeOD-4) 58,41 (d, J = 11,2 Hz, 2H), 8,18 (s, 1H), 8,11 (s, 1H), 7,40 (d, J = 3,6 Hz, 1H), 6,54 (d, J = 3,6 Hz, 1H), 6,44 (s, 1H), 5,40 (s, 1H), 3,74 (s, 2H), 3,20 -3,11 (m, 2H), 3,09 - 3,00 (m, 2H), 2,95 (s, 3H), 2,68 (t, J = 6,7 Hz, 2H), 2,54 - 2,45 (m, 1H), 2,32 (s, 3H), 2,22 - 2,09 (m, 2H), 1,86 - 1,78 (m, 2H), 1,68 - 1,54 (m, 2H).13C NMR (126 MHz, CDCl3+MeOD) 5 151,53, 151,18, 145,10, 144,95, 140,93, 131,84, 131,62, 131,18, 130,43, 125,39, 124,97, 104,64, 104,38, 64,89, 59,01, 57,02, 56,61, 44,40, 42,95, 41,03, 31,15. HRMS (ESI+): [M+H]+: calculated for C24H32N7O2S+(m / z): 482,23327; detected: 482,23291. LC-MS purity 99+ %

[0250]

[0251] 3-({4-[(2-methanesulfonylethyl)(methyl)amino]piperidin-l-yl}methyl)-5-{l / 7-pyrrolo[2,3- Z>]pyridin-5-yl}pyridine-2-amine (22): DIPEA (209 pL; 1.20 mmol), compound 21 (80 mg; 0.24 mmol) in anhydrous DCM (5 mL) and anhydrous MeOH ( 1 mL) at RT. 2-Methylsulfonylethyl bromide (90 mg; 0,48 mmol) was added. The obtained residue was concentrated, diluted with sodium hydrogencarbonate (NaHCOv 30 mL) and extracted by ethyl acetate (EA; 3 x 30 m ). The organic phases were collected, dried over anhydrous NajSCf and filtered. The filtrate was concentrated under vacuum and purified by column chromatography using the mobile phase CHCh / MeOH / NEEOH (25 % aqueous solution) (9:1:0.1) to obtain the pure product 22 as white solid. Yield 61 %.

[0252]

[0253] NMR (500 MHz, CDC13- ) 58,41 - 8,35 (m, 1H), 8,24 - 8,18 (m, 1H), 8,02 (t, J = 1,7 Hz, 1H), 7,47 (t, J = 1,8 Hz, 1H), 7,34 (t, J = 3,0 Hz, 1H), 6,51 (t, J = 3,0 Hz, 1H), 3,49 (s, 2H), 3,10 (t, J = 6,3 Hz, 2H), 3,00 (s, 3H), 2,99 - 2,89 (m, 4H), 2,47 - 2,38 (m, 1H), 2,26 (s, 3H), 2,01 - 1,93 (m, 2H), 1,77 - 1,69 (m, 2H), 1,59 - 1,49 (m, 2H).13C NMR (126 MHZ, CDC13) 5 157,66, 147,46, 144,90, 141,34, 136,84, 126,89, 126,71, 125,85, 125,22, 120,50, 117,24, 100,89, 61,59, 61,16, 52,98, 52,83, 47,95, 42,51, 37,07, 27,98. HRMS (ESI+): [M+H]+: calculated for C22H31N6O2S+(m / z): 443,22237; detected: 443,22205. LC-MS purity 92 %

[0254]

[0255] JV-[2-({l-[(2-amino-5-{l / 7-pyrrolo[2,3-Z>]pyridin-5-yl}pyridin-3-yl)methyl]piperidin-4-yl}(methyl)amino)ethyl]methanesulfonamide (23): DIPEA (209 pL; 1,20 mmol), compound 21 (80 mg; 0,24 mmol) in anhydrous DCM (5 mL) and anhydrous MeOH (1 mL) at RT. N-(2-bromoethyl)methanesulfonamide (97 mg; 0,48 mmol) was added. The obtained residue was concentrated, diluted with sodium hydrogencarbonate (NaHCOv 30 mL) and extracted by ethyl acetate (EA; 3 x 30 mL). The organic phases were collected, dried over anhydrous Na2SC>4 and fdtered. The fdtrate was concentrated under vacuum and purified by column chromatography using the mobile phase CHC McOH / NH-iOH (25 % aqueous solution) (9: 1:0,1) to obtain the pure product 23 as white solid. Yield 63 %. ’H NMR (500 MHz, CDCh-d) 58,39 (d, J = 2,1 Hz, 1H), 8,22 (d, J = 2,4 Hz, 1H), 8,02 (d, J = 2,1 Hz, 1H), 7,48 (d, J = 2,4 Hz, 1H), 7,35 (d, J = 3,5 Hz, 1H), 6,51 (d, J = 3,5 Hz, 1H), 3,49 (s, 2H), 3,17 - 3,12 (m, 2H), 2,95 (s, 3H), 2,68 - 2,60 (m, 2H), 2,43 - 2,34 (m, 1H), 2,23 (s, 3H), 2,00 - 1,93 (m, 2H), 1,90 - 1,83 (m, 2H), 1,75 - 1,68 (m, 2H), 1,58 - 1,45 (m, 2H).13C NMR (126 MHz, CDCh) 5 157,70, 147,49, 144,85, 141,35, 136,82, 126,90, 126,68, 125,80, 125,22, 120,46, 117,25, 100,91, 61,66, 61,17, 52,91, 52,49, 40,32, 40,06, 36,86, 27,97. HRMS (ESI+): [M+H]+: calculated for C22H32N7O2S+(m / z): 458,23327; detected: 458,23312. LC-MS purity 97 %

[0256]

[0257] 3-({4-[methyl(2-phenylethyl)amino]piperidin-l-yl}methyl)-5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}pyridine-2-amine (24): DIPEA (209 pL; 1,20 mmol), compound 21 (80 mg; 0,24 mmol) in anhydrous DCM (5 mL) and anhydrous MeOH (1 mL) at RT. (2-Bromoethyl)benzene (66 pL; 0,48 mmol) was added. The obtained residue was concentrated, diluted with sodium hydrogencarbonate (NaHCOv 30 mL) and extracted by ethyl acetate (EA; 3 x 30 mL). The organic phases were collected, dried over anhydrous NajSCf and filtered. The filtrate was concentrated under vacuum and purified by column chromatograph using the mobile phase CHC13 / MeOH / NH4OH (25 % aqueous solution) (20:1:0,1) to obtain the pure product 24 as white solid. Yield 64 %.

[0258]

[0259] NMR (500 MHz, CDCl3-<7) 5 10,22 (s, 1H), 8,46 (d, J = 2,1 Hz, 1H), 8,27 (d, J = 2,3 Hz, 1H), 8,04 (d, J = 2,1 Hz, 1H), 7,49 (d, J = 2,3 Hz, 1H), 7,40 - 7,36 (m, 1H), 7,31 - 7,26 (m, 2H), 7,23 - 7,14 (m, 3H), 6,56 - 6,50 (m, 1H), 5,77 (bs, 2H), 3,51 (s, 2H), 2,99 - 2,91 (m, 2H), 2,81 - 2,70 (m, 4H), 2,53 - 2,46 (m, 1H), 2,39 (s, 3H), 2,03 - 1,96 (m, 2H), 1,86 - 1,78 (m, 2H), 1,62 - 1,51 (m, 2H).13C NMR (126 MHz, CDC13) 5 157,85, 147,94, 145,11, 141,59, 140,30, 136,69, 128,73, 128,43, 127,08, 126,55, 126,11, 125,79, 125,28, 120,35, 117,18, 101,01, 61,28, 61,07, 55,85, 52,91, 37,93, 34,21, 28,17. HRMS (ESI+): [M+H]+: calculated for C27H33N6+(m / z): 441,27612; detected: 441,27338. LC-MS purity 99 %

[0260]

[0261] 3-{[5-(2-methanesulfonylethyl)-octahydropyrrolo[3,4-c]pyrrol-2-yl]methyl}-5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}pyridine-2-amine (26): DIPEA (156 pL; 0.90 mmol), compound 25 (60 mg; 0.18 mmol) in anhydrous DCM (5 mL) at RT. 2-Methylsulfonylethyl bromide (67 mg; 0.36 mmol) was added. The obtained residue was concentrated, diluted with sodium hydrogencarbonate (NaHCO3; 30 mL) and extracted by ethyl acetate (EA; 3 x 30 mL). The organic phases were collected, dried over anhydrous NajSCL and filtered. The filtrate was concentrated under vacuum and purified by column chromatography using the mobile phase CHCl3 / MeOH / NHiOH (25 % aqueous solution) (20:1:0.1) to obtain the pure product 26 as white solid. Yield 78 %.1H NMR (500 MHz, CDCl3-<7+MeOD-<74) 58,30 - 8,18 (m, 1H), 8,11 - 8,00 (m, 1H), 8,00 - 7,90 (m, 1H), 7,50 - 7,40 (m, 1H), 7,32 - 7,26 (m, 1H), 6,49 - 6,33 (m, 1H), 3,51 (s, 2H), 3,14 - 3,07 (m, 2H), 2,95 (s, 2H), 2,87 - 2,80 (m, 2H), 2,75 - 2,63 (m, 4H), 2,51 - 2,42 (m, 2H), 2,40 - 2,33 (m, 2H), 2,28 - 2,20 (m, 2H).13C NMR (126 MHz, CDCl3+MeOD) 5 161,28, 151,06, 148,07, 144,60, 140,34, 130,84, 130,41, 130,30, 129,05, 124,77, 122,22, 104,58, 64,09, 63,11, 61,61, 57,27, 45,67, 45,65, 33,55. HRMS (ESI+): [M+H]+: calculated for C22H29N6O2S+(m / z): 441,20672; detected: 441,20627. LC-MS purity 97 %

[0262]

[0263] A-(2-{5-[(2-amino-5-{LH-pyrrolo[2,3-Z>]pyridin-5-yl}pyridin-3-yl)methyl]-octahydropyrrolo[3,4-c]pyrrol-2-yl}ethyl)methanesulfonamide (27): DIPEA (192 pL; 1.10 mmol), compound 25 (73 mg; 0.22 mmol) in anhydrous DCM (5 mL) at RT. A-(2-Bromoethyl)methanesulfonamide (88 mg; 0.44 mmol) was added. The obtained residue was concentrated, diluted with sodium hydrogencarbonate (NaHCCF: 30 mL) and extracted by ethyl acetate (EA; 3 x 30 mL). Organic phases were collected, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under vacuum and purified by column chromatography using the mobile phase CHCL / McOH / NH-iOH (25 % aqueous solution) (9:1:0, 1) to obtain the pure product 27 as white solid. Yield 70 %.1H NMR (500 MHz, CDCL-r / ) 58,33 - 8,27 (m, 1H), 8,16 - 8,10 (m, 1H), 8,04 - 7,95 (m, 1H), 7,49 (d, J = 2,3 Hz, 1H), 7,31 (d, J = 3,5 Hz, 1H), 6,51 -6,42 (m, 1H), 3,57 (s, 2H), 3,19 - 3,12 (m, 2H), 2,93 - 2,92 (m, 3H), 2,84 - 2,77 (m, 2H), 2,74 - 2,66 (m, 2H), 2,62 - 2,55 (m, 2H), 2,51 - 2,44 (m, 2H), 2,45 - 2,38 (m, 2H), 2,28 - 2,20 (m, 2H).13C NMR (126 MHz, CDCh) 5 157,37, 147,20, 144,33, 140,84, 136,35, 126,85, 126,59, 126,19, 125,09, 120,71, 118,14, 100,72, 60,33, 59,08, 57,62, 54,53, 41,57, 41,15, 39,98. HRMS (ESI+): [M+H]+: calculated for C22H30N6O2S+(m / z): 456,21762; detected: 456,21722. LC-MS purity 96 %

[0264] Example 2 - Decrease in proliferation of tumor cell lines MV4-11, MOLM 13, and THP 1 due to the compounds of general formula I.

[0265] While the cell line MV4-11 is characterized by a homozygous mutation of FLT3 kinase, MOLM- 13 contains a heterozygous mutation and THP-1 has an unmutated FLT3 kinase. For each compound, the mean growth inhibition IC50 value was determined for the given cell lines. For each compound, the ratio of the specificity of the effect between the THP-1 line without FLT3 mutation and the line carrying the FLT3 mutation (MV4-11 and MOLM- 13) was subsequently calculated. This was then compared with the compound gilteritinib, which is in clinical practice as an FLT3 inhibitor for the therapy of acute myeloid leukemia.

[0266] Cell lines MV4-11, MOLM- 13 and THP-1 were plated in a 96-well plate at an optimal seeding density, which was determined separately for each line. Compounds of general formula I or gilteritinib were added to the cells in a twelve-point concentration curve. Concentration values were optimized for each compound. After 48 hours of incubation under standard conditions (37 °C, 5% CO2, sterile environment), cell viability was assessed using the MTT assay according to the manufacturer's instructions (Merck KGaA). The resulting IC50 values were determined using GraphPad Prism 10. , MV4-11 MOLM-13 THP-1 Specificity Specificity compoundICso(gM)IC50(pM) IC50(pM) THP-1 / MV4-11 THP-l / MOLM-13 1 0.252 0.271 8.06 32 30

[0267] 2 1.039 1.047 20.28 20 19

[0268] 3 2.412 3.222 68.91 29 21

[0269] 4 0.307 0.430 16.97 55 40

[0270] 5 0.389 0.496 11.42 29 23

[0271] 6 0.697 0.987 22.65 33 23

[0272] 7 0.506 0.598 9.73 19 16

[0273] 8 0.495 0.478 32.84 66 69

[0274] 9 0.388 0.494 52.28 135 106 10 0.153 0.244 17.21 113 71 11 0.314 0.558 24.26 77 43 12 0.317 0.468 20.39 64 44 13 0.364 0.670 23.70 65 35 14 0.364 0.947 20.92 58 22 15 1.271 1.424 25.02 20 18 16 0.533 0.478 3.97 7 8

[0275] 17 0.543 0.442 29.02 53 66 18 0.278 0.458 37.87 136 83 19 0.196 0.478 30.48 156 64 20 0.299 0.544 45.48 152 84 21 0.293 0.516 35.95 123 70 22 0.409 0.663 30.75 75 46 23 0.252 0.581 38.92 155 67 24 0.265 0.250 10.33 39 41 25 0.391 0.488 21.57 55 44 26 0.509 0.722 8.85 17 12 27 0.171 0.399 18.50 108 46 gilteritinib 0.010 0.020 0.52 50 27

Claims

1. CLAIMS1. Heterocyclic compound of general formula I4. 6.wherein7.- m = 0 and R2is H; or8.m = 1 and L1together with R2form a moiety -C(=CH-)-, wherein the group =CH- is bound by a single bond to the nitrogen atom (NH); or9.m = 1 and L1together with R2form a moiety -CH=C<, wherein the quarternary carbon is bound to the nitrogen atom and to the bridging methylene;10.I11.- the moiety12.

13. is an alifatic ring having 4 to 7 members, of which one or two members are nitrogen atoms, wherein one nitrogen atom is bound to the bridging methylene;14.- n = 0 or 1 or 2;15.- R1is selected from the group containing C1-C4 alkyl; 4- to 6-membered alifatic ring containing 1 to 2 heteroatoms selected from the group O, N, optionally further substituted by C1-C3 alkyl, (C1-C2 alkyl)-SO2-(Cl-C3 alkylene)-, (C1-C2 alkyl)-SO2-NH-(Cl-C3 alkylene)-; -NR4R5, wherein R4is selected from H, C1-C3 alkyl, R5is selected from C1-C3 alkyl, (C1-C2 alkyl)-SO2-(Cl-C3 alkylene)-, (C1-C2 alkyl)-SO2-NH-(Cl-C3 alkylene)-, phenyl-(Cl-C3 alkylene)-; or16.two R1substituents bound to the same carbon atom or to neighboring carbon atoms form a 4- to 6- membered alifatic ring containing 1 to 2 heteroatoms selected from the group O, N;17.and pharmaceutically acceptable salts thereof with alkali metals or amines, or acid addition salts thereof.18.(C1-C2 alkyl)-SO2-(Cl-C3 alkylene)- is preferably methyl-SO2-ethylene- or ethyl-SO2-ethylene. (C1-C2 alkyl)-SO2-NH-(Cl-C3 alkylene)- is preferably methyl-SO2-NH-ethylene- or ethyl-SO2-NH-ethylene-.19.Phenyl-(C1-C3 alkylene)- is preferably benzyl- or phenylethylene-.

2. Compound according to claim 1, wherein21.(C1-C2 alkyl)-SO2-(Cl-C3 alkylene)- is methyl-SO2-ethylene- or ethyl-SO2-ethylene;22.(C1-C2 alkyl)-SO2-NH-(Cl-C3 alkylene)- is methyl-SO2-NH-ethylene- or ethyl-SO2-NH-ethylene-; or phenyl-(Cl-C3 alkylene)- is benzyl- or phenylethylene-.

3. Compound according to claim 1 or 2, wherein pyrrolopyridine group is bound to the pyridine group in the position of meta or para relative to nitrogen.24.N4. Compound according to any one of claims 1 to 3, wherein the structure26.

27. (R )nis selected from the group:

29.

5. Compound according to any one of claims 1 to 3, selected from the group:32.1 -ethyl-4- [(5 -{ lH-pyrrolo[2,3-b]pyridin-5-yl}- lH-pyrrolo[2,3-b]pyridin-3-yl)methyl]piperazine, 1 -(oxetan-3 -yl)-4- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl } - IH-pyrrolo [2,3 -b]pyridin-3 -yl)methyl]piperazine,33.1 -methyl-4- { 1 - [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - IH-pyrrolo [2,3 -b]pyridin-3 -yl)methyl]piperidin-4-yl}piperazine,34.1 -ethyl-4- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl]piperazine, 1 -methyl-4- { 1 - [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl]piperidin-4-yl}piperazine,35.1 - [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl } - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl]piperidine,36.1 -ethyl-4- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl] - 1,4-diazepane, 2-methyl-6- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl} - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl] -2,6-diazaspiro [3.3 ]heptane,37.1'- [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl } - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl] - 1,4'-bipiperidine, '. '-dimcthy I - 1 - [(5 - { IH-pyrrolo [2,3-b]pyridin-5 -yl} - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl]piperidine-4-amine,38.'-mcthy I - 1 - [(5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl } - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl]piperidine-4-amine,39.JV-(2-methansulfonylethyl)-JV-methyl- 1 -[(5- { lH-pyrrolo[2,3-b]pyridin-5-yl }- lH-pyrrolo[2,3-b]pyridin-2-yl)methyl]piperidine-4-amine,40.JV-{2-[methyl({ l-[(5-{ lH-pyrrolo[2,3-b]pyridin-5-yl}-lH-pyrrolo[2,3-b]pyridin-2-yl)methyl]piperidin-4-yl})amino]ethyl}methanesulfonamide,41.2-({octahydropyrrolo[3,4-c]pyrrol-2-yl}methyl)-5-{lH-pyrrolo[2,3-b]pyridin-5-yl}-lH-pyrrolo[2,3-b]pyridine,42.1 -(oxetan-3 -yl)-4- [(4- { IH-pyrrolo [2,3 -b]pyridin-5 -yl } - IH-pyrrolo [2,3 -b]pyridin-2-yl)methyl]piperazine,43.l-ethyl-4-[(4-{lH-pyrrolo[2,3-b]pyridin-5-yl}-lH-pyrrolo[2,3-b]pyridin-2-yl)methyl]piperazine, 3 - [(4-ethyl- 1,4-diazepan- 1 -yl)methyl] -5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl }pyridine-2-amine,44.3 - { [4-(4-methylpiperazin- 1 -yl)piperidin- 1 -yl] methyl } -5 - { I H-pyrrolo [2,3 -b]pyridin-5 -yl }pyridine-2-amine,45.3-({[ l,4'-bipiperidin]-r-yl}methyl)-5-{ lH-pyrrolo[2,3-b]pyridin-5-yl}pyridine-2-amine,46.3-{[4-(dimethylamino)piperidin-l-yl]methyl}-5-{ lH-pyrrolo[2,3-b]pyridin-5-yl}pyridine-2-amine, 3 - { [4-(methylamino)piperidin- 1 -yl]methyl } -5 - { I H-pyrrolo [2,3 -b]pyridin-5 -yl }pyridine-2-amine, 3 -( {4- [(2-methanesulfonylethyl)(methyl)amino]piperidin- 1 -yl }methyl)-5 - { IH-pyrrolo [2,3 -b]pyridin-5-yl}pyridine-2-amine,47.N-[2-({ l-[(2-amino-5-{ lH-pyrrolo[2,3-b]pyridin-5-yl}pyridin-3-yl)methyl]piperidin-4-yl } (methyl)amino)ethyl]methanesulfonamide,48.3 -( {4- [methyl (2 -phenylethyl)amino]piperidin- 1 -yl}methyl)-5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl}pyridine-2-amine,49.3-({octahydropyrrolo[3,4-c]pyrrol-2-yl}methyl)-5-{lH-pyrrolo[2,3-b]pyridin-5-yl}pyridine-2-amine, 3-{[5-(2-methanesulfonylethyl)-octahydropyrrolo[3,4-c]pyrrol-2-yl]methyl}-5-{ lH-pyrrolo[2,3-b]pyridin-5 -yl }pyridine-2-amine, and50.N-(2- { 5 - [(2-amino-5 - { IH-pyrrolo [2,3 -b]pyridin-5 -yl }pyridin-3 -yl)methyl] -octahydropyrrolo [3,4-c]pyrrol-2-yl } ethyl)methanesulfonamide.

6. Compound of general formula I according to any one of claims 1 to 5 for use as a medicament.

7. Compound of general formula I according to any one of claims 1 to 5 for use in the treatment of tumor diseases.

8. Compound of general formula I according to any one of claims 1 to 5 for use in the treatment of leukaemia, in particular of leukaemia in patients carrying a gene FLT3 mutation.

9. A pharmaceutical preparation, characterized in that it contains at least one compound of general formula I according to any one of claims 1 to 5 and at least one pharmaceutically acceptable excipient.

10. The pharmaceutical preparation according to claim 9, which is in the form selected from the group comprising granules, powders, tablets, gels, capsules, syrups, emulsions, suspensions, formulations for injections, formulations for infusions, sprays and suppositories.

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