Quinoline-2-carboxamide derivatives as RAD51 inhibitors for the treatment of cancer

Abstract

The present invention relates to substituted quinoline derivatives of formula (I) as inhibitors of the activity of RAD51 for the treatment of cancer, cell proliferative disorders or immune disorders.

Description

[0001] NMS-128 SUBSTITUTED QUINOLINE DERIVATIVES AS RAD51 INHIBITORS Field of the invention The present invention relates to novel heterocyclic compounds of formula (I) that show an inhibitory activity toward the DNA-recombinase RAD51 protein, their pharmaceutically acceptable salts, solvates, polymorphs, tautomers, optical and geometric isomers thereof. The compounds may inhibit tumor growth in mammals and may be useful for treating human cancer patients. Aspects of the invention include methods of making, methods of preparing, methods of synthesis and methods of purification of the aforementioned compounds. Background of the invention Synthetic lethality is an interesting chance for discovering new anticancer drugs for personalized targeted therapies. Two genes are synthetically lethal if the perturbation of either gene alone has no effect on cell viability, but the simultaneous detriment of both genes results in cell death. Bioactive molecules can target the synthetically lethal partner of an altered gene in cancer cells but not in normal cells, giving the opportunity to selectively kill cancer cells. [Lucchesi, J. C. et all., Genetics, 1968, 59, 37−44; Kaelin, W. G., et all., Nat. Rev. Cancer, 2005, 5, 689−698; Gupta, A., et all., Curr. Cancer DrugTargets, 2018, 18, 337−346; Chan, D., et all., Nat. Rev. Drug Discovery, 2011, 10, 351−364; Beijersbergen, R., et all., Annu. Rev. Cancer Biol.2017, 1, 141−161; Chen, E., et all. Cell. Mol. Life Sci.2018, 75, 3381−3392; Ashworth, A., et all., Nat. Rev. Clin. Oncol.2018, 15, 564−576; Parameswaran, S., et all.,Trends Cancer, 2019, 5, 11−29]. The DNA repair and DNA damage response (DDR) pathways are suitable for the application of synthetic lethality as a novel therapeutic strategy in oncology [Bhattacharjee, S., et all., IUBMB Life, 2017, 69, 929−937; Minchom, A., et all., Ther. Adv. Med. Oncol., 2018, 10, 1−18; Pilie, P. G., et all., Nat. Rev. Clin. Oncol., 2019, 16, 81−104]. In cells DNA damage occurs continuously due to the incessant exposition to exogenous and endogenous stressors. To overcome this, cells have developed complex coordinated pathways to repair DNA damage and preserve genome integrity. DDR prevents the transmission of altered genetic material to daughter cells and acts as a tumor-suppressive barrier. Weaknesses in DDR are associated with the genome instability causing the accumulation of oncogenic mutations and leading to cancer initiation and progression. Cancer cells with deficiencies in one DDR pathway can become reliant on other pathways for their survival. Targeting these other DDR pathways can potentially cause selective cancer cell death by synthetic lethality [Bagnolini, G., J. Med. Chem.2020, 63, 2588−2619]. RAD51 and its gene family are key regulators of DNA fidelity through diverse roles in double-strand break repair (DBS), replication stress, and meiosis. RAD51 is an ATPase and is one of the pivotal enzymes for DBS repair by the homologous recombination (HR) pathway. RAD51 forms a nucleoprotein filament on single-stranded DNA, and it has the function of finding and invading homologous DNA sequences to enable accurate and timely DNA repair [Braulio Bonilla et all., Annu Rev Genet.2020 Nov 23; 54: 25–46; Qian Chen, at all., Oncol Rep, 2017;38(2):767-774]. RAD51 overexpression is observed in several human malignancies, including pancreatic adenocarcinoma, non-small cell lung cancer and breast cancer and its high expression is related to poor prognosis. RAD51 inhibition could be used as a new prospect for cancer treatment with the potential to enhance the therapeutic window of many established therapeutic strategies across multiple cancer indications [Gu et all. Front.Oncol.,2022, Volume 12, Article 885186]. For example, the overexpression of RAD51 confers resistance to PARP inhibitors in triple negative breast cancer cells [Liu, Y., et all., Clin Cancer Res, 2017, 23(2):514–22]. Furthermore, RAD51 foci formation correlates with resistance to PARP inhibitors in breast cancer patients with germline BRCA mutations [Cruz, C., et all., Ann Oncol, 2018, 29(5):1203–10]. RAD51 is emerging as an interesting therapeutic target for restoring synthetic lethality in tumors that have developed resistance to PARP inhibitors. The importance of RAD51 in DNA DSB repair is demonstrated by studies showing that increased expression of RAD51 and other HR-associated genes in tumor cells is associated with resistance to chemotherapies or radiotherapies that induce DNA damage, suggesting that targeting RAD51 may improve the efficacy of aforementioned DNA-damaging agents [Wang, J., et all., Cancer Manage Res, 2019, 11:3253–64; Xu, Z-Y., et all., J Pharmacol Exp Ther, 2005, 314(2):495–505; Gu et all. Front.Oncol.,2022, Volume 12, Article 885186]. Nowadays, there are some compounds disclosed as RAD51 inhibitors in literature, for instance, in WO2023 / 161782A1, WO2021 / 178531A1, WO2016 / 140971A1, J. Med. Chem.2020, 63, 2588−2619, Cell Chemical Biology, (28), 835–847, June 17, 2021. For all these reasons, there is an increasing demand of novel RAD51 inhibitors that can be useful to treat cancer and other pathologies. Definitions With the term "straight or branched (C1-C6) alkyl", hence comprehensive of (C1-C4) alkyl, we intend any of the groups such as, for instance, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n- pentyl, n-hexyl, and the like. With the term "straight or branched (C2-C6) alkenyl", we intend any of the groups such as, for instance, vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 4-methyl-1-pentenyl, 1-hexenyl, styryl, and the like. With the term "straight or branched (C2-C6) alkynyl" we intend any of the groups such as, for instance, ethynyl, 2-propynyl, 4-pentynyl, and the like. With the term "(C3-C7) cycloalkyl", we intend, unless otherwise provided, 3- to 7-membered all-carbon monocyclic ring. Examples of cycloalkyl groups, without limitation, are cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane. The cycloalkyl ring can be optionally further fused or linked to aromatic and non-aromatic carbocyclic, 3-10 membered heterocyclic and 5-7 membered heteroaryl rings. Not limiting examples of such cycloalkyl ring fused with non-aromatic carbocyclic rings are bicyclo[1.1.0]butane, bicyclo[2.1.0]pentane, bicyclo[3.1.0]hexane, norcarane, 1,2,3,3a,4,5,6,6a- octahydropentalene, decalin. Not limiting examples of such cycloalkyl ring fused with heterocyclic rings are 3-oxabicyclo[3.1.0]hexane, 3-azabicyclo[3.1.0]hexane. Not limiting examples of such cycloalkyl ring linked to non-aromatic carbocyclic rings are spiro[2.2]pentane, spiro[3.3]heptane, spiro[4.4]nonane, spiro[2.4]heptane, spiro[3.4]octane, spiro[2.3]hexane, spiro[3.5]nonane, spiro[2.5]octane. Not limiting examples of such cycloalkyl ring linked to heterocyclic rings are 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 1- oxaspiro[3.3]heptane, 1-azaspiro[3.3]heptane, 1-azaspiro[2.3]hexane. With the term "(C3-C7) cycloalkenyl", we intend, unless otherwise provided, 3- to 7-membered all-carbon monocyclic ring, which contain one or more double bonds but does not have a completely conjugated π- electron system. Examples of cycloalkenyl groups, without limitation, are cyclopentene, cyclohexene, cyclohexadiene, cycloheptene, cycloheptadiene and the like. The term "aryl" refers to a mono-, bi- or poly-carbocyclic hydrocarbon with from 1 to 4 ring systems, optionally further fused or linked to each other by single bonds, wherein at least one of the carbocyclic rings is “aromatic”, wherein the term “aromatic” refers to completely conjugated π-electron bond system. Non limiting examples of such aryl groups are phenyl, α- or β-naphthyl, α- or β-tetrahydronaphthalenyl, biphenyl, and indanyl groups. The term "5-7 membered heteroaryl" refers to aromatic heterocyclic rings, typically 5- to 7-membered heterocycles with from 1 to 3 heteroatoms selected among N, O or S; the 5-7 membered heteroaryl ring can be optionally further fused or linked to aromatic and non-aromatic carbocyclic and heterocyclic rings. Not limiting examples of such 5-7 membered heteroaryl groups are, for instance, pyridyl or pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, imidazolyl, thiazolyl, isothiazolyl, pyrrolyl, furanyl, oxazolyl, isoxazolyl, pyrazolyl, thiophenyl, thiadiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, indazolyl, cinnolinyl, benzo[1,3]dioxolyl, benzo[1,4]dioxinyl, benzothiazolyl, benzothiophenyl, benzofuranyl, isoindolinyl, benzoimidazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, 1,2,3-triazolyl, 1-phenyl-1,2,3-triazolyl, 2,3-dihydroindolyl, 2,3- dihydrobenzofuranyl, 2,3-dihydrobenzothiophenyl, benzopyranyl, 2,3-dihydrobenzoxazinyl, 2,3- dihydroquinoxalinyl and the like. With the term “3-10 membered heterocyclyl”, we intend a 3- to 10-membered, saturated or partially unsaturated carbocyclic ring where one or more carbon atoms are replaced by heteroatoms such as nitrogen, oxygen and sulfur. Sulfur may optionally be oxidized, and nitrogen may optionally bring a substituent and may optionally be quaternized. The aforementioned ring may optionally contain oxidized carbon atom (such as, for instance, a ketone group). Non limiting examples of 3-10 membered heterocyclyl groups are, for instance, aziridinyl, azetidinyl, pyranyl, tetrahydropyranyl, pyrrolidinyl, pyrrolinyl, 3-pyrrolinyl, imidazolinyl, imidazolidinyl, pyrazolidinyl, pyrazolinyl, thiazolinyl, oxazolinyl, 1,3-thiazolidinyl, 1,2-thiazolidinyl 1,3- oxazolidinyl, 1,2-oxazolidinyl, dihydrofuranyl, tetrahydrofuranyl, tetrahydropyridinyl, 3,6-dihydro-2H-pyranyl, 1,3-dioxolanyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, 1,4-dioxanyl, 1,4-diazepanyl, 1,4-oxazepanyl, 1-dioxothianyl, 1,2,3,6-tetrahydropyridinyl, thiomorpholinyl, homopiperazinyl, 2,3,4,7-tetrahydro-1-azepinyl, 3,4-dihydro-2-pyranyl, oxetanyl, oxiranyl and the like. Non limiting examples of 3-10 membered heterocyclyl groups containing oxidized carbon atom are, for instance, 2-oxetanonyl, 3-oxo-pyrrolidynyl, 2-oxo- pyrrolidynyl or 2-pyrrolidonyl or 2-pyrrolidinonyl, 2(1H)-pyrimidinonyl, 2-oxo-piperidinyl, 3-oxo-piperidinyl, 4- oxo-piperidinyl, 2-oxo-piperazinyl, 2-morpholinonyl, 3-morpholinonyl. Non limiting examples of 3-10 membered heterocyclyl groups containing an oxidized sulfur atom are, for instance, 1,3-thiazolidinyl 1,1- dioxide, 1,2-thiazolidinyl 1,1-dioxide, 1,4-thiazinanyl 1,1-dioxide, 1,2-thiazinanyl 1,1-dioxide, 1,4-thiazinanyl 1-oxide, 1,2-thiazinanyl 1-oxide, 1,3-thiazolidinyl 1-oxide, 1,2-thiazolidinyl 1-oxide. The 3-10 membered heterocyclic ring can be optionally further fused or linked to aromatic and non-aromatic carbocyclic, heterocyclic and heteroaryl rings; non limiting examples are 3,8-diazabicyclo[3.2.1]octanyl, 2-oxa-5- azaspiro[3.5]nonanyl, 1,2,3,4-tetrahydroquinolinyl, indolinyl, 1,4-diazabicyclo[2.2.2]octanyl, 1- azabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.1]heptanyl, 4-azaspiro[2.5]octanyl, 5-azaspiro[3.5]nonanyl, 2,5- diazaspiro[3.5]nonanyl, 1,5-diazaspiro[3.5]nonanyl, 1,6-diazaspiro[4.5]decanyl, 2,6-diazaspiro[4.5]decanyl, 1-oxa-6-azaspiro[4.5]decanyl, 2-oxa-6-azaspiro[4.5]decanyl, 4,7-diazaspiro[2.5]octanyl, 5,8- diazaspiro[3.5]nonanyl, 6,9-diazaspiro[4.5]decanyl, 6-azaspiro[4.5]decanyl, 2,5,8-triazaspiro[3.5]nonanyl, 1,6-diazaspiro[4.5]decanyl, 2,6-diazaspiro[4.5]decanyl, 2-oxa-5,8-diazaspiro[3.5]nonanyl, 1-oxa-6,9- diazaspiro[4.5]decanyl, 2-oxa-6,9-diazaspiro[4.5]decanyl, 2,6,9-triazaspiro[4.5]decanyl, 7-oxa-4- azaspiro[2.5]octanyl, 4-oxa-7-azaspiro[2.5]octanyl, 8-oxa-5-azaspiro[3.5]nonanyl, 5-oxa-8- azaspiro[3.5]nonanyl, 9-oxa-6-azaspiro[4.5]decanyl, 6-oxa-9-azaspiro[4.5]decanyl, 8-oxa-2,5- diazaspiro[3.5]nonanyl, 5-oxa-2,8-diazaspiro[3.5]nonanyl, 9-oxa-2,6-diazaspiro[4.5]decanyl, 6-oxa-2,9- diazaspiro[4.5]decanyl, 2,8-dioxa-5-azaspiro[3.5]nonanyl, 2,5-dioxa-8-azaspiro[3.5]nonanyl, 2,6-dioxa-9- azaspiro[4.5]decanyl, 4-azaspiro[2.4]heptanyl, 5-azaspiro[3.4]octanyl, 1-azaspiro[4.4]nonanyl, 2,5- diazaspiro[3.4]octanyl, 2-oxa-5-azaspiro[3.4]octanyl, 1,7-diazaspiro[4.4]nonanyl, 7-oxa-1- azaspiro[4.4]nonanyl, 1-oxa-6-azaspiro[4.4]nonanyl, 2,6-diazaspiro[3.3]heptanyl, 1,6- diazaspiro[3.3]heptanyl, octahydropyrrolo[3,4-b]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 3,6- diazabicyclo[3.2.0]heptanyl, 2,6-diazabicyclo[3.2.0]heptanyl, 3,8-diazabicyclo[4.2.0]octanyl, 3,7- diazabicyclo[4.2.0]octanyl, 2,7-diazabicyclo[4.2.0]octanyl, decahydro-1,6-naphthyridinyl, decahydro-2,6- naphthyridinyl, decahydro-2,7-naphthyridinyl, decahydro-1,7-naphthyridinyl, decahydro-1,8-naphthyridinyl, decahydro-1,5-naphthyridinyl, octahydro-1H-pyrido[3,4-b][1,4]oxazinyl, 1,6-diazaspiro[3.4]octanyl, 2,6- diazaspiro[3.4]octanyl, 2,7-diazaspiro[4.4]nonanyl, octahydro-2H-pyrido[4,3-b]-1,4-oxazinyl, octahydro-1H- pyrrolo[3,4-b]pyridinyl, octahydro-1H-pyrrolo[3,4-c]pyridinyl, octahydropyrrolo[3,4-b]-1,4-oxazinyl, 1,4- diazabicyclo[2.2.1]heptanyl, 4-oxaspiro[2.5]octanyl, octahydro-1H-pyrrolo[3,4-b]pyrazinyl. With the term “halogen” we intend a fluorine, chlorine, bromine or iodine. With the term “straight or branched (C1-C6) haloalkyl”, hence comprehensive of (C1-C3) haloalkyl, we intend any of the above defined C1-C6alkyl groups which are substituted by one or more than one halogen atom such as, for instance, trifluoromethyl and trifluoroethyl. With the term “cyano” we intend a -CN residue. With the term “nitro” we intend a -NO2 group. With the term “alkenyl” or “alkynyl” we intend any of the aforementioned straight or branched (C2-C6) alkyenyl or straight or branched (C2-C6) alkynyl groups. With the terms “(C1-C6) alkoxy”, hence comprehensive of (C1-C3) alkoxy, we intend any of the above straight or branched (C1-C6) alkyl groups linked to the rest of the molecule through an oxygen atom (-O-). With the terms “aryloxy and 3-10 membered heterocyclyloxy” and derivatives thereof, we intend any of the above aryl or 3-10 membered heterocyclyl groups linked to the rest of the molecule through an oxygen atom (-O-). With the term “(C1-C6) haloalkoxy”, hence comprehensive of (C1-C3) haloalkoxy, we intend any of the above straight or branched (C1-C6) alkoxy groups which are substituted by one or more halogen atoms such as, for instance, trifIuoromethyI, trifluoroethyl, 1,1,1,3,3,3-hexafluoropropyl, trifluoromethoxy and the like. With the term “(C1-C6)alkylamino and di(C1-C6)alkylamino”, hence comprehensive of (C1-C3)alkylamino and di(C1-C3)alkylamino, we intend any of the above (C1-C6) alkyl, linked to the rest of the molecule through a nitrogen atom (-N-). Non limiting examples of (C1-C6)alkylamino and di(C1-C6)alkylamino are, for instance, dimethylamine, diethylamine, diisopropylamine, dipropylamine, methylamine, ethylamine, isopropylamine, propylamine, N-ethyl-N-methylamine, methylisopropylamine, methylpropylamine, ethylpropylamine, ethylisopropylamine. From all of the above, it is clear to the skilled person that any group whose name is a composite name such as, for instance, arylamino, has to be intended as conventionally construed by the parts from which it derives, e.g. by an amino group which is further substituted by aryl, wherein aryl is as above defined. Likewise, any of the terms such as, for instance, alkylthio, (C1-C6)alkylamino, di(C1-C6)alkylamino, alkoxycarbonyl, alkoxycarbonylamino, 3-10 membered heterocyclylcarbonyl, 3-10 membered heterocyclylcarbonylamino, cycloalkyIoxycarbonyI and the like, include groups wherein the alkyl, alkoxy, aryl, (C3-C7) cycloalkyl and 3-10 membered heterocyclyl moieties are as above defined. It is known to the person skilled in the art that transformation of a chemical functional group into another may require that one or more reactive centers in the compound containing such functional group have to be protected in order to avoid undesired side reactions. Protection of such reactive centers, and subsequent deprotection at the end of the synthetic transformations, can be accomplished following standard procedures described in the literature (see, for instance, Green, Theodora W. and Wuts, Peter G.M. – Protective Groups in Organic Synthesis, Third Edition, John Wiley & Sons Inc., New York (NY), 1999). Therefore, the term “protecting group” refers to a group used to protect such reactive centers in a chemical synthesis, for example, a hydroxyl group (–OH), an amino group (-NH), a thiol group (-SH), a carbonyl group (-C=O), a carboxylic group (-COOH). Examples of protecting groups are those reported in the literature (see, for instance, ibidem). The term “nitrogen protecting group” refers to a group that with the nitrogen atom form carbamates, amides, cyclic imides, N-alkyl and N-aryl amines. Such protecting groups are well-known in the art (see e.g. ibidem). Non limiting examples of carbamate protecting groups are, for instance, methyl and ethyl carbamate, 9- fluorenylmethyl carbamate (Fmoc), 2,2,2-trichloroethylcarbamate (Troc), t-butyl carbamate (BOC), vinyl carbamate (Voc), allyl carbamate (Alloc), benzyl carbamate (Cbz), p-nitrobenzyl and the like. Non limiting examples of amides are, for instance N-trichloroacetamide, N-trifluoroacetamide (TFA) and the like. Non limiting examples of cyclic imide protecting groups are, for instance, N-phthalimide, N-dithiasuccinoylimide (Dts) and the like. Non limiting examples of N-alkyl and N-aryl protecting groups are, for instance, N- allylamine, N-benzylamine and the like. The term “hydroxyl protecting group” refers to a group that with the oxygen atom form ethers, esters, cyclic acetals or ketals. Such protecting groups are well-known in the art (see e.g. ibidem). Non limiting examples of ethers protecting groups are, for instance, alkyl ethers and benzyl ethers, such as methoxymethyl ether (MOM-OR), tetrahydropyranyl ether (THP-OR), allyl ether (Allyl-OR), benzyl ether (Bn-OR), triphenylmethyl ether (Tr-OR) and the like, or silyl ethers, such as trimethylsilyl ether (TMS-OR), t-butyldimethylsilyl ether (TBS-OR or TBDMS-OR), t-butyldiphenylsilyl ether (TBDPS-OR) diphenylmethylsilyl ether (DPMS-OR) and the like. Non limiting examples of esters protecting groups are, for instance, trifluoroacetate, benzoate (Bz- OR) and carbonates, such as ethylcarbonate and the like. Non limiting examples of cyclic acetals or ketals protecting groups are, for instance, methylene acetal, ethylidene acetal, methoxymethylene acetal and the like. According to the present invention and unless otherwise provided from R1 to R24 may be optionally substituted, in any of their free positions, by one or more groups, for instance 1 to 6 groups, independently selected from: hydroxyl, hydroxy(C1-C6)alkyl, halogen, nitro, oxo group (=O), cyano, (C1-C6)alkyl, polyfluorinated (C1-C6)alkyl , polyfluorinated (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, aryl(C1- C6)alkyl, (C1-C6)alkylaryl, aryl(C1-C6)alkoxy, 5-7 membered heteroaryl , 5-7 membered heteroaryl (C1- C6)alkyl, (C1-C6)alkyl5-7 membered heteroaryl , 3-10 membered heterocyclyl, 3-10 membered heterocyclyl(C1-C6)alkyl, (C1-C6)alkyl3-10 membered heterocyclyl, (C1-C6)alkyl3-10 membered heterocyclyl(C1-C6)alkyl, tri(C1-C6)alkylsilyl, (C3-C7)cycloalkyl, (C1-C6)alkoxy, aryloxy, 3-10 membered heterocyclyloxy, methylenedioxy, (C1-C6)alkylcarbonyloxy, arylcarbonyloxy, di(C1-C6)alkylamino3-10 membered heterocyclyl(C1-C6)alkyl, (C3-C7)cycloalkenyloxy, 3-10 membered heterocyclylcarbonyloxy, (C1- C6)alkylideneaminooxy, carboxy, (C1-C6)alkoxycarbonyl, aryloxycarbonyl, (C3-C7)cycloalkyloxycarbonyl, amino, 3-10 membered heterocyclyl(C1-C6)alkoxycarbonylamino, ureido, (C1-C6)alkylamino, amino(C1- C6)alkyl, di(C1-C6)alkylamino, arylamino, diarylamino, 3-10 membered heterocyclylamino, formylamino, (C1- C6)alkylcarbonylamino, arylcarbonylamino, 3-10 membered heterocyclylcarbonylamino, aminocarbonyl, (C1- C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl, arylaminocarbonyl, 5-7 membered heteroaryl aminocarbonyl, arylaminocarbonyl(C1-C6)alkyl, (C3-C7)cycloalkylaminocarbonyl, 3-10 membered heterocyclylaminocarbonyl, (C1-C6)alkoxycarbonylamino, hydroxyaminocarbonyl, (C1-C6)alkoxyimino, (C1- C6)alkylsulfonylamino, arylsulfonylamino, 3-10 membered heterocyclylsulfonylamino, formyl, (C1- C6)alkylcarbonyl, arylcarbonyl, (C3-C7)cycloalkylcarbonyl, 3-10 membered heterocyclylcarbonyl, 3-10 membered heterocyclylcarbonyl(C1-C6)alkyl, (C1-C6)alkylsulfonyl, polyfluorinated (C1-C6)alkylsulfonyl, arylsulfonyl, aminosulfonyl, (C1-C6)alkylaminosulfonyl, di(C1-C6)alkylaminosulfonyl, arylaminosulfonyl, 3-10 membered heterocyclylaminosulfonyl, arylthio, (C1-C6)alkylthio; Detailed description of the invention The present inventors have discovered that compounds of general formula (I), as defined below, are RAD51 inhibitors. Accordingly, a first object of the present invention is to provide a substituted quinoline derivative of formula (I): wherein: X is a halogen atom; Y is H or a halogen atom; R1, R2, R3 and R4 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, (C3-C7) cycloalkyl; or R1 and R2 and / or R3 and R4 taken together with the carbon atom they are bonded may form a (C3-C7) cycloalkyl; Z is a substituted aryl of formula (IIa) or a substituted heteroaryl selected from the group consisting of (IIb1)- (IIb7): , R5 is - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl, - (C3-C7) cycloalkenyl, - straight or branched (C1-C6) haloalkyl, - straight or branched (C2-C6) alkenyl optionally substituted with: - halogen, - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl, optionally substituted with straight or branched (C1-C6) alkyl, - 5-7 membered heteroaryl optionally substituted with (C1-C6) alkyl, - (C1-C3) alkoxy, - (C1-C3) haloalkoxy, - hydroxyl, - phenyl, - ether group -OR13, - amino group -NR10R11, - amide group -NR17COR18 or - 1-methyl-1,2,3,6-tetrahydropyridine; R6 and R7 the same or differently are each independently: - hydrogen, - halogen, - hydroxyl group, - straight or branched (C1-C6) alkyl, optionally substituted with 3-10 membered heterocyclyl, in its turn optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl, - straight or branched (C1-C6) haloalkyl, - oxetanyl, - (C3-C7) cycloalkyl optionally substituted with: -(C1-C6)alkylamino, -di(C1-C6)alkylamino or -3-10 membered heterocyclyl, - straight or branched (C1-C6) haloalkyl, - phenyl substituted with hydroxyl group, - 5-7 membered heteroaryl optionally substituted with a straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl optionally substituted with: - benzyl, - from one to four straight or branched (C1-C6) alkyl groups in their turn optionally substituted independently with (C3-C7) cycloalkyl, (C1-C3) alkoxy or 3-methylisoxazole ring, - halogen, - (C3-C7) cycloalkyl in its turn optionally substituted with halogen, - straight or branched (C1-C6) haloalkyl, - di(C1-C6)alkylamino, - oxetanyl, - amino group -NR10’R11’, - thioether group -SR12’, - ether group -OR13’, - sulfone group -SO2R14’, - sulfonamide group -SO2NR15’R16’, - amide group -NR17’COR18’; - group COR18’; or R5 and R6 taken together may form a phenyl ring or a 3-10 membered heterocyclic ring optionally substituted with one or two halogens; or R6 and R7 taken together may form a 3-10 membered heterocyclyl optionally substituted with: halogen, a group -COR18’ or straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; R8 is - halogen, - straight or branched (C2-C6) alkenyl optionally substituted with: - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, - (C1-C3) alkoxy, - (C1-C3) haloalkoxy; and R9 is - hydrogen, - halogen, - straight or branched (C2-C6) alkenyl optionally substituted with a (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl optionally substituted with from one to four straight or branched (C1- C6) alkyl groups, - ether group -OR13’, - amide group -NR17’COR18’, wherein: R10 and R11 the same or differently are each independently hydrogen, (C3-C7) cycloalkyl or straight or branched (C1-C6) alkyl; R10’ and R11’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with 1-methylimidazole, - (C3-C7) cycloalkyl or - 3-10 membered heterocyclyl optionally substituted with: -halogen, -straight or branched (C1-C6) alkyl, -(C1-C3) haloalkoxy, -(C3-C7) cycloalkyl or -oxetanyl; R12’ is - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl or - 3-10 membered heterocyclyl optionally substituted with a straight or branched (C1-C6) alkyl or (C3- C7) cycloalkyl; R13 is - straight or branched (C1-C6) alkyl optionally substituted with: - (C3-C7) cycloalkyl in its turn optionally substituted with 1 or two halogens, - straight or branched (C2-C6) alkynyl in its turn optionally substituted with (C3-C7) cycloalkyl, - benzyl group or - N-methyl-piperidinyl; R13’ is - straight or branched (C1-C6) alkyl optionally substituted with: - pyridine, - (C3-C7) cycloalkyl in its turn optionally substituted with di(C1-C6)alkylamino, - di(C1-C6)alkylamino, - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, - straight or branched (C1-C6) haloalkyl, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino or - 3-10 membered heterocyclyl optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - (C3-C7) cycloalkyl, - halogen, - straight or branched (C1-C6) haloalkyl, - oxetanyl; R14’ is straight or branched (C1-C6) alkyl, 3-10 membered heterocyclyl or (C3-C7) cycloalkyl; R15’ and R16’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group, straight or branched (C1-C3) alkoxy, di(C1-C6)alkylamino, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, halogen or (C3-C7) cycloalkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R17 and R17’ the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R18 is (C3-C7) cycloalkyl or 3-10 membered heterocyclyl; and R18’ is - straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino or - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl or halogen; W is a 3-10 membered heterocyclic ring selected from the group consisting of (IIIa), (IIIb1)-(IIIb7), (IIIc1)- (IIIc4) and (IIId1-IIId4):

[0002] , wherein: R19 and R20 the same or differently are each independently hydrogen, halogen, straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, cyano group, OR21 or NR22R23; or R19 and R20 taken together may form a (C3-C7) cycloalkyl ring optionally substituted with straight or branched (C1-C6) alkyl; wherein: R21 is hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R22 and R23 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; and R24 is straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl. Preferred compounds of formula (I) are the compounds wherein: X and Y are as defined above; R1, R2, R3 and R4 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; Z is a substituted aryl selected from the group consisting of (IIa1), (IIa2) and (IIa3) or a substituted heteroaryl selected from the group consisting of (IIb1), (IIb3) and (IIb7): wherein: when Z is a substituted aryl of formula (IIa1): R5 is: - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl, - (C3-C7) cycloalkenyl, - straight or branched (C1-C6) haloalkyl, - straight or branched (C2-C6) alkenyl optionally substituted with: - halogen, - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, wherein the 3-10 membered heterocyclic ring is a 3-5 membered, saturated or partially unsaturated carbocyclic ring wherein one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, or is selected from 3-oxabicyclo[3.1.0]hexyl and 3- azabicyclo[3.1.0]hexyl, - 5-7 membered heteroaryl selected from pyrazolyl and thiophenyl, optionally substituted with (C1-C6) alkyl, - (C1-C3) alkoxy, - (C1-C3) haloalkoxy, - hydroxyl group, - phenyl, - ether group -OR13, - amino group -NR10R11, - amide group -NR17COR18 or - 1-methyl-1,2,3,6-tetrahydropyridine; R6 and R7 the same or differently are each independently: - hydrogen, - halogen, - hydroxyl group, - straight or branched (C1-C6) alkyl optionally substituted with 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclic ring is a 4-6 membered, saturated or partially unsaturated carbocyclic ring where one or two carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, wherein the 4-6 membered ring is optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl, - straight or branched (C1-C6) haloalkyl, - oxetanyl, - (C3-C7) cycloalkyl optionally substituted with: -(C1-C6)alkylamino, -di(C1-C6)alkylamino or -3-10 membered heterocyclyl selected from azetidinyl, aziridinyl and pyrrolidinyl, - straight or branched (C1-C6) haloalkyl, - phenyl substituted with hydroxyl group, - 5-7 membered heteroaryl selected from imidazolyl, pyrazolyl and pyridinyl, optionally substituted with a straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 5-7 membered, saturated or partially unsaturated, carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, one or two carbon atoms may be optionally oxidized, and the aforementioned 5-7 membered ring is optionally substituted with: - benzyl, - from one to four straight or branched (C1-C6) alkyl groups wherein one (C1-C6) alkyl group may be optionally substituted with (C3-C7) cycloalkyl, (C1-C3) alkoxy or 3-methylisoxazole ring, - halogen, - (C3-C7) cycloalkyl in its turn optionally substituted with halogen, - straight or branched (C1-C6) haloalkyl, - di(C1-C6)alkylamino, - oxetanyl, or - 4-6 membered carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, wherein the 4-6 membered ring may be fused or linked with: -phenyl, -(C3-C7) cycloalkyl or - a group selected from azetidinyl, aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxiranyl, oxetanyl and tetrahydrofuranyl, wherein the aforementioned 4-6 membered ring is optionally substituted with straight or branched (C1-C6) alkyl, - amino group -NR10’R11’, - thioether group -SR12’, - ether group -OR13’, - sulfone group -SO2R14’, - sulfonamide group -SO2NR15’R16’, - amide group -NR17’COR18’; - group COR18’; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,4-dioxanyl, morpholinyl and piperidinyl, optionally substituted with halogen, a group -COR18’ or straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted aryl of formula (IIa2): R5 and R6 taken together may form a phenyl ring or a 1,3-dioxolanyl ring optionally substituted with one or two halogens; and R7 is hydrogen or straight or branched (C1-C3) alkoxy; when Z is a substituted aryl of formula (IIa3): R5 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; R6 is hydrogen or amide group -NR17’COR18’; R7 is halogen or hydroxyl group; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,3-dioxolanyl, 1,4 dioxanyl, pyrrolidinyl and piperidinyl, optionally substituted with straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted 5-7 membered heteroaryl selected from the group consisting of (IIb1), (IIb3) and (IIb4): R8 is a halogen or straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; and R9 is - hydrogen, - straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from piperazinyl, morpholinyl, 1,2,3,6-tetrahydropyridinyl and piperidinyl, optionally substituted with from one to four straight or branched (C1-C6) alkyl groups, - ether group -OR13’, - amide group -NR17’COR18’; when Z is a substituted 5-7 membered heteroaryl of formula (IIb7): R8 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; and R9 is hydrogen; wherein: R10 and R11 the same or differently are each independently hydrogen or straight or branched (C1- C6) alkyl; R10’ and R11’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with 1-methylimidazole, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 4-6 membered, saturated or partially unsaturated, carbocyclic ring wherein one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, wherein the 4-6 membered ring is optionally substituted with: -halogen, -straight or branched (C1-C6) alkyl, -(C1-C3) haloalkoxy, -(C3-C7) cycloalkyl or -oxetanyl, wherein the aforementioned 4-6 membered ring can be optionally further linked with (C3-C7) cycloalkyl; R12’ is - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from piperidinyl and pyrrolidinyl, optionally substituted with straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R13 is define above; R13’ is - straight or branched (C1-C6) alkyl optionally substituted with: - pyridine, - (C3-C7) cycloalkyl in its turn optionally substituted di(C1-C6)alkylamino, - di(C1-C6)alkylamino, - 3-10 membered heterocyclyl selected from oxiranyl, oxetanyl, azetidinyl and aziridinyl optionally substituted with straight or branched (C1-C6) alkyl, - straight or branched (C1-C6) haloalkyl, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 4-6 membered, saturated or partially unsaturated, carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, and the aforementioned 4-6 membered ring may be optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - (C3-C7) cycloalkyl, - halogen, - straight or branched (C1-C6) haloalkyl, - oxetanyl, or - 4-6 membered carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, fused or linked with: -(C3-C7) cycloalkyl or -a group selected from azetidinyl, aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxiranyl, oxetanyl and tetrahydrofuranyl, wherein the aforementioned 4-6 membered ring is optionally substituted with straight or branched (C1-C6) alkyl; R14’ is straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R15’ and R16’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group or di(C1-C6)alkylamino, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 4-6 membered saturated carbocyclic ring where one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, optionally substituted with straight or branched (C1-C6) alkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 5-6 membered, saturated carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, optionally substituted with straight or branched (C1-C6) alkyl; R17 and R17’ the same or differently are each independently hydrogen or straight or branched (C1- C6) alkyl; R18 is (C3-C7) cycloalkyl; and R18’ is - straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 3-6 membered, saturated or partially unsaturated, carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, and / or one or 2 carbon atoms are optionally oxidized, the aforementioned 3-6 membered ring may be optionally substituted with straight or branched (C1-C6) alkyl or halogen; W is a 3-10 membered heterocyclic ring, selected from the group consisting of (IIIa), (IIIb1), (IIIb2.1)-(IIIb7.1), (IIIc1)-(IIIc4) and (IIId1)-(IIId4):

[0003] R19, R20, R21, R22, R23 and R24 are as defined above. Further preferred compounds of formula (I) are the compounds wherein: X is a fluorine atom or a chlorine atom; Y is a hydrogen atom, a fluorine atom or a chlorine atom; R1, R2, R3 and R4 the same or differently are each independently selected from hydrogen, straight or branched (C1-C6) alkyl; Z is a substituted aryl selected from the group consisting of (IIa1), (IIa2) and (IIa3) or a substituted heteroaryl selected from the group consisting of (IIb1’), (IIb3’) and (IIb7’): wherein: when Z is a substituted aryl of formula (IIa1): R5 is: - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl, - (C3-C7) cycloalkenyl, - straight or branched (C1-C6) haloalkyl, - straight or branched (C2-C6) alkenyl optionally substituted with: - halogen, - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl selected from azetidinyl, pyrrolidinyl, oxetanyl, 3- oxabicyclo[3.1.0]hexyl and tetrahydrofuranyl, optionally substituted with straight or branched (C1-C6) alkyl, - 5-7 membered heteroaryl selected from pyrazolyl and thiophenyl, optionally substituted with straight (C1-C3) alkyl, - (C1-C3) alkoxy, - (C1-C3) haloalkoxy, - hydroxyl group, - phenyl, - ether group -OR13, - amino group -NR10R11, - amide group -NR17COR18, or - 1-methyl-1,2,3,6-tetrahydropyridine; R6 and R7 the same or differently are each independently - hydrogen, - halogen, - hydroxyl group, - straight or branched (C1-C6) alkyl optionally substituted with 3-10 membered heterocyclyl, selected from pyrrolidinyl, piperidinyl and piperazinyl, wherein the heterocyclyl is optionally substituted with: - from one to three straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl, - straight or branched (C1-C6) haloalkyl, - oxetanyl, - (C3-C7) cycloalkyl optionally substituted with: -(C1-C6)alkylamino, -di(C1-C6)alkylamino or -3-10 membered heterocyclyl selected from azetidinyl, aziridinyl and pyrrolidinyl, - straight or branched (C1-C6) haloalkyl, - phenyl substituted with hydroxyl group, - 5-7 membered heteroaryl selected from imidazolyl, pyrazolyl and pyridinyl, optionally substituted with a straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl selected from: -homopiperazinyl, piperazinyl, morpholinyl, 1,2,3,6-tetrahydropyridinyl, pyrrolidinyl, piperidinyl, 3-pyrrolinyl, 2,3,4,7-tetrahydro-1-azepinyl, 3,4-dihydro-2-pyranyl, 2(1H)- pyrimidinonyl and 2-pyrrolidinonyl, optionally substituted with: - benzyl, - from one to four straight or branched (C1-C6) alkyl groups wherein one (C1-C6) alkyl group may be optionally substituted with (C3-C7) cycloalkyl or 3- methylisoxazole ring, - halogen, - (C3-C7) cycloalkyl in its turn optionally substituted with halogen, - straight or branched (C1-C6) haloalkyl, - di(C1-C6)alkylamino, - oxetanyl, or - 3,8-diazabicyclo[3.2.1]octanyl, 1,2,3,4-tetrahydroquinolinyl, 2-oxa-5-azaspiro[3.5]nonanyl, indolinyl, 2,7-diazaspiro[4.4]nonanyl, 4-azaspiro[2.5]octanyl, 2-oxa-5,8- diazaspiro[3.5]nonanyl, 4,7-diazaspiro[2.5]octanyl, 4-oxa-7-azaspiro[2.5]octanyl, 5-oxa-2,8- diazaspiro[3.5]nonanyl, 2,8-dioxa-5-azaspiro[3.5]nonanyl, 2,6-diazaspiro[3.3]heptanyl, 1,6- diazaspiro[3.3]heptanyl, octahydropyrrolo[3,4-b]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 1,4-diazabicyclo[2.2.1]heptanyl, 1,4-diazabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.2]octanyl, 4-oxaspiro[2.5]octanyl, 4-azaspiro[2.4]heptanyl, 2-oxa-5-azaspiro[3.4]octanyl, 2,5- diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 1,6-diazaspiro[3.4]octanyl and 1,7- diazaspiro[4.4]nonanyl, optionally substituted with straight or branched (C1-C6) alkyl, - amino group -NR10’R11’, - thioether group -SR12’, - ether group -OR13’, - sulfone group -SO2R14’, - sulfonamide group -SO2NR15’R16’, - amide group -NR17’COR18’; - group COR18’; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,4-dioxanyl and piperidinyl, optionally substituted with halogen, a group -COR18’ or straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted aryl of formula (IIa2): R5 and R6 taken together may form a phenyl ring or a 1,3-dioxolanyl ring optionally substituted with one or two halogens; and R7 is hydrogen or straight or branched (C1-C3) alkoxy; when Z is a substituted aryl of formula (IIa3): R5 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; R6 is hydrogen or amide group -NR17’COR18’; R7 is halogen or hydroxyl group; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,3-dioxolanyl and pyrrolidinyl, optionally substituted with straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted 5-7 membered heteroaryl selected from the group consisting of (IIb1’) and (IIb3’): R8 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; and R9 is - hydrogen, - straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from 1,2,3,6-tetrahydropyridinyl and piperidinyl, optionally substituted with from one to four straight or branched (C1-C6) alkyl groups, - ether group -OR13’, - amide group -NR17’COR18’; when Z is a substituted 5-7 membered heteroaryl of formula (IIb7’): R8 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; and R9 is hydrogen; wherein: R10 and R11 are hydrogen; R10’ and R11’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with 1-methylimidazole, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from pyrrolidinyl, piperidinyl and tetrahydropyranyl, optionally substituted with: halogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R12’ is (C3-C7) cycloalkyl; R13 is define above; R13’ is - straight or branched (C1-C6) alkyl optionally substituted with: - pyridine, - (C3-C7) cycloalkyl in its turn optionally substituted with 1 or two halogen or di(C1- C6)alkylamino, - di(C1-C6)alkylamino, - 3-10 membered heterocyclyl selected from oxiranyl, oxetanyl, azetidinyl and aziridinyl, optionally substituted with straight or branched (C1-C6) alkyl, - straight or branched (C1-C6) haloalkyl, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, -3-10 membered heterocyclyl selected from: -oxetanyl, azetidinyl, piperidinyl and pyrrolidinyl, optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - (C3-C7) cycloalkyl, - halogen, - straight or branched (C1-C6) haloalkyl, - oxetanyl, or - 1,4-diazabicyclo[2.2.1]heptanyl, 1,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 4-azaspiro[2.4]heptanyl, 2-oxa-5-azaspiro[3.4]octanyl, 1,6-diazaspiro[3.4]octanyl, 2,6- diazaspiro[3.4]octanyl, 2,7-diazaspiro[4.4]nonanyl, 2,5-diazaspiro[3.4]octanyl, octahydropyrrolo[3,4-b]pyrrolyl and octahydropyrrolo[3,4-c]pyrrolyl, optionally substituted with straight or branched (C1-C6) alkyl; R14’ is as defined above; R15’ and R16’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group or di(C1-C6)alkylamino, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from azetidinyl, tetrahydropyranyl and piperidinyl, optionally substituted with straight or branched (C1-C6) alkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl selected from morpholinyl, piperazinyl and piperidinyl, optionally substituted with straight or branched (C1-C6) alkyl; R17 and R17’ are hydrogen; R18 is as defined above; and R18’ is - straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl selected from oxiranyl, oxetanyl, 2-oxetanonyl, aziridinyl, pyrrolidinyl, piperidinyl and tetrahydrofuranyl, optionally substituted with straight or branched (C1-C6) alkyl or halogen; W is a 3-10 membered heterocyclic ring selected from the group consisting of:

[0004] OHFO , , , X is a fluorine atom; Y is hydrogen atom; R1 and R2 are hydrogen; R3 and R4 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl; Z is a substituted aryl selected from the group consisting of (IIa1) and (IIa3): wherein: when Z is a substituted aryl of formula (IIa1): R5 is: - straight or branched (C2-C6) alkenyl optionally substituted with: - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl selected from 3-oxabicyclo[3.1.0]hexyl and 3- azabicyclo[3.1.0]hexyl, optionally substituted with straight or branched (C1-C6) alkyl, - ether group -OR13; R6 and R7 the same or differently are each independently: - hydrogen, - halogen, - hydroxyl group, - straight or branched (C1-C6) alkyl optionally substituted with 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 4-6 membered, saturated or partially unsaturated carbocyclic ring where one or two carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, wherein the 4-6 membered ring is optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl, - straight or branched (C1-C6) haloalkyl, - oxetanyl, - (C3-C7) cycloalkyl optionally substituted with: -(C1-C6)alkylamino, -di(C1-C6)alkylamino or -3-10 membered heterocyclyl selected from oxetanyl, oxiranyl, azetidinyl and aziridinyl, - straight or branched (C1-C6) haloalkyl, - 5-7 membered heteroaryl selected from imidazolyl and pyrazolyl, optionally substituted with a straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: -5-7 membered, saturated or partially unsaturated, carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, one or two carbon atoms may be optionally oxidized, and the aforementioned 5-7 membered ring is optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl in its turn optionally substituted with halogen, - straight or branched (C1-C6) haloalkyl, - di(C1-C6)alkylamino, - oxetanyl, or -4-6 membered carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, wherein the carbocyclic ring may be fused or linked with - (C3-C7) cycloalkyl, or -a group selected from azetidinyl, aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxiranyl, oxetanyl and tetrahydrofuranyl, wherein the aforementioned 4-6 membered ring is optionally substituted with straight or branched (C1-C6) alkyl, - amino group -NR10’R11’, - ether group -OR13’, - sulfone group -SO2R14’, - sulfonamide group -SO2NR15’R16’, - amide group -NR17’COR18’; - group COR18’; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,4-dioxanyl, morpholinyl and piperidinyl, optionally substituted with halogen, a group -COR18’ or straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted aryl of formula (IIa3): R5 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; R6 is hydrogen or amide group -NR17’COR18’; R7 is halogen or hydroxyl group; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,3-dioxolanyl, 1,4 dioxanyl, pyrrolidinyl and piperidinyl, optionally substituted with straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; wherein: R10’ and R11’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl, -3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 4-6 membered, saturated or partially unsaturated, carbocyclic ring wherein one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, wherein the 4-6 membered ring is optionally substituted with: - halogen, - straight or branched (C1-C6) alkyl, - (C1-C3) haloalkoxy, - (C3-C7) cycloalkyl or - oxetanyl, wherein the aforementioned 4-6 membered ring can be optionally further linked with (C3-C7) cycloalkyl; R13 is straight or branched (C1-C6) alkyl optionally substituted with (C3-C7) cycloalkyl; R13’ is - straight or branched (C1-C6) alkyl optionally substituted with: - (C3-C7) cycloalkyl in its turn optionally substituted with di(C1-C6)alkylamino, - di(C1-C6)alkylamino, - 3-10 membered heterocyclyl selected from oxiranyl, oxetanyl, azetidinyl and aziridinyl optionally substituted with straight or branched (C1-C6) alkyl, - straight or branched (C1-C6) haloalkyl, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 4-6 membered, saturated or partially unsaturated, carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, and the aforementioned 4-6 membered ring may be optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - (C3-C7) cycloalkyl, - halogen, - straight or branched (C1-C6) haloalkyl, - oxetanyl, or - 4-6 membered carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, fused or linked with -(C3-C7) cycloalkyl or -a group selected from azetidinyl, aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxiranyl, oxetanyl and tetrahydrofuranyl, wherein the aforementioned 4-6 membered ring is optionally substituted with straight or branched (C1-C6) alkyl; R14’ is straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R15’ and R16’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group or di(C1-C6)alkylamino, - (C3-C7) cycloalkyl, -3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 4-6 membered saturated carbocyclic ring where one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, optionally substituted with straight or branched (C1-C6) alkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 5-6 membered, saturated carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, optionally substituted with straight or branched (C1-C6) alkyl; R17’ is hydrogen; and R18’ is - straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 3-6 membered, saturated or partially unsaturated, carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, and / or one or two carbon atoms are optionally oxidized, the aforementioned 3-6 membered ring may be optionally substituted with straight or branched (C1-C6) alkyl or halogen; W is a 3-10 membered heterocyclic ring, selected from the group consisting of (IIIb1), (IIIb7.1) and (IIIc1.1)- (IIIc1.4): wherein: R19 and R20 the same or differently are each independently hydrogen, halogen, straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, cyano group, OR21 or NR22R23; or R19 and R20 taken together may form a (C3-C7) cycloalkyl ring optionally substituted with straight or branched (C1-C6) alkyl; wherein: R21 is hydrogen, straight or branched (C1-C6) alkyl; and R22 and R23 are each independently straight or branched (C1-C6) alkyl. Preferred specific compounds of formula (I), or a pharmaceutically acceptable salt thereof, are the compounds listed below: N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-[(1-methylimidazol-2-yl)methyl]amino]phenyl] ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 1); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4,4-difluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 2); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 3); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-isobutoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 4); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]azetidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 5); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(cyclopenten-1-yl)phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 6); N-[2-[(2S,4R)-2-[[(1S)-1-(2-cyclopentylphenyl)ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6- fluoro-quinoline-2-carboxamide (Compound 7); (4R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]-3-[2-[(6-fluoroquinoline-2-carbonyl) amino]acetyl]thiazolidine-4-carboxamide (Compound 8); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl) amino]acetyl]-6,6-dimethyl-morpholine-3-carboxamide (Compound 9); (2R,3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl) amino]acetyl]-2-methyl-morpholine-3-carboxamide (Compound 10); N-[2-[(2S,4R)-2-[[(1S)-1-[4-cyclopentylsulfanyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 11); N-[2-[(2S,4R)-2-[[(1S)-1-[4-cyclopentylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 12); N-[2-[(2S,4R)-2-[[(1R)-1-[4-cyclopentylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 13); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 14); N-[2-[(2S,4R)-2-[[(1R)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 15); N-[2-[(2S,4R)-2-[[(1S)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 16); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-(2-vinylphenyl)ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl] quinoline-2-carboxamide (Compound 17); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-prop-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2- oxo-ethyl]quinoline-2-carboxamide (Compound 18); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-styryl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl] quinoline-2-carboxamide (Compound 19); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-3-phenylprop-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 20); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl) amino]acetyl]morpholine-3-carboxamide (Compound 21); (3S)-N-[(1S)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 22); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylmethyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 23); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(4-methylpiperazin-1-yl)methyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 24); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(4-chlorophenyl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 25); N-[2-[(2S,4R)-2-[[(1R)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 26); N-[2-[(2S,4R)-2-[[(1S)-1-(2-benzyloxy-4-methoxy-phenyl)ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 27); N-[2-[(2S,4R)-2-[[(1R)-1-(2-benzyloxy-4-methoxy-phenyl)ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 28); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 29); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1R)-1-[4-methoxy-2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 30); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-methoxy-2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 31); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 32); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 33); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-(o-tolyl)ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2- carboxamide (Compound 34); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-(trifluoromethyl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo- ethyl]quinoline-2-carboxamide (Compound 35); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1R)-1-[4-methoxy-2-[(1-methyl-4-piperidyl)oxy]phenyl]ethyl] carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 36); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-methoxy-2-[(1-methyl-4-piperidyl)oxy]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 37); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopentylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 38); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclohexylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 39); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-methoxy-2-[(E)-4-methylpent-1-enyl]phenyl]ethyl] carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 40); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(3-cyclopropylprop-2-ynoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 41); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 42); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(3,3-difluorocyclobutyl)methoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 43); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(cyclobutylmethoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 44); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1R)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethyl] carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 45); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethyl] carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 46); N-[2-[(2S)-2-[[(1S)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-methyl- piperazin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 47); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(1-rel-R)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 48); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(1-rel-S)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 49); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(1-rel-R)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 50); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(1-rel-S)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 51); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-sulfamoyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 52); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-sulfamoyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 53); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclobutylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 54); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[cyclohexyl(methyl)amino]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 55); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholino-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 56); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholino-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 57); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2-hydroxyethylsulfamoyl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 58); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2-hydroxyethylsulfamoyl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 59); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 60); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 61); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-[2-(dimethylamino)ethylsulfamoyl]phenyl] ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 62); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[2-(dimethylamino)ethylsulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 63); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 64); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 65); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-sulfamoyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 66); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-sulfamoyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 67); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 68); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl(tetrahydropyran-4-yl)sulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 69); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl(tetrahydropyran-4-yl)sulfamoyl]phenyl] ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 70); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(tetrahydropyran-4-ylsulfamoyl)phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 71); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(tetrahydropyran-4-ylsulfamoyl)phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 72); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 73); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 74); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-(ethylsulfamoyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 75); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(ethylsulfamoyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 76); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-(methylsulfamoyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 77); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(methylsulfamoyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 78); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 79); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 80); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylsulfonyl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 81); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylsulfonyl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 82); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 83); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-4-[2-[(6- fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 84); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(1-methylazetidin-3-yl)sulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 85); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(1-methyl-4-piperidyl)sulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide;hydrochloride (Compound 86); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(cyclohexylsulfamoyl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 87); N-[2-[(2S)-2-[[(1S)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-1-piperidyl]-2-oxo-ethyl]- 6-fluoro-quinoline-2-carboxamide (Compound 88); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-1-piperidyl]-2-oxo-ethyl]- 6-fluoro-quinoline-2-carboxamide (Compound 89); Compound 90: (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 90); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-methyl-piperazin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 91); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-methyl- piperazin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 92); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 93); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 94); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(tetrahydropyran-4-ylsulfamoyl)phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 95); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 96); (4R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-3-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]-1,1-dioxo-1,3-thiazolidine-4-carboxamide (Compound 97); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 98); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 99); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(tetrahydropyran-4-ylsulfamoyl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 100) and N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 101); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 102); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methyl-1,4-diazepan-1-yl)phenyl]ethyl]carbamoyl]- 4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 103); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-4,4-difluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 104); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[4-[(3-methylisoxazol-5-yl)methyl]piperazin-1- yl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 105); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-(4-methylpiperazin-1-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 106); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-4-[2- [(6-fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 107); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 108); N-[2-[(2S,4R)-4-cyano-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-[methyl-(1-methyl-4-piperidyl) amino] phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 109); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4-oxo- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 110); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[4-(cyclohexylmethyl)piperazin-1-yl]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 111); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-oxo-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 112); N-[2-[(2S,4R)-4-cyano-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 113); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-(trifluoromethyl) pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 114); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylmethyl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 115); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(4-methylpiperazin-1-yl)methyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 116); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 117); (3S)-N-[(1S)-1-[4-(cyclohexylsulfamoyl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 118); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(1-methylazetidin-3-yl)sulfamoyl]phenyl]ethyl]-4-[2-[(6- fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 119); N-[2-[(2S,4R)-4-cyano-2-[[(1S)-1-[4-(cyclohexylsulfamoyl)-2-[(E)-2-cyclopropylvinyl]phenyl] ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 120); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(4-benzylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 121); (3S)-N-[(1S)-1-[4-(4-benzylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 122); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(4-benzylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4- cyano-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 123); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- (trifluoromethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 124); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-fluoro-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 125); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-fluoro-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl)amino] acetyl]morpholine-3-carboxamide (Compound 126); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(oxetan-3-yloxy)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 127); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(4-pyridylmethoxy)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 128); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 129); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 130); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-hydroxy-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 131); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-6-hydroxy-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 132); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[4-(dimethylamino)-1-piperidyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 133); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3R,5R)-3,4,5-trimethylpiperazin-1-yl]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 134); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 135); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 136); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(4-cyclopropylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]- 4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 137); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3S)-3,4-dimethylpiperazin-1-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 138); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(2S,6R)-2,6-dimethylmorpholin-4-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 139); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(3,3,5,5-tetramethylpiperazin-1-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 140); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3R)-3,4-dimethylpiperazin-1-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 141); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(2,2-dimethylmorpholin-4-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 142); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl(tetrahydropyran-4-yl)amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 143); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(2R,6R)-2,6-dimethylmorpholin-4-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 144); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3S,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 145); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(2,2-dimethylmorpholin-4-yl)phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 146); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-pyrrolidin-1-yl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 147); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 148); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3-methylimidazol-4-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 149); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2-oxopyrrolidin-1-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 150); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3-pyridyl)phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 151); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3-hydroxyphenyl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 152); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-pyrazol-3-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 153); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3,4-dihydro-2H-pyran-5-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 154); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 155); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 156); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2,3,4,7-tetrahydro-1H-azepin-6-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamidehydrochloride (Compound 157); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl]-4-[2-[(6- fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 158); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 159); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2,5-dihydro-1H-pyrrol-3-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide;hydrochloride (Compound 160); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 161); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,4-tetrahydroquinolin-7-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 162); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-indolin-6-yl-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 163); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-imidazol-4-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 164); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-imidazol-4-yl)phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 165); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-3-methoxyprop-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin- 1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 166); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-3-methoxyprop-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 167); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-3-pyrrolidin-1-ylprop-1-enyl]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide(Compound 168); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-(dimethylamino) pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 169); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-4-hydroxybut-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 170); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(2-methylpyrazol-3-yl)vinyl]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 171); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(2-thienyl)vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]- 2-oxo-ethyl]quinoline-2-carboxamide hydrochloride (Compound 172); 6-fluoro-N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(1-fluorocyclopropyl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 173); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(1-methylcyclopropyl)vinyl]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 174); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(oxetan-3-yl)vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 175); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(2,2-difluorocyclopropyl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 176); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-[(3-rel-R)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 177); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-[(3-rel-S)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 178 ); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-[(3-rel-R)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide(Compound 179); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-[(3-rel-S)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 180); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(2,2-dimethylcyclopropyl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 181); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(2,2-dimethylcyclopropyl)vinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 182); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-(2-methylcyclopropyl)vinyl]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 183); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-rel-[(1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl] vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 184); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-rel-[(1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl] vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 185); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-rel-[(E)-2-[(1S,5R,6s)-3-oxabicyclo[3.1.0]hexan-6-yl]vinyl] phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 186); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-rel-[(1S,2S)-2-fluorocyclopropyl]vinyl]phenyl] ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 187); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-rel-[(1S,2R)-2-fluorocyclopropyl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 188); (3S)-N-[(1S)-1-[2-chloro-6-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl)amino] acetyl]morpholine-3-carboxamide (Compound 189); N-[2-[(2S,4R)-2-[[(1S)-1-[2-chloro-6-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 190); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[(E)-2-cyclopropylvinyl]-1,3-benzodioxol-4-yl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 191); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[(E)-2-cyclopropylvinyl]-1,3-benzodioxol-4-yl]ethyl]carbamoyl]-4-(dimethylamino) pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 192); N-[2-[(2S,4R)-2-[[(1S)-1-(2,2-difluoro-1,3-benzodioxol-4-yl)ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 193); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-(4-methoxy-1-naphthyl)ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl] quinoline-2-carboxamide (Compound 194); N-[2-[(2S,4R)-2-[[(1S)-1-[3-[(E)-2-cyclopropylvinyl]-2-pyridyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 195); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[(E)-2-cyclopropylvinyl]-3-thienyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 196); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-4-(4-methylpiperazin-1-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 197); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl] propyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 198); N-[2-[(2S,4R)-2-[[(1S)-1-[7-[(E)-2-cyclopropylvinyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 199); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[cyclobutyl-(1-methyl-4-piperidyl)amino]-2-[(E)-2-cyclopropylvinyl]phenyl] ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 200); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[cyclobutyl-(1-methyl-4-piperidyl)amino]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 201); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(cyclohexoxy)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 202); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(cyclohexylmethoxy)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 203); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(difluoromethoxy)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 204); 6-chloro-N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]pyrrolidin- 1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 205); 6-chloro-N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]pyrrolidin- 1-yl]-2-oxo-ethyl]-7-fluoro-quinoline-2-carboxamide (Compound 206); N-[2-[(2S,5S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-5-methyl-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 207); N-[2-[(1R,3S,5R)-3-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl] ethyl] carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 208); N-[2-[(1S,3S,5S)-3-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 209); N-[2-[(6S)-6-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-5-azaspiro[2.4]heptan-5-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 210); N-[2-[(1R,2S,5S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 211); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-2-methyl-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 212); N-[(1S)-2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 213); N-[(1R)-2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 214); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-4-methoxy-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide trifluoroacetate (Compound 215); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-4-(4-methylpiperazin-1-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 216); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(3,3,4-trimethylpiperazin-1-yl)phenyl]ethyl]carbamoyl]- 4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 217); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 218); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 219); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]phenyl] ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 220); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 221); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3S)-3-(dimethylamino)-1-piperidyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 222); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-5-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 223); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-5-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 224); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 225); N-[2-[(2S,4R)-2-[[(1S)-1-[4-cyclopropyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 226); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2-oxo-1H-pyrimidin-5-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 227); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3,5-dimethylisoxazol-4-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 228); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 229); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1H-imidazol-5-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 230); N-[2-[(1R,3S,5R)-3-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl] carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamidehydrochloride (Compound 231); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl]carbamoyl]-2- methyl-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 232); N-[2-[(2S,4R)-2-[[(1S)-1-(2-aminophenyl)ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro- quinoline-2-carboxamide (Compound 233); N-[2-[(2S,4R)-2-[[(1S)-1-[5-amino-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 234); N-[2-[(2S,4R)-2-[[(1S)-1-[5-amino-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 235); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(azetidin-3-yl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 236); N-[2-[(2S,4R)-2-[[(1R)-1-[3-[(E)-2-cyclopropylvinyl]-6-[[(2S)-pyrrolidine-2-carbonyl]amino]-2-pyridyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 237); N-[2-[(2S,4R)-2-[[(1R)-1-[3-[(E)-2-cyclopropylvinyl]-6-[[(2R)-pyrrolidine-2-carbonyl]amino]-2-pyridyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 238); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[(E)-2-cyclopropylvinyl]-2-(1,2,3,6-tetrahydropyridin-5-yl)-4-pyridyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 239 ); N-[2-[(2S,4R)-2-[[(1R)-1-[5-[(E)-2-cyclopropylvinyl]-2-(1,2,3,6-tetrahydropyridin-5-yl)-4-pyridyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 240); N-[2-[(2S,4R)-2-[[(1S)-1-[2,5-bis[(E)-2-cyclopropylvinyl]-4-pyridyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 241); N-[2-[(2S,4R)-2-[[(1R)-1-[2,5-bis[(E)-2-cyclopropylvinyl]-4-pyridyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 242); N-[2-[(2S,4R)-2-[[(1S)-1-[3-amino-6-[(E)-2-cyclopropylvinyl]-2-fluoro-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 243); N-[2-[(2S,4R)-2-[[(1S)-1-[4-chloro-2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 244); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[rel-(3S)-3-piperidyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 245); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[rel-(3R)-3-piperidyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 246); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1-methyl-4-piperidyl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 247); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[rel-(3S)-1-cyclopropyl-3-piperidyl]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 248); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[rel-(3R)-1-cyclopropyl-3-piperidyl]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 249); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-1,2,3,4-tetrahydroquinolin-7-yl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 250); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 251); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2R)-pyrrolidine-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 252 ); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(cyclopropanecarbonylamino)phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 253); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S)-pyrrolidine-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 254); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S,4R)-4-fluoropyrrolidine-2-carbonyl]amino]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 255); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2R)-piperidine-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 256); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S)-piperidine-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 257); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S)-1-methylpyrrolidine-2-carbonyl]amino]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamidehydrochloride (Compound 258); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-2-fluoro-3-[[(2R)-pyrrolidine-2-carbonyl]amino]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamidehydrochloride (Compound 259); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-2-fluoro-3-[[(2S)-pyrrolidine-2-carbonyl]amino]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamidehydrochloride (Compound 260); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-1-[(2S)-pyrrolidine-2-carbonyl]-3,4-dihydro-2H-quinolin- 7-yl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 261); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-1-[(2R)-pyrrolidine-2-carbonyl]-3,4-dihydro-2H-quinolin- 7-yl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 262); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2R)-tetrahydrofuran-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 263); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S)-tetrahydrofuran-2-carbonyl]amino]phenyl] ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 264); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[2-(dimethylamino)acetyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 265); N-[2-[(2S,4R)-2-[[(1S)-1-[5-acetamido-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 266); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[[(2S)-aziridine-2-carbonyl]amino]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 267); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(1-methylazetidin-3-yl)vinyl]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 268); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 269); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[rel-(3S)-1-methyl-3-piperidyl]phenyl]ethyl]carbamoyl]- 4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 270); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[rel-(3R)-1-methyl-3-piperidyl]phenyl]ethyl]carbamoyl]- 4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 271); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3R)-1-methylpyrrolidin-3-yl]oxy-phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 272); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3S)-1-methylpyrrolidin-3-yl]oxy-phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 273); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1-methylazetidin-3-yl)oxy-phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 274); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[(3S)-1-cyclopropylpyrrolidin-3-yl]oxy-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 275); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(3S)-1-methyl-3-piperidyl]oxy]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 276); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3S)-pyrrolidin-3-yl]oxy-phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide;hydrochloride (Compound 277); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3R)-pyrrolidin-3-yl]oxy-phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 278); N-[2-[(2S,4R)-2-[[(1S)-1-[5-(azetidin-3-yloxy)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 279); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(3S)-3-piperidyl]oxy]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 280). For a reference to any specific compound of formula (I) of the invention, optionally in the form of a pharmaceutically acceptable salt, see the experimental section and claims. If a stereogenic center or another form of an isomeric center is present in a compound of the present invention, all forms of such isomer or isomers, including enantiomers, diastereomers and epimers, are intended to be covered herein. In some aspects, a compound disclosed herein possesses one or more stereocenters and each stereocenter exists independently in either the R or S configuration. Compounds containing a stereogenic center may be used as a racemic mixture, an enantiomerically enriched mixture, or the racemic mixture may be separated using well-known techniques and an individual enantiomer may be used alone. In cases in which compounds have unsaturated carbon-carbon double bonds, both the cis (Z) and trans (E) isomers are within the scope of this invention. In cases wherein compounds may exist in tautomeric forms, such as keto-enol tautomers, each tautomeric form is contemplated as being included within this invention whether existing in equilibrium or predominantly in one form. Pharmaceutically acceptable salts of the compounds of formula (I) include the salts with inorganic or organic acids, e.g. nitric, hydrochloric, hydrobromic, sulfuric, perchloric, phosphoric, acetic, trifluoroacetic, propionic, glycolic, lactic, oxalic, fumaric, malonic, malic, maleic, tartaric, citric, benzoic, cinnamic, mandelic, methanesulphonic, isethionic and salicylic acid. Pharmaceutically acceptable salts of the compounds of formula (I) also include the salts with inorganic or organic bases, e.g. alkali or alkaline-earth metals, especially sodium, potassium, calcium, ammonium or magnesium hydroxides, carbonates or bicarbonates, acyclic or cyclic amines. Further object of the present invention are compounds of formula (I) as defined above, as well as their isomers, tautomers, hydrates, solvates, complexes, metabolites, prodrugs, carriers and N- oxides. A metabolite of a compound of formula (I) is any compound into which this same compound of formula (I) is converted in vivo, for instance upon administration to a mammal in need thereof. Typically, without however representing a limiting example, upon administration of a compound of formula (I), this same derivative may be converted into a variety of compounds, for instance including more soluble derivatives like hydroxylated derivatives, which are easily excreted. Hence, depending upon the metabolic pathway thus occurring, any of these hydroxylated derivatives may be regarded as a metabolite of the compounds of formula (I). Prodrugs are any covalently bound compounds, which release in vivo the active parent drug according to formula (I). N-oxides are compounds of formula (I) wherein nitrogen and oxygen are tethered through a dative bond. In a second aspect the present invention also provides a process for the preparation of a compound of formula (I) as defined above, by using the reaction routes and synthetic schemes described below, employing the techniques available in the art and starting materials readily available. The preparation of certain embodiments of the present invention is described in the examples that follow, but those of ordinary skill in the art will recognize that the preparations described may be readily adapted to prepare other embodiments of the present invention. For example, the synthesis of non-exemplified compounds according to the invention may be performed by modifications apparent to those skilled in the art, for instance, by appropriately protecting interfering groups, by changing to other suitable reagents known in the art, or by making routine modifications of reaction conditions. Alternatively, other reactions referred to herein or known in the art will be recognized as having adaptability for preparing other compounds of the invention. The compounds of this invention can be prepared from readily available starting materials using the following general methods and procedures. Unless otherwise indicated, the starting materials are known compounds or may be prepared from known compounds according to well-known procedures. It will be appreciated that, where typical or preferred process conditions (i.e., reaction temperatures, times, mole ratios of reactants, solvents, pressures) are described, different process conditions can also be used unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvent used, but such conditions can be determined by one skilled in the art by routine optimization procedures. Intermediate compounds of formula (IX), can be prepared as reported in scheme 1 below: Scheme 1 Step 1.1) mixing a compound of formula (IV) or its corresponding salt, wherein X is a halogen atom and Y with a compound of formula (V) or its corresponding salt, wherein R1 and R2 the same or differently hydrogen, straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, (C3-C7) cycloalkyl; or R1 and R2 taken together with the carbon atom they are bonded may form a (C3-C7) cycloalkyl; and R25 is a group selected from straight or branched (C1-C6) alkyl to give a compound of formula (VI) wherein X, Y, R1, R2 and R25 are Step 1.2) reacting the compound of formula (VI) obtained as described in step 1.1 under acidic or basic hydrolysis conditions to give compound of formula (VII) or its corresponding salt wherein X, Y, R1 and R2 are as Step 1.3) reacting a compound of formula (VII), obtained as described in step 1.2, with a compound of formula (VIII), wherein W is a 3-10 membered from the group consisting of (IIIa), (IIIb1)-(IIIb7), (IIIc1)-(IIIc4) and (IIId1-IIId4):

[0005] , wherein R19 and R20 the same or differently are each independently hydrogen, halogen, straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, cyano group, OR21 or NR22R23; or R19 and R20 taken together may form a (C3-C7) cycloalkyl ring optionally substituted with straight or branched (C1-C6) alkyl; wherein R21 is hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R22 and R23 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; and R24 is straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl, to give a compound of formula (IX) or its corresponding salt wherein X, Y, R1 and R2 are are as defined above. According to step 1.1 of the process, the amidation of a carboxylic acid of formula (IV) or its corresponding salt to yield the corresponding compound of formula (VI), is carried out with a primary amine of formula (V) or its corresponding salt, under basic conditions, preferably with DIPEA or TEA, in a suitable solvent such as DCM, DMF, THF, 1,4-dioxane, or DMA, in the presence of a suitable condensing agent, for instance dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide (EDCI), 3,4-dihydro-3- hydroxy-4-oxo-1,2,3-benzotriazine (DHBT), O-benzotriazolyltetramethylisouronium tetrafluoroborate (TBTU), benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), propylphosponic anhydride (T3P), or 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) at r.t. for a time ranging from about 2 to about 24 h. The said reaction is optionally carried out in the presence of a suitable catalyst such as the 4-dimethylaminopyridine, or in the presence of a further coupling reagent such as N- hydroxybenzotriazole (HOBt). According to step 1.2 of the process, a compound of formula (VI), can be converted into the corresponding derivative of formula (VII) or a salt thereof, through basic or acidic hydrolysis conditions, widely known in the art. Preferably, the reaction is carried out with aqueous alkaline solutions such as aqueous lithium, sodium or potassium hydroxide in the presence of a suitable solvent such as a lower alcohol, THF, DMF or mixtures thereof; preferably the reaction is carried out with lithium hydroxide in THF / MeOH / water mixture, at a temperature ranging from about r.t. to about 80°C and for a time ranging from about 2 to about 24 h. According to the operative conditions being employed, the compound of formula (VII) can be obtained either in its acidic form or, alternatively, as a salt. According to step 1.3 of the process, the amidation of a carboxylic acid of formula (VII) to obtain a compound of formula (IX), is carried out by treating (VII) with 1-Hydroxy-2,5-pyrrolidinedione (NHS) or other suitable acid-activating agent, in presence of other coupling reagents such as dicyclohexylcarbodiimide (DCC) or 1- ethyl-3-(3'-dimethylaminopropyl)carbodiimide (EDCI). The reaction is conducted in a suitable solvent such as DCM, DMF or DMA at r.t. for a time ranging between 2 to 48 h. The obtained reaction mixture is then added to a solution of a compound of formula (VIII), in a suitable solvent such as DMF, THF, Dioxane, water under basic conditions. Preferably the reaction is carried out in a mixture of THF / Water in presence of an aqueous sodium hydrogen carbonate solution. The reaction is carried out at r.t. for a time ranging between 2 to 24 h. According to the operative conditions being employed, the compound of formula (IX) could be obtained either in its acidic form or, alternatively, as a salt. Intermediate compound of formula (IX) can be alternatively prepared as reported in scheme 2 below: Scheme 2 Step with a compound of formula (XI) or its wherein R1, R2, W, R19, R20 and R25 in step 1.1. or step 1.3 and Pg is a nitrogen protecting group, preferably BOC or FMOC, to give a compound of formula (XII) wherein R1, R2, W, R19, R20, R25 Step 2.2) removal of the protecting group (Pg) from the compound of formula (XII) obtained as described in step 2.1 under acidic conditions to yield a primary amine compound of formula (XIII) or its corresponding salt, wherein R1, R2, W, R19, R20 and 2.1. Step 2.3) reacting a compound of formula (XIII) obtained as described in step 2.2 with a compound of formula (IV) wherein X and Y are as defined in step 1.1, to obtain a compound of formula (XIV) wherein X, Y, R1, R2, R19, 1.1 or step 2.1. Step 2.4) reacting compound of formula (XIV) obtained as described in step 2.3 in acidic or basic hydrolysis conditions to give intermediate compound of formula (IX) or its corresponding salt wherein X, Y, R1, R2, W, R19 According to step 2.1 of the process, the amidation of a carboxylic acid of formula (X) or its corresponding salt to yield the corresponding compound of formula (XII), is carried out in the presence of a suitable primary amine of formula (XI), or its corresponding salt according to conditions applied in step 1.1. According to step 2.2 of the process the removal of nitrogen protecting group from compound (XII) to obtain compound (XIII) or its corresponding salt is conducted with well-known literature method depending on the selected protecting group, preferably in acidic conditions by treating compound (XII) with a solution of HCl or TFA in a suitable solvent or mixture of solvents such as dioxane, H2O, DCM, THF. According to step 2.3 of the process the amidation of a carboxylic acid of formula (IV) or its corresponding salt to yield the corresponding compound of formula (XIV), is carried out in the presence of a suitable primary amine of formula (XIII), or its corresponding salt according to conditions applied in step 1.1. According to step 2.4 of the process a compound of formula (XIV), can be converted into the corresponding derivative of formula (IX) or a salt thereof, according to conditions applied in step 1.2. Compounds of formula (I), object of the present invention, can be prepared as reported in scheme 3 below: Scheme 3 Step 3.1) mixing a compound of formula (IX) obtained as described in step 1.3 or 2.4 with a compound of formula (XV) or its corresponding salt, wherein R3 and R4 the same or differently hydrogen, straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, (C3-C7) cycloalkyl; or R3 and R4 taken together with the carbon atom they are bonded may form a (C3-C7) cycloalkyl; Z is a substituted aryl of formula (IIa) or a substituted 5-7 membered heteroaryl selected from the group consisting of (IIb1)-(IIb7): , branched (C1-C6) haloalkyl, straight or branched (C2-C6) alkenyl optionally substituted with halogen, (C3-C7) cycloalkyl optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, 5-7 membered heteroaryl optionally substituted with (C1-C6) alkyl, (C1-C3) alkoxy, (C1-C3) haloalkoxy, hydroxyl, phenyl, ether group -OR13, amino group -NR10R11, amide group -NR17COR18, 1-methyl-1,2,3,6-tetrahydropyridine; R6 and R7 the same or differently are each independently hydrogen, halogen, hydroxyl group, straight or branched (C1-C6) alkyl optionally substituted with 3-10 membered heterocyclyl, in its turn optionally substituted with from one to four straight or branched (C1-C6) alkyl groups, halogen, (C3-C7) cycloalkyl, straight or branched (C1-C6) haloalkyl, oxetanyl, (C3-C7) cycloalkyl optionally substituted with (C1- C6)alkylamino, di(C1-C6)alkylamino or 3-10 membered heterocyclyl, straight or branched (C1-C6) haloalkyl, phenyl substituted with hydroxyl group, 5-7 membered heteroaryl optionally substituted with a straight or branched (C1-C6) alkyl, 3-10 membered heterocyclyl optionally substituted with benzyl, from one to four straight or branched (C1-C6) alkyl groups in their turn optionally substituted independently with (C3-C7) cycloalkyl, (C1-C3) alkoxy or 3-methylisoxazole ring, halogen, (C3-C7) cycloalkyl in its turn optionally substituted with halogen, straight or branched (C1-C6) haloalkyl, di(C1-C6)alkylamino, oxetanyl, amino group -NR10’R11’, thioether group -SR12’, ether group -OR13’, sulfone group -SO2R14’, sulfonamide group - SO2NR15’R16’, amide group -NR17’COR18’, group COR18’; or R5 and R6 taken together may form a phenyl ring or a 3-10 membered heterocyclic ring optionally substituted with one or two halogens; or R6 and R7 taken together may form a 3-10 membered heterocyclyl optionally substituted with: halogen, a group -COR18’, straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1- C6)alkylamino; and R8 is halogen, straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, (C1-C3) alkoxy, (C1-C3) haloalkoxy; and R9 is hydrogen, halogen, straight or branched (C2-C6) alkenyl optionally substituted with a (C3-C7) cycloalkyl, 3-10 membered heterocyclyl optionally substituted with from one to four straight or branched (C1-C6) alkyl groups, ether group -OR13’, amide group -NR17’COR18’; wherein R10 and R11 the same or differently are each independently hydrogen, (C3-C7) cycloalkyl or straight or branched (C1-C6) alkyl; R10’ and R11’ the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl optionally substituted with 1-methylimidazole, (C3-C7) cycloalkyl or 3-10 membered heterocyclyl optionally substituted with halogen, straight or branched (C1-C6) alkyl, (C1-C3) haloalkoxy, (C3- C7) cycloalkyl or oxetanyl; R12’ is straight or branched (C1-C6) alkyl, (C3-C7) cycloalkyl, 3-10 membered heterocyclyl optionally substituted with a straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R13 is straight or branched (C1-C6) alkyl optionally substituted with (C3-C7) cycloalkyl in its turn optionally substituted with 1 or two halogens, straight or branched (C2-C6) alkynyl in its turn optionally substituted with (C3-C7) cycloalkyl, benzyl group or N-methyl-piperidinyl; R13’ is straight or branched (C1-C6) alkyl optionally substituted with pyridine, (C3-C7) cycloalkyl in its turn optionally substituted with di(C1-C6)alkylamino, di(C1- C6)alkylamino, 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, 3- 10 membered heterocyclyl optionally substituted with: from one to four straight or branched (C1-C6) alkyl groups, (C3-C7) cycloalkyl, halogen, straight or branched (C1-C6) haloalkyl, oxetanyl; R14’ is straight or branched (C1-C6) alkyl, 3-10 membered heterocyclyl or (C3-C7) cycloalkyl; R15’ and R16’ the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group, straight or branched (C1-C3) alkoxy or di(C1-C6)alkylamino, (C3-C7) cycloalkyl, 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, halogen or (C3-C7) cycloalkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R17 and R17’ the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R18 is (C3-C7) cycloalkyl or 3-10 membered heterocyclyl; and R18’ is straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, (C3-C7) cycloalkyl optionally substituted with di(C1- C6)alkylamino or 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl or halogen; to give a compound of formula (I) wherein X, Y, R1, R2, R3, steps 1.1, 1.3; or when R5, R6, R7, R8 and R9 are as defined above and / or could additionally be the same or differently each independently triflate group, halogen, -NO2 or -OH, to give an intermediate of formula (XVI) that reacts to give a compound of formula (I) according to the experimental procedures described below. According to step 3.1 of the process the amidation of a carboxylic acid of formula (IX) or its corresponding salt to yield the compound of formula (I) or the intermediate (XVI), is carried out in the presence of a suitable amine of formula (XV) or its corresponding salt, according to conditions applied in step 1.1. Compounds of formula (I), object of the present invention, can be alternatively prepared as reported in scheme 4 below: Scheme 4 Step 4.1) mixing a compound of formula (XVII) wherein Pg, R1 and R2 are as defined R19 and R20 are as defined above in steps 1.3 with a compound of formula (XV) wherein Z, R3 and R4 are as defined above obtain compound (XVIII) wherein Pg, R1, R2, R3, R4, W, R19, R20 and Z are as defined above. Step 4.2) removal of the nitrogen protecting group (Pg) from a compound of formula (XVIII), obtained as described in step 4.1, under acidic or basic conditions depending on the Pg applied, to obtain a primary amine compound of formula (XIX) or its corresponding salt, wherein R1, R2, R3, R4, W R19, R20 in steps 2.1, 1.3 and 3.1. Step 4.3) mixing a compound of formula (XIX) obtained as described in step 4.2 with a compound of formula (IV) wherein X and Y are as defined above in step 1.1, to give a compound of formula (I) wherein X, Y, R1, R2, R3, R4, W, R19, R20 and Z are as defined above in steps 1.1, 1.2 and 3.1. According to step 4.1 of the process the amidation of a carboxylic acid of formula (XVII) or its corresponding salt to yield the corresponding compound of formula (XVIII), is carried out in the presence of a suitable amine of formula (XV) or their corresponding salts, according to conditions applied in step 1.1. According to step 4.2 of the process the removal of nitrogen protecting group, from compound (XVIII) to obtain compound (XIX) or its corresponding salt, is conducted with well-known literature method depending on the selected protecting group, preferably in acidic conditions by treating compound (XVIII) with a solution of HCl or TFA in a suitable solvent or mixture of solvents such as dioxane, H2O, DCM, THF, at r.t.. Alternatively, the deprotection reaction can be carried out in basic condition by treatment of compound (XVIII) with a solution of piperidine in suitable solvent such as DMF or DMA at r.t. According to step 4.3 of the process the amidation of a carboxylic acid of formula (IV) or its corresponding salt to yield the compound of formula (I), is carried out in the presence of a suitable amine of formula (XIX) or its corresponding salt, according to conditions applied in step 1.1. Compounds of formula (I), object of the present invention, can be alternatively prepared as reported in scheme 5 below: Scheme 5 Step 5.1) mixing a compound of formula (XX), or its corresponding salt, wherein W, R19 and R20 are as defined Pg is as defined in step 2.1, with a compound of formula (XV) wherein R3, R4 and Z are as defined in step of formula (XXI) wherein Pg, R3, R4, W, R19 and R20 Step 5.2) removal of the nitrogen protecting group (Pg) from a compound of formula (XXI) obtained as described in step 5.1, with well-known literature method depending on the selected protecting group, to obtain a primary amine compound of formula (XXII) or its corresponding salt, wherein R3, R4, W, R19, R20 and Z are as 1.3 and 3.1. Step 5.3) mixing a compound of formula (XXII) obtained as described in step 5.2 with a compound of formula (VII) obtained as described in step 1.2 wherein R1 and R2 are as defined of formula (I) wherein X, Y, R1, R2, R3, 1.1, 1.3 and 3.1; or when R5, R6, R7, R8 and R9 are as defined above in step 3.1 and / or could additionally be the same or differently each independently triflate group, halogen, -NO2 or -OH, to give an intermediate of formula (XVI) that reacts to give a compound of formula (I) according to the experimental procedures described below. According to step 5.1 of the process the amidation of a carboxylic acid of formula (XX) or its corresponding salt to yield the compound of formula (XXI), is carried out in the presence of a suitable amine of formula (XV) or its corresponding salt, according to reaction conditions applied in step 1.1. According to step 5.2 of the process the removal of nitrogen protecting group from compound (XXI) to obtain compound (XXII) or its corresponding salt is conducted with well-known literature method depending on the depending on the selected protecting group, preferably applying conditions described in step 2.2. According to step 5.3 of the process the amidation of a carboxylic acid of formula (VII) or its corresponding salt to yield the compound of formula (I) or intermediate (XVI), is carried out in the presence of a suitable amine of formula (XXII) or its corresponding salt, according to reaction conditions applied in step 1.1. Compound of general formula (IV), (V), (VIII), (X), (XI), (XX) are either commercially available or can be prepared with knowns methods. Compound of general formula (XV) and (XVII) are either commercially available or can be prepared as describe below in the experimental part or starting from commercially available intermediate through procedure and experimental conditions which are widely known in the art. From all of the above, it is clear to the skilled person that the conversion of a compound of formula (I) into a pharmaceutically acceptable salt thereof or, alternatively, the conversion into the free compound (I) of a corresponding salt, according to procedures well-known in the art, is still within the scope of the invention. When preparing the compounds of formula (I) according to any variant of the process, which are all to be intended as within the scope of the invention, optional functional groups within the starting materials, the reagents or the intermediates thereof, and which could give rise to unwanted side reactions, need to be properly protected according to conventional techniques. Protection of such reactive centers, and subsequent deprotection at the end of the synthetic transformations, can be accomplished following standard procedures described, for instance, in: Green, Theodora W. and Wuts, Peter G.M. – Protective Groups in Organic Synthesis, Third Edition, John Wiley & Sons Inc., New York (NY), 1999. According to any variant of the process for preparing the compounds of the formula (I), the starting materials and any other reactants are known or easily prepared according to known methods. The compounds of general formula (I) as defined above can be converted into pharmaceutically acceptable salts. The synthesis of a compound of general formula (I), according to the synthetic processes described above, can be conducted in a stepwise manner, whereby each intermediate is isolated and purified if needed by standard purification techniques, like, for example, column chromatography, before carrying out the subsequent reaction. Alternatively, two or more steps of the synthetic sequence can be carried out in a so- called “one-pot” procedure, as known in the art, whereby only the compound resultant from the two or more steps is isolated and purified. In cases where a compound of general formula (I) contains one or more asymmetric centers, said compound can be separated into the single stereoisomers by procedures known to those skilled in the art. Such procedures comprise standard chromatographic techniques, including chromatography using a chiral stationary phase, or crystallization. General methods for separation of compounds containing one or more asymmetric centers are reported, for instance, in Jacques, Jean; Collet, André; Wilen, Samuel H., Enantiomers, Racemates, and Resolutions, John Wiley & Sons Inc., New York (NY), 1981. In another aspect, the present invention provides a method of treatment, a disease caused by and / or associated with dysregulated proteins activity involved in DNA repair pathways and genomic stability, preferably RAD51 protein activity, which comprises administering to a mammal in need thereof, more particularly a human, an effective amount of compound of formula (I) as defined above. Furthermore the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, for use in a method of treating a disease caused by and / or associated with dysregulated proteins activity involved in DNA repair pathways and genomic stability, particularly RAD51 protein activity, which comprises administering to a mammal, preferably a human, in need thereof, an effective amount of a compound of formula (I) as defined above. A preferred method of the present invention is to treat a disease caused by and / or associated with dysregulated protein activity involved in DNA repair pathways and genomic stability selected from the group consisting of cancer, cell proliferative disorders and immune disorders. In a more preferred embodiment, the disease is cancer. In a most preferred embodiment the cancer is selected from the group consisting of: carcinomas, such as bladder, breast, kidney, liver, colon, lung, including small cell lung cancer, esophagus, gall-bladder, ovary, pancreas, stomach, cervix, prostate, and skin, including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B-cell lymphoma, angioimmunoblastic T-cell lymphoma, Hodgkin's lymphoma, non- Hodgkin's lymphoma, hairy cell lymphoma and Burkitt's lymphoma; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukemias, myelodysplastic syndrome and promyelocytic leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including glioma, glioblastoma, glioblastoma multiforme, astrocytoma, oligodendroglioma, paraganglioma, neuroblastoma, and schwannomas; and other tumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoacanthoma, thyroid cancers, such as papillary thyroid carcinoma and medullary thyroid carcinoma, Kaposi's sarcoma, chondrosarcoma, and cholangiocarcinoma. Furthermore, the compounds developed in this invention have the potential to impede the growth of blood vessels feeding tumors, halt the spread of metastasis, and restore the sensitivity of chemotherapy-resistant cancer cells. The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutical acceptable salt thereof and at least one pharmaceutically acceptable excipient, carrier and / or diluent. In a further aspect the present invention provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, for treating cancer, which comprises administering to a mammal, preferably a human, in need thereof, an effective amount of a compound of formula (I) as defined above. In a further aspect, the present invention further provides a therapeutic combination comprising a compound of formula (I) with one or more anticancer agents. As used here, the term "anticancer agent" relates to any agent which is administered to oncological patients with the purposes of treating the cancer. The anti-cancer treatment defined above may be applied as monotherapy or may involve, in addition to the herein disclosed compounds of formula (I), conventional surgery, radiotherapy or one or more chemotherapeutics - e.g. cytostatic, cytotoxic agents or immune checkpoint inhibitors. Cytostatic or cytotoxic agents include, but are not limited to antibiotic-type agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-type agents, cyclooxygenase inhibitors (e.g. COX-2 inhibitors), matrixmetalloprotease inhibitors, telomerase inhibitors, tyrosine kinase inhibitors, anti-growth factor receptor agents, anti-HER agents, anti-EGFR agents, anti-angiogenesis agents (e.g. angiogenesis inhibitors), farnesyl transferase inhibitors, ras-raf signal transduction pathway inhibitors, cell cycle inhibitors, other cdks inhibitors, tubulin binding agents, topoisomerase I inhibitors, topoisomerase Il inhibitors aromatase inhibitors, inhibitors of kinesins, therapeutic monoclonal antibodies, inhibitors of mTOR, histone deacetylase inhibitors, PARP1 inhibitors, DNA damage response inhibitors, inhibitors of hypoxic response. Immune checkpoint inhibitors include, but are not limited to compounds with bind to PD-1, PD-L1, CTLA-4, TIM3 (T cell immunoglobulin and mucin-3), OX-40 and its ligand OX40L, LAG-3 (lymphocyte activation gene- 3), KIR (Killer-cell Immunoglobulin like Receptor), VISTA (V-domain Ig-containing suppressor of T cell activation), ID01 (Indoleamine 2,3-dioxygenase), TIGIT (T cell immunoglobulin and ITIM domain), BTLA (B and T lymphocyte attenuator), A2AR (Adenosine receptor A2), SIGLEC7 (Sialic acid-binding immunoglobulin-type lectin 7), GITR (Glucocorticoid-Induced TNFR family Related gene), ICOS (Inducible T-cell costimulator), NOX-2 (nicotinamide adenine dinucleotide phosphate NADPH oxidase isoform 2), Arginase I, CD276 (Cluster of Differentiation 276, also referred to as B7H4), CD27 (Cluster of Differentiation 27) and its ligand CD27 (Cluster of Differentiation 27), CD160 (Cluster of Differentiation 160) and CD39 (Cluster of Differentiation 39). Radiation therapy can be administered through one of several methods, or a combination of methods, including, without limitation, external-beam therapy, internal radiation therapy, implant radiation, stereotactic radiosurgery, systemic radiation therapy, radiotherapy, and permanent or temporary interstitial brachytherapy. If formulated as a fixed dose, such combination products employ the compounds of this invention within the dosage range described below and the other pharmaceutically active agent within the approved dosage range. Additionally, the invention provides a product or kit comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, and one or more chemotherapeutic agents, as a combined preparation for simultaneous, separate or sequential use in anticancer therapy. The compounds of formula (I) of the present invention, suitable for administration to a mammal, e.g. to humans, can be administered by the usual routes and the dosage level depends upon the age, weight, and conditions of the patient and administration route. For example, a suitable dosage adopted for oral administration of a compound of formula (I) may range from about 10 to about 1000 mg per dose, from 1 to 5 times daily. The compounds of the invention can be administered in a variety of dosage forms, e.g. orally, in the form of tablets, capsules, sugar or film coated tablets, liquid solutions or suspensions; rectally in the form of suppositories; parenterally, e.g. intramuscularly, or through intravenous and / or intrathecal and / or intraspinal injection or infusion. The pharmaceutical compositions containing the compounds of the invention are usually prepared following conventional methods and are administered in a suitable pharmaceutical form. For example, the solid oral forms may contain, together with the active compound, diluents, e.g. lactose, dextrose, saccharose, sucrose, cellulose, corn starch or potato starch; lubricants, e.g. silica, talc, stearic acid, magnesium or calcium stearate, and / or polyethylene glycols; binding agents, e.g. starches, arabic gum, gelatine methylcellulose, carboxymethylcellulose or polyvinyl pyrrolidone; disintegrating agents, e.g. starch, alginic acid, alginates or sodium starch glycolate; effervescing mixtures; dyestuffs; sweeteners; wetting agents, such as lecithin, polysorbates, laurylsulphates; and, in general, non-toxic and pharmacologically inactive substances used in pharmaceutical formulations. These pharmaceutical preparations may be manufactured in known manner, for example, by means of mixing, granulating, tabletting, sugar-coating, or film-coating processes. The liquid dispersions for oral administration may be, e.g. syrups, emulsions and suspensions. As an example, the syrups may contain, as a carrier, saccharose or saccharose with glycerine and / or mannitol and sorbitol. The suspensions and the emulsions may contain, as examples of carriers, natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethylcellulose or polyvinyl alcohol. The suspension or solutions for intramuscular injections may contain, together with the active compound, a pharmaceutically acceptable carrier, e.g. sterile water, olive oil, ethyl oleate, glycols, e.g. propylene glycol and, if desired, a suitable amount of lidocaine hydrochloride. The solutions for intravenous injections or infusions may contain, as a carrier, sterile water or preferably they may be in the form of sterile, aqueous, isotonic, saline solutions or they may contain propylene glycol as a carrier. The suppositories may contain, together with the active compound, a pharmaceutically acceptable carrier, e.g. cocoa butter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester surfactant or lecithin. In another aspect the invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, for use as a medicament. Finally, the invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, in the manufacture of a medicament for treating cancer. EXPERIMENTAL SECTION The short forms and abbreviations used herein, as well as throughout the description, have the following meaning: ABBREVIATIONS ACN Acetonitrile AcOH Acetic acid Bn Benzyl BOC-GLY-OH N-(tert-butoxycarbonyl)glycine (Boc)2O di-tert-butyl dicarbonate DCC N,N’-dicyclohexylcarbodiimide DCM Dichloromethane DIPEA N,N-diisopropyethylamine DMA N,N-dimethylacetamide DMF N,N-dimethylformamide DMSO dimethyl sulfoxide DTT Dithiothreitol EA ethyl acetate EDCI N-ethyl-N',N'-diisopropyl carbodiimide hydrochloride eq. equivalent ESI Electrospray ionization Et2O diethyl ether EtOH Ethanol FMOC-OSU N-(9-fluorenylmethoxycarbonyloxy)succinimide g gram / s h hour / s HOBt 1H-benzotriazol-1-ol HPLC High performane liquid Chromatography HRMS High Resolution Mass Spectrometry LAH Lithium aluminum hydride MeOH Methanol min Minute / s mg Milligram / s ABBREVIATIONS mL Milliliter / s mM millimolar mmol Millimole / s MPLC Medium Pressure Liquid Chromatography MSmass spectrometry MTBE Methyl tert-butyl ether MW microwave NBS N-bromosuccinimide NCS N-chlorosuccinimide NMR Nuclear magnetic resonance PDA photodiode array detection PdCl2(dppf) [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride Pd2(dba)3Tris(dibenzylidenaceton)dipalladium(0) PE petroleum ether PyBOP (Benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate QDA single-quadrupole mass detector r.t. room temperature RT retention time SFC Supercritical fluid chromatography TBTU O-(benzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium tetrafluoroborate TEA Triethylamine THF Tetrahydrofuran TLC Thin layer chromatography UPLC Ultra Performance liquid Chromatography Xantphos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene µM micromolar µmolMicromole / s µLMicroliter / s Preparation of compounds of formula (I) For a reference to any specific compound of formula (I) of the invention, optionally in the form of a pharmaceutically acceptable salt, see the experimental section and claims. Referring to the examples that follow, compounds of the present invention were synthesized using the methods described herein, or other methods, which are well known in the art. With the aim at better illustrating the present invention, without posing any limitation to it, the following examples are given. As used herein the symbols and conventions used in the processes, schemes and examples are consistent with those used in the contemporary scientific literature, for example, the Journal of the American Chemical Society or the Journal of Biological Chemistry. Compound names are IUPAC names, generated by using ACD Name (by Advanced Chemistry Development, Inc.). Unless otherwise noted, all materials, including anhydrous solvent such as DMF, THF, DCM, were obtained from commercial suppliers, of the best grade and used without further purification. All reactions involving air- or moisture-sensitive compounds were performed under nitrogen or argon atmosphere. General purification and analytical methods The synthetic preparation of some compounds of formula (I) of the invention is described in the following examples. The compounds of the present invention, as prepared according to the following examples, were also characterized by1H NMR, ESI-MS, HPLC / MS and / or UPLC / HRMS analytical data; HPLC / MS data were collected following any one of the following methods (A – G). Flash Chromatography was performed on silica gel (Merck grade 9395, 60A). HPLC-MS method A HPLC-MS method A was performed on a Waters Acquity Arc equipped with a Waters Acquity QDA detector and a 2998 PDA Detector. Solid phase: Phenomenex Gemini C184.6x50mm 3um. Mobile phase: solvent B water CH3COONH45 mM pH 5.2: ACN 95:5; solvent C ACN: water 95:5; 10 to 90% of C in 5 min; flow 1.2 mL / min HPLC-MS method B HPLC-MS method B was performed on an Agilent 1200 & 6120B. The gradient was 5% B in 0.40 min and 5- 95% B at 0.40-3.40 min, hold on 95% B for 0.45min and then 95-5% B in 0.01min, the flow rate was 0.8 mL / min. Mobile phase A was H2O+10mM NH4HCO3, mobile phase B was acetonitrile. The column used for chromatography was a Xbridge C182.1*50mm column (5um particles). Detection methods are diode array (DAD) detection .MS mode was positive electrospray ionization. MS range was 100-1000. HPLC-MS method C HPLC-MS method C was performed on Agilent 1260 & 6125B. The gradient was 5% B in 0.40min and 5- 95% B in 2.60 min, hold on 95% B in 1.00min and then 95-5% B in 0.01min, the flow rate was 1.0 mL / min. Mobile phase A was 0.04% trifluoroacetic acid in water, mobile phase B was 0.02% trifluoroacetic acid in acetonitrile. The column used for chromatography was a Luna C1850*2.0mm column (5um particles). Detection methods are diode array (DAD) detection. MS mode was positive electrospray ionization. MS range was 100-1000. HPLC-MS method D HPLC-MS method D was performed on a Waters Acquity Arc equipped with a Waters Acquity QDA detector and a 2998 PDA Detector. Solid phase: Waters Xbridge BEH C82.5 um. Mobile phase: solvent B water CH3COONH45 mM pH 5.2: ACN 95:5; solvent C ACN: water 95:5; 10 to 90% of C in 5 min; flow 1.2 mL / min HPLC-MS method E HPLC-MS method E was performed on Agilent 1260 & 6125B. The gradient was 5% B in 0.40min and 5-95% B at 0.40-3.40 min, hold on 95% B for 0.45min and then 95-5% B in 0.01min, the flow rate was 0.8 mL / min. Mobile phase A was H2O+10mM NH4HCO3, mobile phase B was acetonitrile. The column used for chromatography was a Xbridge C182.1*50mm column (5um particles). Detection methods are diode array (DAD) detection. MS mode was positive electrospray ionization. MS range was 100-1000. HPLC-MS method F HPLC-MS method F was performed on a Waters Acquity Arc equipped with a Waters Acquity QDA detector and a 2998 PDA Detector. Solid phase: Phenomenex Gemini C184.6x50mm 3um. Mobile phase: solvent B water CH3COONH45 mM pH 5.2: ACN 95:5; solvent C ACN: water 95:5; 50 to 100% of C in 5 min; flow 1.2 mL / min. HPLC-MS method G HPLC-MS method G was performed on a Shimadzu LC-20AD XR&MS 2020. The column used for chromatography was a Halo C183.0*30mm (5um particles). Detection methods are Evaporative Light- scattering detector (ELSD) and diode array (DAD). MS mode was positive electrospray ionization. MS range was 50-2000. Mobile phase A was 0.04% TFA in water, and mobile phase B was 0.02% TFA in HPLC grade acetonitrile. The gradient was 10-100% B in 0.90 min .10% B in 0.01 min, 10-100% B (0.01-0.50 min) with a hold at 100% B for 0.40 min. The flow rate was 2.0 mL / min (0.00-0.90 min). ESI Electrospray ionization mass spectrometry was performed on a Waters Acquity QDA detector. UPLC / HRMS High Resolution Mass Spectrometry (HRMS) was performed on a Waters Acquity H-class UPLC equipped with a Waters Acquity PDA detector and with Waters Xevo G2-XS Quadrupole Time of Flight Mass Spectrometer (qTOF). Reversed phase chromatography was performed on a Waters BEH C18 UPLC column(2.1 x 50mm, particle size 1.7µ m) kept at 50°C. Two mobile phases were used: phase A 0.1% Formic acid in highly purified water (UPLC-MS grade) and mobile phase B was 0.1% Formic acid in Acetonitrile (UPLC- MS grade). The gradient was run from 5% to 95% of mobile phase B in 4.86 min, hold 95% B 0.64 minutes.Flow rate 0.5 mL / min. Injection volume 1 µ L. The PDA range was 210–400 nm 4.8 nm resolution. The massexperiment type was MSe (Full scan precursor and fragment ion scanning) and it was conducted in resolution mode. The ESI source operated at 150 °C, 0.8 kV capillary voltage, 25 V cone voltage, 1000 L / h desolvation gas flow at 500 °C and 100 L / h nitrogen cone flow. The collision Energy was 4.00 eV for the Low energy acquisition and was 20.0 to 40.0 eV for the high energy ramp. The range 100-2000 m / z was fixed, and all the experiments were carried out at 0.08s as mass scan time. Leucine Enkephalin was chosen as stable, soluble,and appropriate reference compound for real-time single-point accurate mass error correction. 100 pg / µ Lsolution of Leucine Enkephaline was directly introduced in the ESI source during all the acquisition. NMR1H-NMR spectra were recorded at a constant temperature of 25 °C on a Varian INOVA 400 spectrometer operating at 400.5 MHz and equipped with a 5 mm 1H{15N-31P} z-axis PFG Indirect Detection probe, on a Varian INOVA 500 spectrometer operating at 499.7 MHz and equipped with a 5 mm1H{13C-15N} triple resonance Indirect Detection probe, alternatively on Bruker 600 Avance III spectrometer operating at 600.13 MHz equipped with a 5 mm broadband inverse detection BBI Z gradient probe. Chemical shifts were referenced with non deuterated residual solvent signal (DMSO-d6: 2.50 δ: for1H). Data are reported as follows: chemical shift (δ:), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, qt = quintet, br. s = broad singlet, dd = doublet of doublets, ddd = doublet of doublets of doublets, m = multiplet), coupling constants (J, Hz) and number of protons. Examples Intermediate of formula (VI) (Scheme 1) Synthesis of methyl 2-[(6-fluoroquinoline-2-carbonyl)amino]acetate To a solution of g, 235.41 mmol, 32.77 mL, 3 eq) and methyl 2-aminoacetate hydrochloride (9.85 g, 78.47 mmol, 1 eq) in DMF (150 mL), was added HOBt (15.90 g, 117.70 mmol, 1.5 eq) and EDCI (22.56 g, 117.70 mmol, 1.5 eq). The mixture was stirred at 25 °C for 16 h. The reaction mixture was poured carefully dropwise into water, solid precipitation was observed in the solution, filtered and the filter cake was washed with water (50 mL*3). Dried to afford product. The crude was used directly without purification. Methyl 2-[(6-fluoroquinoline-2- carbonyl)amino]acetate (20 g) was obtained as brown solid. ESI [M+H]+=263.0 Intermediate of formula (VII) (Scheme 1) Synthesis of 2-[(6-fluoroquinoline-2-carbonyl)amino]acetic acid To a solution of mmol, 1 eq) in THF (200 mL) and H2O (40 mL), was added LiOH.H2O (9.60 g, 228.80 mmol, 3 eq). The mixture was stirred at 25 °C for 2 h. The reaction mixture was concentrated to remove organic layers, then the aqueous phase diluted with H2O (100 mL) and then added 1 N HCl dropwise to pH=5, solid precipitation was observed in the solution. The reaction mixture was filtered and the filter cake was washed with 50 mL*3 of H2O, dried in vacuum to give product. The crude was used directly without purification.2-[(6-fluoroquinoline-2-carbonyl)amino]acetic acid (13.38 g) was obtained as brown solid. ESI [M+H]+=249.01H NMR (400 MHz, DMSO-d6) δ: 12.91 - 12.57 (m, 1H), 9.13 (br t, J = 6.0 Hz, 1H), 8.57 (d, J = 8.6 Hz, 1H), 8.29 - 8.13 (m, 2H), 7.92 (dd, J = 2.8, 9.3 Hz, 1H), 7.81 (dt, J = 2.9, 8.9 Hz, 1H), 4.05 (d, J = 6.1 Hz, 2H) According to the same methodology, but employing suitable substituted derivatives, the following intermediate compounds of formula (VII) were prepared: (2R)-2-[(6-fluoroquinoline-2-carbonyl)amino]propanoic acid HPLC-MS method A (RT=2.65 min, (2S)-2-[(6-fluoroquinoline-2-carbonyl)amino]propanoic acid HPLC-MS method A (RT=2.65 min, Intermediates of formula (IX) (Scheme 1) Synthesis of (2S,4R)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]-4-hydroxy-pyrrolidine-2- carboxylic acid To a solution of 2-[(6-fluoroquinoline-2-carbonyl)amino]acetic acid (10 g, 40.29 mmol, 1 eq) and 1- hydroxypyrrolidine-2,5-dione (6.03 g, 52.38 mmol, 1.3 eq) in DMF (100 mL) was added EDCI (10.04 g, 52.38 mmol, 1.3 eq). The mixture was stirred at 25 °C for 16 h. The reaction mixture was used for next step directly. (2,5-dioxopyrrolidin-1-yl) 2-[(6-fluoroquinoline-2-carbonyl)amino]acetate (13.5 g, crude) was obtained as brown liquid. ESI [M+H]+=346.2 Synthesis of the title compound (step 2) To a solution of (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid (9.87 g, 75.30 mmol, 2 eq) in THF (50 mL) and H2O (50 mL) was added NaHCO3 (15.82 g, 188.25 mmol, 7.33 mL, 5 eq), the mixture was stirred at 25 °C for 5 min, then (2,5-dioxopyrrolidin-1-yl) 2-[(6-fluoroquinoline-2-carbonyl)amino]acetate (13 g, 37.65 mmol, 1 eq) was added. The mixture was stirred at 25 °C for 2 h. The reaction mixture was concentrated to remove organic layers, then the aqueous phase diluted with H2O (500 mL) and then added 1 N HCl drop wised to pH=5, stand overnight, solid precipitation was observed in the solution. The reaction mixture was filtered and the filter cake was washed with 50 mL*3 of H2O, dried in vacuum to give product. The crude was purified by preparative HPLC (column: Phenomenex luna C18 (250*70mm,15 um); mobile phase: [H2O(0.04%HCl)-ACN];gradient:15%-55% B over 20.0 min). (2S,4R)-1-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]-4-hydroxy-pyrrolidine-2-carboxylic acid (10 g) was obtained as white solid. ESI [M+H]+=362.1 1H NMR (400 MHz, DMSO-d6) δ: 12.58 (br d, J = 1.2 Hz, 1H), 8.95 (br t, J = 5.2 Hz, 1H), 8.58 (d, J = 8.6 Hz, 1H), 8.32 - 8.09 (m, 2H), 7.93 (dd, J = 2.9, 9.3 Hz, 1H), 7.81 (dt, J = 2.9, 8.9 Hz, 1H), 5.34 - 5.11 (m, 1H), 4.40 (br s, 1H), 4.34 - 3.89 (m, 3H), 3.74 - 3.39 (m, 2H), 2.34 - 1.88 (m, 2H) According to the same methodology, but employing suitable substituted derivatives, the following intermediate compounds of formula (IX) were prepared: (3S)-4-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxylic acid HPLC-MS method A (RT=2.497 (3S)-4-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]-6,6-dimethyl-morpholine-3-carboxylic acid HPLC-MS method A (RT=2.77 (2R,3S)-4-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]-2-methyl-morpholine-3-carboxylic acid HPLC-MS method A (RT=2.588 (4R)-3-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]thiazolidine-4-carboxylic acid HPLC-MS method A (RT=2.426 (2S)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]azetidine-2-carboxylic acid HPLC-MS method A (RT=1.925 (2S)-4,4-difluoro-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]pyrrolidine-2-carboxylic acid ESI [M+H]+=382.1 (2S,4R)-4-fluoro-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]pyrrolidine-2-carboxylic acid HPLC-MS method A (RT=2.490 (2S,4R)-4-cyano-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]pyrrolidine-2-carboxylic acid ESI: [M+H]+=371.1 (2S)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]-4-oxo-pyrrolidine-2-carboxylic acid ESI: [M+H]+=360.0 (2S,4R)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]-4-(trifluoromethyl)pyrrolidine-2-carboxylic acid ESI: [M+H]+=360.0 (2S,4R)-4-(dimethylamino)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]pyrrolidine-2-carboxylic acid HPLC-MS method G (RT=0.315 Intermediates of formula (XII) (Scheme 2) Synthesis of methyl (2S)-1-[2-(tert-butoxycarbonylamino)acetyl]piperidine-2-carboxylate To a solution 2-carboxylate hydrochloride (3 g, 16.6 mmol) in dry DCM (100 mL) were sequentially added HOBt (2.93 g, 21.7 mmol, 1.3 eq), EDCI (3.84 g, 20.0 mmol, 1.2 eq) and DIPEA (8.75 mL, 50.1 mmol, 3 eq). The mixture was stirred at 25 °C for 16 h. LC-MS showed the formation of desired product. The reaction mixture was quenched with NaHCO3sat. sol. and extracted with DCM (3x). The organic phase was washed with NH4Cl sat. sol., brine and dried over Na2SO4 anhydrous and evaporated under reduced pressure. The crude of reaction was purified by automatic column chromatography on silica gel, gradient from 0% to 70% EA in hexane, obtaining methyl (2S)-1-[2-(tert-butoxycarbonylamino)acetyl]piperidine-2-carboxylate (2.94 g, 58% yield) as a colorless oil. HPLC-MS method A (RT=3.570 min, [M+H-Boc]+=201.0) According to the same methodology, but employing suitable substituted derivatives, the following intermediate of formula (XII) were prepared: methyl (3S)-4-[2-(tert-butoxycarbonylamino)acetyl]morpholine-3-carboxylate O HPLC-MS method A (RT=2.873 methyl (3S)-4-[2-(tert-butoxycarbonylamino)acetyl]morpholine-3-carboxylate HPLC-MS method A (RT=2.241 Intermediates of formula (XIII) (Scheme 2) Synthesis of methyl (2S)-1-(2-aminoacetyl)piperidine-2-carboxylate hydrochloride To a solution (2.94 g, 2.79 mmol) in THF (10 mL) was added HCl 4M in dioxane (3.48 mL, 13.95 mmol, 5 eq). The reaction mixture was left under magnetic stirring at r.t. overnight. The organic solvent was evaporated under reduced pressure to give methyl (2S)-1-(2-aminoacetyl)piperidine-2-carboxylate hydrochloride (2.32 g, 99 % yield) as a white solid. HPLC-MS method A (RT=0.580 min, [M+H]+=201.3). According to the same methodology, but employing suitable starting materials, the following intermediate compounds of formula (XIII) were prepared: Methyl (3S)-4-(2-aminoacetyl)morpholine-3-carboxylate hydrochloride HPLC-MS method A (RT=0.590 min, Methyl (2S)-1-(2-aminoacetyl)-4-methyl-piperazine-2-carboxylate 2.HCl HPLC-MS method A (RT=0.550 min, Intermediates with formula (XIV) (Scheme 2) Synthesis of methyl (2S)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]piperidine-2-carboxylate and 6-fluoroquinoline-2-carboxylic acid (71 mg, 0.37 mmol, 1.1 eq) in dry DCM (3 mL) were sequentially added HOBt (59 mg, 0.43 mmol, 1.3 eq), EDCI (77mg, 0.40 mmol, 1.2 eq) and DIPEA (0.177 mL, 1.01 mmol, 3 eq). The mixture was stirred at 25 °C for 16 h. The reaction mixture was quenched with NaHCO3sat. sol. and extracted with DCM (3x). The organic phase was washed with NH4Cl sat. sol., brine and dried over Na2SO4 anhydrous and evaporated under reduced pressure. The crude of reaction was purified by automatic column chromatography on silica gel, gradient from 0% to 10% MeOH in DCM, obtaining (2S)-1-[2-[(6- fluoroquinoline-2-carbonyl)amino]acetyl]piperidine-2-carboxylate (68 mg, 54 % yield). HPLC-MS method A (RT=4.252 min, [M+H]+=374.3) According to the same methodology, but employing suitable derivatives, the following intermediate compounds of formula (XIV) were prepared: methyl (3S)-4-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxylate HPLC-MS method A (RT=3.618 methyl (2S)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]-4-methyl-piperazine-2-carboxylate HPLC-MS method A (RT=3.100 Intermediates with formula (IX) (Scheme 2) Synthesis of (2S)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]piperidine-2-carboxylic acid -1-[2-[(6- fluoroquinoline-2-carbonyl)amino]acetyl]piperidine-2-carboxylate (68 mg, 0.18 mmol, 1 eq) in a mixture of H2O (1 mL) and MeOH (1 mL). The reaction mixture was stirred at r.t. overnight. HPLC-MS showed completion of reaction. The organic phase was evaporated under reduced pressure and the aqueous phase was acidified (pH 3) by addition of HCl 0.1 N aqueous solution. The aqueous phase was extracted with EA (3 x 5 mL) and the collected organic phases dried over Na2SO4anhydrous and evaporated under reduced pressure, giving (2S)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]piperidine-2-carboxylic acid (65 mg, 0.10 mmol, 54.6% Yield). HPLC-MS method A (RT=2.759 min, [M+H]+=360.2) According to the same methodology, but employing suitable starting materials, the following intermediate compounds of formula (IX) were prepared: (3S)-4-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxylic acid HPLC-MS method A (RT=2.446 (2S)-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]-4-methyl-piperazine-2-carboxylic acid hydrochloride HPLC-MS method A Intermediates of formula (XV) (Schemes 3, 4, 5) Synthesis of (1R)-1-[4-methoxy-2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethanamine (step 1) To a solution of 1-(2-bromo-4-methoxy-phenyl)ethanone (9 g, 39.29 mmol, 1 eq.) in THF (100 mL) was added (S)-2-methylpropane-2-sulfinamide (9.52 g, 78.58 mmol, 2 eq.) and Ti(OEt)4 (35.85 g, 157.16 mmol, 4 eq.).The mixture was stirred at 70 °C for 16 h. The crude was concentrated used the next step without purification. Compound (S)-N-[1-(2-bromo-4-methoxy-phenyl)ethylidene]-2-methyl-propane-2-sulfinamide (13.05 g, quantitative yield) was obtained as yellow oil. ESI [M+H]+=362.3 Synthesis of (S)-N-[(1R)-1-(2-bromo-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide and (S)-N-[(1S)-1-(2-bromo-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (step 2) To a solution of (S)-N-[1-(2-bromo-4-methoxy-phenyl)ethylidene]-2-methyl-propane-2-sulfinamide (13.05 g, 39.28 mmol) in THF (130 mL) was added NaBH4(5.99 g, 158.33 mmol, 4.03 eq.) under N2and 0°C. The mixture was stirred at 25 °C for 2h. The reaction mixture was quenched by addition of NH4Cl 100 mL at 0 °C, and then diluted with H2O (100 mL) and extracted with DCM mL (200 mL * 3). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The crude was purified by preparative HPLC (column: Welch Xtimate C18250*70mm*10um; mobile phase: [H2O (10mM NH4HCO3) - ACN]; gradient: 40%-60% B over 18.0 min). Compound (S)-N-[(1R)- 1-(2-bromo-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (3.9 g) was obtained as a white solid. HPLC-MS method G (RT=0.492 min, [M+H]+=334.1). Compound (S)-N-[(1S)-1-(2-bromo-4-methoxy- phenyl)ethyl]-2-methyl-propane-2-sulfinamide (6.4 g) was obtained as a white solid. HPLC-MS method G (RT=0.503 min, [M+H]+= 334.1) Synthesis of (1R)-1-(2-bromo-4-methoxy-phenyl)ethanamine (step 3) (S)-N-[(1R)-1-(2-bromo-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (3.9 g, 11.67 mmol) was dissolved in HCl / MeOH (40 mL) .The mixture was stirred at 25 °C for 1h. The crude was concentrated used the next step without purification. Compound (1R)-1-(2-bromo-4-methoxy-phenyl)ethanamine (2.68 g, crude) was obtained as a white solid. HPLC-MS method G (RT=0.294 min, recognized by fragment [C9H10BrO]+= 213.1) Synthesis of tert-butyl N-[(1R)-1-(2-bromo-4-methoxy-phenyl)ethyl]carbamate (step 4) To a solution of (1R)-1-(2-bromo-4-methoxy-phenyl)ethanamine (2.68 g, 11.65 mmol) in DCM (30 mL) was added (Boc)2O (5.08 g, 23.29 mmol, 2 eq) and TEA (4.71 g, 46.59 mmol, 4 eq). The mixture was stirred at 25 °C for 2h. The residue was treated with water (50 mL), extracted with EA (50*3 mL), the combined organic phase was dried over Na2SO4, filtrated and concentrated to give the residue. Compound tert-butyl N-[(1R)- 1-(2-bromo-4-methoxy-phenyl)ethyl]carbamate (5.36 g, crude) was obtained as a yellow oil. HPLC-MS method G (RT=0.570 min, [M-Boc]+=130.1) Synthesis of (1R)-1-(2-bromo-4-methoxy-phenyl)ethanamine (step 5) To a solution of tert-butyl N-[(1R)-1-(2-bromo-4-methoxy-phenyl)ethyl]carbamate (1 g, 3.03 mmol) in 1,4- dioxane (10 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H- pyridine (810.81 mg, 3.63 mmol, 1.2 eq.), Pd(dppf)Cl2(443.17 mg, 0.60 mmol, 0.2 eq.) and K2CO3(837.09 mg, 6.06 mmol, 2 eq.) in H2O (1 mL). The mixture was stirred at 90 °C for 3h. The residue was treated with water (20 mL), extracted with EA (50*3 mL), the combined organic phase was dried over Na2SO4, filtrated and concentrated to give the residue. The crude was purified by column chromatography (SiO2, petroleum ether / ethyl acetate=100 / 1 to 0 / 1). Compound tert-butyl N-[(1R)-1-[4-methoxy-2-(1-methyl-3,6-dihydro-2H- pyridin-4-yl)phenyl]ethyl]carbamate (840 mg) was obtained as a brown solid. HPLC-MS method G (RT=0.359 min, [M+H]+=347.2) Synthesis of the title compound (step 6) Tert-butyl N-[(1R)-1-[4-methoxy-2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethyl]carbamate (840 mg, 2.42 mmol, 1 eq.) was dissolved in HCl / MeOH (4 M, 8.40 mL, 13.86 eq).The mixture was stirred at 25 °C for 1 h. The residue was purified by preparative HPLC (column: Phenomenex luna C18100*40mm*5 um; mobile phase: [H2O (0.04% HCl)-ACN]; gradient:1%-20% B over 8.0 min). Compound (1R)-1-[4-methoxy-2-(1- methyl-3,6-dihydro-2~{H}-pyridin-4-yl)phenyl]ethanamine (486.21 mg) was obtained as yellow solid. HPLC-MS method B (RT=2.103min, recognized by fragment [C15H20NO]+= 230.1) According to the same methodology, but employing suitable starting materials at step 3 and suitable reagents at step 5, the following compounds of formula (XV) were prepared: (1S)-1-[4-methoxy-2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethanamine HPLC-MS method C (RT=0.784 min, += 230.1) (1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethanamine HPLC-MS method B (RT=2.517 min, += 201.1) (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethanamine HPLC-MS method C (RT= 1.879 min, [C14H17O]+= 201.1) (1S)-1-[2-[(E)-2-cyclopentylvinyl]-4-methoxy-phenyl]ethanamine hydrochloride HPLC-MS method B (RT=2.997min, += 229.2) (1S)-1-[2-[(E)-2-cyclohexylvinyl]-4-methoxy-phenyl]ethanamine hydrochloride HPLC-MS method B (RT=3.179min, += 243.2) (1S)-1-[4-methoxy-2-[(E)-4-methylpent-1-enyl]phenyl]ethanamine hydrochloride Cl HNH2HPLC-MS method C (RT=2.217 min, += 217.1) (1S)-1-[2-[(E)-2-cyclobutylvinyl]-4-methoxy-phenyl]ethanamine hydrochloride HPLC-MS method C (RT=2.126 min, += 215.1) According to the same methodology, but employing suitable starting materials at steps 1 and 3 and suitable reagents at step 5, the following compound of formula (XV) was prepared: (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-nitro-phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.361 min, Synthesis of (1R)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethanamine hydrochloride Step 1 Step 2 1) To a mixture of 2-hydroxy-4-methoxy-benzaldehyde (15 g, 98.59 mmol) and (S)-2-methylpropane-2- sulfinamide (19.12 g, 157.74 mmol, 1.6 eq.) in toluene THF (150 mL) was added Ti(OEt)4(35.98 g, 157.74 mmol, 1.6 eq.). The reaction mixture was stirred for 16 h at 20°C under nitrogen atmosphere. The reaction mixture was diluted with EA (30 mL), which was washed with water (2 x 30 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2; PE: EA = 5%-8%). (S)-N-[(2-hydroxy-4-methoxy- phenyl)methylene]-2-methyl-propane-2-sulfinamide (22 g) was obtained as a white solid. ESI [M+H]+=256.1 Synthesis of (S)-N-[(1R)-1-(2-hydroxy-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide and (S)-N-[(1S)-1-(2-hydroxy-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (step 2) To a solution of (S)-N-[(2-hydroxy-4-methoxy-phenyl)methylene]-2-methyl-propane-2-sulfinamide (22.00 g, 86.16 mmol, 1 eq) in THF (220 mL) was added MeMgBr (3 M, 57.44 mL, 2 eq) dropwise at -78°C under N2. The reaction mixture was stirred for 16 h at 20 °C under nitrogen atmosphere. The reaction mixture was quenched by addition water (100 mL) at 0°C and extracted with EA (100mL). The combined organic layers were washed with brine (100mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (column: Agela DuraShell C18 250*70mm*10um; mobile phase: [H2O (10mM NH4HCO3) - ACN]; gradient: 20%-50% B over 17.0 min). (S)-N-[(1R)-1-(2-hydroxy-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (12 g) was obtained as a light yellow solid. HPLC-MS method G (RT=0.379, [M+H]+=272.1)1H NMR (400 MHz, DMSO-d6) δ: 9.44 (s, 1H), 7.15 (d, J = 8.6 Hz, 1H), 6.42 - 6.28 (m, 2H), 5.07 (d, J = 5.8 Hz, 1H), 4.62 (quin, J = 6.4 Hz, 1H), 3.66 (s, 3H), 1.36 (d, J = 6.8 Hz, 3H), 1.09 (s, 9H). (S)-N-[(1S)-1-(2-hydroxy-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (7.9 g) was obtained as a light yellow solid. HPLC-MS method G (RT=0.399, [M+H]+=272.1)1H NMR (400 MHz, DMSO-d6) δ: 9.50 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 6.46 - 6.28 (m, 2H), 5.31 (d, J = 7.1 Hz, 1H), 4.57 (quin, J = 6.8 Hz, 1H), 3.67 (s, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.08 (s, 9H) Synthesis of 2-[(1R)-1-aminoethyl]-5-methoxy-phenol (step 3) A solution of (S)-N-[(1R)-1-(2-hydroxy-4-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (5.00 g, 18.42 mmol) in HCl / dioxane (50 mL) was stirred for 2h at 20°C. The reaction mixture was concentrated under reduced pressure.2-[(1R)-1-aminoethyl]-5-methoxy-phenol (5.4 g, crude) was obtained as a white solid. Synthesis of tert-butyl N-[(1R)-1-(2-hydroxy-4-methoxy-phenyl)ethyl]carbamate (step 4) To a solution of 2-[(1R)-1-aminoethyl]-5-methoxy-phenol (5.3 g, 15.85 mmol) in DCM (1 mL) was added TEA (6.41 g, 63.40 mmol, 4 eq.) and Boc2O (3.80 g, 17.43 mmol, 1.1 eq.). Mixture was stirred for 16h at 20°C. The reaction mixture was slowly quenched with water (10 mL). Mixture was extracted with ethyl acetate (10 mL), which was washed with brine (10 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2; PE: EA=5%-10%). Tert-butyl N-[(1R)-1-(2-hydroxy-4-methoxy-phenyl)ethyl]carbamate (4.4 g) was obtained as a light yellow solid.1H NMR (400 MHz, DMSO-d6) δ: 9.41 (s, 1H), 7.19 - 6.92 (m, 2H), 6.42 - 6.22 (m, 2H), 4.91 - 4.68 (m, 1H), 3.66 (s, 3H), 1.36 (br s, 9H), 1.19 (d, J = 6.8 Hz, 3H) Synthesis of tert-butyl N-[(1R)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethyl]carbamate (step 5) To a solution of Tert-butyl N-[(1R)-1-(2-hydroxy-4-methoxy-phenyl)ethyl]carbamate (500 mg, 1.87 mmol, 1 eq.) in DMF (5 mL) was added bromomethylcyclopropane (303.01 mg, 2.24 mmol, 1.2 eq.) and K2CO3(517.02 mg, 3.74 mmol, 2 eq.). The mixture was stirred for 16h at 20°C. The reaction mixture was diluted with water (20 mL) and the obtained precipitate filtered. Tert-butyl N-[(1R)-1-[2-(cyclopropylmethoxy)-4- methoxy-phenyl]ethyl]carbamate (600 mg, crude) was obtained as a white solid.1H NMR (400 MHz, DMSO-d6) δ: 7.51 – 7.22 (m, 2H), 6.53 – 6.31 (m, 2H), 5.00 - 4.72 (m, 1H), 3.98 - 3.75 (m, 2H), 3.71 (s, 3H), 1.41 - 1.14 (m, 13H), 0.64 - 0.50 (m, 2H), 0.47 - 0.23 (m, 2H) Synthesis of the title compound (step 6) A solution of Tert-butyl N-[(1R)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethyl]carbamate (600 mg, 1.87 mmol) in HCl / MeOH (6 mL) was stirred for 2h at 20°C. The reaction mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Phenomenex luna C18250*50mm*10 um; mobile phase: [H2O(0.05%HCl)-ACN];gradient:10%-40% B over 10.0 min). (1R)-1-[2-(cyclopropylmethoxy)- 4-methoxy-phenyl]ethanamine (160 mg) was obtained as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ: 8.29 (br s, 3H), 7.36 (d, J = 9.1 Hz, 1H), 6.68 - 6.35 (m, 2H), 4.54 (td, J = 6.0, 12.2 Hz, 1H), 3.88 (d, J = 6.9 Hz, 2H), 3.75 (s, 3H), 1.46 (d, J = 6.9 Hz, 3H), 1.35 - 1.17 (m, 1H), 0.72 - 0.49 (m, 2H), 0.43 - 0.20 (m, 2H) According to the same methodology, but employing suitable starting materials at step 3 and suitable reagents at step 5, the following compounds of formula (XV) were prepared: (1S)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethanamine hydrochloride HPLC-MS method C (RT=1.862 min, [C13H17O2]+= 205.1) (1R)-1-(2-benzyloxy-4-methoxy-phenyl)ethanamine hydrochloride HPLC-MS method C (RT=2.004 min, += 241.1) (1S)-1-(2-benzyloxy-4-methoxy-phenyl)ethanamine hydrochloride1H NMR (400 MHz, DMSO-d6) δ: 8.32 (br 2H), 7.46 - 7.38 (m, 3H), 7.37 - 7.29 (m, 1H), 6.70 (d, J = 2.3 Hz, 1H), 6.61 (dd, J = 2.4, 8.5 Hz, 1H), 5.18 (d, J = 2.9 Hz, 2H), 4.58 (br d, J = 5.5 Hz, 1H), 3.75 (s, 3H), 1.45 (d, J = 6.8 Hz, 3H) (1R)-1-[4-methoxy-2-[(1-methyl-4-piperidyl)oxy]phenyl]ethanamine dihydrochloride1H NMR (400 MHz, DMSO-d6) δ: 11.15 - s, 3H), 7.41 (dd, J = 3.0, 8.5 Hz, 1H), 6.80 - 6.50 (m, 2H), 4.96 - 4.32 (m, 2H), 3.77 (d, J = 3.6 Hz, 3H), 3.37 (br s, 1H), 3.33 - 3.02 (m, 3H), 2.89 - 2.69 (m, 3H), 2.30 - 1.83 (m, 4H), 1.55 - 1.35 (m, 3H) (1S)-1-[2-[(3,3-difluorocyclobutyl)methoxy]-4-methoxy-phenyl]ethanamine hydrochloride1H NMR (400 MHz, DMSO-d6) δ: Hz, 1H), 6.68 - 6.53 (m, 2H), 4.52 (br d, J = 6.1 Hz, 1H), 4.09 (dt, J = 3.6, 9.7 Hz, 2H), 3.77 (s, 3H), 2.81 - 2.51 (m, 5H), 1.45 (d, J = 6.8 Hz, 3H) (1S)-1-[2-(cyclobutylmethoxy)-4-methoxy-phenyl]ethanamine hydrochloride HPLC-MS method B (RT=2.561 min, += 219.1) (1S)-1-[2-(3-cyclopropylprop-2-ynoxy)-4-methoxy-phenyl]ethanamine 1H NMR (400 MHz, DMSO-d6) δ: 7.30 (d, J = 8.4 Hz, 1H), 6.61 - 6.48 (m, 2H), 4.72 (d, J = 1.7 Hz, 2H), 4.15 (q, J = 6.5 Hz, 1H), 3.72 (s, 3H), 1.44 - 1.25 (m, 1H), 1.16 (d, J = 6.5 Hz, 3H), 0.86 - 0.72 (m, 2H), 0.63 - 0.49 (m, 2H) Synthesis of (1R)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethanamine hydrochloride O O S OH O N S N O O To a solution of 2-fluoro-4-methoxy-benzaldehyde (200 mg, 1.30 mmol, 1 eq.) in DMF (1 mL) was added Cs2CO3 (845.53 mg, 2.60 mmol, 2 eq.) and spiro[3.3]heptan-2-ol (218.32 mg, 1.95 mmol, 1.5 eq.). The reaction mixture was stirred for 16h at 100°C. The reaction mixture was diluted with water (2 mL) and extracted with EA (2 mL). The combined organic layers were washed with brine (2 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. Residue was purified by preparative TLC (SiO2; PE: EA=5:1).4-methoxy-2-spiro[3.3]heptan-2-yloxy-benzaldehyde (300 mg) was obtained as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ: 10.17 (s, 1H), 7.65 (d, J = 8.8 Hz, 1H), 6.63 (dd, J = 1.8, 8.6 Hz, 1H), 6.45 (d, J = 2.1 Hz, 1H), 4.78 (quin, J = 6.8 Hz, 1H), 3.84 (s, 3H), 2.60 (ddd, J = 3.0, 6.8, 9.7 Hz, 2H), 2.14 - 2.03 (m, 4H), 2.01 - 1.95 (m, 2H), 1.88 - 1.73 (m, 2H) Synthesis of (S)-N-[(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)methylene]-2-methyl-propane-2- sulfinamide (step 2) To a mixture of 4-methoxy-2-spiro[3.3]heptan-2-yloxy-benzaldehyde (300 mg, 1.22 mmol, 1 eq.) and (S)-2- methylpropane-2-sulfinamide (236.20 mg, 1.95 mmol, 1.6 eq.) in THF (3 mL) was added Ti(OEt)4 (444.55 mg, 1.95 mmol, 1.6 eq.). The reaction mixture was stirred for 16 h at 20°C under nitrogen atmosphere. The reaction mixture was diluted with water (30 mL) and extracted with EA (30 mL), which was washed with water (30 mL). The solution was filtered a over celite path. The organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2; PE:EA=3%-5%). (S)-N-[(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)methylene]-2-methyl-propane-2- sulfinamide (220 mg) was obtained as a light yellow oil.1H NMR (400 MHz, CHLOROFORM-d) δ: = 8.93 (s, 1H), 7.94 (d, J = 8.6 Hz, 1H), 6.53 (dd, J = 2.1, 8.7 Hz, 1H), 6.28 (d, J = 2.3 Hz, 1H), 4.57 (quin, J = 7.0 Hz, 1H), 3.85 (s, 3H), 2.62 - 2.51 (m, 2H), 2.28 - 2.15 (m, 2H), 2.13 - 2.05 (m, 2H), 2.01 (br d, J = 7.6 Hz, 2H), 1.94 - 1.78 (m, 2H), 1.25 (s, 9H). Synthesis of (S)-N-[(1R)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethyl]-2-methyl-propane-2- sulfinamide (step 3) To a solution of (S)-N-[(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)methylene]-2-methyl-propane-2- sulfinamide (220 mg, 0.62 mmol) in THF (2 mL) was added MeMgBr (3 M, 419 µL, 2 eq.) dropwise at -78°C under N2. The reaction mixture was stirred for 16 h at 20°C under N2 atmosphere. The reaction mixture was quenched by dropwise addition of water (10 mL) at 0°C, and extracted with EA (10 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (column: Waters Xbridge BEH C18 100*30mm*10um; mobile phase: [H2O(10mM NH4HCO3)-ACN];gradient:40%-75% B over 8.0 min). (S)-N- [(1R)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (120 mg) was obtained as a light yellow solid. HPLC-MS method G (RT=0.605 min, [M+H]+=366.2) Synthesis of the title compound (step 4) A solution of (S)-N-[(1R)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethyl]-2-methyl-propane-2- sulfinamide (120 mg, 0.329 mmol, 1 eq.) in 4M HCl / dioxane (0.5 mL) was stirred for 1 h at 20°C. The reaction mixture was concentrated and swapped with DCM. The residue was purified by preparative HPLC column: Phenomenex Luna C1875*30mm*3um; mobile phase: [water(0.04%HCl)-ACN];gradient:20%-50% B over 8.0 min). (1R)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethanamine (76 mg, 0.256 mmol, 78% yield) was obtained as a white solid. HPLC-MS method C (RT=2.213 min, recognized by fragment [C16H21O2]+= 245.1)1H NMR (400 MHz, DMSO-d6) δ: 8.20 (br s, 3H), 7.34 (d, J = 8.4 Hz, 1H), 6.57 (dd, J = 2.0, 8.5 Hz, 1H), 6.39 (d, J = 2.1 Hz, 1H), 4.65 (quin, J = 6.8 Hz, 1H), 4.54 - 4.41 (m, 1H), 3.75 (s, 3H), 2.62 - 2.52 (m, 2H), 2.11 - 1.93 (m, 6H), 1.82 (quin, J = 7.4 Hz, 2H), 1.43 (d, J = 6.7 Hz, 3H) According to the same methodology, but employing suitable starting materials at step 1, the following intermediate compounds of formula (XV) were prepared: (1R)-1-[2-(1-cyclopropylethoxy)-4-methoxy-phenyl]ethanamine HPLC-MS method G (RT=0.356, min, [C14H19O2]+= 219.2) (1R)-1-[2-[(1-rel-R)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethanamine and (1R)-1-[2-[(1-rel-S)-1- cyclopropylethoxy]-4-methoxy-phenyl]ethanamine (1R)-1-[2-(1- by SFC (column: DAICEL CHIRALCEL OZ 250*25 mm I.D.10um;mobile phase: [CO2-MeOH(0.1%NH3H2O)];B%:33%, isocratic elution mode). (1R)-1-[2-[(1-rel-R)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethanamine (200 mg) was obtained as a yellow oil. HPLC-MS method E (RT=2.352, min, recognized by fragment [C14H19O2]+= 219.2)1H NMR (400 MHz, DMSO-d6) δ: 7.26 (d, J = 8.1 Hz, 1H), 6.50 - 6.39 (m, 2H), 4.16 (d, J = 6.6 Hz, 1H), 4.06 - 3.97 (m, 1H), 3.70 (s, 3H), 2.07 - 1.52 (m, 2H), 1.28 (d, J = 6.0 Hz, 3H), 1.18 (d, J = 6.5 Hz, 3H), 1.08 (br d, J = 7.4 Hz, 1H), 0.47 (dd, J = 1.3, 8.1 Hz, 2H), 0.37 - 0.25 (m, 2H) (1R)-1-[2-[(1-rel-S)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethanamine (220 mg) was obtained as a yellow oil. HPLC-MS method E (RT=2.374, min, recognized by fragment [C14H19O2]+= 219.2)1H NMR (400 MHz, DMSO-d6) δ: 7.26 (d, J = 8.1 Hz, 1H), 6.53 - 6.38 (m, 2H), 4.17 (d, J = 6.5 Hz, 1H), 4.06 - 3.97 (m, 1H), 3.70 (s, 3H), 1.72 (br d, J = 1.4 Hz, 2H), 1.27 (d, J = 6.0 Hz, 3H), 1.17 (d, J = 6.5 Hz, 3H), 1.08 (br d, J = 7.4 Hz, 1H), 0.47 (dd, J = 1.9, 8.3 Hz, 2H), 0.37 - 0.24 (m, 2H) According to the same methodology, but employing (R)-2-methylpropane-2-sulfinamide as reagent at step 2, the following intermediate compounds of formula (XV) were prepared: (1S)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethanamine hydrochloride HPLC-MS method C (RT=2.206, min, += 245.1)1H NMR (400 MHz, DMSO-d6) δ: 8.23 (br s, 3H), 7.35 (d, J = 8.6 Hz, 1H), 6.57 (dd, J = 2.3, 8.5 Hz, 1H), 6.39 (d, J = 2.2 Hz, 1H), 4.65 (quin, J = 6.8 Hz, 1H), 4.54 - 4.36 (m, 1H), 3.75 (s, 3H), 2.63 - 2.52 (m, 2H), 2.16 - 1.91 (m, 6H), 1.89 - 1.72 (m, 2H), 1.43 (d, J = 6.7 Hz, 3H) (1S)-1-[2-[(1-rel-R)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethanamine and (1S)-1-[2-[(1-rel-S)-1- cyclopropylethoxy]-4-methoxy-phenyl]ethanamine (1S)-1-[2-[(1R)-1- was obtained as a yellow oil. HPLC-MS method B (RT=2.454, min, recognized by fragment [C14H19O2]+= 219.2)1H NMR (400 MHz, DMSO-d6) δ: 7.26 (d, J = 8.1 Hz, 1H), 6.50 - 6.39 (m, 2H), 4.17 (d, J = 6.6 Hz, 1H), 4.05 - 3.97 (m, 1H), 3.70 (s, 3H), 1.96 - 1.47 (m, 2H), 1.27 (d, J = 6.0 Hz, 3H), 1.17 (d, J = 6.6 Hz, 3H), 1.08 (br d, J = 7.4 Hz, 1H), 0.47 (dd, J = 2.0, 8.3 Hz, 2H), 0.38 - 0.24 (m, 2H) (1S)-1-[2-[(1S)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethanamine (220 mg) was obtained as a yellow oil. HPLC-MS method E (RT=2.401, min, recognized by fragment [C14H19O2]+= 219.2)1H NMR (400 MHz, DMSO-d6) δ: 7.26 (d, J = 8.1 Hz, 1H), 6.47 - 6.41 (m, 2H), 4.16 (d, J = 6.6 Hz, 1H), 4.07 - 3.94 (m, 1H), 3.70 (s, 3H), 1.90 - 1.47 (m, 2H), 1.28 (d, J = 6.1 Hz, 3H), 1.18 (d, J = 6.6 Hz, 3H), 1.08 (td, J = 5.0, 7.5 Hz, 1H), 0.47 (dd, J = 1.3, 8.0 Hz, 2H), 0.31 (br t, J = 5.9 Hz, 2H) According to the same methodology, using suitable starting material and starting from step 2, the following intermediate compounds of formula (XV) were prepared: 2-[(1S)-1-aminoethyl]-4-bromo-phenol hydrochloride HPLC-MS method G (RT=0.322, min, += 199.2 - 201.0) 2-[(1S)-1-aminoethyl]-4-bromo-5-chloro-phenol hydrochloride HPLC-MS method A (RT=2.65, min, += 233.1 - 235.1) Synthesis of 3-[(1R)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]benzenesulfonamide To a solution of 2-bromo-5-iodo-benzaldehyde (10 g, 32.16 mmol, 1 eq.) in dioxane (100 mL) was added DIPEA (8.31 g, 64.33 mmol, 2 eq.), Xantphos (930.51 mg, 1.61 mmol, 0.05 eq.) and Pd2(dba)3 (883.57 mg, 0.96 mmol, 0.03 eq.), followed by phenylmethanethiol (4.37 g, 35.18 mmol, 1.09 eq.). The solution was stirred at 60 °C for 1 h. The solution was concentrated under reduced pressure and the residue was purified by column chromatography (SiO2, PE / EA = 1 / 0 to 50 / 1). 5-benzylsulfanyl-2-bromo- benzaldehyde (9.5 g) was obtained as yellow solid.1H NMR (400 MHz, DMSO-d6) δ: 10.13 (s, 1H), 7.74 - 7.64 (m, 2H), 7.54 (dd, J = 2.4, 8.4 Hz, 1H), 7.40 - 7.34 (m, 2H), 7.33 - 7.27 (m, 2H), 7.27 - 7.20 (m, 1H), 4.32 (s, 2H). Synthesis of (S)-N-[(5-benzylsulfanyl-2-bromo-phenyl)methylene]-2-methyl-propane-2-sulfinamide (step 2) To a solution of 5-benzylsulfanyl-2-bromo-benzaldehyde (5 g, 16.28 mmol) and (S)-2-methylpropane-2- sulfinamide (2.96 g, 24.41 mmol, 1.5 eq.) in THF (50 mL) was added Ti(OEt)4 (5.94 g, 26.04 mmol, 1.6 eq.) and reaction mixture was stirred at 25 °C for 16 h. The solution was diluted with H2O (100 mL), extracted with EA (3*150 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated under reduce pressure. The residue was purified by column chromatography (SiO2, PE / EA =1 / 0 to 20 / 1). (S)-N-[(5-benzylsulfanyl-2-bromo-phenyl)methylene]-2-methyl-propane-2-sulfinamide (6.2 g) was obtained as yellow oil. ESI [M+H]+=409.9 Synthesis of (S)-N-[(1R)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (S)-N-[(1S)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (step 3) (S)-N-[(5-benzylsulfanyl-2-bromo-phenyl)methylene]-2-methyl-propane-2-sulfinamide (6.2 g, 15.11 mmol, 1 eq.) in THF (60 mL) was cooled to -78 °C, MeMgBr (3 M, 7.55 mL) was added dropwise under N2 atmosphere and the solution was stirred at 25 °C for 2 h. The solution was quenched drop wise by addition of H2O (60 mL), extracted with EA (3*100 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated under reduced pressure to give the residue. The residue was purified by preparative HPLC, column: Welch Xtimate C18 250*70mm*10um; mobile phase: [H2O (10mM NH4HCO3)-ACN]; gradient:38%-68% B over 17.0 min. (S)-N-[(1R)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (2.7 g) was obtained as light yellow solid, HPLC-MS method G (RT=0.582, min, [M+H]+=426.0)1H NMR (400 MHz, DMSO-d6) δ: 7.52 (d, J = 2.2 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.36 - 7.31 (m, 2H), 7.28 (t, J = 7.2 Hz, 2H), 7.26 - 7.19 (m, 1H), 7.13 (dd, J = 2.4, 8.4 Hz, 1H), 5.54 (d, J = 5.8 Hz, 1H), 4.68 (quin, J = 6.4 Hz, 1H), 4.32 - 4.15 (m, 2H), 1.40 (d, J = 6.8 Hz, 3H), 1.09 (s, 9H) (S)-N-[(1S)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (2.0 g) was obtained as yellow oil HPLC-MS method G (RT=0.580, min, [M+H]+=426.1)1H NMR (400 MHz, DMSO-d6) δ: 7.59 (d, J = 1.9 Hz, 1H), 7.46 (br d, J = 8.3 Hz, 1H), 7.40 - 7.32 (m, 2H), 7.29 (br t, J = 7.2 Hz, 2H), 7.26 - 7.20 (m, 1H), 7.17 - 7.08 (m, 1H), 6.00 (br d, J = 7.8 Hz, 1H), 4.76 - 4.58 (m, 1H), 4.35 - 4.16 (m, 2H), 1.31 (br d, J = 6.7 Hz, 3H), 1.09 (s, 9H) Synthesis of (1S)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethanamine (step 4) (S)-N-[(1R)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (1.7 g, 3.99 mmol) in HCl / MeOH (4 M, 17.00 mL, 17.06 eq.) was stirred at 25 °C for 1 h. The solution was concentrated under reduce pressure. The crude was used to next step directly and without further purification. (1S)-1-(5- benzylsulfanyl-2-bromo-phenyl)ethanamine (1.3 g, crude) was obtained as light yellow oil. ESI [M+H]+=322.0 Synthesis of 9H-fluoren-9-ylmethyl N-[(1R)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethyl]carbamate (step 5) (1S)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethanamine (1.3 g, 4.03 mmol) in ACN (15 mL) was added to a solution of Na2CO3 (1.71 g, 16.14 mmol, 4 eq.) in H2O (4.5 mL), then the FMOC-OSU (1.50 g, 4.44 mmol, 1.1 eq.) was added and the solution was stirred at 25 °C for 1 h. The solution was filtrated and the solid was collected. The crude was used to next step directly and without further purification.9H-fluoren-9-ylmethyl N- [(1S)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethyl]carbamate (1.7 g) was obtained as white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.09 (br d, J = 8.1 Hz, 1H), 7.89 (br d, J = 7.5 Hz, 2H), 7.70 (br d, J = 7.4 Hz, 2H), 7.49 - 7.43 (m, 2H), 7.42 - 7.37 (m, 2H), 7.37 - 7.30 (m, 4H), 7.28 - 7.18 (m, 3H), 7.12 (dd, J = 2.0, 8.4 Hz, 1H), 4.93 (quin, J = 7.1 Hz, 1H), 4.38 - 4.11 (m, 5H), 1.28 (br d, J = 7.0 Hz, 3H) Synthesis of 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-5-chlorosulfonyl-phenyl)ethyl]carbamate (step 6) A solution of NCS (674 mg, 5.05 mmol, 2.5 eq.) in THF (11 mL) was added drop wise over 10 min to a solution of 9H-fluoren-9-ylmethyl N-[(1S)-1-(5-benzylsulfanyl-2-bromo-phenyl)ethyl]carbamate (1.1 g, 2.02 mmol) in AcOH (11 mL) / H2O (3.3 mL). The solution was stirred at 25 °C for 0.5 h, then additional NCS (161.86 mg, 1.21 mmol, 0.6 eq.) in THF (2.7 mL) was added drop wise at 25 °C. The solution was diluted with H2O (30 mL), extracted with EA (3*50 mL), the combined organic phases were washed with saturated NaHCO3, dried over Na2SO4, filtrated and concentrated to give the residue. The crude was used to next step directly and without further purification. 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-5-chlorosulfonyl- phenyl)ethyl]carbamate (1.5 g, crude) was obtained as yellow oil. ESI [M+Na]+=542.1 Synthesis of 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-5-sulfamoyl-phenyl)ethyl]carbamate (step 7) NH3.H2O (3.36 g, 28.80 mmol, 10 eq.) was added to a solution of 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo- 5-chlorosulfonyl-phenyl)ethyl]carbamate (1.5 g, 2.88 mmol) in ACN (15 mL) and the solution was stirred at 25 °C for 1 h. The solution was diluted with H2O (30 mL), extracted with EA (3*30 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated to give the residue. The residue was purified by column chromatography (SiO2, PE / EA=1 / 0 to 1 / 1). 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-5-sulfamoyl- phenyl)ethyl]carbamate (720 mg) was obtained as white solid, ESI [M+Na]+=523.01H NMR (400 MHz, DMSO-d6) δ: 8.30 (br d, J = 7.4 Hz, 1H), 7.96 (d, J = 2.3 Hz, 1H), 7.93 - 7.78 (m, 3H), 7.75 - 7.60 (m, 3H), 7.48 (s, 2H), 7.45 - 7.38 (m, 2H), 7.34 (q, J = 7.0 Hz, 2H), 5.02 (quin, J = 7.1 Hz, 1H), 4.37 - 4.16 (m, 3H), 1.33 (br d, J = 6.9 Hz, 3H). Synthesis of 9H-fluoren-9-ylmethyl N-[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-sulfamoyl- phenyl]ethyl]carbamate (step 8) 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-5-sulfamoyl-phenyl)ethyl]carbamate (720 mg, 1.44 mmol), 2-[(E)- 2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (337.22 mg, 1.74 mmol, 1.21 eq) and K2CO3(396.93 mg, 2.87 mmol, 2 eq.) were dissolved in 1,4-dioxane (8 mL) / H2O (1.6 mL). Pd(dppf)Cl2 was added (105.07 mg, 143.60 µmol, 0.1 eq.) and the solution was stirred at 90 °C for 6 h. The solution was diluted with H2O (20 mL), extracted with EA (3*30 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated to give the residue. The crude was used to next step directly and without further purification. 9H-fluoren-9-ylmethyl N-[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-sulfamoyl-phenyl]ethyl]carbamate (1.4 g, crude) was obtained as brown oil. ESI [M+H]+=489.2 Synthesis of the title compound (step 9) To a solution of 9H-fluoren-9-ylmethyl N-[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-sulfamoyl- phenyl]ethyl]carbamate (1.4 g, 2.87 mmol) in DMF (15 mL) was added piperidine (0.565 mL, 5.73 mmol, 2 eq.) and the solution was stirred at 25 °C for 1 h. The solution was diluted with H2O (30 mL), extracted with EA (3*50 mL), the combined organic phases were washed with brine, dried over Na2SO4, filtrated and concentrated to give the residue. The residue was purified by column chromatography (SiO2, EA / MeOH=1 / 0 to 10 / 1) obtaining a brown solid). The residue was purified by preparative HPLC (Column: Waters Xbridge Prep OBD C18150*40mm*10um; mobile phase: [H2O (10mM NH4HCO3)-ACN]; gradient:10%-45% B over 8.0 min.).3-[(1R)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]benzenesulfonamide (130 mg) was obtained as white solid. HPLC-MS method B (RT=2.322 min, recognized by fragment [C13H16NO2S]+= 250.1) According to the same methodology, but employing suitable starting materials at steps 4 and 7, the following intermediate compounds of formula (XV) were prepared: 3-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]benzenesulfonamide HPLC-MS method G (RT=0.316 min, recognized by fragment [C13H16NO2S]+= 250.1) 3-[(1R)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-(2-hydroxyethyl)benzenesulfonamide HPLC-MS method C (RT=1.738 min, += 294.1) 3-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-(2-hydroxyethyl)benzenesulfonamide HPLC-MS method C (RT=1.732 += 294.0) Synthesis of 3-[(1R)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-[2- (dimethylamino)ethyl]benzenesulfonamide dihydrochloride phenyl]ethyl]carbamate (Step 1) To a solution of 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-5-chlorosulfonyl-phenyl)ethyl]carbamate (1.53 g, 2.94 mmol) in DCM (23 mL) was added DIPEA (0.767 mL, 4.41 mmol, 1.5 eq.) and N',N'-dimethylethane- 1,2-diamine (0.385 mL, 3.53 mmol, 1.2 eq.) dropwise, the solution was stirred at 25 °C for 1 h. The solution was diluted with H2O (40 mL), extracted with DCM (3*50 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated to give the residue. The residue was purified by column chromatography (SiO2, Ethyl acetate / MeOH = 1 / 0 to 10 / 1). 9H-fluoren-9-ylmethyl N-[(1R)-1-[2-bromo-5-[2- (dimethylamino)ethylsulfamoyl]phenyl]ethyl]carbamate (1.5 g) was obtained as light yellow oil. ESI [M+H]+=572.1 Synthesis of 3-[(1R)-1-aminoethyl]-4-bromo-N-[2-(dimethylamino)ethyl]benzenesulfonamide (step 2) To a solution of 9H-fluoren-9-ylmethyl N-[(1R)-1-[2-bromo-5-[2- (dimethylamino)ethylsulfamoyl]phenyl]ethyl]carbamate (1.5 g, 1.82 mmol) in DMF (15 mL) was added piperidine (0.268 mL 2.72 mmol, 1.5 eq.) and the solution was stirred at 25 °C for 1 h. The solution was diluted with H2O (30 mL), filtrated and the filtrate was concentrated under reduce pressure. The residue was purified by column chromatography (SiO2, DCM / MeOH=1 / 0 to 5 / 1).3-[(1R)-1-aminoethyl]-4-bromo-N- [2-(dimethylamino)ethyl]benzenesulfonamide (255 mg) was obtained as light yellow oil. ESI [M+H]+=350.0. Synthesis of tert-butyl N-[(1R)-1-[2-bromo-5-[2-(dimethylamino)ethylsulfamoyl]phenyl]ethyl] carbamate (step 3) To a solution of 3-[(1R)-1-aminoethyl]-4-bromo-N-[2-(dimethylamino)ethyl]benzenesulfonamide (250 mg, 713 µmol) in DCM (5 mL) was added TEA (0.990 mL, 1 eq.) and (Boc)2O (233 mg, 1.07 mmol, 1.5 eq.), the solution was stirred at 25 °C for 1 h. The solution was diluted with H2O (20 mL), extracted with DCM (3*30 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated to give the residue. The residue was purified by preparative TLC (SiO2, PE: EA = 1:2). Tert-butyl N-[(1R)-1-[2-bromo-5-[2- (dimethylamino)ethylsulfamoyl]phenyl]ethyl]carbamate (185 mg) was obtained as light yellow oil. Synthesis of tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[2-(dimethylamino)ethylsulfamoyl] phenyl]ethyl]carbamate (step 4) To a solution of tert-butyl N-[(1R)-1-[2-bromo-5-[2-(dimethylamino)ethylsulfamoyl]phenyl]ethyl]carbamate (180 mg, 326.97 µmol), 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (95 mg, 490 µmol, 1.5 eq.) and K2CO3 (90 mg, 653µmol, 2 eq.) in 1,4-dioxane (4 mL) / H2O (1 mL) was added Pd(dppf)Cl2 (23mg, 32 µmol, 0.1 eq.) and the solution was stirred at 90 °C for 2 h. The solution was diluted with H2O (20 mL), extracted with EA (3*30 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated to give the residue. The residue was purified by preparative TLC (SiO2, DCM: MeOH = 10:1). Tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[2-(dimethylamino)ethylsulfamoyl]phenyl]ethyl]carbamate (175 mg) was obtained as brown oil. ESI [M+H]+=438.3. Synthesis of the title compound (step 5) Tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[2-(dimethylamino)ethylsulfamoyl]phenyl]ethyl]carbamate (150 mg, 342.78 µmol) in HCl / dioxane (5 M, 2.46 mL, 35.85 eq.) was stirred at 25 °C for 1 h. The solution was concentrated under reduce pressure to give the residue. The crude was used to next step directly and without further purification. 3-[(1R)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-[2- (dimethylamino)ethyl]benzenesulfonamide dihydrochloride (109 mg, crude) was obtained as brown oil. HPLC-MS method C (RT=1.589 min, [M+H]+= 338.2) According to the same methodology, but employing suitable starting material and reagents at step 1 the following intermediate compounds of formula (XV) were prepared: 3-[(1R)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-[2-(dimethylamino)ethyl]benzenesulfonamide dihydrochloride HPLC-MS method C 3-[(1R)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-methyl-benzenesulfonamide hydrochloride HPLC-MS method C (RT=1.815 min, += 264.0) 3-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-methyl-benzenesulfonamide hydrochloride HPLC-MS method C (RT=1.815 min, += 264.1) 3-[(1R)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-ethyl-benzenesulfonamide hydrochloride HPLC-MS method C (RT=1.845 min, += 278.1) 3-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-N-ethyl-benzenesulfonamide hydrochloride HPLC-MS method C (RT=1.852 min, += 278.1) Synthesis of 4-[(1R)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]benzenesulfonamide hydrochloride To a solution of 2-bromo-4-fluoro-benzaldehyde (30 g, 147 mmol) and Na2CO3(23.49 g, 221 mmol, 1.5 eq.) in DMSO (300 mL) was added BnSH (18.35 g, 147 mmol, 1 eq.). The mixture was stirred at 25 °C for 5 h. The reaction mixture was quenched with H2O (100 mL), filtered to remove the insoluble material, extracted with EA (100 mL * 3), washed with brine (100 mL * 3), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography (SiO2, PE:EA = 1:0 to 100:1).4- benzylsulfanyl-2-bromo-benzaldehyde (25.6 g) was obtained as a white solid.1H NMR (400 MHz, CHLOROFORM-d) δ: = 10.17 (s, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.41 (d, J = 1.6 Hz, 1H), 7.34 - 7.16 (m, 6H), 4.16 (s, 2H) Synthesis of (S)-N-[(4-benzylsulfanyl-2-bromo-phenyl)methylene]-2-methyl-propane-2-sulfinamide (step 2) To a solution of 4-benzylsulfanyl-2-bromo-benzaldehyde (25.6 g, 83.33 mmol) and (S)-2-methylpropane-2- sulfinamide (15.15 g, 125.00 mmol, 1.5 eq.) in THF (250 mL) was added Ti(OEt)4(57.03 g, 250.00 mmol, 3 eq.). The mixture was stirred at 25 °C for 16 h. The reaction mixture was quenched with H2O (300 mL), filtered on celite and then extracted with EA (300 mL * 3), washed with brine (100 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography (SiO2, PE:EA = 200:1 to 80:1) (S)-N-[(4-benzylsulfanyl-2-bromo-phenyl)methylene]-2-methyl-propane-2- sulfinamide (30 g) was obtained as a yellow oil. ESI [M+H]+=410.1. Synthesis of (S)-N-[(1R)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide and (S)-N-[(1S)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (step 3) To a solution of (S)-N-[(4-benzylsulfanyl-2-bromo-phenyl)methylene]-2-methyl-propane-2-sulfinamide (30 g, 73.10 mmol) in THF (300 mL) was added MeMgBr (3 M, 85.28 mL, 3.5 eq.) at -78 °C. The mixture was stirred at 25 °C for 2 h. The reaction mixture was quenched with NH4Cl (5 mL) at 0 °C, and then diluted with H2O (300 mL), extracted with EA (300 mL * 3), washed with brine (300 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by preparative HPLC (column: Welch Xtimate C18250*70mm*10um; mobile phase: [H2O(10mM NH4HCO3)-ACN];gradient:48%-75% B over 24.0 min). (S)-N-[(1R)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide was obtained as a yellow oil. (14.5 g) HPLC-MS method G (RT=0.596 min, [M+H]+= 426.1)1H NMR (400 MHz, DMSO-d6) δ: 7.48 (d, J = 1.9 Hz, 1H), 7.45 - 7.41 (m, 1H), 7.40 - 7.20 (m, 6H), 5.49 (d, J = 5.5 Hz, 1H), 4.77 - 4.62 (m, 1H), 4.28 (s, 2H), 1.40 (d, J = 6.8 Hz, 3H), 1.09 (s, 9H) (S)-N-[(1S)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide was obtained as a yellow oil. (1.89 g) HPLC-MS method G (RT=0.606 min, [M+H]+= 426.1) Synthesis of (1R)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethanamine hydrochloride (step 4) A mixture of (S)-N-[(1R)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (5.8 g, 13.60 mmol) in HCl / MeOH (4 M, 34.80 mL, 10 eq.) was stirred at 25 °C for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue (1R)-1-(4-benzylsulfanyl-2-bromo- phenyl)ethanamine hydrochloride (4.88 g, crude) was obtained as a yellow solid. ESI [M+H]+=305.1 Synthesis of 9H-fluoren-9-ylmethyl N-[(1R)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethyl]carbamate (step 5) To a solution of (1R)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethanamine hydrochloride (4.88 g, 13.60 mmol) in ACN (300 mL) was added Na2CO3 (5.77 g, 54.42 mmol, 4 eq.) in H2O (50 mL), and then FMOC-OSU (6.88 g, 20.41 mmol, 1.5 eq.) was added. The mixture was stirred at 25 °C for 1 h. The reaction mixture was concentrated under reduced pressure to remove ACN. The residue was diluted with H2O (300 mL) and filtered, then the solid was collected. Compound 9H-fluoren-9-ylmethyl N-[(1R)-1-(4-benzylsulfanyl-2-bromo- phenyl)ethyl]carbamate (6.8 g) was obtained as a white solid. ESI [M+Na]+=566.2 Synthesis of 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-4-chlorosulfonyl-phenyl)ethyl]carbamate (step 6) To a solution of 9H-fluoren-9-ylmethyl N-[(1R)-1-(4-benzylsulfanyl-2-bromo-phenyl)ethyl]carbamate (3 g, 4.41 mmol) in AcOH (30 mL) and H2O (10 mL) was added a solution of NCS (1.77 g, 13.22 mmol, 3 eq.) in THF (30 mL). After addition, the mixture was stirred at this temperature for 1 h. Three sequential additions of NCS solution (294.29 mg, 2.20 mmol, 0.5 eq) in THF (3 mL) were performed dropwise till HPLC-MS showed that the starting material was consumed. The solution was diluted with Na2CO3 (pH=7), extracted with EA (3 * 30 mL), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-4-chlorosulfonyl-phenyl)ethyl]carbamate (2.3 g, crude) was obtained as a white solid. ESI [M+Na]+=542.1 Synthesis of 9H-fluoren-9-ylmethyl N-[(1S)-1-(2-bromo-4-sulfamoyl-phenyl)ethyl]carbamate (step 7) To a solution of 9H-fluoren-9-ylmethyl N-[(1R)-1-(2-bromo-4-chlorosulfonyl-phenyl)ethyl]carbamate (2.3 g, 4.13 mmol) in ACN (23 mL) was added NH3.H2O (1.06 mL, 8.25 mmol, 30%,2 eq.). The mixture was stirred at 25 °C for 1h. The mixture was adjusted to pH=7 with 2M HCl. The solution was diluted with H2O (10 mL), extracted with EA (3 * 30 mL), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The crude product was triturated with MTBE for 30 min.9H-fluoren-9-ylmethyl N-[(1S)- 1-(2-bromo-4-sulfamoyl-phenyl)ethyl]carbamate (1.86 g) was obtained as a light yellow solid. ESI [M+Na]+=523.2 Synthesis of 4-[(1R)-1-aminoethyl]-3-bromo-benzenesulfonamide (step 8) To a solution of 9H-fluoren-9-ylmethyl N-[(1S)-1-(2-bromo-4-sulfamoyl-phenyl)ethyl]carbamate (1.86 g, 2.42 mmol) in DMF (19 mL) was added piperidine (0.478 mL, 4.84 mmol, 2 eq.). The mixture was stirred at 25 °C for 1 h. The reaction mixture was quenched by addition H2O (30 mL9 and then filtered and concentrated under reduced pressure to give a residue. 4-[(1R)-1-aminoethyl]-3-bromo-benzenesulfonamide (675 mg, crude) was obtained as a yellow oil. ESI [M+H]+=279.0 Synthesis of 4-[(1R)-1-aminoethyl]-3-bromo-benzenesulfonamide (step 9) To a solution of 4-[(1R)-1-aminoethyl]-3-bromo-benzenesulfonamide (675 mg, 2.14 mmol) in DCM (7 mL) was added Boc2O (700.15 mg, 3.21 mmol, 1.5 eq.) and TEA (0.595 mL 4.28 mmol, 2 eq..). The mixture was stirred at 25 °C for 1 h. The solution was diluted with H2O (30 mL), extracted with DCM (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography (SiO2, PE: EA = 2:1 to 1:1). 4-[(1R)-1-aminoethyl]-3-bromo- benzenesulfonamide (900 mg) was obtained as a white solid. ESI [M+Na]+=401.1 Synthesis of tert-butyl N-[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-sulfamoyl-phenyl]ethyl]carbamate (step 10) To a solution of 4-[(1R)-1-aminoethyl]-3-bromo-benzenesulfonamide (900 mg, 2.37 mmol), 2-[(E)-2- cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (690 mg, 3.56 mmol, 1.5 eq.) and K2CO3 (655 mg, 4.75 mmol, 2 eq.) in dioxane (6 mL) and H2O (1.5 mL) was added Pd(dppf)Cl2(173 mg, 237 µmol, 0.1 eq.). The mixture was stirred at 90 °C for 16 h. The solution was diluted with H2O (30 mL), filtered through celite pad to remove by-product. The filtrate was extracted with EA (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography (SiO2, PE:EA = 10:1 to 3:1). Tert-butyl N-[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-sulfamoyl- phenyl]ethyl]carbamate (810 mg) was obtained as a white solid. ESI [M+Na]+=389.21H NMR (400 MHz, DMSO-d6) δ: 7.80 (d, J = 1.3 Hz, 1H), 7.66 - 7.51 (m, 2H), 7.47 (d, J = 8.3 Hz, 1H), 7.24 (s, 2H), 6.84 (d, J = 15.5 Hz, 1H), 5.80 - 5.66 (m, 1H), 4.95 (br t, J = 7.1 Hz, 1H), 1.75 - 1.64 (m, 1H), 1.36 (s, 9H), 1.24 (br d, J = 6.9 Hz, 3H), 0.85 (dd, J = 2.1, 7.9 Hz, 2H), 0.57 (br s, 2H) Synthesis of the title compound (Step 11) A mixture of tert-butyl N-[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-sulfamoyl-phenyl]ethyl]carbamate (810 mg, 2.21 mmol, 1 eq) in HCl / MeOH (4 M, 30 mL, 54.29 eq) was stirred at 25 °C for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (column: Phenomenex luna C18250*50mm*15um; mobile phase: [H2O (0.04%HCl)-ACN]; gradient: 1%-40% B over 10.0 min).4-[(1R)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]benzenesulfonamide hydrochloride (406.35 mg) was obtained as a white solid. HPLC-MS method C (RT=1.522 min, recognized by fragment [C13H16NO2S]+= 250.1)1H NMR (400 MHz, DMSO-d6) δ: 8.72 (br d, J = 2.8 Hz, 3H), 7.87 (d, J = 1.8 Hz, 1H), 7.80 - 7.74 (m, 1H), 7.73 - 7.67 (m, 1H), 7.39 (s, 2H), 6.86 (d, J = 15.4 Hz, 1H), 5.77 (dd, J = 9.4, 15.4 Hz, 1H), 4.86 - 4.61 (m, 1H), 1.82 - 1.66 (m, 1H), 1.47 (d, J = 6.8 Hz, 3H), 0.86 (dd, J = 2.2, 7.9 Hz, 2H), 0.65 - 0.53 (m, 2H) According to the same methodology, but employing suitable starting materials at step 1 and reagents at step 4 the following intermediate compounds of formula (XV) were prepared: 4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]benzenesulfonamide hydrochloride HPLC-MS method B (RT=2.160 min, += 250.1) 4-[(1R)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]-N-methyl-N-tetrahydropyran-4-yl- benzenesulfonamide hydrochloride HPLC-MS method C (RT=1.890 min, += 348.2) 4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]-N-methyl-N-tetrahydropyran-4-yl- benzenesulfonamide hydrochloride HPLC-MS method C (RT=1.880 min, += 348.2) 4-[(1R)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]-N-tetrahydropyran-4-yl-benzenesulfonamide hydrochloride HPLC-MS method C (RT=1.783 min, += 334.1) 4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]-N-tetrahydropyran-4-yl-benzenesulfonamide hydrochloride HPLC-MS method C (RT=1.791 min, += 334.2) (1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethanamine hydrochloride HPLC-MS method C (RT=1.860 min, += 320.1) (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethanamine hydrochloride HPLC-MS method C (RT=1.859 min, += 320.1) (1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]ethanamine dihydrochloride HPLC-MS method B (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]ethanamine dihydrochloride HPLC-MS method B (1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylsulfonyl)phenyl]ethanamine hydrochloride HPLC-MS method C (RT=2.070 += 318.1) (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylsulfonyl)phenyl]ethanamine hydrochloride HPLC-MS method C += 318.1) 4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]-N-(1-methylazetidin-3-yl)benzenesulfonamide hydrochloride HPLC-MS method B (RT=2.367 min, [M+H] 4-[(1S)-1-aminoethyl]-N-cyclohexyl-3-[(E)-2-cyclopropylvinyl]benzenesulfonamide hydrochloride HPLC-MS method B (RT=2.095 min, += 332.1) N-(1-methyl-4-piperidyl)-4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]benzenesulfonamide hydrochloride HPLC-MS method B (RT=2.468 Synthesis of (1S)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine To a solution of 2-bromo-4-fluoro-benzaldehyde (1 g, 4.93 mmol) and cyclohexyl mercaptan (0.724 mL, 5.91mmol, 1.2 eq.) in DMSO (5 mL) was added K2CO3 (1.36 g, 9.85 mmol, 2 eq). The mixture was stirred at 100 °C for 6 h. The reaction mixture was poured carefully dropwise into water and extracted with DCM (30 mL * 3). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography (SiO2, gradient from 0% to 100% EA in Hexane).2-bromo-4-cyclohexylsulfanyl-benzaldehyde (1.13 g, 3.78 mmol, 76.7% Yield) was obtained as a white solid. Synthesis of (R)-N-[(2-bromo-4-cyclohexylsulfanyl-phenyl)methylene]-2-methyl-propane-2- sulfinamide (step 2) To a solution of 2-bromo-4-cyclohexylsulfanyl-benzaldehyde (1.13 g, 3.78 mmol) in dry THF (19 ml) was added (R)-tert-butanesulfinamide (0.503 g, 4.15 mmol, 1.1 eq.) and titanium (IV) ethoxide (1.72 g, 7.55 mmol, 2 eq.). The solution was left under reflux for 3 h. Water was added to the reaction mixture and the white solid formed was filtered on a short celite pad, washing with EA. Aqueous and organic phases were separated, the organic phase dried over Na2SO4 and evaporated under reduced pressure to obtain crude (R)-N-[(2- bromo-4-cyclohexylsulfanyl-phenyl)methylene]-2-methyl-propane-2-sulfinamide (1.52 g, 3.78 mmol, 100% yield). ESI [M+H]+=404.2 Synthesis of (R)-N-[(1S)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethyl]-2-methyl-propane-2- sulfinamide and (R)-N-[(1R)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethyl]-2-methyl-propane-2- sulfinamide (step 3) To a solution of (R)-N-[(2-bromo-4-cyclohexylsulfanyl-phenyl)methylene]-2-methyl-propane-2-sulfinamide (1.52 g, 3.78 mmol) in THF (20 mL) was added MeMgBr (3 M, 2.64 mL, 2.1 eq.) at -78 °C. The mixture was stirred at 25 °C for 2 h. The reaction mixture was quenched with NH4Cl (5 mL) at 0 °C, and then diluted with H2O (20 mL), extracted with EA (20 mL * 3), washed with brine (20 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography (SiO2, gradient from 0% to 100% EA in Hexane). (R)-N-[(1S)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (0.499 g, 1.19 mmol, 31 % yield) was obtained. HPLC-MS method A (RT=4.43 min, [M+H]+=420.3) (R)-N-[(1R)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (0.122 g, 0.29 mmol, 7 % yield) was obtained. HPLC-MS method A (RT=4.54 min, [M+H]+=420.3) Synthesis of (1S)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethanamine (step 4) Iodine (0.057 g, 0.22 mmol, 0.3 eq.) was added to a solution of (R)-N-[(1S)-1-(2-bromo-4-cyclohexylsulfanyl- phenyl)ethyl]-2-methyl-propane-2-sulfinamide (0.318 g, 0.75 mmol, 1 eq.) in a mixture of THF (2.5 ml) and H2O (0.5 mL). The solution was stirred at 50 °C overnight. The reaction mixture was quenched with NaHCO3 (sat. sol.), diluted with water and extracted with DCM. The organic layers were washed with Na2S2O5(10% aqueous solution), brine, dried over Na2SO4 and evaporated under reduced pressure to give (1S)-1-(2- bromo-4-cyclohexylsulfanyl-phenyl)ethanamine (0.240 g, 0.75 mmol, 100% yield) as a brown oil that was used without further purification for the next step. ESI, recognized by fragment [C14H18BrS]+= 299.1 Synthesis of 9H-fluoren-9-ylmethyl N-[(1S)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethyl]carbamate (step 5) A mixture of (1S)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethanamine (0.240 g, 0.75 mmol), 9- fluorenylmethyl chloroformate (0.217 g, 0.84 mmol, 1.1 eq.) and triethylamine (0.117 mL, 0.84 mmol, 1.1 eq.) in a glass vial was sonicated in a water bath at r.t. for 1 hour. TLC showed disappearance of starting material. The solid mixture was treated with water, the solid filtered and dried. The crude was purified by column chromatography (SiO2, gradient from 0% to 70% EA in Hexane). Obtained 9H-fluoren-9-ylmethyl N-[(1S)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethyl]carbamate as a white solid (0.153 g, 0.28 mmol, 37 % yield) Synthesis of 9H-fluoren-9-ylmethyl N-[(1S)-1-(2-bromo-4-cyclohexylsulfonyl-phenyl)ethyl]carbamate (step 6) 3-chloroperoxybenzoic acid (0.295 g, 0.94 mmol, 3.3 eq., 55 mass%) was added to a solution of 9H-fluoren- 9-ylmethyl N-[(1S)-1-(2-bromo-4-cyclohexylsulfanyl-phenyl)ethyl]carbamate (0.153 g, 0.28 mmol) in DCM (6 mL) kept at 0°C. The reaction mixture was left under magnetic stirring at 0°c for 1 h. HPLC-MS showed formation of the product. The reaction mixture was diluted with DCM and washed with NaHCO3(sat. sol., 2x), brine, dried over Na2SO4 anhydrous and evaporated under reduced pressure. Obtained 9H-fluoren-9-ylmethyl N-[(1S)-1-(2-bromo-4-cyclohexylsulfonyl-phenyl)ethyl]carbamate (0.162 mg, 0.28 mmol, 99% yield). ESI [M+H]+=587.3 Synthesis of the title compound (step 7) In a MW vial, filled with Ar, a suspension of 9H-fluoren-9-ylmethyl N-[(1S)-1-(2-bromo-4-cyclohexylsulfanyl- phenyl)ethyl]carbamate (162 mg, 0.28 mmol), 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (0.31 mmol, 1.1 eq.) [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane complex (23 mg, 0.028 mmol, 0.1 eq.,) and potassium carbonate (0.118 g, 0.85 mmol, 3 eq.) in a degassed mixture of 1,4-dioxane (0.1 M) and water (0.5 M) was irradiated under MW conditions for 2 hours at 110°C. HPLC-MS showed formation of the desired product. Piperidine (0.084 mL, 0.85 mmol, 3 eq.) was added to the reaction mixture that was stirred at r.t. for 1 h. The reaction mixture was filtered through celite (washed with EA), the solvents were evaporated under reduced pressure and the crude of reaction purified by column chromatography (SiO2, gradient from 0% to 10% MeOH in DCM). Obtained (1S)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine (90 mg, 0.26 mmol, 94.7% Yield). HPLC-MS method A (RT=3.27 min, [M+H]+=334.3) According to the same methodology, but employing suitable reagents at step 1 and suitable starting material at step 4 the following intermediate compounds of formula (XV) were prepared: (1R)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine HPLC-MS method D (RT=3.57 min, (1S)-1-[4-cyclopentylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine HPLC-MS method F (RT=0.63min, (1S)-1-[4-cyclopentylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine HPLC-MS method F (RT=0.62 min, According to the same methodology, but employing suitable reagents at step 1 the following intermediate compound was prepared: Synthesis of (R)-N-[(1S)-1-(2-bromo-4-cyclopentylsulfanyl-phenyl)ethyl]-2-methyl-propane-2- sulfinamide HPLC-MS method F (RT=3.91 min, Synthesis of (1S)-1-[4-cyclopentylsulfanyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine trifluoroacetate methyl- propane-2-sulfinamide (step 1) In a µW vial, filled with Ar, a suspension of (R)-N-[(1S)-1-(2-bromo-4-cyclopentylsulfanyl-phenyl)ethyl]-2- methyl-propane-2-sulfinamide (347 mg, 0.85 mmol), 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (1.03 mmol, 1.2 eq.) [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane complex (84 mg, 0.103 mmol, 0.12 eq.) and potassium carbonate (0.355 g, 2.55 mmol, 3 eq.) in a degassed mixture of 1,4-dioxane (0.1 M) and water (0.5 M) was irradiated under µW conditions for 2 hours at 110°C. HPLC-MS showed formation of the desired product. The reaction mixture was filtered through celite (washed with EA), the solvents were evaporated under reduced pressure and the crude of reaction purified by column chromatography (SiO2, gradient from 0% to 100% EA in Hexane). Obtained (R)-N-[(1S)-1-[4-cyclopentylsulfanyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-2-methyl-propane-2- sulfinamide (315 mg, 0.81 mmol, 95%% Yield). HPLC-MS method F (RT=4.61 min, [M+H]+=392.5) Synthesis of the title compound (step 2) (R)-N-[(1S)-1-[4-cyclopentylsulfanyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-2-methyl-propane-2-sulfinamide (50 mg, 0.12 mmol) was dissolved in DCM (1 mL) followed by addition of trifluoroacetic acid (0.5 mL). The reaction mixture was left under magnetic stirring for 1 h at r.t. HPLC-MS showed completion of reaction. The reaction mixture was evaporated under reduced pressure to give (1S)-1-[4-cyclopentylsulfanyl-2-[(E)-2- cyclopropylvinyl]phenyl]ethanamine trifluoroacetic acid (51 mg, quantitative yield). HPLC-MS method F (RT=1.28 min, recognized by fragment [C18H23S]+=271.3) Synthesis of (1S)-1-[2-(cyclopenten-1-yl)phenyl]ethanamine hydrochloride Synthesis of tert-butyl N-[(1S)-1-[2-(cyclopenten-1-yl)phenyl]ethyl]carbamate (step 1) In a µW vial, filled with Ar, a suspension of tert-butyl N-[(1S)-1-(2-bromophenyl)ethyl]carbamate (150 mg, 0.499 mmol), cyclopenten-1-yl boronic acid (1.5 eq., 0.749 mmol), [1,1'- bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane complex (0.1 eq., 0.0499 mmol) and potassium carbonate (3 eq., 1.499 mmol) in a degassed mixture of 1,4-dioxane (0.1 M) and water (0.5 M) was irradiated under MW conditions for 2 hours at 110°C. The solvents were evaporated under reduced pressure and the crude of reaction purified by flash chromatography (hexane / EA 7:3, gradient: 0% + 0-100% + 100%) to obtain tert-butyl N-[(1S)-1-[2-(cyclopenten-1-yl)phenyl]ethyl]carbamate (71 mg, 0.247 mmol, 49% Yield). HPLC-MS method A (RT=5.96 min, [M+H-Boc]+=188.1) Synthesis of the title compound (step 2) In a round-bottom flask, a solution of tert-butyl N-[(1S)-1-[2-(cyclopenten-1-yl)phenyl]ethyl]carbamate (22 mg, 0.0765 mmol) in HCl 4M in 1,4-dioxane (0.1 M, 3.0 mmol) was stirred at r.t. overnight. The solvent was evaporated and the residue was used without further manipulation in the next step. Obtained (1S)-1-[2- (cyclopenten-1-yl)phenyl]ethanamine hydrochloride (quantitative yield). ESI: recognized by fragment [C13H15]+= 171.2 Synthesis of (1S)-1-(2-cyclopentylphenyl)ethanamine - trifluoroacetic acid In a µW vial, a suspension of tert-butyl N-[(1S)-1-[2-(cyclopenten-1-yl)phenyl]ethyl]carbamate (47 mg, 0.164 mmol), palladium 5% on carbon (0.2 g / g, 0.0088 mmol) and 1,4-cyclohexadiene (5 eq., 0.818 mmol) was irradiated under MW conditions for 2 hours at 110°C. The solid was filtered through celite and the filtrate concentrated to obtain tert-butyl N-[(1S)-1-(2-cyclopentylphenyl)ethyl]carbamate (44 mg, 0.152 mmol, 93% yield) as a brown oil. ESI [M+H-Boc]+=190.4 Synthesis of the title compound (step 2) In a round-bottom flask, a solution of tert-butyl N-[(1S)-1-(2-cyclopentylphenyl)ethyl]carbamate (44 mg, 0.152 mmol) in DCM (0.1 M), trifluoroacetic acid (0.25 M, 7.893 mmol) was stirred at r.t. for 2 hours. The solvent was evaporated and the residue used without further manipulation in the next step. Obtained (1S)-1-(2- cyclopentylphenyl)ethanamine trifluoroacetic acid (quantitative yield). ESI: recognized by fragment [C13H17]+= 173.2 Synthesis of (1S)-1-(2-vinylphenyl)ethanamine - trifluoroacetic acid In a µW vial, filled with Ar, a suspension of tert-butyl N-[(1S)-1-(2-bromophenyl)ethyl]carbamate (50 mg, 0.167 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (1.2 eq., 0.1999 mmol), [1,1'- bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane complex (0.1 eq., 0.0136 mmol) and potassium carbonate (3 eq., 0.069 mmol) in a degassed mixture of 1,4-dioxane (0.1 M) and water (0.5 M) was irradiated under MW conditions for 2 hours at 110°C. The solvents were evaporated under reduced pressure and the crude of reaction purified by flash chromatography (hexane / EA 7:3 gradient: 0% + 0-70% + 70%) to obtain tert-butyl N-[(1S)-1-(2-vinylphenyl)ethyl]carbamate (28 mg, 68% Yield). HPLC-MS method A (RT=5.165 min, [M+H-Boc]+=147.3) Synthesis of the title compound (step 2) In a round-bottom flask, a solution of tert-butyl N-[(1S)-1-(2-vinylphenyl)ethyl]carbamate (18 mg, 0.073 mmol) in DCM (0.1 M), trifluoroacetic acid (0.1 M) was stirred at r.t. for 2 hours. The solvent was evaporated and the residue used without further manipulation in the next step. Obtained (1S)-1-(2-vinylphenyl)ethanamine - trifluoroacetic acid (quantitative yield). ESI: recognized by fragment [C10H11]+= 131.1 According to the same methodology, but employing suitable starting materials at step 1, the following compounds of formula (XV) were prepared: (1S)-1-[2-[(E)-prop-1-enyl]phenyl]ethanamine trifluoroacetate ESI: recognized by fragment (1S)-1-[2-[(E)-styryl]phenyl]ethanamine trifluoroacetate ESI: recognized by fragment (1S)-1-[2-[(E)-3-phenylprop-1-enyl]phenyl]ethanamine trifluoroacetate ESI: recognized by fragment (1S)-1-[2-[(E)-2-(4-chlorophenyl)vinyl]phenyl]ethanamine trifluoroacetate HPLC-MS method A (RT = 241.1) (1S)-1-[2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine trifluoroacetate HPLC-MS method A (RT=2.68 171.2) (1S)-1-[2-[(E)-3-methoxyprop-1-enyl]phenyl]ethanamine trifluoroacetate HPLC-MS method A (RT = 2.34 min, += 175.1) (1S)-1-[2-[(E)-3-pyrrolidin-1-ylprop-1-enyl]phenyl]ethanamine trifluoroacetate HPLC-MS method A (RT = 2.99 min, += 214.1) (E)-3-[2-[(1S)-1-aminoethyl]phenyl]prop-2-en-1-ol hydrochloride 1H NMR (400 MHz, METHANOL-d4) δ: Hz, 2H), 7.28 - 7.15 (m, 2H), 6.82 (d, J = 15.6 Hz, 1H), 6.21 - 6.02 (m, 1H), 4.42 (q, J = 6.6 Hz, 1H), 3.69 (t, J = 6.6 Hz, 2H), 2.53 - 2.39 (m, 2H), 1.36 (d, J = 6.7 Hz, 3H) Synthesis of (1S)-1-[4-(4-methylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine dihydrochloride To a solution of 2-bromo-4-fluoro-benzaldehyde (1 g, 4.93 mmol, 1 eq) and 1-methylpiperazine (542.73 mg, 5.42 mmol, 601.03 µL, 1.1 eq) in DMSO (10 mL) was added K2CO3(1.36 g, 9.85 mmol, 2 eq). The mixture was stirred at 100 °C for 6 h. The reaction mixture was poured carefully dropwise into water, filter the brown precipitate and washed with water (30 mL * 3). Dried to afford 2-bromo-4-(4-methylpiperazin-1- yl)benzaldehyde (1.2 g) as a yellow solid.1H NMR (400 MHz, CHLOROFORM-d) δ: = 10.12 (s, 1H), 7.81 (d, J = 9.0 Hz, 1H), 7.00 (d, J = 2.5 Hz, 1H), 6.84 (dd, J = 2.3, 8.9 Hz, 1H), 3.48 - 3.37 (m, 4H), 2.62 - 2.49 (m, 4H), 2.37 (s, 3H) Synthesis of (R)-N-[[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]methylene]-2-methyl-propane-2- sulfinamide (step 2) To a solution of 2-bromo-4-(4-methylpiperazin-1-yl)benzaldehyde (1.2 g, 4.24 mmol, 1 eq) and (R)-(+)-2- methyl-2-propanesulfinamide (770.44 mg, 6.36 mmol, 1.5 eq) in THF (10 mL) was added Ti(OEt)4 (2.90 g, 12.71 mmol, 2.64 mL, 3 eq) at 20 °C. The mixture was stirred at 70 °C for 6 h. The reaction mixture was quenched with H2O (30 mL) and celite filtered. And then extracted with EA (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give (R)-N-[[2-bromo-4-(4-methylpiperazin-1- yl)phenyl]methylene]-2-methyl-propane-2-sulfinamide (1.9 g, crude) as a yellow oil. HPLC-MS method G (RT = 0.354 min, [M+H]+= 388.2) Synthesis of (R)-N-[(1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-2-methyl-propane-2- sulfinamide and (R)-N-[(1R)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-2-methyl-propane-2- sulfinamide (step 3) To a solution of (R)-N-[[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]methylene]-2-methyl-propane-2- sulfinamide (1.6 g, 4.14 mmol, 1 eq) in THF (16 mL) was added MeMgBr (3 M, 2.76 mL, 2 eq) at -78 °C. The mixture was stirred at 20 °C for 3 h. The reaction mixture was quenched with NH4Cl (5 mL) at 0 °C, and then diluted with H2O (30 mL), extracted with EA (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by preparative HPLC (column: Welch Xtimate C18180*70mm#10um; mobile phase: [H2O (10mM NH4HCO3) - ACN]; gradient:28%-58% B over 17.0 min). (R)-N-[(1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-2-methyl-propane-2- sulfinamide (1.01 g) was obtained as a yellow oil. HPLC-MS method G (Rt=0.322 min, [M+H]+= 402.3, 404.2) (R)-N-[(1R)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-2-methyl-propane-2-sulfinamide (130 mg) was obtained as a yellow oil. HPLC-MS method G (Rt=0.354 min, [M+H]+= 402.3, 404.2) Synthesis of (1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethanamine hydrochloride (step 4) A mixture of (R)-N-[(1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-2-methyl-propane-2-sulfinamide (1 g, 2.49 mmol, 1 eq) in HCl / MeOH (4 M, 20 mL, 32.19 eq) was stirred at 20 °C for 1 h. The reaction mixture was concentrated to give (1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethanamine hydrochloride (741 mg, crude) as a yellow solid. HPLC-MS method G (Rt=0.094 min, recognized by fragment [C13H18BrN2]+= 281.2) Synthesis of tert-butyl N-[(1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamate (step 5) To a solution of (1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethanamine – hydrochloride (741 mg, 2.48 mmol, 1 eq) and TEA (502.86 mg, 4.97 mmol, 691.69 µL, 2 eq) in DCM (8 mL) was added Boc2O (813.43 mg, 3.73 mmol, 856.24 µL, 1.5 eq). The mixture was stirred at 20 °C for 1 h. The reaction mixture was diluted with H2O (30 mL), extracted with DCM (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography (SiO2, PE:EA = 1:2 to 0:1) to obtain N-[(1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamate (710 mg) as a yellow solid.1H NMR (400 MHz, CHLOROFORM-d) δ: = 7.18 (d, J = 8.7 Hz, 1H), 7.07 (d, J = 2.4 Hz, 1H), 6.85 (dd, J = 2.5, 8.6 Hz, 1H), 5.00 (br s, 1H), 3.29 - 3.11 (m, 4H), 2.68 - 2.46 (m, 4H), 2.36 (s, 3H), 1.41 (br s, 12H) Synthesis of tert-butyl N-[(1S)-1-[4-(4-methylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl] ethyl] carbamate (step 6) To a solution of N-[(1S)-1-[2-bromo-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamate (530 mg, 1.33 mmol, 1 eq), 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (387.34 mg, 2.00 mmol, 1.5 eq) and K2CO3 (367.77 mg, 2.66 mmol, 2 eq) in dioxane (5 mL) and H2O (1 mL) was added Pd(dppf)Cl2 (97.36 mg, 133.05 µmol, 0.1 eq) under N2atmosphere. The mixture was stirred at 90 °C for 16 h under N2atmosphere. The solution was diluted with H2O (30 mL), filtered through celite pad to remove by-product, extracted with EA (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography (SiO2, PE:EA = 1:1 to 0:1) to obtain N-[(1S)-1- [4-(4-methylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamate (460 mg) as a yellow oil.1H NMR (400 MHz, DMSO-d6) δ: 7.28 (br d, J = 8.1 Hz, 1H), 7.16 (d, J = 8.6 Hz, 1H), 6.90 - 6.66 (m, 3H), 5.66 (br dd, J = 9.1, 15.5 Hz, 1H), 4.84 (br s, 1H), 3.15 - 3.01 (m, 4H), 2.46 - 2.35 (m, 4H), 2.21 (s, 3H), 1.66 - 1.52 (m, 1H), 1.41 - 1.16 (m, 12H), 0.78 (dd, J = 2.4, 7.9 Hz, 2H), 0.56 - 0.46 (m, 2H) Synthesis of the title compound (step 7) A mixture of N-[(1S)-1-[4-(4-methylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamate (460 mg, 1.04 mmol, 1 eq) in HCl / MeOH (4 M, 20 mL, 77.07 eq) was stirred at 20 °C for 1 h. The residue was purified by preparative HPLC (column: Phenomenex luna C18250*50mm*15um; mobile phase: [H2O (0.04% HCl) - ACN]; gradient: 1%-30% B over 10.0 min). (1S)-1-[4-(4-methylpiperazin-1-yl)-2-[(E)-2- cyclopropylvinyl]phenyl]ethanamine – dihydrochloride (319.15 mg) was obtained as a white solid.1H NMR (400 MHz, DMSO-d6) δ: 11.37 (br s, 1H), 8.52 (br s, 3H), 7.48 (d, J = 8.5 Hz, 1H), 7.00 - 6.91 (m, 2H), 6.73 (d, J = 15.4 Hz, 1H), 5.74 (dd, J = 9.3, 15.4 Hz, 1H), 4.66 - 4.50 (m, 1H), 3.93 - 3.76 (m, 2H), 3.44 (br d, J = 8.8 Hz, 2H), 3.23 - 3.00 (m, 4H), 2.78 (d, J = 4.6 Hz, 3H), 1.65 (tt, J = 4.1, 8.5 Hz, 1H), 1.43 (d, J = 6.8 Hz, 3H), 0.88 - 0.74 (m, 2H), 0.61 - 0.46 (m, 2H) Synthesis of (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholino-phenyl]ethanamine hydrochloride 2-bromo-4-fluoro-benzaldehyde (1 g, 4.926 mmol) and morpholine (1.1 eq., 5.418 mmol) were dissolved in dimethyl sulfoxide (6 mL) in presence of potassium carbonate (2 eq., 9.852 mmol). The mixture was heated up at 70°C for 6 hours under magnetic stirring. The reaction was diluted with H2O and the aqueous phase was washed with DCM. The organic phase was dried over Na2SO4anhydrous and evaporated under reduced pressure. The crude of reaction was purified by automatic column on silica gel, gradient from 3% to 50 % EA in hexane to obtain 2-bromo-4-morpholino-benzaldehyde (1.2 g, 4.4 mmol, 90% Yield) as a yellow oil. HPLC- MS method A (RT=3.89 min, [M+H]+=270.1, 272.1) Synthesis of (S)-N-[(2-bromo-4-morpholino-phenyl)methylene]-2-methyl-propane-2-sulfinamide (step 2) A mixture of 2-bromo-4-morpholino-benzaldehyde (1 g, 3.702 mmol), (S)-2-Methylpropane-2-sulphinamide (1.1 eq., 4.072 mmol), and Ti(OEt)4(2 eq., 7.404 mmol) in tetrahydrofuran (5 mL) heated up at reflux under magnetic stirring for 6 hours. Water was added to the reaction mixture, giving a white precipitate that was filtered on a short celite path washing with EA. Aqueous and organic phase were separated, the organic phase dried over Na2SO4 anhydrous and evaporated under reduced pressure. The crude (S)-N-[(2-bromo-4-morpholino-phenyl)methylene]-2-methyl-propane-2-sulfinamide (1.2 g, 3.2 mmol, 87% Yield) was used for next step without further purification. HPLC-MS method A (RT=4.95 min, [M+H]+=373.2, 375.2) Synthesis of (S)-N-[(1S)-1-(2-bromo-4-morpholino-phenyl)ethyl]-2-methyl-propane-2-sulfinamide and (S)-N-[(1R)-1-(2-bromo-4-morpholino-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (step 3) (S)-N-[(2-bromo-4-morpholino-phenyl)methylene]-2-methyl-propane-2-sulfinamide (1.2 g, 3.2 mmol) was dissolved in tetrahydrofuran dry (15 mL) and kept at 0°C (ice bath) while MeMgBr 3.0 M in Et2O (2 eq., 6.4 mmol) was added in portion. The reaction was left to reach r.t. and left under magnetic stirring for 3 hours. MeOH and H2O were added to the mixture to quench the reaction. Organic solvent was evaporated under reduced pressure and the aqueous phase was washed three times with EA. The organic phase collected, dried over Na2SO4 anhydrous and evaporated under reduced pressure. The crude was purified by automatic column on reverse phase, gradient from 5% to 95% ACN in H2O. Obtained (S)-N-[(1R)-1-(2-bromo-4- morpholino-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (0.5 g, 1.284 mmol, 40% Yield). HPLC-MS method A (RT=4.14 min, [M+H]+=389.2, 391.2) Obtained (S)-N-[(1S)-1-(2-bromo-4-morpholino-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (0.037 g, 0.095 mmol, 3% Yield). HPLC-MS method A (RT=4.18 min, [M+H]+=389.2, 391.2) Synthesis of (S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholino-phenyl]ethyl]-2-methyl-propane- 2-sulfinamide (step 4) (S)-N-[(1S)-1-(2-bromo-4-morpholino-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (20 mg, 0.0514 mmol) and 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 eq., 0.0771 mmol) were dissolved in a mixture of 1,4-dioxane (4 mL) and water (0.5 mL). Potassium carbonate (3 eq., 0.154 mmol) was added to the reaction mixture that was degassed with N2 flow for 20 minutes. [1,1'- bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane complex (0.1 eq., 0.00514 mmol) was added to the reaction mixture and vial was subjected to MW irradiation at 110 C° for 2 hours. Solvent was evaporated under reduced pressure and the crude of reaction purified by automatic column chromatography on silica gel: gradient from 5% to 65% EA in DCM to obtain (S)-N-[(1S)-1-[2-[(E)-2- cyclopropylvinyl]-4-morpholino-phenyl]ethyl]-2-methyl-propane-2-sulfinamide (13 mg, 0.0345 mmol, 67% Yield) as a white solid. HPLC-MS method A (RT=4.82 min, [M+H]+=377.1) Synthesis of the title compound (step 5) (S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholino-phenyl]ethyl]-2-methyl-propane-2-sulfinamide (13 mg, 0.0345 mmol) was dissolved in isopropanol (5 mL) followed by addition of HCl in dioxane (2 mL, 8 mmol). The reaction was left under magnetic stirring at r.t. for two hours and the solvent was evaporated under reduced pressure to give (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholino-phenyl]ethanamine - hydrochloride (10 mg, 0.0324 mmol, 94% Yield) that was used in the next step without further purification. HPLC-MS method A (RT=2.68 min, recognized by fragment [C17H22NO]+=256.4) According to the same methodology, but employing suitable starting materials at step 1, the following compound of formula (XV) were prepared: (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-4-(4-methylpiperazin-1-yl)phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.261 min, Synthesis of N-[4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]phenyl]-N,1-dimethyl-piperidin-4- amine - dihydrochloride In a MW vial, an orange suspension of 2-bromo-4-fluorobenzaldehyde (1 g, 4.926 mmol, 1.0 eq.), potassium carbonate (2.247 g, 16.26 mmol, 3.3 eq.) and 1-methyl-4-(methylamino)piperidine (2.084 g, 2.368 mL, 16.26 mmol, 3.3 eq.) in DMSO (5 mL) was heated at T= 90 °C overnight. The reaction was cooled down, poured into water and extracted with DCM. The organic layers were washed with water, brine and dried over Na2SO4.The crude was purified by chromatographic column DCM to DCM / MeOH 95 / 5 to furnish 2-bromo-4-[methyl- (1-methyl-4-piperidyl)amino]benzaldehyde (1.479 g, 4.752 mmol, 96% Yield) as orange oil. HPLC-MS method A (RT=2.16 min, [M+H]+=311.3, 313.3) Synthesis of (R)-N-[[2-bromo-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]methylene]-2-methyl- propane-2-sulfinamide (step 2) A mixture of 2-bromo-4-[methyl-(1-methyl-4-piperidyl)amino]benzaldehyde (1.47 g, 4.723 mmol, 1.0 eq.), (R)- 2-methylpropane-2-sulfinamide (0.6297 g, 5.196 mmol, 1.1 eq.), and Ti(OEt)4(2.155 g, 1.981 mL, 9.447 mmol, 2.0 eq.) in tetrahydrofuran (12 mL) was heated up at reflux under magnetic stirring for 10 hours. Water was added to the reaction mixture, giving a white precipitate that was filtered on a short celite path washing with EA. Aqueous and organic phase were separated, the organic phase dried over Na2SO4anhydrous and evaporated under reduced pressure. The crude (R)-N-[[2-bromo-4-[methyl-(1-methyl-4- piperidyl)amino]phenyl]methylene]-2-methyl-propane-2-sulfinamide (1.343 g, 3.241 mmol, 69% Yield) (as orange gel / foam) was used for next step without further purification. HPLC-MS method A (RT=2.81 min, [M+H]+=414.3, 416.3) Synthesis of (R)-N-[(1S)-1-[2-bromo-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-2-methyl- propane-2-sulfinamide and (R)-N-[(1R)-1-[2-bromo-4-[methyl-(1-methyl-4-piperidyl)amino] phenyl] ethyl]-2-methyl-propane-2-sulfinamide (step 3) (R)-N-[[2-bromo-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]methylene]-2-methyl-propane-2-sulfinamide (1.335 g, 3.221 mmol, 1.0 eq.) was dissolved in tetrahydrofuran dry (25 mL). MeMgBr 3.0 M in Et2O (2.223 g, 2.148 mL, 6.443 mmol, 2.0 eq.) was added drop wise to the reaction mixture kept at -78 C°. The reaction mixture was then left to reach r.t. and left under magnetic stirring for three hours. H2O was added to the mixture to quench the reaction. Organic solvent was evaporated under reduced pressure and the aqueous phase was extracted three times with EA. The organic phase was collected, washed with brine, dried over Na2SO4anhydrous and evaporated under reduced pressure. The crude was purified by chromatographic column DCM / NH3 in MeOH 7N 99 / 1 to 96 / 4. Obtained (R)-N-[(1S)-1-[2-bromo-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-2-methyl-propane-2- sulfinamide (0.4662 g, 1.083 mmol, 33.62% Yield) as white foam. HPLC-MS method A (RT=2.81 min, [M+H]+=430.5, 432.5) Obtained (R)-N-[(1R)-1-[2-bromo-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-2-methyl-propane-2- sulfinamide (0.03 g, 0.06970 mmol, 2.163% Yield). HPLC-MS method A (RT=3.24 min, [M+H]+=430.5, 432.5) Synthesis of (R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino] phenyl] ethyl]-2-methyl-propane-2-sulfinamide (step 4) To a solution of (R)-N-[(1S)-1-[2-bromo-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-2-methyl- propane-2-sulfinamide (0.4662 g, 1.083 mmol, 1.0 eq.) in 1,4-dioxane (10.83 mL) and water (2.166 mL), 2- [(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.2312 g, 0.247 mL, 1.191 mmol, 1.1 eq.), potassium carbonate (0.4491 g, 3.249 mmol, 3.0 eq.) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane complex (0.08844 g, 0.1083 mmol, 0.1 eq.) were added under argon flux. Three cycle of argon / vacuum was performed. The reaction mixture was stirred at 110°C in microwave for 2h. The reaction mixture was filtered through celite (washed with EA), water was added and the mixture was extracted with EA three times, organic layer was washed with brine, dried on Na2SO4and evaporated. The crude was purified by chromatographic column DCM / NH3 in MeOH 7N 99 / 1 to 97 / 3 to afford (R)-N-[(1S)-1-[2-[(E)-2- cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-2-methyl-propane-2-sulfinamide (0.322 g, 0.77 mmol, 71% Yield) as beige foam. HPLC-MS method A (RT=3.02 min, [M+H]+=418.4) Synthesis of the title compound (step 5) (R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-2-methyl- propane-2-sulfinamide (0.322 g, 0.7710 mmol, 1.0 eq.) was dissolved in methanol (4 mL) followed by addition of HCl in dioxane 4M (0.9637 mL, 3.855 mmol, 5.0 eq.). The reaction mixture was left under magnetic stirring for 3 hours. The solvent was evaporated under reduced pressure to give a brown oil that was treated with EtOH / acetone to achieve a beige solid. The solid was filtered to furnish N-[4-[(1S)-1-aminoethyl]-3-[(E)-2- cyclopropylvinyl]phenyl]-N,1-dimethyl-piperidin-4-amine -dihydrochloride (0.259 g, 0.67 mmol, 0.8694 eq., 87% Yield). HPLC-MS method A (RT=1.27 min, recognized by fragment [C20H29N2]+=297.2) According to the same methodology, but employing suitable starting materials at step 1, the following compounds of formula (XV) were prepared: 4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]-N-methyl-N-[(1-methylimidazol-2-yl)methyl]aniline hydrochloride HPLC-MS method A (RT=1.41 min, +=294.2) 4-[(1S)-1-aminoethyl]-N-cyclohexyl-3-[(E)-2-cyclopropylvinyl]-N-methyl-aniline hydrochloride HPLC-MS method A (RT=1.84 min, +=282.4) (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methyl-1,4-diazepan-1-yl)phenyl]ethanamine dihydrochloride ESI: recognized by fragment [C19H28 (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[4-[(3-methylisoxazol-5-yl)methyl]piperazin-1-yl]phenyl] ethanamine dihydrochloride HPLC-MS method A (RT=2.75 +=351.5) (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-(4-methylpiperazin-1-yl)phenyl]ethanamine dihydrochloride HPLC-MS method A (RT=2.95 min, +=287.3) (N-[4-[(1S)-1-aminoethyl]-5-[(E)-2-cyclopropylvinyl]-2-fluoro-phenyl]-N,1-dimethyl-piperidin-4-amine dihydrochloride HPLC-MS method A (RT=1.38 N-[4-[(1S)-1-aminopropyl]-3-[(E)-2-cyclopropylvinyl]phenyl]-N,1-dimethyl-piperidin-4-amine dihydrochloride HPLC-MS method G (RT=0.307 +=311.1) (1S)-1-[4-[4-(cyclohexylmethyl)piperazin-1-yl]-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine dihydrochloride HPLC-MS method C (RT=1.79 (1S)-1-[4-(4-benzylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine dihydrochloride HPLC-MS method G (RT=0.36 N-[4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]phenyl]-N-cyclobutyl-1-methyl-piperidin-4-amine dihydrochloride HPLC-MS method G (RT=0.295 min According to the same methodology, skipping step 2, the following compound of formula (XV) were prepared: (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-fluoro-phenyl]ethanamine hydrochloride HPLC-MS method C (RT=2.89 min, += 189.2) According to the same methodology, but starting from step 2 and employing suitable benzaldehyde as reagent in step 2, the following intermediate compound of formula (XV) were prepared: (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-phenyl]ethanamine hydrochloride HPLC-MS method A (RT=3.05 min, +=201.3) 2-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]phenol hydrochloride (1S)-1-[2-chloro-6-[(E)-2- hydrochloride HPLC-MS method A (RT=2.99 min, [M+H] (1S)-1-[5-[(E)-2-cyclopropylvinyl]-1,3-benzodioxol-4-yl]ethanamine hydrochloride HPLC-MS method A (RT=2.26 min, +=215.3) (1S)-1-[3-[(E)-2-cyclopropylvinyl]-2-pyridyl]ethanamine hydrochloride HPLC-MS method A (RT= 2.49 min, (1S)-1-[7-[(E)-2-cyclopropylvinyl]-2,3,4a,5-tetrahydro-1,4-benzodioxin-6-yl]ethanamine hydrochloride HPLC-MS method A (RT=2.72 min, +=229.3) 5-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-2-methoxy-phenol hydrochloride1H NMR (400 MHz, DMSO-d6) δ: 9.10 (s, 6.92 (d, J = 13.3 Hz, 2H), 6.66 (d, J = 15.4 Hz, 1H), 5.61 (dd, J = 9.2, 15.4 Hz, 1H), 4.67 - 4.53 (m, 1H), 3.79 (s, 3H), 1.68 - 1.55 (m, 1H), 1.40 (d, J = 6.6 Hz, 3H), 0.84 - 0.74 (m, 2H), 0.56 - 0.46 (m, 2H) According to the same methodology, but starting from step 2, employing 2-bromo-5-methoxy-benzaldehyde as reagent in step 2 and employing (R)-N-[(1R)-1-(2-bromo-5-methoxy-phenyl)ethyl]-2-methyl-propane-2- sulfinamide as reagent in step 4, the following intermediate compound of formula (XV) was prepared: (1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-phenyl]ethanamine hydrochloride HPLC-MS method A (RT=3.04 min, +=201.3) According to the same methodology, but employing (R)-N-[(1R)-1-[2-bromo-4-(4-methylpiperazin-1- yl)phenyl]ethyl]-2-methyl-propane-2-sulfinamide as reagent at step 4, the following intermediate compound of formula (XV) was prepared: (1R)-1-[4-(4-methylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine dihydrochloride HPLC-MS method G (Rt=0.281 += 269.2) According to the same methodology, but employing (S)-N-[(1R)-1-(2-bromo-4-morpholino-phenyl)ethyl]-2- methyl-propane-2-sulfinamide as reagent at step 4, the following intermediate compound of formula (XV) was prepared: (1R)-1-[4-morpholino-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine hydrochloride HPLC-MS method A (RT=2.67 min, +=256.3) Synthesis of (1S)-1-[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl) -2-fluoro-phenyl] ethanamine hydrochloride F FO F O FNH N To a solution of 4-bromo-2-fluoro-aniline (5 g, 26.31 mmol, 1 eq) and hexane-2,5-dione (4.51 g, 39.47 mmol, 4.63 mL, 1.5 eq) in toluene (20 mL) was added TsOH.H2O (500 mg, 2.63 mmol, 0.1 eq). The mixture was stirred at 125 °C for 1 h. The residue was purified by column chromatography (SiO2, PE: EA=0-4%) to obtain 1-(4-bromo-2-fluoro-phenyl)-2,5-dimethyl-pyrrole (5 g, 18.65 mmol, 70% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 7.88 - 7.75 (m, 1H), 7.60 - 7.52 (m, 1H), 7.37 (t, J = 8.4 Hz, 1H), 5.83 (s, 2H), 1.92 (s, 6H) 6-bromo-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-benzaldehyde (step 2) To a solution of 1-(4-bromo-2-fluoro-phenyl)-2,5-dimethyl-pyrrole (1.5 g, 5.59 mmol, 1 eq) in THF (20 mL) was added (2,2,6,6-tetramethyl-1-piperidyl) lithium (1 M, 16.78 mL, 3 eq) at -78°C for 0.5 h. Then was added morpholine-4-carbaldehyde (1.29 g, 11.19 mmol, 1.12 mL, 2 eq), the mixture was stirred at -78 °C for 1 h. The reaction mixture was quenched by addition sat. NH4Cl 20mL at 0 °C and extracted with EA (20mL*3). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether: EA = 1% to 5%) to obtain 6-bromo-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-benzaldehyde (1.15 g, 3.88 mmol, 69% yield) as a yellow oil.1H NMR (400 MHz, DMSO-d6) δ: 10.21 (s, 1H), 7.82 - 7.73 (m, 1H), 7.69 - 7.59 (m, 1H), 5.86 (s, 2H), 1.94 (s, 6H) 6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-benzaldehyde (step 3) A mixture of 6-bromo-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-benzaldehyde (1.13 g, 5.83 mmol, 1.5 eq), Pd(dppf)Cl2(284 mg, 388µmol, 0.1 eq), K2CO3(1.61 g, 11.65 mmol, 3 eq) in H2O (1.2 mL) and dioxane (12 mL) was degassed and purged with N2 for 3 times, and then the mixture was stirred at 90 °C for 12hr under N2atmosphere. The reaction mixture was quenched by addition sat. H2O 20 mL and extracted with EA (20mL *3). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, PE: EA = 2% to 5%) to obtain 6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro- benzaldehyde (900 mg, 2.41 mmol, 62% yield) as a yellow oil. HPLC-MS method C RT=0.652 min, [M+H]+= 284 N-[[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-phenyl]methylene]-2-methyl- propane-2-sulfinamide (step 4) To a solution of 6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-benzaldehyde (900 mg, 3.18 mmol, 1 eq) and (R)-2-methylpropane-2-sulfinamide (577mg, 4.76 mmol, 1.5 eq) in THF (20 mL) was added Ti(OEt)4(2.17 g, 9.53 mmol, 1.98 mL, 3 eq). The mixture was stirred at 70 °C for 16 h. The residue is treated with water (20 mL), extracted with EA (30 * 3 mL), the combined organic phase was dried over Na2SO4, filtrated and concentrated to give N-[[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro- phenyl]methylene]-2-methyl-propane-2-sulfinamide (1.4 g, crude) as a yellow oil. HPLC-MS method C RT=0.683 min, [M+H]+= 387.0 N-[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-phenyl]ethyl]-2-methyl- propane-2-sulfinamide (step 5) To a solution of N-[[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-phenyl]methylene]-2- methyl-propane-2-sulfinamide (1.4 g, 3.62 mmol, 1 eq) in THF (20 mL) was added MeMgBr (3 M, 4.23 mL, 3.5 eq) at -60°C. The mixture was stirred at 20°C for 16 h. The reaction mixture was quenched dropwise to NH4Cl 30 mL at 0°C and extracted with EA (30mL*3). The combined organic layers were washed with brine 50 mL, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: WePure Biotech XP tC18250*70*10um; mobile phase: [H2O (10mM NH4HCO3)-ACN]; gradient: 50%-85% B over 20.0 min) to obtain N-[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-3-(2,5- dimethylpyrrol-1-yl)-2-fluoro-phenyl]ethyl]-2-methyl-propane-2-sulfinamide (500 mg, 1.24 mmol, 34% yield) and N-[(1R)-1-[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-phenyl]ethyl]-2-methyl- propane-2-sulfinamide (240 mg, 596 µmol, 17% yield) N-[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-phenyl]ethyl]-2-methyl-propane-2- sulfinamide1H NMR (400 MHz, DMSO-d6) δ: 7.30 (d, J = 8.2 Hz, 1H), 7.24 - 7.11 (m, 1H), 6.91 (d, J = 15.6 Hz, 1H), 5.81 - 5.77 (m, 2H), 5.76 - 5.70 (m, 1H), 5.52 (d, J = 6.3 Hz, 1H), 4.94 - 4.82 (m, 1H), 1.91 (d, J = 3.7 Hz, 6H), 1.74 - 1.60 (m, 1H), 1.49 (d, J = 6.9 Hz, 3H), 1.06 (s, 9H), 0.90 - 0.78 (m, 2H), 0.62 - 0.49 (m, 2H) N-[(1R)-1-[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-phenyl]ethyl]-2-methyl-propane-2- sulfinamide 1H NMR (400 MHz, DMSO-d6) δ: 7.31 (d, J = 8.3 Hz, 1H), 7.22 - 7.13 (m, 1H), 6.94 (d, J = 15.6 Hz, 1H), 5.82 - 5.78 (m, 2H), 5.78 - 5.72 (m, 1H), 5.36 (d, J = 3.7 Hz, 1H), 4.97 - 4.86 (m, 1H), 1.89 (d, J = 2.7 Hz, 6H), 1.72 - 1.59 (m, 1H), 1.55 (d, J = 6.9 Hz, 3H), 1.04 (s, 9H), 0.87 - 0.79 (m, 2H), 0.60 - 0.51 (m, 2H) Synthesis of title compound (step 6) A mixture of N-[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-3-(2,5-dimethylpyrrol-1-yl)-2-fluoro-phenyl]ethyl]-2-methyl- propane-2-sulfinamide (225 mg, 558µmol, 1 eq) in HCl / MeOH (4 M, 3 mL, 21.47 eq) was stirred at 20°C for 1 h. The reaction mixture was concentrated under reduced pressure to give (1S)-1-[6-[(E)-2-cyclopropylvinyl]- 3-(2,5-dimethylpyrrol-1-yl) -2-fluoro-phenyl]ethanamine; hydrochloride (167 mg, crude) as a yellow oil. HPLC-MS method C RT=0.444 min, [M+H]+= 316.0 Synthesis of (1S)-1-[4-[(E)-2-cyclopropylvinyl]-3-thienyl]ethanamine 1) A mixture of 4-bromothiophene-3-carbaldehyde (1 g, 5.23 mmol, 1.0 eq.), (R)-2-methylpropane-2-sulfinamide (0.699 g, 5.76 mmol, 1.1 eq.), and Ti(OEt)4(2.39 g, 2.195 mL, 10.47 mmol, 2.0 eq.) in THF (13 mL) was heated up at reflux under magnetic stirring for 4h. The reaction was cooled down and water was added to the mixture, giving a white precipitate that was filtered on a short celite path washing with EA. Aqueous and organic phase were separated, the organic phase dried over Na2SO4anhydrous and evaporated under reduced pressure. The crude (R)-N-[(4-bromo-3-thienyl)methylene]-2-methyl-propane-2-sulfinamide (1530 mg, 5.2 mmol, 99% Yield) (as yellow oil) was used for next step without further purification. HPLC-MS method A RT=3.88 min, [M+H]+= 295.9 Synthesis of (R)-N-[(1S)-1-(4-bromo-3-thienyl)ethyl]-2-methyl-propane-2-sulfinamide (step 2) (R)-N-[(4-bromo-3-thienyl)methylene]-2-methyl-propane-2-sulfinamide (1.53 g, 5.2 mmol, 1.0 eq.) was dissolved in THF dry (39 mL). MeMgBr 3.0 M solution in Et2O (3.59 g, 3.47 mL, 10.4 mmol, 2.0 eq.) was added drop wise to the reaction mixture kept at -78°C. The reaction mixture was then left to reach r.t. and left under magnetic stirring for 4 hours. H2O was added to the mixture to quench the reaction. Organic solvent was evaporated under reduced pressure and the aqueous phase was extracted three times with EA. The organic phase was collected, washed with brine, dried over Na2SO4 anhydrous and evaporated under reduced pressure. The crude was purified by chromatographic column DCM / Acetone 95 / 5 to 9 / 1 to furnish (R)-N-[(1S)-1-(4-bromo-3-thienyl)ethyl]-2-methyl-propane-2-sulfinamide (0.397 g, 1.28 mmol, 0.246 eq., 25% Yield) as pale yellow oil. HPLC-MS method A RT=2.7 min, [M+H]+= 311.9 Synthesis of (R)-N-[(1S)-1-[4-[(E)-2-cyclopropylvinyl]-3-thienyl]ethyl]-2-methyl-propane-2- sulfinamide (step 3) To a solution of (R)-N-[(1S)-1-(4-bromo-3-thienyl)ethyl]-2-methyl-propane-2-sulfinamide (0.397 g, 1.28 mmol, 1.0 eq.) in 1,4-dioxane (12.8 mL) and water (2.6 mL), 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (0.273 g, 0.29 mL, 1.41 mmol, 1.1 eq.), Potassium carbonate (0.53 g, 3.84 mmol, 3.0 eq.) and [1,1'-Bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane complex (0.105 g, 0.128 mmol, 0.1 eq.) were added under argon flux. Three cycle of argon / vacuum was performed. The reaction mixture was stirred at T = 110°C in microwave for 2h. The reaction mixture was filtered through celite (washed with EA), water was added and the mixture was extracted with EA three times, organic layer was washed with brine, dried on Na2SO4and evaporated. The crude was purified by chromatographic column Hexane / EA 7 / 3 to 3 / 7 to achieve (R)-N-[(1S)-1-[4-[(E)-2-cyclopropylvinyl]-3-thienyl]ethyl]-2-methyl-propane-2-sulfinamide (0.302 g, 1.015 mmol, 79% Yield) as yellow oil. HPLC-MS method A RT=4.16 min, [M+H]+= 298.1 Synthesis of the title compound (step 4) In a µW vial, to a solution of (R)-N-[(1S)-1-[4-[(E)-2-cyclopropylvinyl]-3-thienyl]ethyl]-2-methyl-propane-2- sulfinamide (0.15 g, 0.51 mmol, 1.0 eq.) in THF (1.7 mL) and water (0.338 mL), iodine (0.0387 g, 0.152 mmol, 0.3 eq.) was added portion wise and the reaction mixture stirred at r.t. overnight. The reaction mixture was quenched with NaHCO3(sat. sol.), diluted with water and extracted with DCM. The organic layers were washed with Na2S2O5 (10% sol), brine and dried over Na2SO4. Obtained (1S)-1-[4-[(E)-2-cyclopropylvinyl]- 3-thienyl]ethanamine (0.053 g, 0.274 mmol, 54% Yield) as a brown oil, used without further purification in the successive step. HPLC-MS method A RT=2.69 min, recognized by fragment [C11H13S]+=177.1 Synthesis of 6-[(1R)-1-aminoethyl]-5-[(E)-2-cyclopropylvinyl]pyridin-2-amine hydrochloride BocBoc To a solution of methyl 6-amino-3-bromo-pyridine-2-carboxylate (5 g, 21.64 mmol, 1 eq), 2-[(E)-2- cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6.30 g, 32.46 mmol, 1.5 eq) and K2CO3(5.98 g, 43.28 mmol, 2 eq) in dioxane (50 mL) and H2O (13 mL) was added Pd(dppf)Cl2(1.58 g, 2.16 mmol, 0.1 eq). The mixture was stirred at 90 °C for 16 h under N2 atmosphere. The solution was diluted with H2O (30 mL), filtered through Celite pad to remove by-product, extracted with EA (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography hexane / EA 1 / 1 to obtain 6-amino-3-[(E)-2-cyclopropylvinyl]pyridine-2-carboxylate (4.57 g, 19.47 mmol, 90% yield) as a yellow solid. HPLC-MS method G (RT=0.359 min, [M+H]+ = 219.1) Synthesis of methyl 6-[bis(tert-butoxycarbonyl)amino]-3-[(E)-2-cyclopropylvinyl]pyridine-2- carboxylate (step 2) To a solution of 6-amino-3-[(E)-2-cyclopropylvinyl]pyridine-2-carboxylate (3.4 g, 15.58 mmol, 1 eq) in DCM (40 mL) was added Boc2O (10.20 g, 46.74 mmol, 10.74 mL, 3 eq) and DMAP (285 mg, 2.34 mmol, 0.15 eq). The mixture was stirred at 20 °C for 3 h. The reaction mixture was quenched with H2O (30 mL), extracted with DCM (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by chromatographic column hexane / EA 95 / 5 to 9 / 1 to obtain 6- [bis(tert-butoxycarbonyl)amino]-3-[(E)-2-cyclopropylvinyl]pyridine-2-carboxylate (5.65 g, 12 mmol, 78% yield) as a white oil. HPLC-MS method G (RT=0.649 min, [M+H]+ = 419.2) Synthesis of tert-butyl N-tert-butoxycarbonyl-N-[5-[(E)-2-cyclopropylvinyl]-6-(hydroxymethyl)-2- pyridyl]carbamate (step 3) To a solution of 6-[bis(tert-butoxycarbonyl)amino]-3-[(E)-2-cyclopropylvinyl]pyridine-2-carboxylate (5.65 g, 13.50 mmol, 1 eq) in THF (60 mL) was added DIBAL-H (1 M, 32.40 mL, 2.4 eq) at -78 °C. The mixture was stirred at 20 °C for 2 h under N2 atmosphere. After the reaction mixture was cooled to 0 °C, the reaction mixture was quenched by addition of 4.6 mL of H2O, followed by 4.6 mL of 15% aqueous NaOH and 13 mL of H2O. After being stirred at room temperature for 30 min, the solid was removed by filtration. The filtrate was concentrated to dryness to give crude product. The residue was purified by column chromatography hexane / EA 9 / 1 to 8 / 2 to obtain tert-butyl N-tert-butoxycarbonyl-N-[5-[(E)-2-cyclopropylvinyl]-6- (hydroxymethyl)-2-pyridyl]carbamate (4.8 g, 9.83 mmol, 73% yield) as a white oil. HPLC-MS method G (RT=0.612 min, [M+H]+ = 391.2) Synthesis of tert-butyl N-[5-[(E)-2-cyclopropylvinyl]-6-(hydroxymethyl)-2-pyridyl]carbamate (step 4) To a solution of tert-butyl N-tert-butoxycarbonyl-N-[5-[(E)-2-cyclopropylvinyl]-6-(hydroxymethyl)-2- pyridyl]carbamate (236 mg, 604.40 µmol, 1 eq) in MeOH (10 mL) was added K2CO3 (417.67 mg, 3.02 mmol, 5 eq). The mixture was stirred at 45 °C for 4 h. The reaction mixture was quenched with H2O (30 mL), extracted with EA (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give tert-butyl N-[5-[(E)-2-cyclopropylvinyl]-6-(hydroxymethyl)-2-pyridyl]carbamate (180 mg, crude) as a white solid. HPLC-MS method G (RT=0.429 min, [M+H]+ = 291.1) Synthesis of tert-butyl N-[5-[(E)-2-cyclopropylvinyl]-6-formyl-2-pyridyl]carbamate (step 5) To a solution of N-[5-[(E)-2-cyclopropylvinyl]-6-(hydroxymethyl)-2-pyridyl]carbamate (600 mg, 2.07 mmol, 1 eq) in DCM (10 mL) was added Dess-Martin (1.31 g, 3.10 mmol, 960.33 µL, 1.5 eq). The mixture was stirred at 20 °C for 2 h. The reaction mixture was quenched with NaHCO3 (30 mL), extracted with DCM (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by column chromatography hexane / EA 9 / 1 to obtain tert-butyl N-[5-[(E)-2-cyclopropylvinyl]-6- formyl-2-pyridyl]carbamate (380 mg, 1.23 mmol, 59% yield) as a yellow solid. HPLC-MS method G (RT=0.624 min, [M+H]+ = 289.3) Synthesis of tert-butyl N-[6-[(E)-[(R)-tert-butylsulfinyl]iminomethyl]-5-[(E)-2-cyclopropylvinyl]-2- pyridyl]carbamate (step 6) To a solution of tert-butyl N-[5-[(E)-2-cyclopropylvinyl]-6-formyl-2-pyridyl]carbamate (266 mg, 922.52 µmol, 1 eq) and (R)-2-methylpropane-2-sulfinamide (134.17 mg, 1.11 mmol, 1.2 eq) in DCM (5 mL) was added CuSO4.5H2O (276.41 mg, 1.11 mmol, 1.2 eq). The mixture was stirred at 20 °C for 2 h. The reaction mixture was filtered and concentrated to give a crude product. The residue was purified by column chromatography hexane / EA 9 / 1 to obtain tert-butyl N-[6-[(E)-[(R)-tert-butylsulfinyl]iminomethyl]-5-[(E)-2-cyclopropylvinyl]-2- pyridyl]carbamate (352 mg, 872 µmol, 95% yield) as a yellow solid. HPLC-MS method G (RT=0.644 min, [M+H]+ = 392.2) Synthesis of tert-butyl N-[6-[(1R)-1-[[(R)-tert-butylsulfinyl]amino]ethyl]-5-[(E)-2-cyclopropylvinyl]-2- pyridyl]carbamate (step 7) To a solution of tert-butyl N-[6-[(E)-[(R)-tert-butylsulfinyl]iminomethyl]-5-[(E)-2-cyclopropylvinyl]-2- pyridyl]carbamate (508 mg, 1.30 mmol, 1 eq) in THF (6 mL) was added MeMgBr (3 M, 1.30 mL, 3 eq) at - 78 °C. The mixture was stirred at 20 °C for 2 h. The reaction mixture was quenched with NH4Cl (1 mL) at 0 °C, and then diluted with H2O (30 mL), extracted with EA (30 mL * 3), washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by prep-HPLC (column: WePure Biotech XPt C18150*40*7 um; mobile phase: [H2O(10mM NH4HCO3)-ACN]; gradient:60%- 90% B over 8.0 min) to obtain tert-butyl N-[6-[(1R)-1-[[(R)-tert-butylsulfinyl]amino]ethyl]-5-[(E)-2- cyclopropylvinyl]-2-pyridyl]carbamate (380 mg, 839 µmol, 65% yield) as a yellow solid. HPLC-MS method G (RT=0.604 min, [M+H]+ = 408.2) Synthesis of the title compound (step 8) A mixture of tert-butyl N-[6-[(1R)-1-[[(R)-tert-butylsulfinyl]amino]ethyl]-5-[(E)-2-cyclopropylvinyl]-2- pyridyl]carbamate (100 mg, 245.36 µmol, 1 eq) in HCl / MeOH (4 M, 5.00 mL, 81.51 eq) was stirred at 50 °C for 3 h. The solution was concentrated to give a crude product. The residue was purified by prep-HPLC (column: Phenomenex luna C18100*40mm*5 um; mobile phase: [H2O(0.04% HCl)-ACN]; gradient:1%-30% B over 8.0 min) to obtain 6-[(1R)-1-aminoethyl]-5-[(E)-2-cyclopropylvinyl]pyridin-2-amine hydrochloride (38.48 mg, 154.33 µmol, 63% yield) as a light yellow solid.1H NMR (400 MHz, DMSO-d6) δ: 8.94 - 8.03 (m, 3H), 7.75 (br d, J = 1.8 Hz, 1H), 6.79 - 6.46 (m, 2H), 5.64 (br dd, J = 9.4, 15.1 Hz, 1H), 4.72 (br s, 2H), 1.62 (tt, J = 4.1, 8.5 Hz, 1H), 1.47 (br d, J = 3.6 Hz, 3H), 0.89 - 0.73 (m, 2H), 0.59 - 0.43 (m, 2H) According to the same methodology, starting form step 6 and employing 5-bromo-2-chloro-pyridine-4- carbaldehyde as starting material, the following intermediate was prepared: 1-(5-bromo-2-chloro-4-pyridyl)ethanamine hydrochloride HPLC-MS method G (RT=0.292 min, [M+H] Synthesis of (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-isobutoxy-phenyl]ethanamine hydrochloride (step 1) To a solution of 2-bromo-5-methoxy-benzaldehyde (8.5 g, 39.53 mmol, 1 eq) in THF (100 mL) was added (S)-2-methylpropane-2-sulfinamide (9.58 g, 79.05 mmol, 2 eq) and Ti(OEt)4 (36.07 g, 158 mmol, 32.79 mL, 4 eq). The mixture was stirred at 70 °C for 16 h. The solution was diluted with ice water (20 mL), extracted with EA (3*50 mL), the combined organic phase was dried over Na2SO4, filtrated and concentrated to give the residue. The crude was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 100 / 1 to 0 / 1). (S)-N-[(2-bromo-5-methoxy-phenyl)methylene]-2-methyl-propane-2-sulfinamide (12.4 g) was obtained as a white solid.1H NMR (400 MHz, DMSO-d6) δ: 8.76 (s, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 3.2 Hz, 1H), 7.16 (dd, J = 3.2, 8.8 Hz, 1H), 3.82 (s, 3H), 1.20 (s, 9H) Synthesis of (S)-N-[(1R)-1-(2-bromo-5-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide and (S)-N-[(1S)-1-(2-bromo-5-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (step 2) To a solution of (S)-N-[(2-bromo-5-methoxy-phenyl)methylene]-2-methyl-propane-2-sulfinamide (12 g, 37.71 mmol, 1 eq) in THF (100 mL) was added MeMgBr (3 M, 25.14 mL, 2 eq) at -50°C and N2. The mixture was stirred at 25°C and N2for 2 h. The solution was diluted with ice water (300 mL), extracted with EA (3*500 mL), the combined organic phase was dried over Na2SO4, filtrated and concentrated to give the residue. The crude was purified by preparative HPLC (neutral condition; column: Waters Xbridge BEH C18 250*70mm*10um;mobile phase: [H2O(10mM NH4HCO3)-ACN];gradient:40%-60% B over 20.0 min.). (S)-N- [(1S)-1-(2-bromo-5-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (4.2 g) was obtained as yellow oil. HPLC-MS method G (RT=0.489 min, [M+H]+= 334.2, 336.2)1H NMR (400 MHz, DMSO-d6) δ: 7.45 (d, J = 8.7 Hz, 1H), 7.20 (d, J = 3.1 Hz, 1H), 6.79 (dd, J = 3.1, 8.7 Hz, 1H), 5.98 (d, J = 7.7 Hz, 1H), 4.64 (quin, J = 6.9 Hz, 1H), 3.75 (s, 3H), 1.32 (d, J = 6.7 Hz, 3H), 1.09 (s, 9H) (S)-N-[(1R)-1-(2-bromo-5-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (6.4 g) was obtained as a white solid. HPLC-MS method G (RT=0.474 min, [M+H]+= 334.2, 336.2)1H NMR (400 MHz, DMSO- d6) δ: = 7.45 (d, J = 8.7 Hz, 1H), 7.14 (d, J = 3.1 Hz, 1H), 6.78 (dd, J = 3.1, 8.8 Hz, 1H), 5.52 (d, J = 5.4 Hz, 1H), 4.68 (quin, J = 6.4 Hz, 1H), 3.73 (s, 3H), 1.42 (d, J = 6.7 Hz, 3H), 1.12 (s, 9H) Synthesis of (1S)-1-(2-bromo-5-methoxy-phenyl)ethanamine hydrochloride (step 3) A solution of (S)-N-[(1S)-1-(2-bromo-5-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (4.2 g, 12.56 mmol, 1 eq) in HCl / MeOH (4 M, 42.00 mL, 13.37 eq) was stirred at 25 °C for 1h. The solvent was evaporated under reduced pressure to give (1S)-1-(2-bromo-5-methoxy-phenyl)ethanamine hydrochloride (2.9 g, crude) as a white solid that was used in the next step without purification. HPLC-MS method G (RT=0.292 min, recognized by fragment [C9H10BrO]+= 214.0, 216.0) Synthesis of 4-bromo-3-[(1S)-1-aminoethyl]phenol (step 4) To a solution of (1S)-1-(2-bromo-5-methoxy-phenyl)ethanamine hydrochloride (2.9 g, 12.60 mmol, 1 eq) in DCM (15 mL) was added BBr3 (6.31 g, 25.21 mmol, 2.43 mL, 2 eq) at 0°C and N2.The reaction was stirred 2h at 0°C and N2. The mixture was quenched with ice water 20 mL, after pH adjustment to 5-6 the water was extracted with EA:MeOH = 3:1 (5*50 mL). The organic phase was dried over Na2SO4, filtrated and concentrated to give 4-bromo-3-[(1S)-1-aminoethyl]phenol (2.8 g, crude) as a white solid, that was used in the next step without further purification. HPLC-MS method G (RT=0.239 min, recognized by fragment [C8H8BrO]+= 199.0, 201.0) Synthesis of tert-butyl N-[(1S)-1-(2-bromo-5-hydroxy-phenyl)ethyl]carbamate (step 5) To a solution of 4-bromo-3-[(1S)-1-aminoethyl]phenol (2.62 g, 12.13 mmol, 1 eq) in DCM (30 mL) was added TEA (3.68 g, 36.38 mmol, 5.06 mL, 3 eq) and (Boc)2O (2.65 g, 12.13 mmol, 2.79 mL, 1 eq) at 0°C and N2. The reaction was stirred 2h at 0°C and N2. The mixture was quenched with ice water 50 mL and extracted with DCM (3*50 mL), the combined organic phase was dried over Na2SO4, filtrated and concentrated. The residue was purified by preparative HPLC (neutral condition; column: Waters Xbridge BEH C18250*50 mm*10 um; mobile phase: [H2O (10mM NH4HCO3) - ACN]; gradient: 30%-70% B over 10.0 min). tert-butyl N-[(1S)-1-(2-bromo-5-hydroxy-phenyl)ethyl]carbamate (2.25 g) was obtained as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ: 9.81 - 9.47 (m, 1H), 7.56 (br d, J = 7.6 Hz, 1H), 7.28 (d, J = 8.6 Hz, 1H), 6.85 (d, J = 3.0 Hz, 1H), 6.57 (dd, J = 3.0, 8.6 Hz, 1H), 4.92 - 4.64 (m, 1H), 1.44 - 1.11 (m, 12H) Synthesis of tert-butyl N-[(1S)-1-[5-hydroxy-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamate (step 6) To a solution of tert-butyl N-[(1S)-1-(2-bromo-5-hydroxy-phenyl)ethyl]carbamate (1.5 g, 4.74 mmol, 1 eq) in 1,4-dioxane (15 mL) was added 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.10 g, 5.69 mmol, 1.2 eq), K2CO3 (1.31 g, 9.49 mmol, 2 eq) in H2O (1.5 mL) and Pd(dppf)Cl2 (694 mg, 948.80 µmol, 0.2 eq). The reaction was stirred at 90 °C for 2h with N2. Water (20mL) was added, and the mixture was extracted with EA (3*50 mL), the combined organic phase was dried over Na2SO4, filtrated and concentrated. The residue was purified by preparative HPLC (neutral condition; column: Waters Xbridge BEH C18 250*50mm*10um; mobile phase: [H2O (10mM NH4HCO3) - ACN]; gradient: 40%-60% B over 10.0 min). tert-butyl N-[(1S)-1-[5-hydroxy-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamate (1.05 g) was obtained as a yellow solid.1H NMR (400 MHz, DMSO- d6) δ: = 9.26 (br s, 1H), 7.38 (br d, J = 7.7 Hz, 1H), 7.15 (d, J = 8.5 Hz, 1H), 6.72 (d, J = 2.6 Hz, 1H), 6.63 (d, J = 15.5 Hz, 1H), 6.54 (dd, J = 2.6, 8.4 Hz, 1H), 5.46 (br dd, J = 9.0, 15.4 Hz, 1H), 4.99 - 4.67 (m, 1H), 1.56 (tdd, J = 4.3, 8.5, 12.8 Hz, 1H), 1.40 - 1.17 (m, 12H), 0.82 - 0.69 (m, 2H), 0.45 (br d, J = 2.0 Hz, 2H) According to the same methodology, but employing 2-bromo-4-methoxy-benzaldehyde at step 1, the following intermediate was prepared: tert-butyl N-[(1S)-1-[4-hydroxy-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamate HPLC-MS method A (RT = 4.75 min, [M- Synthesis of tert-butyl-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-isobutoxy-phenyl]ethyl]carbamate (step 7) Tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-phenyl]ethyl]carbamate (0.055 g, 0.181 mmol, 1.0 eq.) was dissolved in N,N-dimethylformamide (2 mL) followed by addition of cesium carbonate (0.087 g, 0.453 mmol, 2.5 eq.) and 1-iodo-2-methyl-propane (0.083 g, 0.053 mL, 0.453 mmol, 2.5 eq.). The reaction was left under magnetic stirring 6 h at 120 °C. The solvent was evaporated under reduced pressure and the crude dissolved in EA and washed with NaOH 0.1N aqueous solution. The organic phase was dried over Na2SO4anhydrous, filtrated and evaporated under reduced pressure to give tert-butyl-N-[(1S)-1-[2-[(E)-2- cyclopropylvinyl]-5-isobutoxy-phenyl]ethyl]carbamate (0.05 g) that was used in the next step without further purification. Synthesis of the title compound (step 8) Tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-isobutoxy-phenyl]ethyl]carbamate (0.05 g, 0.139 mmol, 1.0 eq.) was dissolved in dichloromethane (3 mL) and HCl in 1,4-dioxane 4M was added (10 eq., 1.391 mmol). The reaction was stirred at r.t. overnight. The solution was evaporated under vacuum and the desired product (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-isobutoxy-phenyl]ethanamine hydrochloride (0.04 g, 0.135 mmol, 97 % Yield) was used as salt in the next step. HPLC-MS method A (RT = 3.85 min., recognized by fragment [C17H23O]+= 243.3 According to the same methodology, but employing suitable starting materials at step 7, the following compounds of formula (XV) were prepared: (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(oxetan-3-yloxy)phenyl]ethanamine hydrochloride HPLC-MS method C (RT=2.80 min, += 243.2) (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(oxetan-3-yloxy)phenyl]ethanamine hydrochloride HPLC-MS method C (RT=3.05 += 278.2) (1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(difluoromethoxy)phenyl]ethanamine hydrochloride HPLC-MS method A (RT=3.12 min) (1S)-1-[4-(cyclohexoxy)-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine hydrochloride HPLC-MS method F (RT=1.79 min, O]+= 269.4) (1S)-1-[4-(cyclohexylmethoxy)-2-[(E)-2-cyclopropylvinyl]phenyl]ethanamine hydrochloride HPLC-MS method F (RT=2.33 min, O]+= 283.3) According to the same methodology, applying condition reported at step 8 to tert-butyl N-[(1S)-1-[5-hydroxy- 2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamate, the following compound of formula (XV) was prepared: 3-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]phenol hydrochloride HPLC-MS method A (RT=2.32 min, According to the same methodology, applying condition reported at step 8 to tert-butyl N-[(1S)-1-[4-hydroxy- 2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamate, the following compound of formula (XV) was prepared: 4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]phenol hydrochloride HPLC-MS method B (RT=4.72 min, Synthesis of [4-[(1S)-1-aminoethyl]-3-[(E)-2-cyclopropylvinyl]phenyl] trifluoromethanesulfonate hydrochloride Synthesis trifluoromethanesulfonate (step1) Et3N (0.53 mL, 3.78 mmol, 2.0 eq.) and N-Phenylbis(trifluoromethanesulfonimide) (0.676 g, 1.89 mmol, 1.0 eq.) were added to a solution of tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-hydroxy- phenyl]ethyl]carbamate (0.570 g, 1.89 mmol) in DCM (7 mL). The reaction mixture was stirred at r.t. overnight. HPLC-MS analysis showed formation of the desired product. Solvent was evaporated under reduce pressure, the reaction mixture diluited with EA and washed with 0.1 N citric acid solution and brine. The organic phase was dried over Na2SO4 anhydrous and evaporated under reduced pressure. The crude was purified by automatic chromatographic column on silica gel, gradient from Hexane / AcOEt 95 / 5 to 90 / 10 to give [4-[(1S)- 1-(tert-butoxycarbonylamino)ethyl]-3-[(E)-2-cyclopropylvinyl]phenyl] trifluoromethanesulfonate (0.510 g, 1.17 mmol, 62 % Yield) as white glassy solid. HPLC-MS method F (RT=4.72 min, [M-H]-=434.4) Synthesis of titled compound (step 2) 1-(tert-butoxycarbonylamino)ethyl]-3-[(E)-2-cyclopropylvinyl]phenyl] trifluoromethanesulfonate (0.05 g, 0.11 mmol) was dissolved in DCM (2 mL). HCl in dioxane (4 M, 0.140 mL, 0.57 mmol, 5 eq.) was added to the reaction mixture that was left under magnetic stirring at r.t. for 3 hours. HPLC-Ms showed completion of reaction. The solvent was evaporated under reduced pressure to give [4-[(1S)-1-(tert- butoxycarbonylamino)ethyl]-3-[(E)-2-cyclopropylvinyl]phenyl] trifluoromethanesulfonate (0.042 g, quant.Yield) as white solid. HPLC-MS method A (RT=3.91 min, recognized by fragment [C14H14F3O3S]+= 319.3) According to the same methodology, but employing suitable starting material, the following intermediate compound of formula (XV) was prepared: [5-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-2-methoxy-phenyl] trifluoromethanesulfonate hydrochloride HPLC-MS method F (RT=1.33 min, += 349.1) [3-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]phenyl] trifluoromethanesulfonate hydrochloride HPLC-MS method A (RT=2.18 min, += 319.3) Synthesis of (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylmethyl)phenyl]ethanamine trifluoroacetate To a solution of methyl 4-[(1S)-1-aminoethyl]benzoate (4 g, 22.32 mmol, 1 eq) in H2SO4(147.20 g, 1.50 mol, 80.00 mL, 67.24 eq) was added NBS (3.97 g, 22.32 mmol, 1 eq), the reaction was stirred at 25 °C for 16 h. The solution was added to the ice water (150 mL) drop wise, adjusted pH=7-8 by saturated Na2CO3, extracted with EA (3*300 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated. The residue was purified by column chromatography (SiO2, DCM / MeOH = 1 / 0 to 100 / 1) to obtain methyl 4-[(1S)- 1-aminoethyl]-3-bromo-benzoate (1.78 g, 6.90 mmol, 31% yield) as yellow oil.1H NMR (400 MHz, DMSO-d6) δ: 8.03 (d, J = 1.4 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 7.88 - 7.82 (m, 1H), 4.31 (q, J = 6.5 Hz, 1H), 3.85 (s, 3H), 2.07 (br s, 2H), 1.22 (d, J = 6.6 Hz, 3H). Synthesis of methyl 3-bromo-4-[(1S)-1-(tert-butoxycarbonylamino)ethyl]benzoate (step 2) To a solution of 4-[(1S)-1-aminoethyl]-3-bromo-benzoate (1.78 g, 6.90 mmol, 1 eq) in DCM (18 mL) was added TEA (1.40 g, 13.79 mmol, 1.92 mL, 2 eq) and Boc2O (2.26 g, 10.34 mmol, 2.38 mL, 1.5 eq), the solution was stirred at 25 °C for 1 h. The reaction was diluted with H2O (30 mL), extracted with DCM (3*30 mL), the combined organic phases were washed with brine, dried over Na2SO4, filtrated and concentrated. The residue was purified by column chromatography (SiO2, DCM / MeOH = 1 / 0 to 100 / 1) to obtain methyl 3- bromo-4-[(1S)-1-(tert-butoxycarbonylamino)ethyl]benzoate (1.86 g, 5.19 mmol, 75% yield) as yellow solid.1H NMR (400 MHz, DMSO-d6) δ: 8.05 (d, J = 1.5 Hz, 1H), 7.96 (br d, J = 7.9 Hz, 1H), 7.75 (br d, J = 7.1 Hz, 1H), 7.57 (d, J = 8.1 Hz, 1H), 4.92 (br t, J = 6.9 Hz, 1H), 3.85 (s, 3H), 1.35 (s, 9H), 1.26 (br d, J = 6.9 Hz, 3H). Synthesis of tert-butyl N-[(1S)-1-[2-bromo-4-(hydroxymethyl)phenyl]ethyl]carbamate (step 3) A solution of 3-bromo-4-[(1S)-1-(tert-butoxycarbonylamino)ethyl]benzoate (1.86 g, 5.19 mmol, 1 eq) in THF (20 mL) was cooled to 0 °C, then the LAH (2.5 M, 3.12 mL, 1.5 eq) was added and the solution was stirred at 25 °C for 1 h. The reaction was quenched H2O (0.3 mL), then the NaOH (15% in H2O, 0.3 mL) was added, the solution was stirred for 10 min, filtrated and washed with EA (30 mL), the filtrate was extracted with EA (3*30 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated to give tert-butyl N-[(1S)-1-[2-bromo-4-(hydroxymethyl)phenyl]ethyl]carbamate (1.65 g, crude). HPLC-MS method B (RT = 2.748 min., [M +H] = 330.2, 332.2) Synthesis of tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(hydroxymethyl)phenyl]ethyl] carbamate (step 4) To a solution of tert-butyl N-[(1S)-1-[2-bromo-4-(hydroxymethyl)phenyl]ethyl]carbamate (0.95 g, 2.88 mmol, 1 eq) in 1,4-dioxane (10 mL) and H2O (2.5 mL), 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (0.67 g, 3.45 mmol, 1.2 eq), K2CO3(0.795 g, 5.75 mmol, 2 eq) and Pd(dppf)Cl2(0.211 g, 287.69 µmol, 0.1 eq) were added. The reaction was stirred at 90 °C for 2 h. The solution was diluted with H2O, the mixture was extracted with EA and the combined organic phase was dried over Na2SO4, filtrated and concentrated. The residue was purified by preparative HPLC (neutral condition), column: Waters Xbridge BEH C18250*50mm*10um; mobile phase: [H2O (10mM NH4HCO3)-ACN]; gradient:25%-65% B over 10.0 min. Tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(hydroxymethyl)phenyl]ethyl]carbamate (0.675 g, 2.13 mmol, 74% yield) was obtained as white solid.1H NMR (400 MHz, DMSO-d6) δ: 7.42 (br d, J = 8.2 Hz, 1H), 7.32 - 7.21 (m, 2H), 7.10 (br d, J = 7.6 Hz, 1H), 6.78 (d, J = 15.5 Hz, 1H), 5.63 (br dd, J = 9.0, 15.3 Hz, 1H), 5.08 (br s, 1H), 4.97 - 4.84 (m, 1H), 4.41 (br s, 2H), 1.64 (dt, J = 3.6, 8.2 Hz, 1H), 1.35 (s, 9H), 1.22 (br d, J = 6.8 Hz, 3H), 0.84 - 0.76 (m, 2H), 0.51 (br s, 2H). Synthesis of [4-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-[(E)-2-cyclopropylvinyl]phenyl]methyl methanesulfonate (step 5) In a dry round-bottom flask filled with Ar, to a solution of tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4- (hydroxymethyl)phenyl]ethyl]carbamate (0.3 g, 0.945 mmol) and TEA (3.5 eq., 3.308 mmol) in DCM dry (0.1 M) cooled to 0 °C, was added methanesulfonyl chloride (2 eq., 1.890 mmol) dropwise and, after removal of the ice-bath, the reaction mixture was stirred at r.t. overnight. The reaction mixture was diluted with DCM, washed with water and brine, dried over Na2SO4and filtrated. The solvent was evaporated under reduced pressure to get the crude product [4-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-[(E)-2- cyclopropylvinyl]phenyl]methyl methanesulfonate (0.295 g, 0.746 mmol, 79% Yield). Synthesis of tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylmethyl)phenyl] ethyl] carbamate (step 6) In a round-bottom flask, a suspension of [4-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-[(E)-2- cyclopropylvinyl]phenyl]methyl methanesulfonate (0.14 g, 0.354 mmol), piperidine (1 eq., 0.354 mmol) and potassium carbonate (3 eq., 1.062 mmol) in tetrahydrofuran (0.2 M) was stirred under reflux (70 °C) overnight. The solvent was evaporated under reduced pressure and the residue was dissolved in EA, washed with water (x1), brine (x1), dried over Na2SO4and filtrated. The solvent was evaporated under reduced pressure to obtain tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylmethyl)phenyl]ethyl]carbamate (0.081 g, 0.211 mmol, 60% Yield). HPLC-MS method A (R = 3.796 min., [M+H]+= 385.2) Synthesis of the title compound (step 7) In a round-bottom flask, a solution of tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1- piperidylmethyl)phenyl]ethyl]carbamate (0.081 g, 0.211 mmol) in DCM (0.1 M) and (0.1 M, 27.34 mmol) was stirred at r.t. for two hours. The solvent was evaporated and the residue used without further manipulation. Obtained (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylmethyl)phenyl]ethanamine trifluoroacetic acid (0.042 g, 0.211 mmol, quantitative yield). HPLC-MS method A (R = 1.327 min, recognized by fragment [C19H26N]+= 268.2) According to the same methodology, but employing the suitable reagent at step 6, the following intermediate compound of formula (XV) was prepared: (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(4-methylpiperazin-1-yl)methyl]phenyl]ethanamine trifluoroacetate HPLC-MS method A (R = 1.252 min., recognized by fragment [C19H27N2]+= 283.2) Synthesis of (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethanamine hydrochloride 2-bromo-4-fluoro-benzaldehyde (10 g, 49.26 mmol, 1 eq) and sodium methanesulfinate (8.04 g, 78.81 mmol, 1.6 eq) was dissolved in DMSO (100 mL) and heated at 100°C for 22h. The reaction was allowed to cool to room temperature and then poured into ice water (300mL). The resulting precipitated was collected by filtration and dried.2-bromo-4-methylsulfonyl-benzaldehyde (12 g, crude) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 10.65 (s, 1H), 8.53 - 8.41 (m, 2H), 8.21 (d, J = 7.9 Hz, 1H), 3.60 (s, 3H) Synthesis of (S)-N-[(2-bromo-4-methylsulfonyl-phenyl)methylene]-2-methyl-propane-2-sulfinamide (step 2) To a mixture of 2-bromo-4-methylsulfonyl-benzaldehyde (6 g, 22.80 mmol, 1 eq) and (S)-2-methylpropane- 2-sulfinamide (2.76 g, 22.80 mmol, 1 eq) in THF (200 mL) was added Ti(OEt)4(5.20 g, 22.80 mmol, 4.73 mL, 1 eq). The reaction mixture was stirred for 16 h at 20°C under nitrogen protection. The reaction mixture was diluted with water (50 mL) and ethyl acetate (50 mL). Solution was filtered over celite. The organic layer was separated, washed with brine (50mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatographic column (SiO2; PE: EA=5%-8%). (S)-N-[(2-bromo-4- methylsulfonyl-phenyl)methylene]-2-methyl-propane-2-sulfinamide (2 g) was obtained as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ: = 9.01 (s, 1H), 8.31 - 8.18 (m, 2H), 7.95 (dd, J = 1.2, 8.2 Hz, 1H), 3.11 (s, 3H), 1.30 (s, 9H) Synthesis of (S)-N-[(1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]-2-methyl-propane-2-sulfinamide and (S)-N-[(1R)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (step 3) To a solution of (S)-N-[(2-bromo-4-methylsulfonyl-phenyl)methylene]-2-methyl-propane-2-sulfinamide (1.75 g, 4.78 mmol, 1 eq) in THF (18 mL) was added MeMgBr (3 M, 4.57 mL, 2 eq) dropwise at -78°C under N2. The reaction mixture was stirred for 16 h at 20°C under nitrogen protection. The mixture was quenched dropwise with water (30 mL) at 0°C and extracted with EA (30mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude was purified by preparative HPLC (column: Welch Xtimate C18180*70mm#10um; mobile phase: [H2O (10mM NH4HCO3) - ACN]; gradient: 25%-60% B over 20.0 min). (S)-N-[(1R)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (0.22 g, 575.41 µmol, 8.4% yield) was obtained as a white solid. HPLC-MS method G (RT = 0.387 min, [M+H]+= 383.2)1H NMR (400 MHz, CHLOROFORM-d) δ: = 8.13 (d, J = 1.8 Hz, 1H), 7.88 (dd, J = 1.8, 8.2 Hz, 1H), 7.68 (d, J = 8.2 Hz, 1H), 5.09 (dq, J = 3.3, 6.6 Hz, 1H), 3.45 (br d, J = 2.6 Hz, 1H), 3.09 (s, 3H), 1.56 (d, J = 6.7 Hz, 3H), 1.24 (s, 9H). (S)-N-[(1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (1.4 g, 3.66 mmol, 77%) was obtained as a white solid. HPLC-MS method G (RT = 0.413 min, [M+H]+= 383.2)1H NMR (400 MHz, CHLOROFORM-d) δ: = 8.14 (d, J = 1.8 Hz, 1H), 7.90 (dd, J = 1.8, 8.2 Hz, 1H), 7.69 (d, J = 8.1 Hz, 1H), 5.00 (quin, J = 6.2 Hz, 1H), 3.68 (br d, J = 4.9 Hz, 1H), 3.08 (s, 3H), 1.54 (d, J = 6.7 Hz, 3H), 1.26 (s, 9H) Synthesis of (1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethanamine hydrochloride (step 4) A solution of (S)-N-[(1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (1.4 g, 3.66 mmol, 1 eq) in 4M HCl / MeOH (1 mL) was stirred for 1h at 20°C. The reaction was concentrated and (1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethanamine hydrochloride (1 g, crude) was obtained as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ: 8.87 (br s, 3H), 8.20 (d, J = 1.7 Hz, 1H), 8.12 - 7.98 (m, 2H), 4.70 (br s, 1H), 3.32 (s, 3H), 1.52 (d, J = 6.8 Hz, 3H) Synthesis of tert-butyl N-[(1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]carbamate (step 5) To a solution of (1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethanamine – hydrochloride (1 g, 3.18 mmol, 1 eq.) in DCM (10 mL) was added TEA (1.29 g, 12.71 mmol, 1.77 mL, 4 eq) and Boc2O (0.763 g, 3.50 mmol, 803.21 µL, 1.1 eq). the reaction was stirred for 16h at 20°C. The mixture was diluted with water and extracted with DCM. The combined organic layers were washed with brined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by chromatographic column (SiO2; PE: EA=1:1) to obtain tert-butyl N-[(1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]carbamate (0.34 g, 0.899 mmol, 28% Yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ: 8.05 (d, J = 1.8 Hz, 1H), 7.93 (dd, J = 1.8, 8.2 Hz, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.52 - 7.20 (m, 1H), 4.98 (quin, J = 7.1 Hz, 1H), 3.23 (s, 3H), 1.37 - 1.29 (m, 12H) Synthesis of tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamate (step 6) To a solution of tert-butyl N-[(1S)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]carbamate (0.34 g, 0.899 mmol, 1 eq) in 1,4-dioxane (4 mL) and H2O (1 mL) was added K2CO3(248.45 mg, 1.80 mmol, 2 eq) and 2-[(E)-2- cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.262 g, 1.35 mmol, 1.5 eq), Pd(dppf)Cl2(65.77 mg, 0.0899 mmol, 0.1 eq) was added under N2. The reaction was stirred for 2h at 90°C. The mixture was diluted with water and extracted with EA. The combined organic layers were washed with brined, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The crude was purified by chromatographic column (SiO2; PE: EA=25-30%) to furnish tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4- methylsulfonyl-phenyl]ethyl]carbamate (0.3 g) as a yellow solid. HPLC-MS method G (RT=0.519min, [M+Na]+=388.0) Synthesis of the title compound (step 7) A solution of tert-butyl N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamate (0.3 g, 0.821 mmol, 1 eq) in 4M HCl / MeOH (3 mL) was stirred for 1h at 20°C. The reaction was concentrated and the residue was purified by preparative HPLC (column: Phenomenex luna C18250*50mm*15um; mobile phase: [H2O (0.04%HCl)-ACN]; gradient: 5%-40% B over 10.0 min). (1S)-1-[2-[(E)-2-cyclopropylvinyl]-4- methylsulfonyl-phenyl]ethanamine hydrochloride (0.133 g, 0.443 mmol, 54% yield) was obtained as a white solid.1H NMR (400 MHz, DMSO-d6) δ: 8.71 (br s, 3H), 7.93 (s, 1H), 7.88 - 7.80 (m, 2H), 6.85 (d, J = 15.4 Hz, 1H), 5.90 (dd, J = 9.4, 15.5 Hz, 1H), 4.77 (br d, J = 6.8 Hz, 1H), 3.25 (s, 3H), 1.73 (tq, J = 4.4, 8.6 Hz, 1H), 1.48 (d, J = 6.8 Hz, 3H), 0.94 - 0.81 (m, 2H), 0.67 - 0.55 (m, 2H) According to the same methodology, but employing (S)-N-[(1R)-1-(2-bromo-4-methylsulfonyl-phenyl)ethyl]- 2-methyl-propane-2-sulfinamide as reagent at step 4, the following intermediate compound of formula (XV) was prepared: (1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethanamine hydrochloride1H NMR (400 MHz, DMSO- d6) δ: 8.74 1.1 Hz, 1H), 7.88 - 7.79 (m, 2H), 6.86 (d, J = 15.4 Hz, 1H), 5.90 (dd, J = 9.4, 15.4 Hz, 1H), 4.77 (br s, 1H), 3.25 (s, 3H), 1.73 (tt, J = 4.1, 8.6 Hz, 1H), 1.48 (d, J = 6.7 Hz, 3H), 0.96 - 0.79 (m, 2H), 0.71 - 0.53 (m, 2H) Synthesis of (1S)-1-[2-[(E)-2-(2-thienyl)vinyl]phenyl]ethanamine hydrochloride To a mixture of 1-bromo-2-(diethoxyphosphorylmethyl)benzene (2 g, 1 eq.) in toluene (20 mL) was added Pd(PPh3)4(1.51 g, 1.30 mmol, 0.2 eq.) under N2atmosphere then tributyl(1-ethoxyvinyl)stannane (5.17 g, 14.33 mmol, 2.2 eq.) was added . The mixture was stirred at 120 °C for 4 h. HPLC-MS showed completion of reaction. The reaction mixture was concentrated under reduced pressure to give a residue. The reaction was directly for next step. 1-(diethoxyphosphorylmethyl)-2-(1-ethoxyvinyl)benzene (1.9 g, crude) was obtained as a yellow liquid. Synthesis of 1-[2-(diethoxyphosphorylmethyl)phenyl]ethanone (step 2) To a solution of 1-(diethoxyphosphorylmethyl)-2-(1-ethoxyvinyl)benzene (1.9 g, 6.37 mmol, 1 eq.) in ACN (5 mL) was added HCl (3 M, 15 mL, 7.07 eq). The mixture was stirred at 20 °C for 1 h. HPLC-MS showed formation of the product. The crude was purified by column chromatography on silica gel (PE:EA=40-42%). 1-[2-(diethoxyphosphorylmethyl)phenyl]ethanone (1.58 g, 64% yield) was obtained as a light yellow oil. HPLC-MS method G (RT=0-406 min, [M+H]+ = 271.0) Synthesis of (S)-N-[1-[2-(diethoxyphosphorylmethyl)phenyl]ethylidene]-2-methyl-propane-2- sulfinamide (step 3) To a solution of 1-[2-(diethoxyphosphorylmethyl)phenyl]ethanone (1.58 g, 5.85 mmol, 1 eq.) in THF (17 mL) was added Ti(OEt)4(4.00 g, 17.54 mmol, 3 eq.) under N2athmosphere, followed by (S)-2-methylpropane-2- sulfinamide (2.13 g, 17.54 mmol, 3 eq.).The mixture was stirred at 70 °C for 16 h. HPLC-MS showed the reaction was finished and desired product was observed. The solution was diluted with water (20ml) and ethyl acetate (20ml), filtrated and extracted. The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a crude product. The reaction was directly used for next step without further purification. (S)-N-[1-[2-(diethoxyphosphorylmethyl)phenyl]ethylidene]-2- methyl-propane-2-sulfinamide (2.45 g, crude) was obtained as a yellow oil. HPLC-MS method G (RT=0.431 min, [M+H]+ = 374.2) Synthesis of ((S)-N-[(1S)-1-[2-(diethoxyphosphorylmethyl)phenyl]ethyl]-2-methyl-propane-2- sulfinamide (step 4) To a solution of (S)-N-[1-[2-(diethoxyphosphorylmethyl)phenyl]ethylidene]-2-methyl-propane-2-sulfinamide (2.45 g, 6.56 mmol, 1 eq.) in THF (30 mL) was added NaBH4(992 mg, 26.24 mmol, 4 eq.) at 0°C .The mixture was stirred at 20 °C for 2 h. The reaction mixture was quenched with sat. NH4Cl(15mL) and then extracted with EA (20mL), washed with brine (15mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by by prep-TLC (SiO2, PE: EA = 0:1). (S)-N-[(1S)-1-[2- (diethoxyphosphorylmethyl)phenyl]ethyl]-2-methyl-propane-2-sulfinamide (0.6 g, 1.41 mmol, 21% yield) was obtained as a light brown oil. HPLC-MS method G (RT=0.437 min, [M+H]+ = 376.0) Synthesis of (S)-2-methyl-N-[(1S)-1-[2-[(E)-2-(2-thienyl)vinyl]phenyl]ethyl]propane-2-sulfinamide (step 5) To a solution of ((S)-N-[(1S)-1-[2-(diethoxyphosphorylmethyl)phenyl]ethyl]-2-methyl-propane-2-sulfinamide (250 mg, 1 eq.) and thiophene-2-carbaldehyde (89 mg, 799 µmol, 1.2 eq.) in THF (5 mL) was added NaH (66 mg, 1.66 mmol, 60% purity, 2.5 eq) at 0 °C .The mixture was stirred at 20 °C for 1 hr. HPLC-MS showed the reaction was finished and desired product was observed. The reaction mixture was quenched with sat. NH4Cl (5 mL) and then extracted with EA (10 mL), washed with brine (5 mL), dried over Na2SO4, filtered and concentrated to give a crude product. The residue was purified by prep-TLC (SiO2, PE: EA = 1:1). (S)- 2-methyl-N-[(1S)-1-[2-[(E)-2-(2-thienyl)vinyl]phenyl]ethyl]propane-2-sulfinamide (140 mg, 56 % yield,) was obtained as a yellow oil. HPLC-MS method G (RT=0.576 min, [M+H]+ = 334.2) Synthesis of (1S)-1-[2-[(E)-2-(2-thienyl)vinyl]phenyl]ethanamine hydrochloride (step 6) A solution of HCl / MeOH (4 M, 2 mL, 19.06 eq) was added to (S)-2-methyl-N-[(1S)-1-[2-[(E)-2-(2- thienyl)vinyl]phenyl]ethyl]propane-2-sulfinamide (140 mg, 1 eq.). The mixture was stirred at 20 °C for 1 hr. HPLC-Ms (ET91150-5-P1A1, RT=0.352 min, Ms+1=230.1) showed the reaction was finished and desired product was observed. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna C18100*40mm*5 um; mobile phase: [H2O (0.04% HCl)-ACN]; gradient: 1% - 60% B over 8.0 min). (1S)-1-[2-[(E)-2-(2- thienyl)vinyl]phenyl]ethanamine hydrochloride (90 mg, 89% yield) was obtained as a yellow oil. HPLC-MS method G (RT=0.352 min, [M+H]+= 230.1) According to the same methodology, the following intermediate compounds of formula (XV) were prepared: (1S)-1-[2-[(E)-2-(2-methylpyrazol-3-yl)vinyl]phenyl]ethanamine;hydrochloride HPLC-MS method G (RT=0.313 min, (1S)-1-[2-[(E)-2-(1-fluorocyclopropyl)vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.344 min, += 189.0) (1S)-1-[2-[(E)-2-(1-methylcyclopropyl)vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.372 min, [C13H16]+= 185.0) (1S)-1-[2-[(E)-2-(oxetan-3-yl)vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.258 min, (1S)-1-[2-[(E)-2-(2,2-difluorocyclopropyl)vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.258 min, [C13H14F2]+= 207.0) (1S)-1-[2-[(E)-2-(2,2-dimethylcyclopropyl)vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.399 min, (1S)-1-[2-[(E)-2-(2-methylcyclopropyl)vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.367 min, [C14H17]+= 185.2) (1S)-1-[2-[(E)-2-[rel-(1S,2S)-2-fluorocyclopropyl]vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.349 min, += 189.0) (1S)-1-[2-[(E)-2-[rel-(1S,2R)-2-fluorocyclopropyl]vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.342 min, += 189.0) (1S)-1-(4-methoxy-1-naphthyl)ethanamine hydrochloride HPLC-MS method A (RT=0.342 += 189.0) Synthesis of (1S)-1-[2-[(E)-2-[(3-rel-R)-tetrahydrofuran-3-yl]vinyl]phenyl]ethanamine hydrochloride and (1S)-1-[2-[(E)-2-[(3-rel-S)-tetrahydrofuran-3-yl]vinyl]phenyl]ethanamine hydrochloride 2-tetrahydrofuran-3-ylvinyl]phenyl]ethyl]propane-2-sulfinamide (285 mg) was separated by two sequential SFC purification: 1) column: REGIS (s,s) WHELK-O1 (250mm*30mm,5um); mobile phase: [CO2-IPA(0.1% NH3H2O)]; B%:45%, isocratic elution mode) 2) column: DAICEL CHIRALPAK AD (250mm*50mm,10um); mobile phase: [Heptane-EtOH (0.1%NH3H2O)]; B%:15%, isocratic elution mode. Obtained (S)-2-methyl-N-[(1S)-1-[2-[(E)-2-[(3-rel-R)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl]propane-2- sulfinamide (75 mg, 21% yield) as colorless oil, HPLC-MS method G (RT=0.488 min, [M+H]+ = 322.0) and (S)-2-methyl-N-[(1S)-1-[2-[(E)-2-[(3-rel-S)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl]propane-2-sulfinamide (50 mg, 14% yield) as colorless oil, HPLC-MS method G (RT=0.473 min, [M+H]+ = 322.0) The intermediates were treated as reported above to obtain (1S)-1-[2-[(E)-2-[(3-rel-R)-tetrahydrofuran-3- yl]vinyl]phenyl]ethanamine hydrochloride, HPLC-MS method G (RT=0.327 min, [M+H]+ = 218.0) and (1S)-1- [2-[(E)-2-[(3-rel-S)-tetrahydrofuran-3-yl]vinyl]phenyl]ethanamine hydrochloride, HPLC-MS method G (RT=0.318 min, [M+H]+ = 218.0) According to the same methodology, the following intermediate compounds of formula (XV) were prepared: (1S)-1-[2-[(E)-2-rel-[(1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl]vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.532 min, (1S)-1-[2-[(E)-2-rel-[(1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl]vinyl]phenyl]ethanamine hydrochloride HPLC-MS method G (RT=0.525 min, Synthesis of 5-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-2-(4-methylpiperazin-1-yl)phenol hydrochloride

[0006] To a solution of compound 2-bromo-4-fluoro-5-methoxy-benzaldehyde (5 g, 21.46 mmol, 1 eq.) in DMSO (50 mL) was added K2CO3 (7.41 g, 53.64 mmol, 2.5 eq) and 1-methylpiperazine (2.15 g, 21.46 mmol, 2.38 mL, 1 eq). The mixture was stirred at 100 °C for 12 h. The reaction mixture was quenched by addition sat. H2O 100 mL and extracted with EA 100mL *5. The combined organic layers were washed with brine 500 mL, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, DCM: MeOH = 100:1 to 10:1) to obtain 2-bromo-5-methoxy-4-(4- methylpiperazin-1-yl)benzaldehyde (5 g, 15.96 mmol, 74% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 10.02 (s, 1H), 7.29 (s, 1H), 7.07 (s, 1H), 3.84 (s, 3H), 3.26 - 3.15 (m, 4H), 2.47 - 2.38 (m, 4H), 2.21 (s, 3H) Synthesis of 2-bromo-5-hydroxy-4-(4-methylpiperazin-1-yl)benzaldehyde (step 2) To a solution of 2-bromo-5-methoxy-4-(4-methylpiperazin-1-yl)benzaldehyde (3 g, 9.58 mmol, 1 eq) in AcOH (15 mL) was added HBr (22.35 g, 132.59 mmol, 15 mL, 48% purity, 13.84 eq) at 0°C. The mixture was stirred at 130°C for 16 h. The solution was quenched with Na2CO3 (15 mL) and H2O (15 mL), extracted with EA (15*2 mL), the combined organic phases were dried over Na2SO4, filtrated and concentrated. The residue was purified by column and prep-TLC (SiO2, DCM: MeOH = 10:1) to obtain 2-bromo-5-hydroxy-4-(4- methylpiperazin-1-yl)benzaldehyde (1.07 g, 3.58 mmol, 37% yield) as a yellow solid. HPLC-MS method C (RT = 0.327 min, [M+H]+= 299) Synthesis of (R)-N-[[2-bromo-5-hydroxy-4-(4-methylpiperazin-1-yl)phenyl]methylene]-2-methyl- propane-2-sulfinamide (step 3) To a solution of 2-bromo-5-hydroxy-4-(4-methylpiperazin-1-yl)benzaldehyde (1.07 g, 3.58 mmol, 1 eq) and (R)-2-methylpropane-2-sulfinamide (650.24 mg, 5.36 mmol, 1.5 eq) in THF (15 mL) was added Ti(OEt)4(2.45 g, 10.73 mmol, 2.23 mL, 3 eq). The mixture was stirred at 70 °C for 16 h. The residue is treated with water (15mL), extracted with EA (15 * 3 mL), the combined organic phase was dried over Na2SO4, filtrated and concentrated to give (R)-N-[[2-bromo-5-hydroxy-4-(4-methylpiperazin-1-yl)phenyl]methylene]-2-methyl- propane-2-sulfinamide (930 mg, crude) as a yellow solid. HPLC-MS method C (RT = 0.378min, [M+H]+= 402) Synthesis of (R)-N-[(1S)-1-[2-bromo-5-hydroxy-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-2-methyl- propane-2-sulfinamide (step 4) To a solution of (R)-N-[[2-bromo-5-hydroxy-4-(4-methylpiperazin-1-yl)phenyl]methylene]-2-methyl-propane- 2-sulfinamide (930 mg, 2.31 mmol, 1 eq) in THF (15 mL) was added MeMgBr (3 M, 2.70 mL, 3.5 eq) at - 60°C. The mixture was stirred at 20°C for 16 h. The reaction mixture was quenched dropwise to NH4Cl 15 mL at 0°C and extracted with EA 15mL*3. The combined organic layers were washed with brine 40mL, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Welch Xtimate C18250*70mm*10um; mobile phase: [H2O (10mM NH4HCO3)-ACN]; gradient:10%-45% B over 20.0 min) to obtain (R)-N-[(1S)-1-[2-bromo-5-hydroxy-4-(4-methylpiperazin-1- yl)phenyl]ethyl]-2-methyl-propane-2-sulfinamide (140 mg, 334.62 µmol, 15% yield) a white solid.1H NMR (400 MHz, DMSO- d6) δ: = 9.39 (br s, 1H), 6.93 (s, 1H), 6.87 (s, 1H), 5.29 (d, J = 4.4 Hz, 1H), 4.73 - 4.46 (m, 1H), 2.94 (br s, 4H), 2.44 (br s, 4H), 2.21 (s, 3H), 1.35 (d, J = 6.6 Hz, 3H), 1.16 - 1.07 (m, 9H) Synthesis of (R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-4-(4-methylpiperazin-1- yl)phenyl]ethyl]-2-methyl-propane-2-sulfinamide (step 5) A mixture of (R)-N-[(1S)-1-[2-bromo-5-hydroxy-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-2-methyl-propane-2- sulfinamide (140 mg, 334.62 µmol, 1 eq), 2-[(E)-2-cyclopropylvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (97.41 mg, 501.92 µmol, 1.5 eq), Pd(dppf)Cl2(24.48 mg, 33.46 µmol, 0.1 eq), K2CO3(138.74 mg, 1.00 mmol, 3 eq) in dioxane (3 mL) and H2O (0.3 mL) was degassed and purged with N2 for 3 times, and then the mixture was stirred at 90 °C for 16 h under N2atmosphere. The reaction mixture was quenched by addition sat. H2O 3 mL and extracted with EA 2mL *3. The combined organic layers were washed with brine 10 mL, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO2, DCM: MeOH = 10:1) to obtain (R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-4-(4- methylpiperazin-1-yl)phenyl]ethyl]-2-methyl-propane-2-sulfinamide (90 mg, 221.90 µmol, 66% yield) as a yellow oil. HPLC-MS method B (RT = 0.383 min, [M+H]+= 406) Synthesis of the title compound (step 6) A solution of (R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-2- methyl-propane-2-sulfinamide (90 mg, 221.90 µmol, 1 eq) in HCl / MeOH (4 M, 3 mL, 54.08 eq) was stirred at 20°C for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna C18100*40mm*5 um; mobile phase: [H2O(0.04% HCl)-ACN]; gradient:1%-30% B over 8.0 min) to obtain 5-[(1S)-1-aminoethyl]-4-[(E)-2-cyclopropylvinyl]-2-(4- methylpiperazin-1-yl)phenol; hydrochloride (37.72 mg, 110.35 µmol, 50% yield) as a white solid.1H NMR (400 MHz, DMSO- d6) δ: = 11.20 (br d, J = 2.6 Hz, 1H), 10.19 - 8.91 (m, 1H), 8.42 (br s, 3H), 6.99 - 6.86 (m, 1H), 6.66 (d, J = 15.4 Hz, 1H), 5.66 - 5.44 (m, 1H), 4.69 - 4.45 (m, 1H), 3.54 - 3.35 (m, 4H), 3.27 - 3.11 (m, 2H), 3.10 - 2.95 (m, 2H), 2.78 (d, J = 4.6 Hz, 3H), 1.67 - 1.54 (m, 1H), 1.42 (d, J = 6.7 Hz, 3H), 0.83 - 0.73 (m, 2H), 0.57 - 0.47 (m, 2H) Synthesis of 1-[7-[(1S)-1-aminoethyl]-6-hydroxy-3,4-dihydro-2H-quinolin-1-yl]-2,2,2-trifluoro- ethanone; hydrochloride (step 1) To a suspension of AlCl3 (29.83 g, 223.74 mmol, 12.23 mL, 4 eq) in DCE (150 mL) was added slowly a solution of 2,2,2-trifluoro-1-(6-methoxy-3,4-dihydro-2H-quinolin-1-yl)ethenone (14.5 g, 55.94 mmol, 1 eq) and acetyl chloride (13.17 g, 167.81 mmol, 11.93 mL, 3 eq) in DCE (150 mL) at 0°C. Mixture was stirred at 20°C for 16h. The reaction mixture was added slowly with water 300 mL at 0°C and extracted with DCM 300mL. The combined organic layers were washed with brine 300mL, dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by MPLC (SiO2; hexane: EA=3-6%) to obtain 1-(7-acetyl-6-hydroxy-3,4-dihydro-2H-quinolin-1-yl)-2,2,2-trifluoro-ethanone (13.9 g, 47.42 mmol, 85% yield) as a light yellow solid.1H NMR (400 MHz, DMSO- d6) δ: = 11.69 (s, 1H), 8.04 (br s, 1H), 6.87 (s, 1H), 3.80 (t, J = 6.3 Hz, 2H), 2.81 (br t, J = 6.7 Hz, 2H), 2.58 (s, 3H), 2.00 (quin, J = 6.6 Hz, 2H) Synthesis of (S)-N-[1-[6-hydroxy-1-(2,2,2-trifluoroacetyl)-3,4-dihydro-2H-quinolin-7-yl]ethylidene]-2- methyl-propane-2-sulfinamide (step 2) To a solution of 1-(7-acetyl-6-hydroxy-3,4-dihydro-2H-quinolin-1-yl)-2,2,2-trifluoro-ethanone (13.9 g, 47.42 mmol, 1 eq.) and (S)-2-methylpropane-2-sulfinamide (1.5 eq) in THF (140 mL) was added Ti(OEt)4 (3 eq). The mixture was stirred at 65 °C for 1hr. The residue is diluted with water (150 mL), extracted with EA (100 mL), the combined organic phase was washed with brine (150 mL) and dried over Na2SO4, filtrated and concentrated to give the residue. Residue was purified by MPLC (SiO2; hexane: EA=10-15%) to obtain (S)- N-[1-[6-hydroxy-1-(2,2,2-trifluoroacetyl)-3,4-dihydro-2H-quinolin-7-yl]ethylidene]-2-methyl-propane-2- sulfinamide (6.5 g, 16.65 mmol, 35% yield) as a yellow solid.1H NMR (400 MHz, DMSO- d6) δ: = 13.17 - 12.56 (m, 1H), 8.35 - 7.40 (m, 1H), 7.05 - 6.70 (m, 1H), 3.79 (br s, 2H), 2.90 - 2.65 (m, 5H), 2.09 - 1.84 (m, 2H), 1.20 (s, 9H) Synthesis of (S)-N-[(1S)-1-[6-hydroxy-1-(2,2,2-trifluoroacetyl)-3,4-dihydro-2H-quinolin-7-yl]ethyl]-2- methyl-propane-2-sulfinamide (step 3) To a solution of N-[1-[6-hydroxy-1-(2,2,2-trifluoroacetyl)-3,4-dihydro-2H-quinolin-7-yl]ethylidene]-2-methyl- propane-2-sulfinamide (6.5 g, 16.65 mmol, 1 eq) in THF (65 mL) was added NaBH4 (1.89 g, 49.95 mmol, 3 eq) at -60°C .The mixture was stirred at -60 °C for 1h. The reaction mixture was dropwise into 0.1M HCl (50mL) at 0°C, and then extracted with EA (50mL), washed with water (50mL) and brine (50mL), dried over Na2SO4, filtered and concentrated to give a crude product. Residue was purified by prep-HPLC (column: Welch Xtimate C18250*100mm#10um; mobile phase: [H2O (10mM NH4HCO3)-ACN]; gradient: 35%-65% B over 20.0 min) to obtain (S)-N-[(1S)-1-[6-hydroxy-1-(2,2,2-trifluoroacetyl)-3,4-dihydro-2H-quinolin-7-yl]ethyl]- 2-methyl-propane-2-sulfinamide (1 g, 2.29 mmol, 14% yield) as a yellow solid. HPLC-MS method E (RT = 1.273 min, [M+H]+= 393.0) Synthesis of the title compound (step 3) A solution of (S)-N-[(1S)-1-[6-hydroxy-1-(2,2,2-trifluoroacetyl)-3,4-dihydro-2H-quinolin-7-yl]ethyl]-2-methyl- propane-2-sulfinamide (1 g, 2.29 mmol, 1 eq) in HCl / MeOH (4 M, 15.70 eq) was stirred at 20 °C for 1h. The reaction mixture was concentrated to obtain 1-[7-[(1S)-1-aminoethyl]-6-hydroxy-3,4-dihydro-2H-quinolin-1- yl]-2,2,2-trifluoro-ethanone; hydrochloride (0.828 g, crude, HCl) was obtained as a white solid. HPLC-MS method G (RT = 0.350 min, recognized by fragment [C13H13F3NO2]+= 272.2) Intermediates of formula (XVI) (Scheme 3) Synthesis of [3-[(E)-2-cyclopropylvinyl]-4-[(1S)-1-[[(2S,4R)-4-fluoro-1-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]pyrrolidine-2-carbonyl]amino]ethyl]phenyl] trifluoromethanesulfonate carbonyl)amino]acetyl]pyrrolidine-2-carboxylic acid hydrochloride (0.027 g, 0.068 mmol, 1.0 eq.), [4-[(1S)-1- aminoethyl]-3-[(E)-2-cyclopropylvinyl]phenyl] trifluoromethanesulfonate hydrochloride (0.030 g, 0.081 mmol, 1.2 eq.), EDCI (0.016 g, 0.081 mmol, 1.2 eq.), HOBt (0.01186 g, 0.08780 mmol, 1.300 eq.) and DIPEA (0.052 g, 0.071 mL, 0.405 mmol, 6.0 eq.) in DCM dry (0.68 mL) was stirred at r.t. overnight. Then the mixture was diluted in EA and washed with 0.1 N citric acid solution, NaHCO3 sat. aqueous solution and brine. The organic phase was dried over Na2SO4anhydrous and evaporated under reduced pressure. The crude was purified by chromatographic column hexane / ethyl acetate 1 / 1 to 2 / 8 to give [3-[(E)-2-cyclopropylvinyl]-4-[(1S)-1- [[(2S,4R)-4-fluoro-1-[2-[(6-fluoroquinoline-2-carbonyl)amino]acetyl]pyrrolidine-2- carbonyl]amino]ethyl]phenyl] trifluoromethanesulfonate (0.042 g, 0.062 mmol, 91% Yield) UPLC (210-400 nm): Rt: 4.30 min. HRMS (ESI) calcd for C31H29F5N4O6S [M+H]+ 681.1801, found 681.1796 According to the same methodology, but employing suitable substituted starting materials, the following intermediate compounds of formula (XVI) were prepared: [4-[(E)-2-cyclopropylvinyl]-3-[(1S)-1-[[(2S,4R)-4-fluoro-1-[2-[(6-fluoroquinoline-2carbonyl)amino] acetyl]pyrrolidine-2-carbonyl]amino]ethyl]phenyl] trifluoromethanesulfonate HRMS (ESI) calcd for [3-[(E)-2-cyclopropylvinyl]-4-[(1S)-1-[[(2S,4...

Claims

1. CLAIMS 1. A compound of formula (I): wherein:X is a halogen atom; Y is H or a halogen atom; R1, R2, R3 and R4 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, (C3-C7) cycloalkyl; or R1 and R2 and / or R3 and R4 taken together with the carbon atom they are bonded may form a (C3-C7) cycloalkyl; Z is a substituted aryl of formula (IIa) or a substituted heteroaryl selected from the group consisting of (IIb1)- (IIb7): ,R5 is- straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl, - (C3-C7) cycloalkenyl, - straight or branched (C1-C6) haloalkyl, - straight or branched (C2-C6) alkenyl optionally substituted with: - halogen, - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl, optionally substituted with straight or branched (C1-C6) alkyl, - 5-7 membered heteroaryl optionally substituted with (C1-C6) alkyl, - (C1-C3) alkoxy, - (C1-C3) haloalkoxy, - hydroxyl, - phenyl, - ether group -OR13, - amino group -NR10R11, - amide group -NR17COR18, or - 1-methyl-1,2,3,6-tetrahydropyridine; R6 and R7 the same or differently are each independently: - hydrogen, - halogen, - hydroxyl group, - straight or branched (C1-C6) alkyl, optionally substituted with 3-10 membered heterocyclyl, in its turn optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl, - straight or branched (C1-C6) haloalkyl, - oxetanyl, - (C3-C7) cycloalkyl, optionally substituted with: - (C1-C6)alkylamino, - di(C1-C6)alkylamino or - 3-10 membered heterocyclyl,- straight or branched (C1-C6) haloalkyl, - phenyl substituted with hydroxyl group, - 5-7 membered heteroaryl optionally substituted with a straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl optionally substituted with: - benzyl, - from one to four straight or branched (C1-C6) alkyl groups in their turn optionally substituted independently with (C3-C7) cycloalkyl, (C1-C3) alkoxy or 3-methylisoxazole ring, - halogen, - (C3-C7) cycloalkyl in its turn optionally substituted with halogen, - straight or branched (C1-C6) haloalkyl, - di(C1-C6)alkylamino, - oxetanyl, - amino group -NR10’R11’, - thioether group -SR12’, - ether group -OR13’, - sulfone group -SO2R14’, - sulfonamide group -SO2NR15’R16’, - amide group -NR17’COR18’; - group COR18’; or R5 and R6 taken together may form a phenyl ring or a 3-10 membered heterocyclic ring optionally substituted with one or two halogens; or R6 and R7 taken together may form a 3-10 membered heterocyclyl optionally substituted with: halogen, a group -COR18’ or straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; R8 is - halogen, - straight or branched (C2-C6) alkenyl optionally substituted with: - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, - (C1-C3) alkoxy,- (C1-C3) haloalkoxy; and R9 is - hydrogen, - halogen, - straight or branched (C2-C6) alkenyl optionally substituted with a (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl optionally substituted with from one to four straight or branched (C1- C6) alkyl groups, - ether group -OR13’, - amide group -NR17’COR18’, wherein: R10 and R11 the same or differently are each independently hydrogen, (C3-C7) cycloalkyl or straight or branched (C1-C6) alkyl; R10’ and R11’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with 1-methylimidazole, - (C3-C7) cycloalkyl or - 3-10 membered heterocyclyl optionally substituted with: - halogen, - straight or branched (C1-C6) alkyl, - (C1-C3) haloalkoxy, - (C3-C7) cycloalkyl or - oxetanyl; R12’ is - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl or - 3-10 membered heterocyclyl optionally substituted with a straight or branched (C1-C6) alkyl or (C3- C7) cycloalkyl; R13 is - straight or branched (C1-C6) alkyl optionally substituted with: - (C3-C7) cycloalkyl in its turn optionally substituted with 1 or two halogens, - straight or branched (C2-C6) alkynyl in its turn optionally substituted with (C3-C7) cycloalkyl, - benzyl group or - N-methyl-piperidinyl;R13’ is - straight or branched (C1-C6) alkyl optionally substituted with: - pyridine, - (C3-C7) cycloalkyl in its turn optionally substituted with di(C1-C6)alkylamino, - di(C1-C6)alkylamino, - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, - straight or branched (C1-C6) haloalkyl, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino or - 3-10 membered heterocyclyl optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - (C3-C7) cycloalkyl, - halogen, - straight or branched (C1-C6) haloalkyl, - oxetanyl; R14’ is straight or branched (C1-C6) alkyl, 3-10 membered heterocyclyl or (C3-C7) cycloalkyl; R15’ and R16’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group, straight or branched (C1-C3) alkoxy, di(C1-C6)alkylamino, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, halogen or (C3-C7) cycloalkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R17 and R17’ the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl, (C3-C7) cycloalkyl; R18 is (C3-C7) cycloalkyl or 3-10 membered heterocyclyl; and R18’ is - straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino or - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl or halogen;W is a 3-10 membered heterocyclic ring selected from the group consisting of (IIIa), (IIIb1)-(IIIb7), (IIIc1)- (IIIc4) and (IIId1-IIId4): ,or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, cyano group, OR21 or NR22R23; or R19 and R20 taken together may form a (C3-C7) cycloalkyl ring optionally substituted with straight or branched (C1-C6) alkyl; wherein: R21 is hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R22 and R23 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; and R24 is straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; or a pharmaceutically acceptable salt thereof.

2. The compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof wherein:R1, R2, R3 and R4 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; Z is a substituted aryl selected from the group consisting of (IIa1), (IIa2) and (IIa3):or a substituted heteroaryl selected from the group consisting of (IIb1), (IIb3) and (IIb7), wherein: when Z is a substituted aryl of formula (IIa1): R5 is: - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl, - (C3-C7) cycloalkenyl, - straight or branched (C1-C6) haloalkyl, - straight or branched (C2-C6) alkenyl optionally substituted with: - halogen, - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl optionally substituted with straight or branched (C1-C6) alkyl, wherein the 3-10 membered heterocyclic ring is a 3-5 membered, saturated or partially unsaturated carbocyclic ring wherein one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, or is selected from 3-oxabicyclo[3.1.0]hexyl and 3- azabicyclo[3.1.0]hexyl, - 5-7 membered heteroaryl selected from pyrazolyl and thiophenyl, optionally substituted with (C1-C6) alkyl, - (C1-C3) alkoxy, - (C1-C3) haloalkoxy, - hydroxyl group, - phenyl, - ether group -OR13, - amino group -NR10R11,- amide group -NR17COR18 or - 1-methyl-1,2,3,6-tetrahydropyridine; R6 and R7 the same or differently are each independently: - hydrogen, - halogen, - hydroxyl group, - straight or branched (C1-C6) alkyl optionally substituted with 3-10 membered heterocyclyl, wherein the 3-10 membered heterocyclic ring is a 4-6 membered, saturated or partially unsaturated carbocyclic ring where one or two carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, wherein the 4-6 membered ring is optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl, - straight or branched (C1-C6) haloalkyl, - oxetanyl, - (C3-C7) cycloalkyl optionally substituted with: - (C1-C6)alkylamino, - di(C1-C6)alkylamino or - 3-10 membered heterocyclyl selected from azetidinyl, aziridinyl and pyrrolidinyl, - straight or branched (C1-C6) haloalkyl, - phenyl substituted with hydroxyl group, - 5-7 membered heteroaryl selected from imidazolyl, pyrazolyl and pyridinyl, optionally substituted with a straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 5-7 membered, saturated or partially unsaturated, carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, one or two carbon atoms may be optionally oxidized, and the aforementioned 5-7 membered ring is optionally substituted with: - benzyl, - from one to four straight or branched (C1-C6) alkyl groups wherein one (C1-C6) alkyl group may be optionally substituted with (C3-C7) cycloalkyl, (C1-C3) alkoxy or 3-methylisoxazole ring, - halogen,- (C3-C7) cycloalkyl in its turn optionally substituted with halogen, - straight or branched (C1-C6) haloalkyl, - di(C1-C6)alkylamino, - oxetanyl, or - 4-6 membered carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, wherein the 4-6 membered ring may be fused or linked with: -phenyl, -(C3-C7) cycloalkyl or - a group selected from azetidinyl, aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxiranyl, oxetanyl and tetrahydrofuranyl, wherein the aforementioned 4-6 membered ring is optionally substituted with straight or branched (C1-C6) alkyl, - amino group -NR10’R11’, - thioether group -SR12’, - ether group -OR13’, - sulfone group -SO2R14’, - sulfonamide group -SO2NR15’R16’, - amide group -NR17’COR18’; - group COR18’; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,4-dioxanyl, morpholinyl and piperidinyl, optionally substituted with halogen, a group -COR18’ or straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted aryl of formula (IIa2): R5 and R6 taken together may form a phenyl ring or a 1,3-dioxolanyl ring optionally substituted with one or two halogens; and R7 is hydrogen or straight or branched (C1-C3) alkoxy; when Z is a substituted aryl of formula (IIa3): R5 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; R6 is hydrogen or amide group -NR17’COR18’; R7 is halogen or hydroxyl group; orR6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,3-dioxolanyl, 1,4 dioxanyl, pyrrolidinyl and piperidinyl, optionally substituted with straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted 5-7 membered heteroaryl selected from the group consisting of (IIb1), (IIb3) and (IIb4): R8 is a halogen or straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; and R9 is - hydrogen, - straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from piperazinyl, morpholinyl, 1,2,3,6-tetrahydropyridinyl and piperidinyl, optionally substituted with from one to four straight or branched (C1-C6) alkyl groups, - ether group -OR13’, - amide group -NR17’COR18’; when Z is a substituted 5-7 membered heteroaryl of formula (IIb7): R8 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; and R9 is hydrogen; wherein: R10 and R11 the same or differently are each independently hydrogen or straight or branched (C1- C6) alkyl; R10’ and R11’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with 1-methylimidazole, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 4-6 membered, saturated or partially unsaturated, carbocyclic ring wherein one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, wherein the 4-6 membered ring is optionally substituted with: - halogen, - straight or branched (C1-C6) alkyl, - (C1-C3) haloalkoxy, - (C3-C7) cycloalkyl or - oxetanyl,wherein the aforementioned 4-6 membered ring can be optionally further linked with (C3-C7) cycloalkyl; R12’ is - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from piperidinyl and pyrrolidinyl, optionally substituted with straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R13’ is - straight or branched (C1-C6) alkyl optionally substituted with: - pyridine, - (C3-C7) cycloalkyl in its turn optionally substituted di(C1-C6)alkylamino, - di(C1-C6)alkylamino, - 3-10 membered heterocyclyl selected from oxiranyl, oxetanyl, azetidinyl and aziridinyl optionally substituted with straight or branched (C1-C6) alkyl, - straight or branched (C1-C6) haloalkyl, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 4-6 membered, saturated or partially unsaturated, carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, wherein the aforementioned 4-6 membered ring may be optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - (C3-C7) cycloalkyl, - halogen, - straight or branched (C1-C6) haloalkyl, - oxetanyl, or - 4-6 membered carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, fused or linked with: -(C3-C7) cycloalkyl or -a group selected from azetidinyl, aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxiranyl, oxetanyl and tetrahydrofuranyl, wherein the aforementioned 4-6 membered ring is optionally substituted with straight or branched (C1-C6) alkyl; R14’ is straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R15’ and R16’ the same or differently are each independently:- hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group or di(C1-C6)alkylamino, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 4-6 membered saturated carbocyclic ring where one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, optionally substituted with straight or branched (C1-C6) alkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 5-6 membered, saturated carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, optionally substituted with straight or branched (C1-C6) alkyl; R17 and R17’ the same or differently are each independently hydrogen or straight or branched (C1- C6) alkyl; R18 is (C3-C7) cycloalkyl; and R18’ is - straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 3-6 membered, saturated or partially unsaturated, carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, and / or one or 2 carbon atoms are optionally oxidized, wherein the aforementioned 3-6 membered ring may be optionally substituted with straight or branched (C1-C6) alkyl or halogen; W is a 3-10 membered heterocyclic ring, selected from the group consisting of (IIIa), (IIIb1), (IIIb2.1)-(IIIb7.1), (IIIc1)-(IIIc4) and (IIId1)-(IIId4):

3. The compound of formula (I) according to claim 2 or a pharmaceutically acceptable salt thereof wherein: X is a fluorine atom or a chlorine atom; Y is a hydrogen atom, a fluorine atom or a chlorine atom; R1, R2, R3 and R4 the same or differently are each independently selected from hydrogen, straight or branched (C1-C6) alkyl; Z is a substituted aryl selected from the group consisting of (IIa1), (IIa2) and (IIa3) or a substituted heteroaryl selected from the group consisting of (IIb1’), (IIb3’) and (IIb7’):wherein:when Z is a substituted aryl of formula (IIa1): R5 is: - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl, - (C3-C7) cycloalkenyl, - straight or branched (C1-C6) haloalkyl, - straight or branched (C2-C6) alkenyl optionally substituted with: - halogen, - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl selected from azetidinyl, pyrrolidinyl, oxetanyl, 3- oxabicyclo[3.1.0]hexyl and tetrahydrofuranyl, optionally substituted with straight or branched (C1-C6) alkyl, - 5-7 membered heteroaryl selected from pyrazolyl and thiophenyl, optionally substituted with straight (C1-C3) alkyl, - (C1-C3) alkoxy, - (C1-C3) haloalkoxy, - hydroxyl group, - phenyl, - ether group -OR13, - amino group -NR10R11, - amide group -NR17COR18, or - 1-methyl-1,2,3,6-tetrahydropyridine; R6 and R7 the same or differently are each independently - hydrogen, - halogen,- hydroxyl group, - straight or branched (C1-C6) alkyl optionally substituted with 3-10 membered heterocyclyl, selected from pyrrolidinyl, piperidinyl and piperazinyl, wherein the heterocyclyl is optionally substituted with: - from one to three straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl, - straight or branched (C1-C6) haloalkyl, - oxetanyl, - (C3-C7) cycloalkyl optionally substituted with: - (C1-C6)alkylamino, - di(C1-C6)alkylamino or - 3-10 membered heterocyclyl selected from azetidinyl, aziridinyl and pyrrolidinyl, - straight or branched (C1-C6) haloalkyl, - phenyl substituted with hydroxyl group, - 5-7 membered heteroaryl selected from imidazolyl, pyrazolyl and pyridinyl, optionally substituted with a straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl selected from: - homopiperazinyl, piperazinyl, morpholinyl, 1,2,3,6-tetrahydropyridinyl, pyrrolidinyl, piperidinyl, 3-pyrrolinyl, 2,3,4,7-tetrahydro-1-azepinyl, 3,4-dihydro-2-pyranyl, 2(1H)- pyrimidinonyl and 2-pyrrolidinonyl, optionally substituted with: - benzyl, - from one to four straight or branched (C1-C6) alkyl groups wherein one (C1-C6) alkyl group may be optionally substituted with (C3-C7) cycloalkyl or 3- methylisoxazole ring, - halogen, - (C3-C7) cycloalkyl in its turn optionally substituted with halogen, - straight or branched (C1-C6) haloalkyl, - di(C1-C6)alkylamino, - oxetanyl, or -3,8-diazabicyclo[3.2.1]octanyl, 1,2,3,4-tetrahydroquinolinyl, 2-oxa-5-azaspiro[3.5]nonanyl, indolinyl, 2,7-diazaspiro[4.4]nonanyl, 4-azaspiro[2.5]octanyl, 2-oxa-5,8- diazaspiro[3.5]nonanyl, 4,7-diazaspiro[2.5]octanyl, 4-oxa-7-azaspiro[2.5]octanyl, 5-oxa-2,8- diazaspiro[3.5]nonanyl, 2,8-dioxa-5-azaspiro[3.5]nonanyl, 2,6-diazaspiro[3.3]heptanyl, 1,6-diazaspiro[3.3]heptanyl, octahydropyrrolo[3,4-b]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 1,4-diazabicyclo[2.2.1]heptanyl, 1,4-diazabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.2]octanyl, 4-oxaspiro[2.5]octanyl, 4-azaspiro[2.4]heptanyl, 2-oxa-5-azaspiro[3.4]octanyl, 2,5- diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 1,6-diazaspiro[3.4]octanyl and 1,7- diazaspiro[4.4]nonanyl, optionally substituted with straight or branched (C1-C6) alkyl, - amino group -NR10’R11’, - thioether group -SR12’, - ether group -OR13’, - sulfone group -SO2R14’, - sulfonamide group -SO2NR15’R16’, - amide group -NR17’COR18’; - group COR18’; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,4-dioxanyl and piperidinyl, optionally substituted with halogen, a group -COR18’, straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted aryl of formula (IIa2): R5 and R6 taken together may form a phenyl ring or a 1,3-dioxolanyl ring optionally substituted with one or two halogens; and R7 is hydrogen or straight or branched (C1-C3) alkoxy; when Z is a substituted aryl of formula (IIa3): R5 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; R6 is hydrogen or amide group -NR17’COR18’; R7 is halogen or hydroxyl group; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,3-dioxolanyl and pyrrolidinyl, optionally substituted with straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted 5-7 membered heteroaryl selected from the group consisting of (IIb1’) and (IIb3’): R8 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; and R9 is - hydrogen,- straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from 1,2,3,6-tetrahydropyridinyl and piperidinyl, optionally substituted with from one to four straight or branched (C1-C6) alkyl groups, - ether group -OR13’, - amide group -NR17’COR18’; when Z is a substituted 5-7 membered heteroaryl of formula (IIb7’): R8 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; and R9 is hydrogen; wherein: R10 and R11 are hydrogen; R10’ and R11’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with 1-methylimidazole, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from pyrrolidinyl, piperidinyl and tetrahydropyranyl, optionally substituted with: halogen, straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R12’ is (C3-C7) cycloalkyl; R13’ is - straight or branched (C1-C6) alkyl optionally substituted with: - pyridine, - (C3-C7) cycloalkyl in its turn optionally substituted with 1 or two halogen or di(C1- C6)alkylamino, - di(C1-C6)alkylamino, - 3-10 membered heterocyclyl selected from oxiranyl, oxetanyl, azetidinyl and aziridinyl, optionally substituted with straight or branched (C1-C6) alkyl, - straight or branched (C1-C6) haloalkyl, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, -3-10 membered heterocyclyl selected from: - oxetanyl, azetidinyl, piperidinyl and pyrrolidinyl, optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - (C3-C7) cycloalkyl, - halogen, - straight or branched (C1-C6) haloalkyl,- oxetanyl, or -1,4-diazabicyclo[2.2.1]heptanyl, 1,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 4-azaspiro[2.4]heptanyl, 2-oxa-5-azaspiro[3.4]octanyl, 1,6-diazaspiro[3.4]octanyl, 2,6- diazaspiro[3.4]octanyl, 2,7-diazaspiro[4.4]nonanyl, 2,5-diazaspiro[3.4]octanyl, octahydropyrrolo[3,4-b]pyrrolyl and octahydropyrrolo[3,4-c]pyrrolyl, optionally substituted with straight or branched (C1-C6) alkyl; R15’ and R16’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group or di(C1-C6)alkylamino, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl selected from azetidinyl, tetrahydropyranyl and piperidinyl, optionally substituted with straight or branched (C1-C6) alkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl selected from morpholinyl, piperazinyl and piperidinyl, optionally substituted with straight or branched (C1-C6) alkyl; R17 and R17’ are hydrogen; and R18’ is - straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl selected from oxiranyl, oxetanyl, 2-oxetanonyl, aziridinyl, pyrrolidinyl, piperidinyl and tetrahydrofuranyl, optionally substituted with straight or branched (C1-C6) alkyl or halogen; W is a 3-10 membered heterocyclic ring selected from the group consisting of:OHFO , ,R13, R14’ and R18 are as defined in claim 2.

4. The compound of formula (I) according to any of claims 1-3 or a pharmaceutically acceptable salt thereof wherein:X is a fluorine atom; Y is hydrogen atom; R1 and R2 are hydrogen; R3 and R4 the same or differently are each independently hydrogen, straight or branched (C1-C6) alkyl; Z is a substituted aryl selected from the group consisting of (IIa1) and (IIa3):wherein: when Z is a substituted aryl of formula (IIa1): R5 is: - straight or branched (C2-C6) alkenyl optionally substituted with: - (C3-C7) cycloalkyl, optionally substituted with 1 or 2 groups selected from halogen and straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl selected from 3-oxabicyclo[3.1.0]hexyl and 3- azabicyclo[3.1.0]hexyl, optionally substituted with straight or branched (C1-C6) alkyl, - ether group -OR13; R6 and R7 the same or differently are each independently: - hydrogen, - halogen, - hydroxyl group, - straight or branched (C1-C6) alkyl optionally substituted with 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 4-6 membered, saturated or partially unsaturated carbocyclic ring where one or two carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, wherein the 4-6 membered ring is optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl, - straight or branched (C1-C6) haloalkyl, - oxetanyl,- (C3-C7) cycloalkyl optionally substituted with: - (C1-C6)alkylamino, - di(C1-C6)alkylamino or - 3-10 membered heterocyclyl selected from oxetanyl, oxiranyl, azetidinyl and aziridinyl, - straight or branched (C1-C6) haloalkyl, - 5-7 membered heteroaryl selected from imidazolyl and pyrazolyl, optionally substituted with a straight or branched (C1-C6) alkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 5-7 membered, saturated or partially unsaturated, carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, one or two carbon atoms may be optionally oxidized, and the aforementioned 5-7 membered ring is optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - halogen, - (C3-C7) cycloalkyl in its turn optionally substituted with halogen, - straight or branched (C1-C6) haloalkyl, - di(C1-C6)alkylamino, - oxetanyl, or - 4-6 membered carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, wherein the carbocyclic ring may be fused or linked with - (C3-C7) cycloalkyl, or -a group selected from azetidinyl, aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxiranyl, oxetanyl and tetrahydrofuranyl, wherein the aforementioned 4-6 membered ring is optionally substituted with straight or branched (C1-C6) alkyl, - amino group -NR10’R11’, - ether group -OR13’, - sulfone group -SO2R14’, - sulfonamide group -SO2NR15’R16’, - amide group -NR17’COR18’; - group COR18’; orR6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,4-dioxanyl, morpholinyl and piperidinyl, optionally substituted with halogen, a group -COR18’, straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; when Z is a substituted aryl of formula (IIa3): R5 is straight or branched (C2-C6) alkenyl optionally substituted with (C3-C7) cycloalkyl; R6 is hydrogen or amide group -NR17’COR18’; R7 is halogen or hydroxyl group; or R6 and R7 taken together may form a 3-10 membered heterocyclyl selected from 1,3-dioxolanyl, 1,4 dioxanyl, pyrrolidinyl and piperidinyl, optionally substituted with straight or branched (C1-C6) alkyl in its turn optionally substituted with (C1-C6)alkylamino or di(C1-C6)alkylamino; wherein: R10’ and R11’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 4-6 membered, saturated or partially unsaturated, carbocyclic ring wherein one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, wherein the 4-6 membered ring is optionally substituted with: -halogen, -straight or branched (C1-C6) alkyl, -(C1-C3) haloalkoxy, -(C3-C7) cycloalkyl or -oxetanyl, wherein the aforementioned 4-6 membered ring can be optionally further linked with (C3-C7) cycloalkyl; R13 is straight or branched (C1-C6) alkyl optionally substituted with (C3-C7) cycloalkyl; R13’ is - straight or branched (C1-C6) alkyl optionally substituted with: - (C3-C7) cycloalkyl in its turn optionally substituted with di(C1-C6)alkylamino, - di(C1-C6)alkylamino,- 3-10 membered heterocyclyl selected from oxiranyl, oxetanyl, azetidinyl and aziridinyl optionally substituted with straight or branched (C1-C6) alkyl, - straight or branched (C1-C6) haloalkyl, - (C3-C7) cycloalkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is: - 4-6 membered, saturated or partially unsaturated, carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, wherein the aforementioned 4-6 membered ring may be optionally substituted with: - from one to four straight or branched (C1-C6) alkyl groups, - (C3-C7) cycloalkyl, - halogen, - straight or branched (C1-C6) haloalkyl, - oxetanyl, or - 4-6 membered carbocyclic ring wherein one or two carbon atoms are replaced by heteroatoms selected form nitrogen and oxygen, fused or linked with -(C3-C7) cycloalkyl or -a group selected from azetidinyl, aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxiranyl, oxetanyl and tetrahydrofuranyl, wherein the aforementioned 4-6 membered ring is optionally substituted with straight or branched (C1-C6) alkyl; R14’ is straight or branched (C1-C6) alkyl or (C3-C7) cycloalkyl; R15’ and R16’ the same or differently are each independently: - hydrogen, - straight or branched (C1-C6) alkyl optionally substituted with hydroxyl group or di(C1-C6)alkylamino, - (C3-C7) cycloalkyl, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 4-6 membered saturated carbocyclic ring where one carbon atom is replaced by heteroatoms selected from nitrogen and oxygen, optionally substituted with straight or branched (C1-C6) alkyl; or R15’, R16’ taken together with the nitrogen atom they are bonded may form a 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 5-6 membered, saturated carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, optionally substituted with straight or branched (C1-C6) alkyl;R17’ is hydrogen; and R18’ is - straight or branched (C1-C6) alkyl optionally substituted with di(C1-C6)alkylamino, - 3-10 membered heterocyclyl, wherein 3-10 membered heterocyclic ring is a 3-6 membered, saturated or partially unsaturated, carbocyclic ring where one or 2 carbon atoms are replaced by heteroatoms selected from nitrogen and oxygen, and / or one or two carbon atoms are optionally oxidized, the aforementioned 3-6 membered ring may be optionally substituted with straight or branched (C1-C6) alkyl or halogen; W is a 3-10 membered heterocyclic ring, selected from the group consisting of (IIIb1), (IIIb7.1) and (IIIc1.1)- (IIIc1.4):wherein: R19 and R20 the same or differently are each independently hydrogen, halogen, straight or branched (C1-C6) alkyl, straight or branched (C1-C6) haloalkyl, cyano group, OR21 or NR22R23; or R19 and R20 taken together may form a (C3-C7) cycloalkyl ring optionally substituted with straight or branched (C1-C6) alkyl; wherein: R21 is hydrogen, straight or branched (C1-C6) alkyl; and R22 and R23 are straight or branched (C1-C6) alkyl.

5. The compounds of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof selected from the group consisting of: N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-[(1-methylimidazol-2- yl)methyl]amino]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2- carboxamide (Compound 1); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4,4-difluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 2); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4- piperidyl)amino]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2- carboxamide (Compound 3);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-isobutoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 4); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]azetidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 5); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(cyclopenten-1-yl)phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 6); N-[2-[(2S,4R)-2-[[(1S)-1-(2-cyclopentylphenyl)ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6- fluoro-quinoline-2-carboxamide (Compound 7); (4R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]-3-[2-[(6-fluoroquinoline-2-carbonyl) amino]acetyl]thiazolidine-4-carboxamide (Compound 8); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl) amino]acetyl]-6,6-dimethyl-morpholine-3-carboxamide (Compound 9); (2R,3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl) amino]acetyl]-2-methyl-morpholine-3-carboxamide (Compound 10); N-[2-[(2S,4R)-2-[[(1S)-1-[4-cyclopentylsulfanyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 11); N-[2-[(2S,4R)-2-[[(1S)-1-[4-cyclopentylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 12); N-[2-[(2S,4R)-2-[[(1R)-1-[4-cyclopentylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 13); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 14); N-[2-[(2S,4R)-2-[[(1R)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 15); N-[2-[(2S,4R)-2-[[(1S)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 16); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-(2-vinylphenyl)ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl] quinoline-2-carboxamide (Compound 17); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-prop-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2- oxo-ethyl]quinoline-2-carboxamide (Compound 18); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-styryl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo- ethyl]quinoline-2-carboxamide (Compound 19);6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-3-phenylprop-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 20); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl) amino]acetyl]morpholine-3-carboxamide (Compound 21); (3S)-N-[(1S)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 22); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylmethyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 23); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(4-methylpiperazin-1-yl)methyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 24); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(4-chlorophenyl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 25); N-[2-[(2S,4R)-2-[[(1R)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 26); N-[2-[(2S,4R)-2-[[(1S)-1-(2-benzyloxy-4-methoxy-phenyl)ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 27); N-[2-[(2S,4R)-2-[[(1R)-1-(2-benzyloxy-4-methoxy-phenyl)ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 28); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 29); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1R)-1-[4-methoxy-2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 30); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-methoxy-2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 31); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 32); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 33); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-(o-tolyl)ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2- carboxamide (Compound 34); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-(trifluoromethyl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo- ethyl]quinoline-2-carboxamide (Compound 35);6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1R)-1-[4-methoxy-2-[(1-methyl-4-piperidyl)oxy]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 36); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-methoxy-2-[(1-methyl-4-piperidyl)oxy]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 37); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopentylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 38); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclohexylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 39); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-methoxy-2-[(E)-4-methylpent-1-enyl]phenyl]ethyl] carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 40); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(3-cyclopropylprop-2-ynoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 41); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 42); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(3,3-difluorocyclobutyl)methoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 43); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(cyclobutylmethoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 44); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1R)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 45); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-(4-methoxy-2-spiro[3.3]heptan-2-yloxy-phenyl)ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 46); N-[2-[(2S)-2-[[(1S)-1-[4-cyclohexylsulfonyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-methyl- piperazin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 47); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(1-rel-R)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 48); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(1-rel-S)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 49); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(1-rel-R)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 50); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(1-rel-S)-1-cyclopropylethoxy]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 51);N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-sulfamoyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 52); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-sulfamoyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 53); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclobutylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 54); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[cyclohexyl(methyl)amino]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 55); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholino-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 56); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholino-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 57); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2-hydroxyethylsulfamoyl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 58); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2-hydroxyethylsulfamoyl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 59); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 60); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 61); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-[2-(dimethylamino)ethylsulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 62); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[2-(dimethylamino)ethylsulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 63); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 64); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 65); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-sulfamoyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 66); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-sulfamoyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 67);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 68); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl(tetrahydropyran-4-yl)sulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 69); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl(tetrahydropyran-4-yl)sulfamoyl]phenyl] ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 70); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(tetrahydropyran-4-ylsulfamoyl)phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 71); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(tetrahydropyran-4-ylsulfamoyl)phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 72); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 73); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 74); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-(ethylsulfamoyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 75); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(ethylsulfamoyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 76); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-5-(methylsulfamoyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 77); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(methylsulfamoyl)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 78); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 79); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 80); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylsulfonyl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 81); N-[2-[(2S,4R)-2-[[(1R)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylsulfonyl)phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 82); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 83);(3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-4-[2-[(6- fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 84); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(1-methylazetidin-3-yl)sulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 85); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(1-methyl-4-piperidyl)sulfamoyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide;hydrochloride (Compound 86); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(cyclohexylsulfamoyl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 87); N-[2-[(2S)-2-[[(1S)-1-[2-(cyclopropylmethoxy)-4-methoxy-phenyl]ethyl]carbamoyl]-1-piperidyl]-2-oxo-ethyl]- 6-fluoro-quinoline-2-carboxamide (Compound 88); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-1-piperidyl]-2-oxo-ethyl]- 6-fluoro-quinoline-2-carboxamide (Compound 89); Compound 90: (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 90); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-methyl-piperazin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 91); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-methyl- piperazin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 92); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 93); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 94); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(tetrahydropyran-4-ylsulfamoyl)phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 95); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 96); (4R)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]-3-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]-1,1-dioxo-1,3-thiazolidine-4-carboxamide (Compound 97); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 98); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-morpholinosulfonyl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 99);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(tetrahydropyran-4-ylsulfamoyl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 100) and N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 101); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 102); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methyl-1,4-diazepan-1-yl)phenyl]ethyl]carbamoyl]- 4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 103); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-4,4-difluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 104); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[4-[(3-methylisoxazol-5-yl)methyl]piperazin-1- yl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 105); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-(4-methylpiperazin-1-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 106); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl]-4-[2- [(6-fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 107); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 108); N-[2-[(2S,4R)-4-cyano-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-fluoro-4-[methyl-(1-methyl-4-piperidyl) amino] phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 109); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4-oxo- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 110); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[4-(cyclohexylmethyl)piperazin-1-yl]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 111); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-oxo-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 112); N-[2-[(2S,4R)-4-cyano-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 113); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-(trifluoromethyl) pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 114); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-piperidylmethyl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 115);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(4-methylpiperazin-1-yl)methyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 116); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 117); (3S)-N-[(1S)-1-[4-(cyclohexylsulfamoyl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 118); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(1-methylazetidin-3-yl)sulfamoyl]phenyl]ethyl]-4-[2-[(6- fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 119); N-[2-[(2S,4R)-4-cyano-2-[[(1S)-1-[4-(cyclohexylsulfamoyl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 120); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(4-benzylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4- hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 121); (3S)-N-[(1S)-1-[4-(4-benzylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 122); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(4-benzylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4- cyano-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 123); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- (trifluoromethyl)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 124); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-fluoro-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 125); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-fluoro-phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2-carbonyl)amino] acetyl]morpholine-3-carboxamide (Compound 126); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(oxetan-3-yloxy)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 127); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(4-pyridylmethoxy)phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 128); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 129); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 130); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-hydroxy-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 131);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-6-hydroxy-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 132); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[4-(dimethylamino)-1-piperidyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 133); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3R,5R)-3,4,5-trimethylpiperazin-1-yl]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 134); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 135); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 136); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(4-cyclopropylpiperazin-1-yl)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]- 4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 137); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3S)-3,4-dimethylpiperazin-1-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 138); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(2S,6R)-2,6-dimethylmorpholin-4-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 139); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(3,3,5,5-tetramethylpiperazin-1-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 140); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3R)-3,4-dimethylpiperazin-1-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 141); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(2,2-dimethylmorpholin-4-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 142); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl(tetrahydropyran-4-yl)amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 143); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(2R,6R)-2,6-dimethylmorpholin-4-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 144); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[(3S,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 145); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(2,2-dimethylmorpholin-4-yl)phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 146); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-pyrrolidin-1-yl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 147);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 148); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3-methylimidazol-4-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 149); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2-oxopyrrolidin-1-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 150); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3-pyridyl)phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 151); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3-hydroxyphenyl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 152); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-pyrazol-3-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 153); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3,4-dihydro-2H-pyran-5-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 154); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 155); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 156); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2,3,4,7-tetrahydro-1H-azepin-6-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 157); (3S)-N-[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl]-4-[2-[(6- fluoroquinoline-2-carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 158); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 159); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2,5-dihydro-1H-pyrrol-3-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide;hydrochloride (Compound 160); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 161);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,4-tetrahydroquinolin-7-yl)phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 162); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-indolin-6-yl-phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 163); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-imidazol-4-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 164); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1H-imidazol-4-yl)phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 165); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-3-methoxyprop-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin- 1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 166); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-3-methoxyprop-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 167); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-3-pyrrolidin-1-ylprop-1-enyl]phenyl]ethyl] carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide(Compound 168); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 169); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-4-hydroxybut-1-enyl]phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 170); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(2-methylpyrazol-3-yl)vinyl]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 171); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(2-thienyl)vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]- 2-oxo-ethyl]quinoline-2-carboxamide hydrochloride (Compound 172); 6-fluoro-N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(1-fluorocyclopropyl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 173); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(1-methylcyclopropyl)vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 174); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(oxetan-3-yl)vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1- yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 175); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(2,2-difluorocyclopropyl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 176); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-[(3-rel-R)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 177);6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-[(3-rel-S)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 178 ); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-[(3-rel-R)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide(Compound 179); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-[(3-rel-S)-tetrahydrofuran-3-yl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 180); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(2,2-dimethylcyclopropyl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 181); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(2,2-dimethylcyclopropyl)vinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 182); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-(2-methylcyclopropyl)vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 183); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-rel-[(1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6- yl]vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 184); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-rel-[(1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6- yl]vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 185); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-rel-[(E)-2-[(1S,5R,6s)-3-oxabicyclo[3.1.0]hexan-6- yl]vinyl]phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 186); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-rel-[(1S,2S)-2-fluorocyclopropyl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 187); 6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-[2-[(E)-2-rel-[(1S,2R)-2-fluorocyclopropyl]vinyl]phenyl]ethyl] carbamoyl]pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 188); (3S)-N-[(1S)-1-[2-chloro-6-[(E)-2-cyclopropylvinyl]phenyl]ethyl]-4-[2-[(6-fluoroquinoline-2- carbonyl)amino]acetyl]morpholine-3-carboxamide (Compound 189); N-[2-[(2S,4R)-2-[[(1S)-1-[2-chloro-6-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 190); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[(E)-2-cyclopropylvinyl]-1,3-benzodioxol-4-yl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 191); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[(E)-2-cyclopropylvinyl]-1,3-benzodioxol-4-yl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 192); N-[2-[(2S,4R)-2-[[(1S)-1-(2,2-difluoro-1,3-benzodioxol-4-yl)ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 193);6-fluoro-N-[2-[(2S,4R)-4-fluoro-2-[[(1S)-1-(4-methoxy-1-naphthyl)ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxo- ethyl]quinoline-2-carboxamide (Compound 194); N-[2-[(2S,4R)-2-[[(1S)-1-[3-[(E)-2-cyclopropylvinyl]-2-pyridyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo- ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 195); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[(E)-2-cyclopropylvinyl]-3-thienyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 196); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-4-(4-methylpiperazin-1-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 197); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl] propyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 198); N-[2-[(2S,4R)-2-[[(1S)-1-[7-[(E)-2-cyclopropylvinyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 199); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[cyclobutyl-(1-methyl-4-piperidyl)amino]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 200); N-[2-[(2S,4R)-2-[[(1S)-1-[4-[cyclobutyl-(1-methyl-4-piperidyl)amino]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 201); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(cyclohexoxy)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 202); N-[2-[(2S,4R)-2-[[(1S)-1-[4-(cyclohexylmethoxy)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 203); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(difluoromethoxy)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 204); 6-chloro-N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]pyrrolidin- 1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 205); 6-chloro-N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]pyrrolidin- 1-yl]-2-oxo-ethyl]-7-fluoro-quinoline-2-carboxamide (Compound 206); N-[2-[(2S,5S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-5-methyl-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 207); N-[2-[(1R,3S,5R)-3-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 208); N-[2-[(1S,3S,5S)-3-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 209);N-[2-[(6S)-6-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-5-azaspiro[2.4]heptan-5-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 210); N-[2-[(1R,2S,5S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 211); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-[methyl-(1-methyl-4-piperidyl)amino]phenyl]ethyl] carbamoyl]-2-methyl-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 212); N-[(1S)-2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 213); N-[(1R)-2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methylsulfonyl-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-1-methyl-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 214); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-hydroxy-4-methoxy-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide trifluoroacetate (Compound 215); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-methoxy-4-(4-methylpiperazin-1-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 216); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(3,3,4-trimethylpiperazin-1-yl)phenyl]ethyl]carbamoyl]- 4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 217); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(4-methylpiperazin-1-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 218); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[methyl-(1-methyl-4-piperidyl)amino] phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 219); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 220); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 221); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3S)-3-(dimethylamino)-1-piperidyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 222); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-5-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 223); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-5-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4- (dimethylamino)pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 224); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 225);N-[2-[(2S,4R)-2-[[(1S)-1-[4-cyclopropyl-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 226); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(2-oxo-1H-pyrimidin-5-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 227); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(3,5-dimethylisoxazol-4-yl)phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 228); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1H-pyrazol-4-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 229); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-(1H-imidazol-5-yl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 230); N-[2-[(1R,3S,5R)-3-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl] carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 231); N-[2-[(2S)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl]carbamoyl]-2- methyl-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide formate (Compound 232); N-[2-[(2S,4R)-2-[[(1S)-1-(2-aminophenyl)ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro- quinoline-2-carboxamide (Compound 233); N-[2-[(2S,4R)-2-[[(1S)-1-[5-amino-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 234); N-[2-[(2S,4R)-2-[[(1S)-1-[5-amino-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1- yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 235); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-(azetidin-3-yl)vinyl]phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 236); N-[2-[(2S,4R)-2-[[(1R)-1-[3-[(E)-2-cyclopropylvinyl]-6-[[(2S)-pyrrolidine-2-carbonyl]amino]-2-pyridyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 237); N-[2-[(2S,4R)-2-[[(1R)-1-[3-[(E)-2-cyclopropylvinyl]-6-[[(2R)-pyrrolidine-2-carbonyl]amino]-2-pyridyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 238); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[(E)-2-cyclopropylvinyl]-2-(1,2,3,6-tetrahydropyridin-5-yl)-4-pyridyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 239 ); N-[2-[(2S,4R)-2-[[(1R)-1-[5-[(E)-2-cyclopropylvinyl]-2-(1,2,3,6-tetrahydropyridin-5-yl)-4-pyridyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 240);N-[2-[(2S,4R)-2-[[(1S)-1-[2,5-bis[(E)-2-cyclopropylvinyl]-4-pyridyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 241); N-[2-[(2S,4R)-2-[[(1R)-1-[2,5-bis[(E)-2-cyclopropylvinyl]-4-pyridyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2- oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 242); N-[2-[(2S,4R)-2-[[(1S)-1-[3-amino-6-[(E)-2-cyclopropylvinyl]-2-fluoro-phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 243); N-[2-[(2S,4R)-2-[[(1S)-1-[4-chloro-2-[(E)-2-cyclopropylvinyl]-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 244); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[rel-(3S)-3-piperidyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 245); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[rel-(3R)-3-piperidyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 246); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1-methyl-4-piperidyl)phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 247); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[rel-(3S)-1-cyclopropyl-3-piperidyl]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 248); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[rel-(3R)-1-cyclopropyl-3-piperidyl]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 249); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-1,2,3,4-tetrahydroquinolin-7-yl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 250); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-4-methoxy-5-(1,2,3,6-tetrahydropyridin-5-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 251); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2R)-pyrrolidine-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 252 ); N-[2-[(2S,4R)-2-[[(1S)-1-[2-(cyclopropanecarbonylamino)phenyl]ethyl]carbamoyl]-4-hydroxy-pyrrolidin-1-yl]- 2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 253); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S)-pyrrolidine-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 254);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S,4R)-4-fluoropyrrolidine-2-carbonyl]amino] phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 255); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2R)-piperidine-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 256); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S)-piperidine-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 257); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S)-1-methylpyrrolidine-2-carbonyl]amino] phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 258); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-2-fluoro-3-[[(2R)-pyrrolidine-2-carbonyl]amino] phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamidehydrochloride (Compound 259); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-2-fluoro-3-[[(2S)-pyrrolidine-2-carbonyl]amino] phenyl] ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamidehydrochloride (Compound 260); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-1-[(2S)-pyrrolidine-2-carbonyl]-3,4-dihydro-2H-quinolin- 7-yl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 261); N-[2-[(2S,4R)-2-[[(1S)-1-[6-[(E)-2-cyclopropylvinyl]-1-[(2R)-pyrrolidine-2-carbonyl]-3,4-dihydro-2H-quinolin- 7-yl]ethyl]carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide(Compound 262); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2R)-tetrahydrofuran-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 263); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(2S)-tetrahydrofuran-2-carbonyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 264); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[2-(dimethylamino)acetyl]amino]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 265); N-[2-[(2S,4R)-2-[[(1S)-1-[5-acetamido-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro-pyrrolidin- 1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 266); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[[(2S)-aziridine-2-carbonyl]amino]-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 267); 6-fluoro-N-[2-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[2-[(E)-2-(1-methylazetidin-3-yl)vinyl]phenyl]ethyl]carbamoyl] pyrrolidin-1-yl]-2-oxo-ethyl]quinoline-2-carboxamide (Compound 268);N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 269); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[rel-(3S)-1-methyl-3-piperidyl]phenyl]ethyl]carbamoyl]- 4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 270); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[rel-(3R)-1-methyl-3-piperidyl]phenyl]ethyl]carbamoyl]- 4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 271); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3R)-1-methylpyrrolidin-3-yl]oxy-phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 272); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3S)-1-methylpyrrolidin-3-yl]oxy-phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 273); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-(1-methylazetidin-3-yl)oxy-phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 274); N-[2-[(2S,4R)-2-[[(1S)-1-[5-[(3S)-1-cyclopropylpyrrolidin-3-yl]oxy-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 275); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(3S)-1-methyl-3-piperidyl]oxy]phenyl]ethyl] carbamoyl]-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide (Compound 276); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3S)-pyrrolidin-3-yl]oxy-phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide;hydrochloride (Compound 277); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[(3R)-pyrrolidin-3-yl]oxy-phenyl]ethyl]carbamoyl]-4- fluoro-pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 278); N-[2-[(2S,4R)-2-[[(1S)-1-[5-(azetidin-3-yloxy)-2-[(E)-2-cyclopropylvinyl]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 279); N-[2-[(2S,4R)-2-[[(1S)-1-[2-[(E)-2-cyclopropylvinyl]-5-[[(3S)-3-piperidyl]oxy]phenyl]ethyl]carbamoyl]-4-fluoro- pyrrolidin-1-yl]-2-oxo-ethyl]-6-fluoro-quinoline-2-carboxamide hydrochloride (Compound 280).

6. A process for the preparation of a compound of formula (I) or a pharmaceutical acceptable salt thereof, as defined in claim 1, said process comprises the following steps: Step 1.1) mixing a compound of formula (IV) or its corresponding salt, (IV)wherein X and Y are as defined in claim 1, with a compound of formula (V) or its corresponding salt,wherein R1 and R2 are as defined in claim 1 and R25 is a group selected from straight or branched (C1-C6) alkyl to give a compound of formula (VI) wherein X, Y, R1, R2 and R25Step 1.2) reacting the compound of formula (VI) obtained as described in step 1.1 under acidic or basic hydrolysis conditions to give compound of formula (VII) or its corresponding salt wherein X, Y, R1 and R2 are asStep 1.3) reacting a compound of formula (VII), obtained as described in step 1.2, with a compound of formula (VIII), wherein W, R19 and R20 are as defined inintermediate compound of formula (IX) or its corresponding saltwherein X, Y, R1, R2, W, R19 andalternatively, intermediate compound of formula (IX) can be prepared according to the following steps: Step 2.1) mixing a compound of formula (X) or its corresponding salt with a compound of formula (XI) or itswherein R1, R2, W, R19 and R20 are as R25 is as defined above in step 1.1 and Pg is anitrogen protecting group, preferably BOC or FMOC, to give a compound of formula (XII) Step 2.2) removal of the protecting formula (XII) obtained as described instep 2.1 under acidic conditions to yield a primary amine compound of formula (XIII) or its corresponding salt,wherein R1, R2, W, R19, R20 are as defined above in step 1.1;Step 2.3) reacting a compound of formula (XIII) obtained as described in step 2.2 with a compound of formula (V) as defined in step 1.1, to obtain a compound of formula (XIV) wherein X, Y, R1, R2, R19, R20defined above in step 1.1; Step 2.4) reacting compound of formula (XIV) obtained as described in step 2.3 in acidic or basic hydrolysis conditions to give intermediate compound of formula (IX) or its corresponding salt wherein X, Y, R1, R2, W, R19finally, compounds of formula (I), object of the present invention, can be prepared according to the following steps: Step 3.1) mixing a compound of formula (IX) obtained as described in step 1.3 or 2.4 with a compound of formula (XV) or its corresponding salt, (XV)wherein R3, R4 and Z are as defined in claim 1, to give a compound of formula (I)wherein X, Y, R1, R2, R3,alternatively, compounds of formula (I), object of the present invention, can be prepared according to the following steps: Step 4.1 mixing a compound of formula (XVII) wherein Pg is as defined above in step and R20 are as defined in claim 1, with acompound of formula (XV) wherein Z, R3 and R4 are as defined incompound (XVIII)Step 4.2 removal of the nitrogen protecting group (Pg) from a compound of formula (XVIII), obtained as described in step 4.1, under acidic or basic conditions depending on the Pg applied, to obtain a primary amine compound of formula (XIX) or its corresponding salt,wherein R1, R2, R3, R4, W, R19, R20 1;Step 4.3 mixing a compound of formula (XIX) obtained as described in step 4.2 with a compound of formula (IV) of formula (I) wherein X, Y, R1, R2,R3, R4, W, R19, R20 and Z are as defined in claim 1; or alternatively, compounds of formula (I), object of the present invention, can be prepared according the following steps: Step 5.1 mixing a compound of formula (XX), or its corresponding salt, wherein W, R19 and R20 are as defined is as defined in step 2.1, with a compound offormula (XV) wherein R3, R4 and Z are as defined in claimcompound of formula (XXI)Step 5.2 removal of the nitrogen a compound of formula (XXI), obtained asdescribed in step 5.1, with well-known literature method depending on the selected protecting group, to obtain a primary amine compound of formula (XXII) or its corresponding salt, wherein R3, R4, W, R19, R20 and Z are as1; Step 5.3 mixing a compound of formula (XXII), obtained as described in step 5.2, with a compound of formula (VII), obtained as described in step 1.2 to obtain a compound of formula (I)wherein X, Y, R1, R2, R3,7. A compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, for use in a method of treating a disease caused by and / or associated with dysregulated proteins activity involved inDNA repair pathways and genomic stability, which comprises administering to a mammal in need thereof, an effective amount of a compound of formula (I) as defined in claim 1.

8. The compound for use according to claim 7, wherein the disease is selected from the group consisting of cancer, cell proliferative disorders and immune disorders.

9. The compound for use according to any of claims 7 or 8 wherein the cancer is selected from the group consisting of: carcinomas, such as bladder, breast, kidney, liver, colon, lung, including small cell lung cancer, esophagus, gall-bladder, ovary, pancreas, stomach, cervix, prostate, and skin, including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B-cell lymphoma, angioimmunoblastic T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma and Burkitt's lymphoma; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukemias, myelodysplastic syndrome and promyelocytic leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including glioma, glioblastoma, glioblastoma multiforme, astrocytoma, oligodendroglioma, paraganglioma, neuroblastoma, and schwannomas; and other tumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoacanthoma, thyroid cancers, such as papillary thyroid carcinoma and medullary thyroid carcinoma, Kaposi's sarcoma, chondrosarcoma, and cholangiocarcinoma.

10. A compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, for use as a medicament.

11. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutical acceptable salt thereof, as defined in claim 1 and at least one pharmaceutically acceptable excipient, carrier and / or diluent.

12. A therapeutic combination comprising a compound of formula (I) with one or more anticancer agents.

13. A method of treatment a disease caused by and / or associated with dysregulated proteins activity involved in DNA repair pathways and genomic stability which comprises administering to a mammal in need thereof an effective amount of compound of formula (I) as defined in claim 1.

14. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in claim 1 in the manufacture of a medicament for treating cancer.

15. A product or kit comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, and one or more chemotherapeutic agents, as a combined preparation for simultaneous, separate or sequential use in anticancer therapy.

16. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, for treating cancer, which comprises administering to a mammal in need thereof, an effective amount of a compound of formula (I) as defined in claim 1.

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