Gram-negative bacterial efflux pump inhibitors

Abstract

The present invention relates to novel Gram-negative bacterial efflux pump inhibitors. Furthermore, the present invention relates to the use of Gram-negative bacterial efflux pump inhibitors to prevent and / or treat antibiotic resistance by enhancing the activity of antibiotics. Infections caused by multidrug-resistant (MDR) Gram-negative bacteria are a major threat to global healthcare. The present inventors have discovered a novel class of resistance nodule partitioning-efflux pump inhibitors. The present inventors have tested the effect of these inhibitors on inhibiting the growth of various bacteria and on enhancing antibiotic activity in various bacteria. In particular, the present inventors have tested the effect of these inhibitors on E. coli, A. baumannii, K. pneumoniae and P. aeruginosa.

Description

[Technical field]

[0001] The present invention relates to novel Gram-negative bacterial efflux pump inhibitors. Furthermore, the present invention relates to the use of Gram-negative bacterial efflux pump inhibitors for preventing and / or treating antibiotic resistance by enhancing the activity of antibiotics.

[0002] background Infections caused by multidrug-resistant (MDR) Gram-negative bacteria are a major threat to global healthcare, and R&D into novel antibiotics has been identified as a key priority by the World Health Organization. Among many antibiotic-specific resistance mechanisms, multidrug efflux catalyzed by bacterial efflux pumps is a major factor that defines both innate and acquired multidrug resistance phenotypes in Gram-negative bacteria. In particular, efflux pumps belonging to the resistance nodule distribution (RND) superfamily can efflux a large number of chemically diverse antibiotic molecules, which is a major barrier to antibiotic efficacy and drug development (Li XZ, Plesiat P, Nikaido H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev. 2015,28,337-418. doi:10.1128 / CMR.00117-14).

[0003] RND-type efflux pumps contain three components that assemble into a trimolecular complex that spans the entire envelope of Gram-negative bacteria (Du, D., Wang-Kan, X., Neuberger, A. et al. Multidrug efflux pumps: structure, function and regulation. Nat Rev Microbiol. 2018,16,523-539. doi.org / 10.1038 / s41579-018-0048-6). A typical RND-type efflux pump is the AcrA-AcrB-TolC trimolecular system from Escherichia coli, where AcrB is an inner membrane component, AcrA is a periplasmic adaptor protein, and TolC is an outer membrane channel.

[0004] Considering the important role of RND pumps in innate and adaptive antibiotic resistance in Gram-negative bacteria, great efforts have been made to discover and develop efflux pump inhibitors (EPIs). Characterized EPIs include Phe-Arg β-naphthylamides (PAβN), 1-(1-naphthylmethyl)-piperazines (NMPs), pyridopyrimidines (e.g., D13-9001), and pyranopyridines (MBX series), which inhibit RND pump-mediated efflux and enhance the antibiotic activity of all known substrates of the pump in Gram-negative pathogens (Opperman TJ, Nguyen ST. Recent advances toward a molecular mechanism of efflux pump inhibition. Front Microbiol. 2015, 6, 421. doi: 10.3389 / fmicb.2015.00421).

[0005] To identify novel efflux pump inhibitors (EPIs), we used phenotypic assays to screen a chemical library of 1,280 compounds at 300 μM in combination with a sub-active dose of pyridomycin, an antibiotic identified as a particularly good substrate for the AcrAB-TolC efflux pump.

[0006] Thus, in the present invention, the inventors have discovered a novel class of RND-EPIs, which can be used to enhance the activity of antibiotics.

[0007] Detailed Description Therefore, the present invention relates to a compound of formula (I): [ka] [In the formula, - X may be selected from CH and N; - Y may be selected from CH and N; X and Y are not CH at the same time. - R 1 may be selected from a halogen atom; a -(C1-C3) alkyl group; a -(C1-C3) halogenoalkyl group; a -(C1-C3) alkoxy group or a nitrile group; - R 2 a halogen atom, excluding fluorine atom; an -(C1-C6)alkyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkenyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkynyl group optionally substituted with one heteroatom selected from O, N or S; a -(C1-C3)alkoxy group; a -(C1-C3)halogenoalkyl group; a -COORa group; a -N(H)Rb-Ra group; an -(C1-C3)alkyl group optionally substituted with an -(C2-C6)alkynyl-(C6-C 10 ) aryl groups, wherein the -(C1-C3) alkyl group is optionally substituted with an -NRR' group; CONH-(C6-C3) optionally substituted with an -(C1-C3) alkyl group; 10 )aryl groups, wherein the -(C1-C3)alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C3)alkyl optionally substituted by an -NRR' group; 10)aryl groups; -O-(C1-C3)alkyl-(C6-C7)alkyl groups optionally substituted with -NRR' groups; 10 )aryl groups; (5-6 membered)heteroaryl groups optionally substituted by (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S and optionally substituted by -NRR' groups; -CONH-(C1-C3)alkyl-(C6-C3)alkyl-(C6-C3)alkyl optionally substituted by halogen atoms, methyl groups or methoxy groups; 10 ) an aryl group; or R 2 is taken together with the carbon atom at the 6-position to form a fused phenyl or (5-6 membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR a (4-10 membered) heterocycle optionally substituted by one or more of R' groups or carbonyl, said -(C1-C3)alkyl group being optionally substituted by an NRR' group; an NH-heterocycle containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; a (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, a methyl group optionally substituted by 1-3 fluorine atoms, a methoxy group optionally substituted by 1-3 fluorine atoms, a -NRR' group or an OH-substituted (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, 10)aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 and optionally substituted with one or more of the following groups: - Ra is selected from -(C1-C6)alkyl groups; -(C1-C4)alkyl groups optionally substituted with halogen atoms, -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms; -(C1-C3)alkyl-phenyl groups optionally substituted with -(C1-C3)alkyl groups, said -(C1-C3)alkyl groups being substituted with -NRR' groups or -(C1-C3)alkyl-(5-6 membered)heteroaryl groups optionally substituted with halogen atoms, methyl groups optionally substituted with 1 to 3 fluorine atoms, methoxy groups optionally substituted with 1 to 3 fluorine atoms, - R and R' are the same or different and are selected from -(C1-C3)alkyl groups and H; Rb is selected from carbonyl and SO2; - R 3 is selected from heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, optionally substituted by -(C1-C3)alkyl or -NRR' groups, and -NH-heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, - R 7 and R 8are the same or different and selected from H, -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups, said -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups being optionally substituted by -NRR' groups. or a pharma- ceutically acceptable salt, or an optical isomer, racemate, diastereoisomer, enantiomer or tautomer thereof, However, the following compounds: 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperazine; 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; 1-(5-bromo-3-chloro-2-pyridyl)-4-methyl-piperazine; 1-[2-chloro-4-(trifluoromethyl)phenyl]piperazine hydrochloride; 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperidin-4-amine; 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-1,4-diazepane; Methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; 1-(3-chloro-5-methyl-2-pyridyl)piperazine; 1-(5-bromo-3-chloro-2-pyridyl)piperazine; 2-Chloro-3-piperazin-1-yl-quinoxaline hydrochloride; 1-[3-Bromo-5-(trifluoromethyl)-2-pyridyl]-4-methyl-piperazine; 3-Methyl-2-piperazin-1-yl-quinoline hydrochloride; 2-Piperazin-1-ylquinoline-3-carbonitrile hydrochloride; 3-[(3R)-3-Methylpiperazin-1-yl]quinoxalin-2-ol hydrochloride; 2-Chloro-3-(4-ethylpiperazin-1-yl)quinoxaline; 3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,2,4-oxadiazole; (1R,5S)-N-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-3-azabicyclo[3.1.0]hexan-6-amine; 2-Methoxy-3-piperazin-1-yl-quinoxaline hydrochloride; 2-Chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline; 3-Cyano-2-(4-methyl-piperazino)-5-(pyrid-4-yl)-pyridine; Methyl 5-chloro-6-4-methylpiperazin-1-yl)nicotinate; (1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylpiperazine; 1-(3,5-Dichloro-2-pyridyl)piperazine; hydrochloride; 2-Methoxy-3-(4-methylpiperazin-1-yl)quinoxaline; 2-Ethoxy-3-(4-methylpiperazin-1-yl)quinoxaline; 2-Methyl-3-(4-methylpiperazin-1-yl)quinoxaline; 2-Ethyl-3-(4-methylpiperazin-1-yl)quinoxaline; 2-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)quinoxaline; 2-Bromo-3-(4-methylpiperazin-1-yl)quinoxaline; 2-Chloro-3-(4-methyl-1,4-diazepan-1-yl)quinoxaline; 3,6-dichloro-2-(4-methylpiperazin-1-yl)quinoxaline; 2,6,7-trichloro-3-(4-methylpiperazin-1-yl)quinoxaline; 1-(3-chloroquinoxalin-2-yl)-N-methyl-pyrrolidin-3-amine 2-Chloro-3-[(3S)-3-methylpiperazin-1-yl]quinoxaline hydrochloride; and 4-Bromo-1-piperazin-1-yl-isoquinoline This relates to compounds other than those listed above.

[0008] The present invention also relates to a pharmaceutical composition comprising a compound of formula (I) as described above and a pharma- ceutically acceptable excipient.

[0009] Furthermore, the present invention relates to a compound of formula (I): [ka] [In the formula, - X may be selected from CH and N; - Y may be selected from CH and N; - R 1 may be selected from a halogen atom; a -(C1-C3) alkyl group; a -(C1-C3) halogenoalkyl group; a -(C1-C3) alkoxy group; a nitrile group; R 1 is combined with Y to form fused phenyl groups at the 3- and 4-positions, - R 2 a halogen atom, excluding fluorine atom; an -(C1-C6)alkyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkenyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkynyl group optionally substituted with one heteroatom selected from O, N or S; a -(C1-C3)alkoxy group; a -(C1-C3)halogenoalkyl group; a -COORa group; a -N(H)Rb-Ra group; an -(C1-C3)alkyl group optionally substituted with an -(C2-C6)alkynyl-(C6-C 10 ) aryl groups, wherein the -(C1-C3) alkyl group is optionally substituted with an -NRR' group; CONH-(C6-C3) optionally substituted with an -(C1-C3) alkyl group; 10)aryl groups, wherein the -(C1-C3)alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C3)alkyl optionally substituted by an -NRR' group; 10 )aryl groups; -O-(C1-C3)alkyl-(C6-C7)alkyl groups optionally substituted with -NRR' groups; 10 )aryl groups; (5-6 membered)heteroaryl groups optionally substituted by (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S and optionally substituted by -NRR' groups; -CONH-(C1-C3)alkyl-(C6-C3)alkyl-(C6-C3)alkyl optionally substituted by halogen atoms, methyl groups or methoxy groups; 10 ) an aryl group; or R 2is taken together with the carbon atom at the 6-position to form a fused phenyl or (5-6 membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR a (4-10 membered) heterocycle optionally substituted by one or more of R' groups or carbonyl, said -(C1-C3)alkyl group being optionally substituted by an NRR' group; an NH-heterocycle containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; a (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, a methyl group optionally substituted by 1-3 fluorine atoms, a methoxy group optionally substituted by 1-3 fluorine atoms, a -NRR' group or an OH-substituted (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, 10 )aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 and optionally substituted with one or more of the following groups: - Ra is selected from -(C1-C6)alkyl groups; -(C1-C4)alkyl groups optionally substituted with halogen atoms, -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms; -(C1-C3)alkyl-phenyl groups optionally substituted with -(C1-C3)alkyl groups, said -(C1-C3)alkyl groups being substituted with -NRR' groups or -(C1-C3)alkyl-(5-6 membered)heteroaryl groups optionally substituted with halogen atoms, methyl groups optionally substituted with 1 to 3 fluorine atoms, methoxy groups optionally substituted with 1 to 3 fluorine atoms, - R and R' are the same or different and are selected from -(C1-C3)alkyl groups and H; Rb is selected from carbonyl and SO2; - R 3 is selected from heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, optionally substituted by -(C1-C3)alkyl or -NRR' groups, and -NH-heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, R 7 and R 8 are the same or different and selected from H, -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups, said -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups being optionally substituted by -NRR' groups. or a pharma- ceutically acceptable salt, or an optical isomer, racemate, diastereoisomer, enantiomer or tautomer thereof.

[0010] The present invention also provides a method for treating a bacterial infection, comprising administering to a subject in need of treatment for a bacterial infection a compound of formula (I): [ka] [In the formula, - X may be selected from CH and N; - Y may be selected from CH and N; - R 1 may be selected from a halogen atom; a -(C1-C3) alkyl group; a -(C1-C3) halogenoalkyl group; a -(C1-C3) alkoxy group; a nitrile group; R 1 is combined with Y to form fused phenyl groups at the 3- and 4-positions, - R 2 a halogen atom, excluding fluorine atom; an -(C1-C6)alkyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkenyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkynyl group optionally substituted with one heteroatom selected from O, N or S; a -(C1-C3)alkoxy group; a -(C1-C3)halogenoalkyl group; a -COORa group; a -N(H)Rb-Ra group; an -(C1-C3)alkyl group optionally substituted with an -(C2-C6)alkynyl-(C6-C 10 ) aryl groups, wherein the -(C1-C3) alkyl group is optionally substituted with an -NRR' group; CONH-(C6-C3) optionally substituted with an -(C1-C3) alkyl group; 10 )aryl groups, wherein the -(C1-C3)alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C3)alkyl optionally substituted by an -NRR' group; 10 )aryl groups; -O-(C1-C3)alkyl-(C6-C7)alkyl groups optionally substituted with -NRR' groups; 10)aryl groups; (5-6 membered)heteroaryl groups optionally substituted by (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S and optionally substituted by -NRR' groups; -CONH-(C1-C3)alkyl-(C6-C3)alkyl-(C6-C3)alkyl optionally substituted by halogen atoms, methyl groups or methoxy groups; 10 ) an aryl group; or R 2 is taken together with the carbon atom at the 6-position to form a fused phenyl or (5-6 membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR a (4-10 membered) heterocycle optionally substituted by one or more of R' groups or carbonyl, said -(C1-C3)alkyl group being optionally substituted by an NRR' group; an NH-heterocycle containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; a (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, a methyl group optionally substituted by 1-3 fluorine atoms, a methoxy group optionally substituted by 1-3 fluorine atoms, a -NRR' group or an OH-substituted (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, 10 )aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R8 and optionally substituted with one or more of the following groups: -Ra is selected from -(C1-C6)alkyl groups; -(C1-C4)alkyl groups optionally substituted with halogen atoms, -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms; -(C1-C3)alkyl-phenyl groups optionally substituted with -(C1-C3)alkyl groups, said -(C1-C3)alkyl groups being substituted with -NRR' groups, or -(C1-C3)alkyl-(5-6 membered)heteroaryl groups optionally substituted with halogen atoms, methyl groups optionally substituted with 1 to 3 fluorine atoms, methoxy groups optionally substituted with 1 to 3 fluorine atoms, - R and R' are the same or different and are selected from -(C1-C3)alkyl groups and H; Rb is selected from carbonyl and SO2; - R 3 is selected from heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, optionally substituted by -(C1-C3)alkyl or -NRR' groups, and -NH-heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, R 7 and R 8 are the same or different and selected from H, -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups, said -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups being optionally substituted by -NRR' groups. or a pharma- ceutically acceptable salt, or optical isomer, racemate, diastereoisomer, enantiomer, or tautomer thereof.

[0011] Unless otherwise stated, the terms used above or hereinafter in relation to the compounds of formula (I) have the meanings given below.

[0012] "Halogen" refers to a fluorine, chlorine, bromine or iodine atom, in particular a bromine, iodine or chlorine atom.

[0013] "Alkyl" refers to an aliphatic-hydrocarbon group which may be straight-chained or branched, and unless otherwise specified, is (C1-C6) alkyl or (C1-C4) alkyl or (C1-C3) alkyl having 1-6 or 1-4 or 1-3 carbon atoms in the chain. In particular, the alkyl group is (C1-C3) alkyl having 1-3 carbon atoms in the chain. Branched chain means that one or more alkyl groups, such as methyl, ethyl or propyl, are attached to a straight-chain alkyl chain. Exemplary alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, 2,2-dimethylbutyl, n-pentyl, n-hexyl, in particular methyl or ethyl. As mentioned, the alkyl may be substituted by one heteroatom selected from O, N or S (it is understood that one of the carbons of the alkyl group is substituted by O, N or S).

[0014] "Halogenoalkyl" refers to an aliphatic-hydrocarbon group, which may be straight-chained or branched, having 1 to 3 carbon atoms in the chain, in which one or more hydrogen atoms are replaced by halogen atoms, such as fluorine, chlorine, bromine or iodine atoms, in particular by one or more fluorine atoms (C1-C3)halogenoalkyl. Exemplary halogenoalkyl include trifluoromethyl.

[0015] "Nitrile" is [ka] Refers to...

[0016] "Alkoxy" refers to a single alkyl group, as defined above, attached to an oxygen atom. Examples of straight or branched (C1-C3)alkoxy include methoxy (CH3O) and ethoxy (CH3CHO-). The alkoxy may be substituted with one or more fluorine atoms, for example, trifluoromethoxy.

[0017] "Alkenyl" refers to an aliphatic hydrocarbon group containing a carbon-carbon double bond, which may be straight or branched, and unless otherwise specified, is (C2-C6) alkenyl having 2 to 6 carbon atoms in the chain. Preferred alkenyl groups are (C2-C3) alkenyl having 2 to 3 carbon atoms in the chain. Exemplary alkenyl groups include ethenyl, n-propenyl, i-propenyl, n-butenyl, i-butenyl, 2,2-dimethylbut-1-enyl, n-pentenyl, especially propenyl. As mentioned, the alkenyl may be substituted by one heteroatom selected from O, N or S (it is understood that one of the carbons of the alkyl group is substituted by O, N or S).

[0018] "Alkynyl" refers to an aliphatic hydrocarbon group containing a carbon-carbon triple bond, which may be straight or branched, and unless otherwise specified, is (C2-C6) alkynyl having 2 to 6 carbon atoms in the chain. Preferred alkynyl groups are (C3-C5) alkynyl having 3 to 5 carbon atoms in the chain. Exemplary alkynyl groups include ethynyl, propynyl, but-1-ynyl, but-2-ynyl, pent-1-ynyl. As mentioned, the alkynyl may be substituted with one heteroatom selected from O, N, or S (it is understood that one of the carbons of the alkyl group is substituted with O, N, or S).

[0019] "Aryl" refers to an aromatic monocyclic or polycyclic hydrocarbon ring system of 6 to 10 carbon atoms, preferably 6 carbon atoms. Exemplary aryl groups include phenyl, naphthyl, biphenyl, especially phenyl. Said aryl or phenyl may be one or more halogen atoms, such as fluorine, bromine, iodine or chlorine, in particular chlorine; one or more (C1-C4) alkyl or (C1-C3) alkyl, such as methyl, said alkyl optionally substituted with 1 to 3 fluorine atoms (e.g. trifluoromethyl); one or more (C1-C3) alkoxy, such as methoxy, said alkoxy optionally substituted with 1 to 3 fluorine atoms (e.g. trifluoromethoxy); an NRR' group (R and R' are as defined herein), in particular NH; a (4-8 membered) heterocycle having at least one N; an NH-heterocycle; an aryl of 6 to 10 carbon atoms, preferably 6 carbon atoms, optionally substituted with an NRR' group (R and R' are as defined herein) (e.g. NH); NR 7 R 8 Group(R 7 and R 8 is optionally substituted with (as defined herein).

[0020] "Heteroaryl" refers to an aromatic monocyclic, bicyclic or polycyclic ring of 5 to 12, especially 5 to 6, rings, in which at least one member of the ring is a heteroatom. The heteroatom can be O, S or N, especially N. In particular, each ring contains 1 to 3 heteroatoms. When bicyclic or polycyclic rings are contemplated, at least one of the rings is aromatic, while the other rings may be non-aromatic, for example, 1,2,3,4-tetrahydroisoquinoline and isoindoline. Examples include pyrrolyl, pyridyl, oxadiazole, thiazole, oxazole, triazole, pyrazolyl, pyrimidinyl, pyrazinyl, indolyl, imidazolyl, especially pyridyl, triazole or oxadiazole. Said heteroaryl may be substituted by one or more halogen atoms, such as fluorine, bromine, iodine or chlorine, in particular chlorine; one or more (C1-C4)alkyl or (C1-C3)alkyl, such as methyl, where the alkyl is substituted with 1 to 3 fluorine atoms (e.g. trifluoromethyl) or NRR' groups, where R and R' are as defined herein, in particular methylamine, ethylamine or propylamine; one or more (C1-C3)alkoxy, such as methoxy, where the alkoxy is optionally substituted with one or more fluorine atoms (e.g. trifluoromethoxy); a (4-8 membered) heterocycle having at least one N; an NH-heterocycle; an aryl of 6 to 10 carbon atoms, preferably 6 carbon atoms, optionally substituted with an NRR' group, where R and R' are as defined herein (e.g. methylamine or ethylamine); NR 7 R 8 Group(R 7 and R 8 is optionally substituted with (as defined herein).

[0021] "-(C1-C3)alkyl-phenyl" or "-(C1-C3)alkyl-(5-6 membered)heteroaryl" is R ais linked to the oxygen atom of COO- or Rb of -N(H)Rb- is linked to the carbon of the alkyl group. In particular, -(C1-C3)alkyl-phenyl is benzyl, ethylphenyl or propylphenyl. As mentioned above, phenyl can be optionally substituted, in particular, by halogen atoms, such as fluorine, bromine, iodine or chlorine, in particular chlorine; (C1-C4)alkyl or (C1-C3)alkyl, such as methyl, said alkyl optionally substituted with 1 to 3 fluorine atoms (e.g. trifluoromethyl); (C1-C3)alkoxy, such as methoxy, said alkoxy optionally substituted with one or more fluorine atoms (e.g. trifluoromethoxy).

[0022] "-CO-NH-(C1-C3) alkyl-(C6-C 10 "-(C1-C3)alkyl" means that the aryl is linked to the alkyl group by a carbon of the alkyl group. In particular, -(C1-C3)alkyl-(C6-C3)aryl" means that the aryl is linked to the alkyl group by a carbon of the alkyl group. 10 )Aryl is (C1-C3)alkyl-phenyl, especially benzyl, ethylphenyl or propylphenyl. As mentioned above, phenyl can be optionally substituted, especially by halogen atoms, such as fluorine, bromine, iodine or chlorine, especially chlorine; methyl or methoxy.

[0023] "-CONH-(C6-C 10 "Aryl" means that the nitrogen atom of -CO-NH- is linked to the carbon of an aryl. In particular, -CONH-(C6-C 10 ) Aryl- is -CONH-phenyl. As mentioned above, phenyl may in particular be substituted by an NRR' group. R and R' are as defined herein, in particular ethylamine.

[0024] "-(C1-C3) alkyl-O-(C6-C 10"(C1-C3)aryl" means that an alkyl group is linked to an oxygen atom through a carbon of the alkyl group, and the oxygen atom is also linked to a carbon of the aryl group. In particular, -(C1-C3)alkyl-O-(C6-C3)aryl means that an alkyl group is linked to an oxygen atom through a carbon of the alkyl group, and the oxygen atom is also linked to a carbon of the aryl group. 10 )Aryl- is (C1-C3)alkyl-O-phenyl, especially methyl-O-phenyl. As mentioned above, phenyl may in particular be substituted by an NRR' group. R and R' are as defined herein, especially methylamine.

[0025] "-O-(C1-C3) alkyl-(C6-C 10 "-O-(C1-C3)alkyl-(C6-C7)aryl" means that an alkyl group is linked to an oxygen atom by one of the carbons of the alkyl group and another carbon of the alkyl group is linked to a carbon of an aryl group. In particular, -O-(C1-C3)alkyl-(C6-C7)aryl means that an alkyl group is linked to an oxygen atom by one of the carbons of the alkyl group and another carbon of the alkyl group is linked to a carbon of an aryl group. 10 )Aryl is -O-(C1-C3)alkyl-phenyl, especially -O-methyl-phenyl. As mentioned above, phenyl may in particular be substituted by an NRR' group. R and R' are as defined herein, in particular methylamine.

[0026] In N(H)Rb-Ra, Rb is directly linked to the nitrogen atom.

[0027] "Carbonyl" refers to C=O.

[0028] "Heterocycle" or "heterocycloalkyl" refers to a saturated or partially unsaturated, non-aromatic, stable, 4-10 membered monocyclic, bicyclic or polycyclic ring, which may be optionally bridged, and in which at least one member of the ring is a nitrogen atom. The bridge contains 0-2 carbon atoms between the two members of the heterocycle. In particular, each ring contains 1 or 2 nitrogen atoms. Suitable heterocycles are also disclosed in the Handbook of Chemistry and Physics, 76th Edition, CRC Press, Inc., 1995-1996, pages 225 to 226, the disclosure of which is incorporated herein by reference. Examples of heterocycloalkyl include, but are not limited to, piperazine, diazepane, piperidine, pyrrolidine, imidazolidine, morpholine, azetidine, diazabicyclooctanyl, diazabicycloheptanyl, and azabicyclohexanyl. Said heterocycle is optionally substituted by a (C1-C3) alkyl, in particular methyl, or NRR' group, where R and R' are as defined herein, in particular NH2.

[0029] "NH-heterocycle" means that the heterocycle is linked to the nitrogen atom of the NH by a carbon or nitrogen atom of the heterocycle.

[0030] The term "substituted," unless otherwise indicated, generally refers to substitution with one or more substituents, which may be the same or different, and are specified herein.

[0031] The compounds of formula (I) described herein may contain one or more asymmetric carbon atoms. They may therefore exist in the form of enantiomers or diastereoisomers. These enantiomers and diastereoisomers and their mixtures, including racemic mixtures, form part of the present invention.

[0032] The compounds of formula (I) described herein can be provided in the form of a free base or in the form of an addition salt with an acid, which also form part of the present invention.

[0033] These salts are advantageously prepared with pharma-ceutically acceptable acids, although salts with other acids useful, for example, for the purification or isolation of the compounds of formula (I) described herein also form part of the invention.

[0034] As used herein, the phrase "pharmacologically acceptable" refers to those compounds, materials, excipients, compositions or dosage forms that are, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other significant complications, commensurate with a reasonable benefit / risk ratio.

[0035] As used herein, "pharmaceutically acceptable salts" refers to derivatives of the disclosed compounds, in which the parent compound is modified by forming an acid or base salt thereof. Pharmaceutically acceptable salts include the conventional non-toxic salts or quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, and the like (including mono-, di-, or tri-salts thereof), and salts prepared from organic acids, such as formic acid, acetic acid, propionic acid, succinic acid, tartaric acid, citric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, trifluoroacetic acid, glucoronic acid, glutamic acid, benzoic acid, salicylic acid, toluenesulfonic acid, oxalic acid, fumaric acid, maleic acid, lactic acid, and the like. Further addition salts include ammonium salts, for example tromethamine, meglumine, epolamine, etc., metal salts, for example sodium, potassium, calcium, zinc or magnesium.

[0036] The pharma- ceutically acceptable salts of the present invention can be synthesized from the parent compound containing a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or free base form of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent, or a mixture thereof. Generally, non-aqueous solvents such as ether, dioxane, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. A list of suitable salts can be found in Remington's Pharmaceutical Sciences, 20 th ed., Mack Publishing Company, Easton, PA, 2000, the disclosure of which is incorporated herein by reference.

[0037] compound As mentioned, the compounds of the present invention have the formula (I): [ka] [In the formula, - X may be selected from CH and N; - Y may be selected from CH and N; X and Y are not CH at the same time. - R 1 may be selected from a halogen atom; a -(C1-C3) alkyl group; a -(C1-C3) halogenoalkyl group; a -(C1-C3) alkoxy group or a nitrile group; - R 2a halogen atom, excluding fluorine atom; an -(C1-C6)alkyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkenyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkynyl group optionally substituted with one heteroatom selected from O, N or S; a -(C1-C3)alkoxy group; a -(C1-C3)halogenoalkyl group; a -COORa group; a -N(H)Rb-Ra group; an -(C1-C3)alkyl group optionally substituted with an -(C2-C6)alkynyl-(C6-C 10 ) aryl groups, wherein the -(C1-C3) alkyl group is optionally substituted with an -NRR' group; CONH-(C6-C3) optionally substituted with an -(C1-C3) alkyl group; 10 )aryl groups, wherein the -(C1-C3)alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C3)alkyl optionally substituted by an -NRR' group; 10 )aryl groups; -O-(C1-C3)alkyl-(C6-C7)alkyl groups optionally substituted with -NRR' groups; 10 )aryl groups; (5-6 membered)heteroaryl groups optionally substituted by (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S and optionally substituted by -NRR' groups; -CONH-(C1-C3)alkyl-(C6-C3)alkyl-(C6-C3)alkyl optionally substituted by halogen atoms, methyl groups or methoxy groups; 10 ) an aryl group; or R 2is taken together with the carbon atom at the 6-position to form a fused phenyl or (5-6 membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR a (4-10 membered) heterocycle optionally substituted by one or more of R' groups or carbonyl, said -(C1-C3)alkyl group being optionally substituted by an NRR' group; an NH-heterocycle containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; a (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, a methyl group optionally substituted by 1-3 fluorine atoms, a methoxy group optionally substituted by 1-3 fluorine atoms, a -NRR' group or an OH-substituted (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, 10 )aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 and optionally substituted with one or more of the following groups: -Ra is selected from -(C1-C6)alkyl groups; -(C1-C4)alkyl groups optionally substituted with halogen atoms, -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms; -(C1-C3)alkyl-phenyl groups optionally substituted with -(C1-C3)alkyl groups, said -(C1-C3)alkyl groups being substituted with -NRR' groups, or -(C1-C3)alkyl-(5-6 membered)heteroaryl groups optionally substituted with halogen atoms, methyl groups optionally substituted with 1 to 3 fluorine atoms, methoxy groups optionally substituted with 1 to 3 fluorine atoms, - R and R' are the same or different and are selected from -(C1-C3)alkyl groups and H; Rb is selected from carbonyl and SO2; - R 3 is selected from heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, optionally substituted by -(C1-C3)alkyl or -NRR' groups, and -NH-heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, R 7 and R 8 are the same or different and selected from H, -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups, said -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups being optionally substituted by -NRR' groups. or a pharma- ceutically acceptable salt, or an optical isomer, racemate, diastereoisomer, enantiomer or tautomer thereof, However, the following compounds: 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperazine; 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; 1-(5-bromo-3-chloro-2-pyridyl)-4-methyl-piperazine; 1-[2-chloro-4-(trifluoromethyl)phenyl]piperazine hydrochloride; 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperidin-4-amine; 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-1,4-diazepane; Methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; 1-(3-chloro-5-methyl-2-pyridyl)piperazine; 1-(5-bromo-3-chloro-2-pyridyl)piperazine; 2-Chloro-3-piperazin-1-yl-quinoxaline hydrochloride; 1-[3-Bromo-5-(trifluoromethyl)-2-pyridyl]-4-methyl-piperazine; 3-Methyl-2-piperazin-1-yl-quinoline hydrochloride; 2-Piperazin-1-ylquinoline-3-carbonitrile hydrochloride; 3-[(3R)-3-Methylpiperazin-1-yl]quinoxalin-2-ol hydrochloride; 2-Chloro-3-(4-ethylpiperazin-1-yl)quinoxaline; 3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,2,4-oxadiazole; (1R,5S)-N-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-3-azabicyclo[3.1.0]hexan-6-amine; 2-Methoxy-3-piperazin-1-yl-quinoxaline hydrochloride; 2-Chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline; 3-Cyano-2-(4-methyl-piperazino)-5-(pyrid-4-yl)-pyridine; Methyl 5-chloro-6-4-methylpiperazin-1-yl)nicotinate; (1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylpiperazine; 1-(3,5-Dichloro-2-pyridyl)piperazine; hydrochloride; 2-Methoxy-3-(4-methylpiperazin-1-yl)quinoxaline; 2-Ethoxy-3-(4-methylpiperazin-1-yl)quinoxaline; 2-Methyl-3-(4-methylpiperazin-1-yl)quinoxaline; 2-Ethyl-3-(4-methylpiperazin-1-yl)quinoxaline; 2-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)quinoxaline; 2-Bromo-3-(4-methylpiperazin-1-yl)quinoxaline; 2-Chloro-3-(4-methyl-1,4-diazepan-1-yl)quinoxaline; 3,6-dichloro-2-(4-methylpiperazin-1-yl)quinoxaline; 2,6,7-trichloro-3-(4-methylpiperazin-1-yl)quinoxaline; 1-(3-chloroquinoxalin-2-yl)-N-methyl-pyrrolidin-3-amine 2-Chloro-3-[(3S)-3-methylpiperazin-1-yl]quinoxaline hydrochloride; and 4-Bromo-1-piperazin-1-yl-isoquinoline The compounds are excluding the above.

[0038] In particular, the compound represented by formula (I) is - R 1 may be selected from a halogen atom; a -(C1-C3) alkyl group; a -(C1-C3) halogenoalkyl group or a -(C1-C3) alkoxy group; and / or - R 2a halogen atom, excluding fluorine and chlorine atoms; an -(C1-C6)alkyl group optionally substituted with one heteroatom selected from O, N, or S; an -(C2-C6)alkenyl group optionally substituted with one heteroatom selected from O, N, or S; an -(C2-C6)alkynyl group optionally substituted with one heteroatom selected from O, N, or S; a -(C1-C3)alkoxy group; a -(C2-C3)halogenoalkyl group; a -COORa group; a -N(H)Rb-Ra group; an -(C1-C3)alkyl group optionally substituted with an -(C2-C6)alkynyl-(C6-C 10 ) aryl groups, in which the -(C1-C3) alkyl group is optionally substituted with an -NRR' group; CONH-(C6-C3) optionally substituted with an -(C1-C3) alkyl group; 10 )aryl groups, in which the -(C1-C3)alkyl group is optionally substituted with an -NRR' group; -(C1-C3)alkyl-O-(C6-C3)alkyl optionally substituted with an -NRR' group; 10 )aryl groups; -O-(C1-C3)alkyl-(C6-C7)alkyl groups optionally substituted with -NRR' groups; 10 )aryl groups; (5-6 membered)heteroaryl groups optionally substituted by (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S and optionally substituted by -NRR' groups; -CONH-(C1-C3)alkyl-(C6-C3)alkyl-(C6-C3)alkyl optionally substituted by halogen atoms, methyl groups or methoxy groups; 10 ) an aryl group; or R 2is taken together with the carbon atom at the 6th position to form a fused phenyl or (5-6 membered) heteroaryl at the 5th and 6th positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR (4-10 membered) heterocycles optionally substituted by one or more of R' groups or carbonyl, wherein said -(C1-C3)alkyl groups are optionally substituted by NRR' groups; NH-heterocycles containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; (C6-C3) alkyl groups optionally substituted by one or more of halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or OH. 10 )aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 and optionally substituted with one or more of the following groups: The other substituents are as defined above, with the proviso that - R 1 is a halogen, and R 3 is piperazine, X and Y are not simultaneously N, - R 1 is a halogen, and R 3 is piperazine, R2 However, it is characterized in that it is not COOCH3.

[0039] In particular, -R 1 is a halogen atom and / or -R 2 may be selected from -(C2-C6)alkynyl groups optionally substituted with one heteroatom selected from O, N or S; or R 2 is taken together with the carbon atom at the 6-position to form a fused phenyl or (5-6 membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR a (4-10 membered) heterocycle optionally substituted by one or more of R' groups or carbonyl, said -(C1-C3)alkyl group being optionally substituted by an NRR' group; an NH-heterocycle containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; a (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, a methyl group optionally substituted by 1-3 fluorine atoms, a methoxy group optionally substituted by 1-3 fluorine atoms, a -NRR' group or an OH-substituted (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, 10)aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 and optionally substituted with one or more of the following groups: The other substituents are as defined above, with the proviso that -R 1 is a halogen, and R 3 is piperazine, with the proviso that X and Y are not simultaneously N.

[0040] In particular, - X may be selected from CH and N; - Y may be selected from CH and N; X and Y are not CH or N at the same time.

[0041] In a preferred embodiment, R 3 is selected from heterocycles containing 4 to 10 members and having at least one N, in particular piperazine, said heterocycles optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, and optionally substituted by -(C1-C3)alkyl groups or -NRR' groups.

[0042] In particular, the compound of formula (I) - X is N and Y is CH and / or - R 1 is selected from chlorine, bromine and iodine and / or - R 2 is an iodine; an -(C2-C6)alkynyl group, in particular a pentynyl group, optionally substituted with an -NRR' group; an -(C2-C6)alkynyl-(C6-C6) group, optionally substituted with an -(C1-C3)alkyl group; 10)aryl groups, in particular ethynyl-phenyl, in which the -(C1-C3)alkyl group is optionally substituted by an -NRR' group; the -COORa group; (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S, and optionally substituted by an -NRR' group, in particular (5-6-membered)heteroaryl groups, in particular oxadiazole, optionally substituted by an -NRR' group, in particular ethyl; R 2 optionally substituted by one or more of the following together with the carbon atom in the 6-position: halogen atoms, in particular chlorine, bromine and iodine; one or more -(C1-C4)alkyl groups, in particular methyl groups; (4-10 membered) heterocycles having at least one N, in particular piperazine, pyrrolidine and imidazolidine, the heterocycle being optionally substituted by a (C1-C3)alkyl group, in particular methyl, an NRR' group or carbonyl, the -(C1-C3)alkyl group being optionally substituted by an NRR' group; halogen atoms, in particular fluorine and chlorine, a methyl group optionally substituted by three fluorine atoms, a methoxy group, a -NRR' group or a (C1-C3)alkyl group optionally substituted by OH (C6-C 10 )aryl groups, in particular phenyl; NH-heterocycles containing 4 to 10 members and having at least one N, in particular piperazine; (5 to 12 membered)heteroaryls optionally substituted by (C1-C3)alkyl groups optionally substituted by -NRR' groups, in particular pyridine and triazole; NR 7 R 8 and / or forming a fused phenyl optionally substituted with a group - Ra is selected from phenyl groups optionally substituted by -(C1-C3)alkyl groups, which are optionally substituted by NRR' groups, - R and R' are identical or different and are selected from -(C1-C3)alkyl groups, in particular methyl and H; and / or - R 3 is piperazine optionally substituted by methyl and / or - R 7 and R8 are the same or different and selected from H, -(C1-C4)alkyl groups, in particular ethyl, propyl and butyl, and -CO-(C1-C3)alkyl groups, in particular -CO-CH2-, said -(C1-C3)alkyl groups and -CO-(C1-C3)alkyl groups being optionally substituted by -NH2.

[0043] In particular, the compound of formula (I) - X is N and Y is CH and / or - R 1 is selected from chlorine, bromine and iodine and / or - R 2 is selected from iodine; an -(C2-C6)alkynyl group, in particular a pentynyl group, optionally substituted by an -NRR' group; a -COORa group; a (C1-C3)alkyl group having at least one heteroatom selected from O, N or S, optionally substituted by an -NRR' group, in particular a (5-6 membered)heteroaryl group, in particular an oxadiazole, optionally substituted by an ethyl group; R 2 may be taken together with the carbon atom in the 6-position to represent a halogen atom, in particular chlorine, bromine and iodine; one or more -(C1-C4)alkyl groups, in particular methyl groups; a (4-10 membered) heterocycle having at least one N, in particular piperazine; a (C1-C3)alkyl group optionally substituted by an -NRR' group, in particular methyl (C6-C 10 ) aryl groups, in particular phenyl; NR 7 R 8 and / or forming a fused phenyl optionally substituted with a group - Ra is selected from phenyl groups optionally substituted by -(C1-C3)alkyl groups, which are optionally substituted by NRR' groups, - R and R' are H and / or - R 3 is piperazine optionally substituted by methyl and / or - R 7 and R8 are the same or different and selected from H, -(C1-C3)alkyl groups, in particular ethyl and propyl, and -CO-(C1-C3)alkyl groups, in particular -CO-CH2-, said -(C1-C3)alkyl groups and -CO-(C1-C3)alkyl groups being optionally substituted by -NH2.

[0044] In one embodiment, the compound of formula (I) is - 1-(5-bromo-3-chloro-2-pyridyl)piperazine hydrochloride; - 1-(3-chloro-5-iodo-2-pyridyl)piperazine; - 1-(3-chloro-5-methyl-2-pyridyl)-4-methyl-piperazine; - 1-(3-chloro-5-methyl-2-pyridyl)piperazine hydrochloride; - N-[5-chloro-6-(4-methylpiperazin-1-yl)-3-pyridyl]acetamide; - N-(5-chloro-6-piperazin-1-yl-3-pyridyl)acetamide hydrochloride; - N-(5-chloro-6-piperazin-1-yl-3-pyridyl)methanesulfonamide hydrochloride; - methyl 5-chloro-6-(4-methylpiperazin-1-yl)pyridine-3-carboxylate; - Ethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - benzyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - 2-Phenylethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - 3-phenylpropyl 5-chloro-6-piperazin-1-yl-pyridine-3 carboxylate hydrochloride; - p-Tolylmethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - (4-Chlorophenyl)methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - (4-Methoxyphenyl)methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - 2-(4-chlorophenyl)ethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - [4-(2-aminoethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-chloro-2-(4-methylpiperazin-1-yl)quinoline; - 3-chloro-2-piperazin-1-yl-quinoline; - 3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Bromo-2-piperazin-1-yl-quinoline hydrochloride; - 3-bromo-2-piperazin-1-yl-6-(trifluoromethyl)quinoline hydrochloride; - 3-Bromo-6-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methyl-piperazine; - 2-chloro-3-piperazin-1-yl-quinoline hydrochloride; - 1-[3-bromo-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; - 3-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 1-[5-iodo-3-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; - 1-(3-chloro-5-iodo-2-pyridyl)piperazine; - 3-chloro-2-(1,4-diazepan-1-yl)quinoline; - 2-chloro-3-(3,8-diazabicyclo[3.2.1]octan-3-yl)quinoxaline hydrochloride; - N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinolin-2-amine hydrochloride; - 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperidin-4-amine; - 1-(3-chloro-5-methoxy-2-pyridyl)piperazine hydrochloride; - (1R,5S)-N-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-3-azabicyclo[3.1.0]hexan-6-amine formic acid; - 3-(4-chlorophenyl)propyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - [3-(aminomethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 5-chloro-N-[(4-chlorophenyl)methyl]-6-piperazin-1-yl-pyridine-3-carboxamide hydrochloride; - N-[4-(2-aminoethyl)phenyl]-5-chloro-6-piperazin-1-yl-pyridine-3-carboxamide dihydrochloride; - 2,6-dichloro-3-piperazin-1-yl-quinoline hydrochloride; - 2-chloro-6-methyl-3-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2-(3,8-diazabicyclo[3.2.1]octan-8-yl)quinoline hydrochloride; - 2-chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline hydrochloride; - N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinoxalin-2-amine hydrochloride; - 3-Bromo-6-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2,6-di(piperazin-1 yl)quinoline dihydrochloride; - 2-Methoxy-3-piperazin-1-yl-quinoxaline 2,2,2-trifluoroacetic acid; - 2-chloro-3-(3,6-diazabicyclo[3.1.1]heptan-3-yl)quinoxaline trifluoromethanesulfonic acid; and - 2-chloro-3-(4-ethylpiperazin-1-yl)quinoxaline hydrochloride; - 4-(2-aminoethyl)-N-(5-chloro-6-piperazin-1-yl-3-pyridyl)benzamide dihydrochloride; - phenyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate 2,2,2-trifluoroacetic acid; - 2-(5-chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,3,4-oxadiazole; - 3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,2,4-oxadiazole hydrochloride; - 3-(5-chloro-6-piperazin-1-yl-3-pyridyl)prop-2-yn-1-amine 2,2,2-trifluoroacetic acid; - 5-(5-chloro-6-piperazin-1-yl-3-pyridyl)pent-4-yn-1-amine 2,2,2-trifluoroacetic acid; - 4-(5-chloro-6-piperazin-1-yl-3-pyridyl)but-3-yn-1-amine 2,2,2-trifluoroacetic acid; - 3-chloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-6-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 6-Bromo-3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2-piperazin-1-yl-1,5-naphthyridine hydrochloride; - 2-chloro-6-methoxy-3-piperazin-1-yl-quinoxaline hydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)ethane-1,2-diamine dihydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)propane-1,3-diamine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)piperazin-2-one dihydrochloride; - 2-amino-N-(3-chloro-2-piperazin-1-yl-6-quinolyl)acetamide dihydrochloride; - [3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]methanamine dihydrochloride; - 2-[3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; - 3-[3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]propan-1-amine dihydrochloride; - [3-[(5-chloro-6-piperazin-1-yl-3-pyridyl)methoxy]phenyl]methanamine dihydrochloride; - [3-[(5-chloro-6-piperazin-1-yl-3-pyridyl)oxymethyl]phenyl]methanamine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-(4-piperidyl)quinolin-6-amine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)piperidin-4-amine dihydrochloride; - 3-chloro-6-(1,4-diazepan-1-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - (3R)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3R)-pyrrolidin-3-yl]quinolin-6-amine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)azetidin-3-amine dihydrochloride; - 3-chloro-6-(2,6-diazaspiro[3.3]heptan-2-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-6-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-6-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-2-piperazin-1-yl-6-(1-piperidyl)quinoline hydrochloride; - 4-(3-chloro-2-piperazin-1-yl-6-quinolyl)morpholine hydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]methanamine dihydrochloride; - 2-[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]ethanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-yl]methanamine dihydrochloride - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-piperidyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - 1-(3-chloro-5-ethynyl-2-pyridyl)piperazine; - 3,7-dichloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-6-phenyl-2-piperazin-1-yl-quinoline hydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanol hydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N-methyl-methanamine dihydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N,N-dimethyl-methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-piperidyl]methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-yl]methanamine dihydrochloride; - (3R)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3R)-pyrrolidin-3-yl]quinolin-6-amine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3S)-3-piperidyl]quinolin-6-amine dihydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)butane-1,4-diamine dihydrochloride; - (1S)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - (1R)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-fluoro-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-pyridyl]methanamine dihydrochloride; - 3-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]propan-1-amine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3,8-dichloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one hydrochloride; - 1-[3-chloro-5-(2-phenylethynyl)-2-pyridyl]piperazine 2,2,2-trifluoroacetic acid; - 2-[2-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 2-[3-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 2-[4-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 3-chloro-2-piperazin-1-yl-6-(1,2,3,4-tetrahydroisoquinolin-5-yl)quinoline dihydrochloride; - 3-chloro-6-isoindolin-4-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-6-isoindolin-5-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]propan-2-amine dihydrochloride; - 2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-2-yl]methanamine dihydrochloride; - 2-[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-2-yl]ethanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]methanamine dihydrochloride; - 2-[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]ethanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]ethanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-3-yl]methanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-3-yl]ethanamine dihydrochloride; - 3-(2-aminoethyl)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one dihydrochloride; - 1-(2-aminoethyl)-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-[2-(dimethylamino)ethyl]pyrrolidin-2-one dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-[2-(dimethylamino)ethyl]imidazolidin-2-one dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-3-yl]methanamine dihydrochloride; - 2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-3-yl]ethanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-5-yl]methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,3,4-oxadiazol-2-yl]methanamine dihydrochloride; - 2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,3,4-oxadiazol-2-yl]ethanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)oxazol-2-yl]methanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)oxazol-2-yl]ethanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)thiazol-2-yl]methanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)thiazol-2-yl]ethanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-imidazol-2-yl]methanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-imidazol-2-yl]ethanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-1,2,4-triazol-5-yl]methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-1,2,4-triazol-5-yl]ethanamine dihydrochloride; - 6-[3-(aminomethyl)phenyl]-N-[(1S,5R)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinolin-2-amine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methyl-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [2-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [2-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-pyridyl]methanamine dihydrochloride; - [6-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-pyridyl]methanamine dihydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-pyridyl]methanamine dihydrochloride; - [6-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrazin-2-yl]methanamine dihydrochloride; - 3-chloro-6-imidazol-1-yl-2-piperazin-1-yl-quinoline hydrochloride; and - (1S,4S)-2-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-2,5-diazabicyclo[2.2.1]heptane formic acid is selected from.

[0045] In another embodiment, the compound of formula (I) is - 1-(3-chloro-5-iodo-2-pyridyl)piperazine; - [4-(2-aminoethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-chloro-2-(4-methylpiperazin-1-yl)quinoline; - 3-chloro-2-piperazin-1-yl-quinoline; - 3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Bromo-2-piperazin-1-yl-quinoline hydrochloride; - 2-chloro-3-piperazin-1-yl-quinoxaline hydrochloride; - 3-iodo-2-piperazin-1-yl-quinoline hydrochloride; - [3-(aminomethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-Bromo-6-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Bromo-6-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2,6-di(piperazin-1 yl)quinoline dihydrochloride; - 3-chloro-6-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 6-Bromo-3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 2-[3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; - 2-chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline hydrochloride; - 5-(5-chloro-6-piperazin-1-yl-3-pyridyl)pent-4-yn-1-amine 2,2,2-trifluoroacetic acid; - 3-chloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)ethane-1,2-diamine dihydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)propane-1,3-diamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - 2-Amino-N-(3-chloro-2-piperazin-1-yl-6-quinolyl)acetamide dihydrochloride. - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]methanamine dihydrochloride; - 2-[2-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 2-[3-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 2-[4-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 3,7-dichloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)butane-1,4-diamine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3S)-3-piperidyl]quinolin-6-amine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-piperidyl]methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-yl]methanamine dihydrochloride; - (3R)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanol hydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N-methyl-methanamine dihydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N,N-dimethyl-methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]propan-2-amine dihydrochloride; - (1S)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - (1R)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 3-chloro-2-piperazin-1-yl-6-(1,2,3,4-tetrahydroisoquinolin-5-yl)quinoline dihydrochloride; - 3-chloro-6-isoindolin-4-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 3-Chloro-6-isoindolin-5-yl-2-piperazin-1-yl-quinoline dihydrochloride - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-fluoro-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-pyridyl]methanamine dihydrochloride; - 3-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]propan-1-amine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3,8-dichloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one hydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methyl-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [2-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [2-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; and [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-pyridyl]methanamine dihydrochloride is selected from.

[0046] The compounds provided herein can be formulated into pharmaceutical compositions, optionally by admixture with one or more pharma- ceutically acceptable excipients.

[0047] For this reason, the present invention also relates to a pharmaceutical composition comprising a compound of formula (I) as defined in this section, and a pharma- ceutically acceptable excipient.

[0048] Such compositions may be prepared for oral administration, in particular in the form of tablets or capsules, in particular orodispersible (lyoc) tablets, or for parenteral administration, in particular in the form of solutions, suspensions or emulsions.

[0049] It can be prepared by any method well known in the pharmaceutical art, for example, as described in Remington: The Science and Practice of Pharmacy, 20th ed.; Gennaro, AR, Ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2000. Pharmaceutically compatible binding agents and / or adjuvant materials can be included as part of the composition. Oral compositions will generally include an inert diluent carrier or an edible carrier. It can be administered in unit dosage form, where the term "unit dosage" refers to a single dosage that can be administered to a patient, can be easily handled and packaged, and remains as a physically and chemically stable unit dosage containing either the active compound itself or a pharma-ceutically acceptable composition.

[0050] Tablets, pills, powders, capsules, lozenges, etc. may contain one or more of the following ingredients or compounds of similar nature: binders, such as microcrystalline cellulose or gum tragacanth; diluents, such as starch or lactose; disintegrants, such as starch and cellulose derivatives; lubricants, such as magnesium stearate; lubricants, such as colloidal silicon dioxide; sweeteners, such as sucrose or saccharin, or flavorings, such as peppermint or methyl salicylate. Capsules can be in the form of hard capsules or soft capsules, which are generally made from gelatin blends and starch capsules, optionally blended with plasticizers. In addition, dosage unit forms may contain various other materials that modify the physical form of the dosage unit, such as coatings of sugar, shellac, or enteric agents. Other oral dosage forms, such as syrups or elixirs, may contain sweeteners, preservatives, dyes, colorings, and flavorings. In addition, the active compounds may be incorporated into fast dissolving, slow release or extended release preparations and formulations, where such extended release formulations are preferably bimodal.

[0051] Liquid preparations for administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Liquid compositions may also include binders, buffers, preservatives, chelating agents, sweeteners, flavorings and colorants, and the like. Non-aqueous solvents include alcohol, propylene glycol, polyethylene glycol, acrylate copolymers, vegetable oils, such as olive oil, and organic esters, such as ethyl oleate. Aqueous carriers include mixtures of alcohol and water, hydrogels, buffer media, and saline. In particular, biocompatible and biodegradable lactide polymers, lactide / glycolide copolymers, or polyoxyethylene-polyoxypropylene copolymers may be useful excipients for controlling the release of active compounds. Intravenous vehicles may include fluid and nutrient replenishers, electrolyte replenishers, such as those based on Ringer's dextrose, and the like.

[0052] Examples of modes of administration include parenteral, eg, subcutaneous, intramuscular, intravenous, intradermal, and oral administration.

[0053] Compounds for Use / Methods of Treatment As already mentioned, the present invention also relates to a compound of formula (I): [ka] [In the formula, - X may be selected from CH and N; - Y may be selected from CH and N; - R 1 may be selected from a halogen atom; a -(C1-C3) alkyl group; a -(C1-C3) halogenoalkyl group; a -(C1-C3) alkoxy group; a nitrile group; R 1 is combined with Y to form fused phenyl groups at the 3- and 4-positions, - R 2a halogen atom, excluding fluorine atom; an -(C1-C6)alkyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkenyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkynyl group optionally substituted with one heteroatom selected from O, N or S; a -(C1-C3)alkoxy group; a -(C1-C3)halogenoalkyl group; a -COORa group; a -N(H)Rb-Ra group; an -(C1-C3)alkyl group optionally substituted with an -(C2-C6)alkynyl-(C6-C 10 ) aryl groups, in which the -(C1-C3) alkyl group is optionally substituted with an -NRR' group; CONH-(C6-C3) optionally substituted with an -(C1-C3) alkyl group; 10 )aryl groups, wherein the -(C1-C3)alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C3)alkyl optionally substituted by an -NRR' group; 10 )aryl groups; -O-(C1-C3)alkyl-(C6-C7)alkyl groups optionally substituted with -NRR' groups; 10 )aryl groups; (5-6 membered)heteroaryl groups optionally substituted by (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S and optionally substituted by -NRR' groups; -CONH-(C1-C3)alkyl-(C6-C3)alkyl-(C6-C3)alkyl optionally substituted by halogen atoms, methyl groups or methoxy groups; 10 ) an aryl group; or R 2is taken together with the carbon atom at the 6th position to form a fused phenyl or (5-6 membered) heteroaryl at the 5th and 6th positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR (4-10 membered) heterocycles optionally substituted by one or more of R' groups or carbonyl, wherein said -(C1-C3)alkyl groups are optionally substituted by NRR' groups; NH-heterocycles containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; (C6-C3) alkyl groups optionally substituted by one or more of halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or OH. 10 )aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 and optionally substituted with one or more of the following groups: - Ra is selected from -(C1-C6)alkyl groups; -(C1-C4)alkyl groups optionally substituted with halogen atoms, -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms; -(C1-C3)alkyl-phenyl groups optionally substituted with halogen atoms, -(C1-C4)alkyl groups optionally substituted with 1 to 3 fluorine atoms, -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms; -(C1-C3)alkyl groups optionally substituted with -NRR' groups, or -(C1-C3)alkyl-(5-6 membered)heteroaryl groups optionally substituted with halogen atoms, methyl groups optionally substituted with 1 to 3 fluorine atoms, methoxy groups optionally substituted with 1 to 3 fluorine atoms, - R and R' are the same or different and are selected from -(C1-C3)alkyl groups and H; Rb is selected from carbonyl and SO2; - R 3 is selected from heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, optionally substituted by -(C1-C3)alkyl or -NRR' groups, and -NH-heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, R 7 and R 8 are the same or different and selected from H, -(C1-C6)alkyl and -CO-(C1-C6)alkyl groups, said -(C1-C6)alkyl and -CO-(C1-C6)alkyl groups being optionally substituted by -NRR' groups. or a pharma- ceutically acceptable salt, or an optical isomer, racemate, diastereoisomer, enantiomer or tautomer thereof.

[0054] In one embodiment, - X may be selected from CH and N; - Y may be selected from CH and N; - R 1 may be selected from a halogen atom; a -(C1-C3) alkyl group; a -(C1-C3) halogenoalkyl group; a -(C1-C3) alkoxy group; a nitrile group; R 1 is combined with Y to form fused phenyl groups at the 3- and 4-positions, - R 2 a halogen atom, other than a fluorine atom; an -(C1-C6) alkyl group optionally substituted with one heteroatom selected from O, N, or S; an -(C2-C6) alkenyl group optionally substituted with one heteroatom selected from O, N, or S; an -(C2-C6) alkynyl group optionally substituted with one heteroatom selected from O, N, or S; a -(C1-C3) alkoxy group; a -(C1-C3) halogenoalkyl group; a -COORa group; a -N(H)Rb-Ra group; a CONH-(C6-C6) optionally substituted with a -(C1-C3) alkyl group; 10 )aryl groups, wherein the -(C1-C3)alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C3)alkyl optionally substituted by an -NRR' group; 10 )aryl groups; -O-(C1-C3)alkyl-(C6-C7)alkyl groups optionally substituted with -NRR' groups; 10 )aryl groups; (5-6 membered)heteroaryl groups optionally substituted by (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S and optionally substituted by -NRR' groups; -CONH-(C1-C3)alkyl-(C6-C3)alkyl-(C6-C3)alkyl optionally substituted by halogen atoms, methyl groups or methoxy groups; 10 ) an aryl group; or R 2is taken together with the carbon atom at the 6-position to form a fused phenyl or (5-6 membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3) (4-10 membered) heterocycles optionally substituted by alkyl groups, NRR' groups or carbonyls, said -(C1-C3)alkyl groups being optionally substituted by NRR' groups; NH-heterocycles containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; (C6-C3) optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, (C1-C3)alkyl groups optionally substituted by -NRR' groups or OH; 10 )aryl groups; (5-6 membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1 to 3 fluorine atoms, methoxy groups optionally substituted by 1 to 3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 is optionally substituted by a group; - Ra is selected from -(C1-C6)alkyl groups; -(C1-C4)alkyl groups optionally substituted with halogen atoms, -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms; -(C1-C3)alkyl-phenyl groups optionally substituted with -(C1-C3)alkyl groups, said -(C1-C3)alkyl groups being substituted with -NRR' groups or -(C1-C3)alkyl-(5-6 membered)heteroaryl groups optionally substituted with halogen atoms, methyl groups optionally substituted with 1 to 3 fluorine atoms, methoxy groups optionally substituted with 1 to 3 fluorine atoms, - R and R' are the same or different and are selected from -(C1-C3)alkyl groups and H; Rb is selected from carbonyl and SO2; - R 3 is selected from heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, optionally substituted by -(C1-C3)alkyl or -NRR' groups, and -NH-heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, R 7 and R 8 are the same or different and selected from H, -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups, said -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups being optionally substituted with -NRR' groups.

[0055] especially, - R 1 may be selected from a halogen atom; a -(C1-C3) alkyl group; a -(C1-C3) halogenoalkyl group, a -(C1-C3) alkoxy group or a nitrile group; and / or - R 2a halogen atom, excluding fluorine atom; an -(C1-C6)alkyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkenyl group optionally substituted with one heteroatom selected from O, N or S; an -(C2-C6)alkynyl group optionally substituted with one heteroatom selected from O, N or S; a -(C1-C3)alkoxy group; a -(C1-C3)halogenoalkyl group; a -COORa group; a -N(H)Rb-Ra group; an -(C1-C3)alkyl group optionally substituted with an -(C2-C6)alkynyl-(C6-C 10 ) aryl groups, wherein the -(C1-C3) alkyl group is optionally substituted with an -NRR' group; CONH-(C6-C3) optionally substituted with an -(C1-C3) alkyl group; 10 )aryl groups, wherein the -(C1-C3)alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C3)alkyl optionally substituted by an -NRR' group; 10 )aryl groups; -O-(C1-C3)alkyl-(C6-C7)alkyl groups optionally substituted with -NRR' groups; 10 )aryl groups; (5-6 membered)heteroaryl groups optionally substituted by (C1-C3)alkyl groups having at least one heteroatom selected from O, N or S and optionally substituted by -NRR' groups; -CONH-(C1-C3)alkyl-(C6-C3)alkyl-(C6-C3)alkyl optionally substituted by halogen atoms, methyl groups or methoxy groups; 10 ) an aryl group; or R 2is taken together with the carbon atom at the 6-position to form a fused phenyl or (5-6 membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR a (4-10 membered) heterocycle optionally substituted by one or more of R' groups or carbonyl, said -(C1-C3)alkyl group being optionally substituted by an NRR' group; an NH-heterocycle containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; a (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, a methyl group optionally substituted by 1-3 fluorine atoms, a methoxy group optionally substituted by 1-3 fluorine atoms, a -NRR' group or an OH-substituted (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, 10 )aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 and optionally substituted with one or more of the following groups: - Ra is selected from -(C1-C6)alkyl groups; -(C1-C4)alkyl groups optionally substituted with halogen atoms, -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms; -(C1-C3)alkyl-phenyl groups optionally substituted with -(C1-C3)alkyl groups, said -(C1-C3)alkyl groups being substituted with -NRR' groups or -(C1-C3)alkyl-(5-6 membered)heteroaryl groups optionally substituted with halogen atoms, methyl groups optionally substituted with 1 to 3 fluorine atoms, methoxy groups optionally substituted with 1 to 3 fluorine atoms, - R and R' are the same or different and are selected from -(C1-C3)alkyl groups and H; Rb is selected from carbonyl and SO2; and / or - R 3 is selected from heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, optionally substituted by -(C1-C3)alkyl or -NRR' groups, and -NH-heterocycles containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, R 7 and R 8 are the same or different and selected from H, -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups, said -(C1-C6)alkyl groups and -CO-(C1-C6)alkyl groups being optionally substituted with -NRR' groups.

[0056] In particular, - R 1 is a halogen atom and / or - R 2 may be selected from -(C2-C6)alkynyl groups optionally substituted with one heteroatom selected from O, N or S; or R2 is taken together with the carbon atom at the 6-position to form a fused phenyl or (5-6 membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, said fused phenyl or heteroaryl having one or more of the following: one or more halogen atoms, one or more -(C1-C4)alkyl groups, one or more -(C1-C3)halogenoalkyl groups, one or more -(C1-C3)alkoxy groups optionally substituted with 1 to 3 fluorine atoms, at least one N, and optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, -(C1-C3)alkyl groups, NR a (4-10 membered) heterocycle optionally substituted by one or more of R' groups or carbonyl, said -(C1-C3)alkyl group being optionally substituted by an NRR' group; an NH-heterocycle containing 4-10 members, having at least one N and not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1-2 carbon atoms; a (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, a methyl group optionally substituted by 1-3 fluorine atoms, a methoxy group optionally substituted by 1-3 fluorine atoms, a -NRR' group or an OH-substituted (C6-C3) alkyl group optionally substituted by one or more of halogen atoms, 10 )aryl groups; (5-12-membered)heteroaryl optionally substituted by halogen atoms, methyl groups optionally substituted by 1-3 fluorine atoms, methoxy groups optionally substituted by 1-3 fluorine atoms, -NRR' groups or (C1-C3)alkyl groups optionally substituted by OH; NR 7 R 8 and / or - X may be selected from CH and N; - Y may be selected from CH and N; X and Y are not simultaneously CH or N and / or - R 3is selected from heterocycles containing 4 to 10 members and having at least one N, in particular piperazine, said heterocycles optionally containing no or a bridge of 1 to 2 carbon atoms between the two members of the heterocycle, and optionally substituted by -(C1-C3)alkyl or -NRR' groups.

[0057] In particular, the compound is - X and Y are N or X is N and Y is CH; and / or - R 1 is a halogen atom and / or - R 2 may be selected from: a halogen atom, excluding fluorine and chlorine atoms; a -(C2-C6)alkynyl group optionally substituted by a -NRR' group; a -COORa group; a (5-6 membered) heteroaryl group optionally substituted by a (C1-C3)alkyl group having at least one heteroatom selected from O, N or S and optionally substituted by a -NRR' group; R 2 is taken together with the carbon atom in the 6-position and is optionally substituted by: one or more halogen atoms; one or more -(C1-C4)alkyl groups; a (4-10 membered) heterocycle having at least one N and which does not contain a bridge of carbon atoms between the two members of the heterocycle or which optionally contains a bridge of 1-2 carbon atoms; a (C1-C3)alkyl group optionally substituted by an -NRR' group 10 ) aryl group; NR 7 R 8 and / or forming a fused phenyl in the 5- and 6-positions, which are optionally substituted by a group; - Ra is a phenyl group optionally substituted by a -(C1-C3)alkyl group, optionally substituted by a NRR' group, and / or - R and R' are H and / or - R 3is a heterocycle containing 4 to 10 members, having at least one N, not containing a bridge of carbon atoms between the two members of the heterocycle or optionally containing a bridge of 1 to 2 carbon atoms, and optionally substituted by a methyl or an -NRR' group; and / or - R 7 and R 8 are the same or different and selected from H, -(C1-C3)alkyl and -CO-(C1-C3)alkyl, wherein the -(C1-C3)alkyl and -CO-(C1-C3)alkyl groups are optionally substituted by -NH.

[0058] In particular, the compound represented by formula (I) is - X and Y are N or X is N and Y is CH; and / or - R 1 is selected from chlorine, bromine and iodine and / or - R 2 is selected from a halogen atom, in particular iodine; an -(C2-C6)alkynyl group, in particular a pentynyl group, optionally substituted by an -NRR' group; a -COORa group; a (C1-C3)alkyl group having at least one heteroatom selected from O, N or S, optionally substituted by an -NRR' group, in particular a (5-6 membered)heteroaryl group, in particular an oxadiazole group, optionally substituted by an -NRR' group, in particular an ethyl group; R 2 taken together with the carbon atom in the 6-position represent halogen atoms, in particular chlorine, bromine and iodine; one or more -(C1-C4)alkyl groups, in particular methyl groups; (4-10 membered) heterocycles containing at least one N, in particular piperazine; (C1-C3)alkyl groups optionally substituted by -NRR' groups, in particular methyl (C6-C 10 ) aryl groups, in particular phenyl; NR 7 R 8 and / or forming a fused phenyl optionally substituted with a group - Ra is selected from the group consisting of a phenyl group optionally substituted by a -(C1-C3)alkyl group substituted by a NRR' group, - R and R' are H and / or - R 3 is piperazine optionally substituted by methyl and / or - R 7 and R 8 are the same or different and selected from H, -(C1-C3)alkyl groups, in particular ethyl and propyl, and -CO-(C1-C3)alkyl groups, in particular -CO-CH2-, said -(C1-C3)alkyl groups and -CO-(C1-C3)alkyl groups being optionally substituted by -NH2.

[0059] In one embodiment, the compound is: - 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-4-methyl-piperazine; - 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperazine; - 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; - 1-(5-bromo-3-chloro-2-pyridyl)-4-methyl-piperazine; - 1-(5-bromo-3-chloro-2-pyridyl)piperazine hydrochloride; - 1-(3-chloro-5-iodo-2-pyridyl)piperazine; - 1-(3-chloro-5-methyl-2-pyridyl)-4-methyl-piperazine; - 1-(3-chloro-5-methyl-2-pyridyl)piperazine hydrochloride; - N-[5-chloro-6-(4-methylpiperazin-1-yl)-3-pyridyl]acetamide; - N-(5-chloro-6-piperazin-1-yl-3-pyridyl)acetamide hydrochloride; - N-(5-chloro-6-piperazin-1-yl-3-pyridyl)methanesulfonamide hydrochloride; - methyl 5-chloro-6-(4-methylpiperazin-1-yl)pyridine-3-carboxylate; - methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - Ethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - benzyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - 2-Phenylethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - 3-phenylpropyl 5-chloro-6-piperazin-1-yl-pyridine-3 carboxylate hydrochloride; - p-Tolylmethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - (4-Chlorophenyl)methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - (4-Methoxyphenyl)methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - 2-(4-chlorophenyl)ethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - [4-(2-aminoethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-chloro-2-(4-methylpiperazin-1-yl)quinoline; - 3-chloro-2-piperazin-1-yl-quinoline; - 3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Bromo-2-piperazin-1-yl-quinoline hydrochloride; - 3-bromo-2-piperazin-1-yl-6-(trifluoromethyl)quinoline hydrochloride; - 3-Bromo-6-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methyl-piperazine; - 1-[2-chloro-4-(trifluoromethyl)phenyl]piperazine hydrochloride; - 2-chloro-3-piperazin-1-yl-quinoline hydrochloride; - 2-chloro-3-piperazin-1-yl-quinoxaline hydrochloride; - 1-[3-bromo-5-(trifluoromethyl)-2-pyridyl]-4-methyl-piperazine; - 1-[3-bromo-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; - 3-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 3-Methyl-2-piperazin-1-yl-quinoline hydrochloride; - 2-piperazin-1-ylquinoline-3-carbonitrile hydrochloride; - 1-[5-iodo-3-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; - 1-(3-chloro-5-iodo-2-pyridyl)piperazine; - 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-1,4-diazepane; - 3-chloro-2-(1,4-diazepan-1-yl)quinoline; - 2-chloro-3-(3,8-diazabicyclo[3.2.1]octan-3-yl)quinoxaline hydrochloride; - 3-[(3R)-3-methylpiperazin-1-yl]quinoxalin-2-ol hydrochloride; - 2-chloro-3-[(3S)-3-methylpiperazin-1-yl]quinoxaline hydrochloride; - N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinolin-2-amine hydrochloride; - 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperidin-4-amine; - 1-(3-chloro-5-methoxy-2-pyridyl)piperazine hydrochloride; - (1R,5S)-N-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-3-azabicyclo[3.1.0]hexan-6-amine formic acid; - 3-(4-chlorophenyl)propyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - [3-(aminomethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 5-chloro-N-[(4-chlorophenyl)methyl]-6-piperazin-1-yl-pyridine-3-carboxamide hydrochloride; - N-[4-(2-aminoethyl)phenyl]-5-chloro-6-piperazin-1-yl-pyridine-3-carboxamide dihydrochloride; - 2,6-dichloro-3-piperazin-1-yl-quinoline hydrochloride; - 2-chloro-6-methyl-3-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2-(3,8-diazabicyclo[3.2.1]octan-8-yl)quinoline hydrochloride; - 2-chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline hydrochloride; - N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinoxalin-2-amine hydrochloride; 3-Bromo-6-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2,6-di(piperazin-1 yl)quinoline dihydrochloride; - 2-Methoxy-3-piperazin-1-yl-quinoxaline 2,2,2-trifluoroacetic acid; - 2-chloro-3-(3,6-diazabicyclo[3.1.1]heptan-3-yl)quinoxaline trifluoromethanesulfonic acid; - 2-chloro-3-(4-ethylpiperazin-1-yl)quinoxaline hydrochloride; - 4-(2-aminoethyl)-N-(5-chloro-6-piperazin-1-yl-3-pyridyl)benzamide dihydrochloride; - phenyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate 2,2,2-trifluoroacetic acid; - 3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,2,4-oxadiazole hydrochloride; - 3-(5-chloro-6-piperazin-1-yl-3-pyridyl)prop-2-yn-1-amine 2,2,2-trifluoroacetic acid; - 5-(5-chloro-6-piperazin-1-yl-3-pyridyl)pent-4-yn-1-amine 2,2,2-trifluoroacetic acid; - 4-(5-chloro-6-piperazin-1-yl-3-pyridyl)but-3-yn-1-amine 2,2,2-trifluoroacetic acid; - 3-chloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-6-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 6-Bromo-3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2-piperazin-1-yl-1,5-naphthyridine hydrochloride; - 2-chloro-6-methoxy-3-piperazin-1-yl-quinoxaline hydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)ethane-1,2-diamine dihydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)propane-1,3-diamine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)piperazin-2-one dihydrochloride; - 2-amino-N-(3-chloro-2-piperazin-1-yl-6-quinolyl)acetamide dihydrochloride; - [3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]methanamine dihydrochloride; - 2-[3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; - 3-[3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]propan-1-amine dihydrochloride; - [3-[(5-chloro-6-piperazin-1-yl-3-pyridyl)methoxy]phenyl]methanamine dihydrochloride; - [3-[(5-chloro-6-piperazin-1-yl-3-pyridyl)oxymethyl]phenyl]methanamine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-(4-piperidyl)quinolin-6-amine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)piperidin-4-amine dihydrochloride; - 3-chloro-6-(1,4-diazepan-1-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - (3R)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3R)-pyrrolidin-3-yl]quinolin-6-amine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)azetidin-3-amine dihydrochloride; - 3-chloro-6-(2,6-diazaspiro[3.3]heptan-2-yl)-2-piperazin-1-yl-quinoline dihydrochloride - 3-chloro-6-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-6-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-2-piperazin-1-yl-6-(1-piperidyl)quinoline hydrochloride; - 4-(3-chloro-2-piperazin-1-yl-6-quinolyl)morpholine hydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]methanamine dihydrochloride; - 2-[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]ethanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-yl]methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-piperidyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - 1-(3-chloro-5-ethynyl-2-pyridyl)piperazine; - 3,7-dichloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-6-phenyl-2-piperazin-1-yl-quinoline hydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanol hydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N-methyl-methanamine dihydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N,N-dimethyl-methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-piperidyl]methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-yl]methanamine dihydrochloride; - (3R)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3R)-pyrrolidin-3-yl]quinolin-6-amine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3S)-3-piperidyl]quinolin-6-amine dihydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)butane-1,4-diamine dihydrochloride; - (1S)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - (1R)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-fluoro-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-pyridyl]methanamine dihydrochloride; - 3-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]propan-1-amine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3,8-dichloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one hydrochloride; - 1-[3-chloro-5-(2-phenylethynyl)-2-pyridyl]piperazine 2,2,2-trifluoroacetic acid; - 2-[2-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 2-[3-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 2-[4-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 3-chloro-2-piperazin-1-yl-6-(1,2,3,4-tetrahydroisoquinolin-5-yl)quinoline dihydrochloride; - 3-chloro-6-isoindolin-4-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-6-isoindolin-5-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]propan-2-amine dihydrochloride; - 2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-2-yl]methanamine dihydrochloride; - 2-[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-2-yl]ethanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]methanamine dihydrochloride; - 2-[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]ethanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]ethanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-3-yl]methanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-3-yl]ethanamine dihydrochloride; - 3-(2-aminoethyl)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one dihydrochloride; - 1-(2-aminoethyl)-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-[2-(dimethylamino)ethyl]pyrrolidin-2-one dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-[2-(dimethylamino)ethyl]imidazolidin-2-one dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-3-yl]methanamine dihydrochloride; - 2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-3-yl]ethanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-5-yl]methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,3,4-oxadiazol-2-yl]methanamine dihydrochloride; - 2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,3,4-oxadiazol-2-yl]ethanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)oxazol-2-yl]methanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)oxazol-2-yl]ethanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)thiazol-2-yl]methanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)thiazol-2-yl]ethanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-imidazol-2-yl]methanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-imidazol-2-yl]ethanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-1,2,4-triazol-5-yl]methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-1,2,4-triazol-5-yl]ethanamine dihydrochloride; - 6-[3-(aminomethyl)phenyl]-N-[(1S,5R)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinolin-2-amine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methyl-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [2-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [2-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-pyridyl]methanamine dihydrochloride; - [6-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-pyridyl]methanamine dihydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-pyridyl]methanamine dihydrochloride; - [6-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrazin-2-yl]methanamine dihydrochloride; - 3-chloro-6-imidazol-1-yl-2-piperazin-1-yl-quinoline hydrochloride; and - (1S,4S)-2-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-2,5-diazabicyclo[2.2.1]heptane formic acid is selected from.

[0060] In another embodiment, the compound is - 1-(3-chloro-5-iodo-2-pyridyl)piperazine; - [4-(2-aminoethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-chloro-2-(4-methylpiperazin-1-yl)quinoline; - 3-chloro-2-piperazin-1-yl-quinoline; - 3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Bromo-2-piperazin-1-yl-quinoline hydrochloride; - 2-chloro-3-piperazin-1-yl-quinoxaline hydrochloride; - 3-iodo-2-piperazin-1-yl-quinoline hydrochloride; - [3-(aminomethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-Bromo-6-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Bromo-6-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2,6-di(piperazin-1 yl)quinoline dihydrochloride; - 3-chloro-6-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 6-Bromo-3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 2-[3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; - 2-chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline hydrochloride; - 5-(5-chloro-6-piperazin-1-yl-3-pyridyl)pent-4-yn-1-amine 2,2,2-trifluoroacetic acid; - 3-chloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)ethane-1,2-diamine dihydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)propane-1,3-diamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; 2-Amino-N-(3-chloro-2-piperazin-1-yl-6-quinolyl)acetamide dihydrochloride. - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]methanamine dihydrochloride; - 2-[2-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 2-[3-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 2-[4-[2-(5-chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetic acid; - 3,7-dichloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)butane-1,4-diamine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3S)-3-piperidyl]quinolin-6-amine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-piperidyl]methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-yl]methanamine dihydrochloride; - (3R)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanol hydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N-methyl-methanamine dihydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N,N-dimethyl-methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]propan-2-amine dihydrochloride; - (1S)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - (1R)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 3-chloro-2-piperazin-1-yl-6-(1,2,3,4-tetrahydroisoquinolin-5-yl)quinoline dihydrochloride; - 3-chloro-6-isoindolin-4-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 3-Chloro-6-isoindolin-5-yl-2-piperazin-1-yl-quinoline dihydrochloride - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-fluoro-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-pyridyl]methanamine dihydrochloride; - 3-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]propan-1-amine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3,8-dichloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one hydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methyl-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [2-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [2-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; and - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-pyridyl]methanamine dihydrochloride is selected from.

[0061] When administered in combination with an antibiotic, the compounds can be used to treat bacterial infections.

[0062] In particular, the compounds of formula (I) defined in this section allow for the treatment of both antibiotic-susceptible and antibiotic-resistant bacteria in combination with antibiotics.

[0063] "Antibiotic resistance" is well known in the art. Bacteria can acquire resistance, but they can also be innately resistant to antibiotic molecules. Antibiotic efflux pumps can be involved in both of these processes. The expression of basal efflux pumps can make bacteria innately resistant to some antibiotics, while mutations that lead to the overexpression of these pumps can result in acquired resistance. The compounds of the present invention act on both of these forms of resistance.

[0064] As a result, the compounds of the present invention can be used to prevent and / or treat infections caused by bacteria with innate and / or acquired antibiotic resistance.

[0065] Examples include infections such as pneumonia, bronchitis, ear infections, meningitis, urinary tract infections, sepsis and sexually transmitted diseases.

[0066] In particular, the compounds are used to prevent and / or treat Gram-negative bacteria that have innate or acquired antibiotic resistance.

[0067] In one embodiment, the compounds are used to prevent and / or treat a subject suffering from an infection caused by a Gram-negative bacteria with innate and acquired antibiotic resistance.

[0068] As used herein, "Gram-negative bacteria" has its general meaning known in the art.

[0069] Examples include Escherichia coli (E. coli), Salmonella, Shigella and other enterobacteria, Pseudomonas, Moraxella, Helicobacter, Campylobacter, Stenotrophomonas, Bdellovibrio, acetic acid bacteria, Legionella, cyanobacteria, spirochetes, green sulfur bacteria and green non-sulfur bacteria, Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis, Haemophilus influenza, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens, Helicobacter pylori, Salmonella enteritidis, Salmonella typhi and Acinetobacter baumannii.

[0070] In particular, said Gram-negative bacteria are selected from E. coli, K. pneumoniae and other Enterobacteriaceae, A. baumannii, P. aeruginosa, Neisseria gonorrhoeae, Shigella species.

[0071] In particular, said compound is a Gram-negative bacterial efflux pump inhibitor. "Bacterial efflux pump" is well known in the art. Efflux pump is a bacterial transport protein involved in the extrusion of substrate from bacteria to the external environment. In the context of the present invention, particularly, efflux pumps belonging to the resistance nodule distribution (RND) superfamily in Gram-negative bacteria are contemplated. RND pumps are highly conserved among Gram-negative bacteria, and many efflux pump inhibitors show broad spectrum RND pump inhibition due to the conserved binding pocket interaction. Such are the residues that interact with the compounds presented herein.

[0072] In particular, compounds of formula (I) are capable of binding to the transmembrane domain, thereby exerting an allosteric influence on the conformational promoter cycle and on the drug efflux process.

[0073] The present invention also relates to a method for treating a bacterial infection, comprising administering to a subject in need of such treatment a compound of formula (I) as defined in this section in combination with an antibiotic.

[0074] In particular, as mentioned above, the compounds of formula (I) are gram-negative bacterial efflux pump inhibitors.

[0075] In particular, the methods of the present invention allow for the prevention and / or treatment of gram-negative bacteria when given in combination with an antibiotic.

[0076] In particular, said Gram-negative bacteria are selected from E. coli, K. pneumoniae and other Enterobacteriaceae, A. baumannii, P. aeruginosa, Neisseria gonorrhoeae and Shigella species.

[0077] The terms "treat", "treating", "treated" or "treatment" refer to therapeutic treatments aimed at eliminating or reducing antibiotic resistance. Beneficial or desired clinical results include, but are not limited to, elimination of resistance, alleviation of resistance, reduction in the severity of the condition, stabilization of the condition (i.e., not worsening), delay or slowing of the progression of the condition. In particular, as used in the context of the present invention, treatment of antibiotic resistance refers to the elimination or reduction of the resistance phenomenon.

[0078] As used in the context of the present invention, the term "prevent", "prevention", "preventing" or "prevented" refers to the prevention of the onset, recurrence or spread of antibiotic resistance or one or more symptoms thereof. In certain embodiments, the term refers to treatment with or administration of the compounds provided herein before resistance develops, particularly to patients at risk of antibiotic resistance. The term encompasses the inhibition or reduction of resistance. In particular, in certain embodiments, subjects with a family history of infections associated with antibiotic resistance are candidates for a prevention regimen. In addition, subjects with a history of recurrent symptoms and / or resistance are also potential candidates for prevention. In this regard, the term "prevention" can be used interchangeably with the term "prophylactic treatment".

[0079] In particular, subjects in need of prevention and / or treatment against antibiotic resistance are those suffering from a disease caused by bacteria, in particular the gram-negative bacteria described herein.

[0080] In the context of the present invention, the identification of subjects in need of treatment for the conditions described herein is performed as mentioned above and is within the ability and knowledge of one of ordinary skill in the art. A skilled clinician can readily identify subjects in need of such treatment by the techniques mentioned above.

[0081] Therapeutically effective amounts can be easily determined by diagnosticians who are skilled in the art by using conventional techniques and observing the results obtained under similar circumstances. In determining a therapeutically effective amount, a number of factors are considered by diagnosticians. These factors include, but are not limited to, the species of the subject; its size, age and general health condition; the specific disease and / or bacteria involved; the degree of involvement or severity of disease and / or resistance; the response of the individual subject; the specific compound administered; the mode of administration; the bioavailability characteristics of the administered preparation; the selected dosing schedule; the use of concomitant drugs and other relevant circumstances.

[0082] As used herein, "effective amount" refers to an amount effective to reduce, eliminate, treat or inhibit antibiotic resistance. The term "inhibit" is intended to refer to all processes that may slow, interrupt, arrest or stop the progression of antibiotic resistance, but does not necessarily indicate complete elimination of symptoms of all diseases and conditions, and is intended to include prophylactic treatment and chronic use.

[0083] The term "patient" or "subject" refers to a warm-blooded animal, e.g., a mammal, particularly a human, unless otherwise specified, male or female, suffering from or capable of suffering from antibiotic resistance, as described herein.

[0084] The amount of a compound of the invention required to achieve a desired biological effect will vary depending on a number of factors, including the dosage of the drug administered, the chemical properties of the compound utilized (e.g., hydrophobicity), the potency of the compound, the type of resistance, the resistance state in the patient, and the route of administration.

[0085] The compounds provided herein can be formulated into pharmaceutical compositions, optionally by admixture with one or more pharma- ceutically acceptable excipients.

[0086] Such compositions may be prepared for oral administration, in particular in the form of tablets or capsules, in particular orodispersible (lyoc) tablets, or for parenteral administration, in particular in the form of solutions, suspensions or emulsions.

[0087] For example, Remington: The Science and Practice of Pharmacy, 20 thThe composition may be prepared by any method known in the pharmaceutical art, as described in, for example, ed.; Gennaro, AR, Ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2000. Pharmaceutically compatible binding agents and / or adjuvant materials may be included as part of the composition. Oral compositions will generally include an inert diluent carrier or an edible carrier. They may be administered in unit dosage form, where the term "unit dosage" refers to a single dosage that can be administered to a patient, can be easily handled and packaged, and remains as a physically and chemically stable unit dosage containing either the active compound itself or a pharma-ceutically acceptable composition.

[0088] Tablets, pills, powders, capsules, lozenges, etc. may contain one or more of the following ingredients or compounds of similar nature: binders, such as microcrystalline cellulose or gum tragacanth; diluents, such as starch or lactose; disintegrants, such as starch and cellulose derivatives; lubricants, such as magnesium stearate; lubricants, such as colloidal silicon dioxide; sweeteners, such as sucrose or saccharin, or flavorings, such as peppermint or methyl salicylate. Capsules can be in the form of hard capsules or soft capsules, which are generally made from gelatin blends and starch capsules, optionally blended with plasticizers. In addition, dosage unit forms may contain various other materials that modify the physical form of the dosage unit, such as coatings of sugar, shellac, or enteric agents. Other oral dosage forms, such as syrups or elixirs, may contain sweeteners, preservatives, dyes, colorings, and flavorings. In addition, the active compounds may be incorporated into fast dissolving, slow release or extended release preparations and formulations, where such extended release formulations are preferably bimodal.

[0089] Liquid preparations for administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Liquid compositions may also include binders, buffers, preservatives, chelating agents, sweeteners, flavorings and colorants, and the like. Non-aqueous solvents include alcohol, propylene glycol, polyethylene glycol, acrylate copolymers, vegetable oils, such as olive oil, and organic esters, such as ethyl oleate. Aqueous carriers include mixtures of alcohol and water, hydrogels, buffer media, and saline. In particular, biocompatible and biodegradable lactide polymers, lactide / glycolide copolymers, or polyoxyethylene-polyoxypropylene copolymers may be useful excipients for controlling the release of active compounds. Intravenous vehicles may include fluid and nutrient replenishers, electrolyte replenishers, such as those based on Ringer's dextrose, and the like.

[0090] Examples of modes of administration include parenteral, eg, subcutaneous, intramuscular, intravenous, intradermal, and oral administration.

[0091] Manufacturing method The present invention also relates to methods for preparing the compounds of formula (I) described herein.

[0092] The compounds and methods of the present invention can be prepared in many ways well known to those skilled in the art. The compounds can be synthesized, for example, by applying or adapting the methods described below or variations thereof that will be understood by those skilled in the art. Appropriate modifications and substitutions will be readily apparent and well known to those skilled in the art or will be readily available from the scientific literature.

[0093] It will be understood that the compounds of the present invention may contain one or more asymmetrically substituted carbon atoms and may be isolated in optically active or racemic forms.Thus, all chiral, diastereomeric, racemic, isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated.Methods for preparing and isolating such optically active forms are well known in the art.

[0094] For example, mixtures of stereoisomers can be separated by standard techniques including, but not limited to, separation of racemates, normal phase, reverse phase and chiral chromatography, preferential salt formation, recrystallization, etc., or by either chiral synthesis from chiral starting materials or deliberate synthesis of targeted chiral centers.

[0095] The compounds of the present invention can be prepared by a variety of synthetic routes. The reagents and starting materials are commercially available or readily synthesized by those of ordinary skill in the art using well-known techniques. Unless otherwise specified, all substituents are as previously defined.

[0096] In the reactions described below, reactive functional groups, such as hydroxyl, amino, imino, thio or carboxy groups, may need to be protected if desired in the final product to avoid unwanted participation in the reaction. Conventional protecting groups can be used according to standard practice. See, for example, TW Greene and PGM Wuts in Protective Groups in Organic Chemistry, 4th ed.(2007), John Wiley & Sons Inc., 1999;JFW McOmie in Protective Groups in Organic Chemistry, Plenum Press, 1973.

[0097] The compound thus prepared can be recovered from the reaction mixture by conventional means.For example, the compound can be recovered by distilling off the solvent from the reaction mixture, or, if necessary, by distilling off the solvent from the reaction mixture, pouring the residue into water, followed by extraction with a water-immiscible organic solvent and distilling off the solvent from the extract.Furthermore, if necessary, the product can be further purified by various well-known techniques, such as recrystallization, reprecipitation, or various chromatographic techniques, particularly column chromatography or preparative thin-layer chromatography.

[0098] The reactions can be carried out by the person skilled in the art by applying or adapting the methods illustrated in the examples below.

[0099] In particular, compounds of formula (I) can be prepared according to protocols 1 to 5, as referred to in part A of the experimental part below.

[0100] Furthermore, the process of the present invention may also comprise the additional step of isolating the compound of formula (I), which may be accomplished by any of the conventional means known to those skilled in the art, such as the recovery methods described above.

[0101] Generally, the starting products are primarily commercially available from Fisher scientific, Fluorochem, Enamine or Sigma-Aldrich or other typical chemical suppliers or can be obtained by application or adaptation of any method known or described in the examples.

[0102] In the context of the present invention, "a compound for use in the prophylaxis or treatment" is understood to be equivalent to "use of a compound for the prophylaxis or treatment" and "use of a compound for the manufacture of a medicament for the prophylaxis or treatment".

[0103] The invention will be further illustrated by the following examples.

[0104] Working Example Part A - Synthesis of Compounds of the Invention Preparation of Compounds of Formula (I) Protocol 1 [ka] The chlorinated derivatives (0.2-1.3 mmol, 1 equiv.), the appropriate amine (1.2-5.6 equiv.) and NEt3 (1.3-2.2 equiv.) were dissolved in MeCN or toluene (0.8-5 mL). The mixtures were heated at 50°C, 80°C or 110°C for 2 h to 6 d, cooled to room temperature and then purified by flash or reverse phase chromatography.

[0105] Protocol 2 [ka] The chlorinated derivatives (0.2-2.2 mmol, 1 equiv.), the appropriate amine (1.5-3.2 equiv.), t-BuONa (1.4-2.5 equiv.), BINAP (0.03-0.08 equiv.), and Pd(OAc)2 (0.02-0.07 equiv.) were dissolved in toluene (0.6-3.0 mL) under argon. The mixtures were heated at 110°C for 2 h-3 d, cooled to room temperature, dried under vacuum, and purified by flash or reverse phase chromatography.

[0106] Protocol 3 The appropriate Boc-protected compound (0.04-0.7 mmol, 1 equiv.) was dissolved in 1,4-dioxane (0.3-3.0 mL) and 4N HCl in 1,4-dioxane (8-28 equiv.) was added. The mixture was stirred at room temperature for 3 h-5 days. The mixture was filtered under vacuum and if the compound precipitated, it was either rinsed with petroleum ether and MeOH or the mixture was evaporated under vacuum.

[0107] Protocol 4 [ka] Intermediate 22 (4.86 mmol, 1 equiv), NaOH (8.0 equiv) and 1.5 mL of water were stirred in 20 mL of methanol at 65° C. for 1 h. The reaction was diluted with water and then acidified with 1N aqueous HCl. The aqueous layer was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and evaporated under reduced pressure to give Intermediate 51.

[0108] Intermediate 51 (0.30-0.50 mmol, 1 equiv.) was stirred in EtOAc (1.5 mL) with NEt3 or K2CO3 (2-2.5 equiv.) and COMU (1.5-2.5 equiv.) at room temperature for 10 min. The corresponding alcohol or amine was then added (1.5 equiv.) and the reaction was stirred at room temperature for 1-24 h. If the product precipitated, it was isolated by filtration. If not, the reaction was washed once with 1N aqueous HCl and twice with saturated NaHCO3 solution and the product was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and evaporated under vacuum. Intermediates were purified by reverse or normal phase chromatography.

[0109] Protocol 5 [ka] A 1M solution of isopropyl chloroformate in toluene (1.5 equiv.) was added to 3 mL of anhydrous THF under argon. Intermediate 51 (1.7 mmol, 1 equiv.) and NEt3 (1.2 equiv.) were dissolved in 3 mL of anhydrous THF and added dropwise to the isopropyl chloroformate solution at 0°C. The reaction was allowed to warm to room temperature and stirred overnight. A saturated solution of NaHCO3 was added and the product was extracted twice with EtOAc. The organic layer was washed once with a saturated solution of NaHCO3 and once with brine, dried over MgSO4, and evaporated under reduced pressure. A solution of the previous compound (0.4-0.5 mmol, 1 equiv.) dissolved in 1 mL of anhydrous THF was added dropwise to a solution of the corresponding alcohol or amine (1.2-1.5 equiv.) and tBuOK or Na2CO3 (1.6-2.0 equiv.) dissolved in 1 mL of anhydrous THF at 0°C. The mixture was stirred at room temperature for 2-4 h. The reaction was diluted with EtOAc and then washed once with 1N aqueous HCl and twice with saturated NaHCO3 solution. The organic layers were combined, washed with saturated NaCl solution, dried over MgSO4, and evaporated in vacuo. The intermediate was purified by flash chromatography.

[0110] Intermediates Intermediates 1-4, 70: To a solution of 3-ethoxyacryloyl chloride (1.0 equiv.) in THF (4.0-9.3 mL) at 0° C. was added the corresponding aniline (4.0-9.4 mmol, 1 equiv.) and pyridine (1.5-1.6 equiv.). The mixture was stirred at room temperature overnight. The reaction was quenched with water, extracted three times with EtOAc, washed with brine, dried over MgSO4, and then evaporated under reduced pressure. The crude product was purified by flash chromatography. [Table 1]

[0111] Intermediates 5-8, 71: The corresponding starting intermediates (0.88-7.1 mmol, 1 equiv.) were added in portions to concentrated sulfuric acid (28 equiv.) at 0° C. The resulting mixture was stirred at room temperature for 2-3 h. The suspension was cooled at 0° C., quenched with Na2CO3 solution until pH=7-8, extracted three times with EtOAc, washed with brine, dried over MgSO4, and then evaporated under reduced pressure. [Table 2]

[0112] Intermediates 9-12, 72-74, 122: To a solution of the corresponding starting intermediate (0.9-4.8 mmol) in anhydrous DMF (2.4-13.0 mL) was added NBS or NCS (1.1-2.5 equiv.). The mixture was stirred at 60° C. for 1 h to overnight. The solution was cooled to room temperature, quenched with water, extracted three times with EtOAc, washed with brine, dried over MgSO4, evaporated under reduced pressure, and then purified by flash chromatography. [Table 3] TIFF2024527427000014.tif138165

[0113] Intermediates 13-16, 75-77, 123: To the corresponding starting intermediates (0.37-2.04 mmol) was added POCl3 (28-32 equiv.). The mixture was stirred at 100°C for 10 min-1 h, then the reaction mixture was poured onto ice, diluted with DCM, basified with NaOH, and extracted three times with DCM. The organic phase was washed with brine, dried over MgSO4, and then evaporated under reduced pressure. [Table 4] TIFF2024527427000016.tif126165

[0114] Intermediates 17–35, 78–81, and 124 were prepared according to Protocol 1. [Table 5] TIFF2024527427000018.tif238165 TIFF2024527427000019.tif198165 TIFF2024527427000020.tif240165 TIFF2024527427000021.tif202165 TIFF2024527427000022.tif164165

[0115] Intermediates 36-50 and 82 were prepared according to protocol 2. [Table 6] TIFF2024527427000024.tif214165 TIFF2024527427000025.tif241165 TIFF2024527427000026.tif236165

[0116] Intermediates 51-60 and 83 were prepared according to protocol 4. [Table 7] TIFF2024527427000028.tif211165 TIFF2024527427000029.tif194165

[0117] Intermediates 61-63 were prepared according to protocol 5. [Table 8]

[0118] Intermediate 64: tert-Butyl 4-(3-chloro-5-ethoxycarbonyl-2-pyridyl)piperazine-1-carboxylate [ka] Intermediate 51 (0.28 mmol) was dissolved in anhydrous DMF (1 mL) and potassium carbonate (2 equiv.) was added. The reaction mixture was stirred at room temperature for 5 min, then iodoethane (50 equiv.) was added. The reaction mixture was stirred at 100° C. overnight, then cooled to room temperature. The mixture was poured into a separatory funnel with EtOAc. The organic phase was washed twice with 1N HCl, once with brine, dried over MgSO4, then evaporated under reduced pressure. The residue was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-90 / 10) to give the title compound. Yield: 40%; 1 H NMR (300 MHz, CD2Cl2):δ 1.40 (t, J = 7.1 Hz, 3H), 1.50 (s, 9H), 3.50-3.54 (m, 4H), 3.57-3.61 (m, 4H), 4.37 (q, J = 7.1 Hz, 2H), 8.17 (d, J = 2.0 Hz, 1H), 8.76 (d, J = 2.0 Hz, 1H) ppm;[ES+ MS] m / z 370 (MH + ).

[0119] Intermediate 65: tert-Butyl 4-(5-amino-3-chloro-2-pyridyl)piperazine-1-carboxylate [ka] Intermediate 26 (1 mmol, 1 eq.), tBuOK (1.2 eq.) and bis(pinacolato)diboron (3.1 eq.) were heated in iPrOH at 110° C. for 4 h. The reaction was evaporated under reduced pressure and the product was purified by flash chromatography (DCM / MeOH 100 / 0-95 / 5) to give the title compound. Yield: 100%; 1H NMR (300 MHz, CD2Cl2):δ 1.45 (s, 9H), 3.03-3.08 (m, 4H), 3.48-3.69 (m, 6H), 7.06 (d, J = 2.6 Hz, 1H), 7.70 (d, J = 2.7 Hz, 1H) ppm; [ES+ MS] m / z 313 (MH + ).

[0120] Intermediate 66: tert-Butyl 4-(5-acetamido-3-chloro-2-pyridyl)piperazine-1-carboxylate [ka] A mixture of intermediate 65 (0.12 mmol, 1 eq.) and acetyl acetate (480 μL) was stirred at room temperature for 3 days. The reaction was washed with saturated NaHCO3 and extracted with EtOAc. The organic layers were combined, washed with brine, dried over MgSO4 and evaporated under reduced pressure. The product was purified by flash chromatography (DCM / MeOH 100 / 0-95 / 5) to give the title compound. Yield: 38%; 1 H NMR (300 MHz, CD2Cl2):δ 1.46 (s, 9H), 2.13 (s, 3H), 3.16-3.23 (m, 4H), 3.50-3.58 (m, 4H), 7.37 (s, 1H), 8.09 (d, J = 2.5 Hz, 1H), 8.15 (d, J = 2.5 Hz, 1H) ppm;[ES+ MS] m / z 355 (MH + ).

[0121] Intermediate 67: tert-Butyl 4-[3-chloro-5-(methanesulfonamido)-2-pyridyl]piperazine-1-carboxylate [ka] A mixture of intermediate 65 (0.47 mmol, 1 equiv.) and methanesulfonyl chloride (1.5 equiv.) in anhydrous pyridine (1 mL) was stirred at room temperature for 2 h. Water was added and the product was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-60 / 40) to give the title compound. Yield: 100%; 1 H NMR (300 MHz, CD2Cl2):δ 1.46 (s, 9H), 2.99 (s, 3H), 3.24-3.30 (m, 4H), 3.52-3.58 (m, 4H), 6.52 (s, 1H), 7.66 (d, J = 2.5 Hz, 1H), 8.07 (d, J = 2.5 Hz, 1H) ppm;[ES+ MS] m / z 391 (MH + ).

[0122] Intermediate 68: tert-Butyl 4-(3-iodo-2-quinolyl)piperazine-1-carboxylate [ka] A dry 10 mL tube was charged with intermediate 27 (0.17 mmol, 1 equiv), CuI (0.08 equiv) and sodium iodide (2.0 equiv). The tube was purged with argon for 30 min, then 1,4-dioxane (2.0 mL) and a solution of (1R,2R)-N1,N2-dimethylcyclohexane-1,2-diamine in 1,4-dioxane (0.1 equiv) were added. The mixture was heated at 110° C. for 3 days, and CuI (0.66 equiv) and (1R,2R)-N1,N2-dimethylcyclohexane-1,2-diamine (0.2 equiv) were added in small portions until the reaction was complete. After 21 days, the reaction was quenched with water and extracted twice with EtOAc. The organic layer was washed with brine, dried over MgSO4 and then evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0 to 90 / 10) to give the title compound. Yield: 30%; [ES+ MS] m / z 440 (MH +).

[0123] Intermediate 69: tert-Butyl 4-(3-methoxyquinoxalin-2-yl)piperazine-1-carboxylate [ka] Intermediate 29 (0.29 mmol, 1 equiv.) and K2CO3 (4 equiv.) in MeOH (1 mL) were heated at 65° C. for 1.5 h. The reaction mixture was cooled to room temperature and then to 0° C. Cold water was added and the precipitate was filtered to give the desired compound. Yield: 74%; 1 H NMR (300 MHz, CD2Cl2): δ 1.47 (s, 9H), 3.54-3.59 (m, 4H), 3.62-3.68 (m, 4H), 4.10 (s, 3H), 7.36-7.47 (m, 2H), 7.68 (dd, J = 2.4, 7.1 Hz, 2H) ppm;[ES+ MS] m / z 345 (MH + ).

[0124] Intermediates 84–86: tert-Butyl 4-(3-chloro-6-iodo-2-quinolyl)piperazine-1-carboxylate 79 (0.2 mmol, 1 equiv.), the appropriate amine (1.5–3.2 equiv.), Cs2CO3 (1.4–2.8 equiv.), Xantphos (0.08–0.09 equiv.), and Pd2dba3 (0.04–0.07 equiv.) were dissolved in 1,4-dioxane (0.8–1.0 mL) under argon. The mixtures were heated at 100 °C overnight–2 days, cooled to room temperature, dried under vacuum, and purified by flash chromatography. [Table 9]

[0125] Intermediate 87: tert-Butyl 4-(2,3-dichloro-6-quinolyl)-3-oxo-piperazine-1-carboxylate [ka] 2,3-Dichloro-6-iodo-quinoline 16 (0.6 mmol, 1 equiv.), tert-butyl 3-oxopiperazine-1-carboxylate (1.0 equiv.), Cs2CO3 (1.4 equiv.), Xantphos (0.04 equiv.), Pd2dba3 (0.02 equiv.) were dissolved in 1,4-dioxane (2.5 mL) under argon. The mixture was heated at 100° C. overnight, cooled to room temperature and dried under vacuum. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-50 / 50) to give the title compound. Yield: 84%; 1 H NMR (300 MHz, CD2Cl2):δ 1.49 (s, 9H), 3.81-3.84 (m, 4H), 4.25 (s, 2H), 7.70 (d, J = 2.3 Hz, 1H), 7.75 (dd, J = 2.4, 9.0 Hz, 1H), 8.00 (d, J = 9.0 Hz, 1H), 8.26 (s, 1H) ppm;[ES+ MS] m / z 396 (MH + ).

[0126] Intermediate 88: tert-Butyl 4-[2-(4-tert-butoxycarbonylpiperazin-1-yl)-3-chloro-6-quinolyl]-3-oxo-piperazine-1-carboxylate [ka] tert-Butyl 4-(2,3-dichloro-6-quinolyl)-3-oxo-piperazine-1-carboxylate 87 (0.4 mmol, 1 eq.), tert-butyl piperazine-1-carboxylate (1.5 eq.), t-BuONa (1.4 eq.), BINAP (0.02 eq.), Pd(OAc)2 (0.03 eq.) were dissolved in toluene (1.8 mL) under argon. The mixture was heated at 110° C. overnight, cooled to room temperature and dried under vacuum. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-20 / 80) to give the title compound. Yield: 26%; 1H NMR (300 MHz, CD2Cl2):δ 1.47 (s, 9H), 1.49 (s, 9H), 3.41-3.46 (m, 4H), 3.59-3.63 (m, 4H), 3.79 (s, 4H), 4.22 (s, 2H), 7.54-7.58 (m, 2H), 7.82 (dd, J = 0.7, 9.6 Hz, 1H), 8.05 (s, 1H) ppm;[ES+ MS] m / z 546 (MH + ).

[0127] Intermediate 89: tert-Butyl 4-[5-[[4-[2-(tert-butoxycarbonylamino)ethyl]benzoyl]amino]-3-chloro-2-pyridyl]piperazine-1-carboxylate [ka] 4-[2-(tert-butoxycarbonylamino)ethyl]benzoic acid (1.5 eq.) was stirred with NEt3 (3 eq.) and COMU (3 eq.) in EtOAc (2 mL) for 10 min at room temperature. Then, a solution of intermediate 65 (0.50 mmol, 1 eq.) in EtOAc (1 mL) was added and the reaction was stirred at room temperature for 48 h. The reaction was washed once with 1N aqueous HCl solution, twice with saturated NaHCO3 solution and the product was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and evaporated under vacuum. The crude product was purified by reverse phase chromatography (MeOH / H2O 10 / 90-100 / 0) to give the title compound. Yield: 25%; 1H NMR (300 MHz, CD2Cl2):δ 1.41 (s, 9H), 1.46 (s, 9H), 2.86 (t, J = 6.9 Hz, 2H), 3.22-3.26 (m, 4H), 3.37 (q, J = 6.7 Hz, 2H), 3.53-3.58 (m, 4H), 4.61 (brs, 1H), 7.34 (d, J = 8.2 Hz, 2H), 7.81 (d, J = 8.2 Hz, 2H), 7.86 (brs, 1H), 8.23 ​​(d, J= 2.5 Hz, 1H), 8.30 (d, J = 2.4 Hz, 1H) ppm;[ES+ MS] m / z 560 (MH + ).

[0128] Intermediate 90: tert-Butyl 4-[3-chloro-5-(5-methyl-1,3,4-oxadiazol-2-yl)-2-pyridyl]piperazine-1-carboxylate [ka] Intermediate 51 (0.14 mmol, 1 eq.), acetohydrazide (1.4 eq.), NEt3 (5 eq.) and T3P 50% in EtOAc (3.5 eq.) were placed in 500 μL of EtOAc at 80° C. After a total of 48 h, the reaction was stopped. It was diluted with EtOAc and washed twice with water and twice with saturated NaHCO3. The organic layer was then washed with brine, dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-60 / 40) to give the title compound. Yield: 43%; 1 H NMR (300 MHz, CD2Cl2):δ 1.46 (s, 9H), 2.57 (s, 3H), 3.44-3.50 (m, 4H), 3.53-3.59 (m, 4H), 8.18 (d, J = 2.1 Hz, 1H), 8.73 (d, J = 2.1 Hz, 1H) ppm;[ES+ MS] m / z 380 (MH + ).

[0129] Intermediate 91: tert-Butyl 4-[3-chloro-5-[(Z)-N'-hydroxycarbamimidoyl]-2-pyridyl]piperazine-1-carboxylate [ka] Intermediate 81 (0.47 mmol, 1 equiv.), hydroxylamine hydrochloride (1.5 equiv.) and NEt3 (1.6 equiv.) were heated to reflux in 1 mL of absolute ethanol for 1 h. The solvent was evaporated under reduced pressure and the residue was dissolved in EtOAc. It was washed twice with water. The organic layer was then washed with brine, dried over MgSO4 and evaporated under reduced pressure to give the title compound. Yield: 98%; 1 H NMR (300 MHz, CD2Cl2):δ 1.46 (s, 9H), 3.32-3.38 (m, 4H), 3.53-3.57 (m, 4H), 4.81 (brs, 2H), 6.75 (brs, 1H), 7.86 (d, J = 2.1 Hz, 1H), 8.38 (d, J = 2.1 Hz, 1H) ppm;[ES+ MS] m / z 356 (MH + ).

[0130] Intermediate 92-95: To a mixture of intermediate 91 (0.30-0.50 mmol, 1 equiv.), the corresponding carboxylic acid (1.1 equiv.) and NEt3 (5 equiv.) in EtOAc (2 mL) was added T3P 50% in EtOAc (3.5 equiv.) dropwise. The reaction was heated at 80° C. for 16-24 h. The reaction was diluted with EtOAc and washed twice with water and twice with saturated NaHCO3 solution. The organic layer was then washed with brine, dried over MgSO4 and evaporated under reduced pressure. [Table 10]

[0131] Intermediate 96: tert-Butyl 4-(3-chloro-5-iodo-2-pyridyl)piperazine-1-carboxylate [ka] A round bottom flask was charged with CuI (5 mol%), sodium iodide (2 equiv.) and intermediate 23 (4.0 mmol, 1 equiv.). The flask was purged with argon for 30 min, then dry dioxane (8.7 mL) and trans-N1,N2-dimethylcyclohexane-1,2-diaminedioxane (0.1 equiv.) were added. The solution was heated at 110° C. under argon. After 7, 11, 13 and 15 days, 5 mol% CuI, 2 equiv. NaI and 0.1 equiv. of trans-N1,N2-dimethylcyclohexane-1,2-diaminedioxane were added. After 12 days of reaction, 5 mL of dioxane was also added. After a total of 16 days, the reaction was stopped. The reaction mixture was diluted with EtOAc and washed twice with H2O. The organic layer was then washed with brine, dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0 to 70 / 30) to give the title compound. Yield: 77%; 1 H NMR (300 MHz, CD2Cl2):δ 1.45 (s, 9H), 3.25-3.30 (m, 4H), 3.50-3.56 (m, 4H), 7.88 (d, J= 2.0 Hz, 1H), 8.33 (d, J = 2.0 Hz, 1H) ppm;[ES+ MS] m / z 424 (MH + ).

[0132] Intermediates 97-99, 109, 111: In a tube, intermediate 96 (0.19-0.91 mmol, 1 equiv.), the corresponding alkyne (1.0-2.3 equiv.), Pd(PPh3)2Cl2 (0.02-0.18 equiv.) and CuI (0.06-0.6 equiv.) were added. The tube was purged with argon for 30 min, then anhydrous MeCN (1.0-4.0 mL) and NEt3 (12-20 equiv.) were added. The mixture was heated at 50°C by conventional heating or at 100°C under microwave irradiation for 1-56 h. The reaction mixture was filtered through a plug of Celite and diluted with EtOAc. The organic layer was washed twice with 1N aqueous HCl, once with water, and once with brine. It was then dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0 to 80 / 20) or by reversed phase flash chromatography (MeOH or MeCN / water 10 / 90 to 100 / 0). [Table 11]

[0133] Intermediate 100: tert-Butyl 4-[3-chloro-5-(hydroxymethyl)-2-pyridyl]piperazine-1-carboxylate [ka] The tube containing intermediate 22 (1.50 mmol, 1 equiv.) was purged under argon for 15 min. Then, 6 mL of dry tetrahydrofuran was added and the reaction was cooled at 0° C. 2.0 M LiBH4 in THF (4 equiv.) was added and the reaction was allowed to warm to room temperature and stirred for 3 days. The reaction mixture was quenched with EtOAc and washed twice with water. The aqueous layer was then extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, and evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-50 / 50) to give the title compound. Yield: 43%; 1H NMR (300 MHz, CD2Cl2):δ 1.46 (s, 9H), 3.24-3.29 (m, 4H), 3.52-3.57 (m, 4H), 4.60 (s, 2H), 7.66 (d, J = 2.1 Hz, 1H), 8.13 (d, J = 2.1 Hz, 1H) ppm;[ES+ MS] m / z 328 (MH + ).

[0134] Intermediate 101: tert-Butyl 4-[3-chloro-5-(methylsulfonyloxymethyl)-2-pyridyl]piperazine-1-carboxylate [ka] Intermediate 100 (0.27 mmol, 1 equiv) was dissolved in dichloromethane (1 mL) cooled at 0° C. and methanesulfonyl chloride (2 equiv) was added. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction was quenched with water and extracted with DCM to give the title compound. Yield: 84%.

[0135] Intermediate 102: tert-Butyl 4-[5-[[3-[(tert-butoxycarbonylamino)methyl]phenoxy]methyl]-3-chloro-2-pyridyl]piperazine-1-carboxylate [ka] tert-Butyl N-[(3-hydroxyphenyl)methyl]carbamate (1.2 eq.) and cesium carbonate (1.3 eq.) were heated at 70° C. in dry DMF (1.3 mL). After 10 min, a solution of intermediate 101 (0.23 mmol, 1 eq.) in dry DMF (1 mL) was added and the reaction was heated for 4 h. DMF was evaporated under reduced pressure, the residue was dissolved in EtOAc and washed twice with 1N aqueous HCl. The organic layer was then washed with brine, dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-70 / 30) to give the title compound. Yield: 59%; 1 H NMR (300 MHz, CD2Cl2):δ 1.44 (s, 9H), 1.46 (s, 9H), 3.27-3.32 (m, 4H), 3.52-3.59 (m, 4H), 4.26 (d, J = 6.1 Hz, 2H), 4.97 (s, 2H), 6.82-6.92 (m, 3H), 7.26 (t, J = 8.0 Hz, 1H), 7.72 (d, J = 2.1 Hz, 1H), 8.22 (d, J = 2.1 Hz, 1H) ppm;[ES+ MS] m / z 533 (MH + ).

[0136] Intermediate 103: tert-Butyl N-[[3-[(5,6-dichloro-3-pyridyl)oxymethyl]phenyl]methyl]carbamate [ka] 5,6-Dichloropyridin-3-ol (0.44 mmol, 1 eq.), tert-butyl N-[[3-(bromomethyl)phenyl]methyl]carbamate (2 eq.) and K2CO3 (2.5 eq.) in DMF (1.2 mL) were heated at 80° C. for 1 h. The reaction was diluted with EtOAc and washed twice with water. The organic layer was then washed with brine, dried over MgSO4 and evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-80 / 20) and by reverse phase chromatography (MeCN 0.1% formic acid / water 0.1% formic acid 10 / 90-100 / 0). Yield: 74%; 1 H NMR (300 MHz, CD2Cl2):δ 1.44 (s, 9H), 4.31 (d, J= 6.2 Hz, 2H), 4.98 (brs, 1H), 5.09 (s, 2H), 7.26-7.40 (m, 4H), 7.43 (d, J = 2.8 Hz, 1H), 8.05 (d, J = 2.8 Hz, 1H) ppm;[ES+ MS] m / z 383 (MH + ).

[0137] Intermediate 104: tert-Butyl 4-[5-[[3-[(tert-butoxycarbonylamino)methyl]phenyl]methoxy]-3-chloro-2-pyridyl]piperazine-1-carboxylate [ka] In a tube, intermediate 103 (0.12 mmol, 1 equiv), boc-piperazine (1.8 equiv), Pd(OAc)2 (4 mol%), BINAP (4 mol%), and tBuONa (1.7 equiv) were purged under argon for 15 min. Then, dry toluene (0.2 mL) was added and the mixture was heated at 110° C. overnight. The reaction mixture was filtered through a plug of Celite and rinsed with EtOAc. It was concentrated under reduced pressure and the residue was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-70 / 30) to give the title compound. Yield: 67%; 1H NMR (300 MHz, CD2Cl2):δ 1.44 (s, 9H), 1.46 (s, 9H), 3.10-3.16 (m, 4H), 3.51-3.57 (m, 4H), 4.30 (d, J = 6.1 Hz, 2H), 5.00-5.08 (m, 3H), 7.24-7.39 (m, 5H), 7.95 (d, J = 2.7 Hz, 1H) ppm;[ES+ MS] m / z 533 (MH + ).

[0138] Intermediate 105: tert-Butyl 4-[6-[3-[(tert-butoxycarbonylamino)methyl]phenyl]-3-chloro-2-quinolyl]piperazine-1-carboxylate [ka] tert-Butyl 4-(6-bromo-3-chloro-2-quinolyl)piperazine-1-carboxylate 78 (0.2 mmol, 1 equiv.), [3-[(tert-butoxycarbonylamino)methyl]phenyl]boronic acid (1.0 equiv.), K2CO3 (1.6 equiv.) were dissolved in a mixture of DME / EtOH / H2O (2 / 1 / 2) (5 mL). Pd(PPh3)2Cl2 (0.1 equiv.) was then added and the suspension was heated at 90° C. under argon for 1 h. The reaction was diluted with CH2Cl2 and washed twice with water. The organic layer was then washed with brine, dried over MgSO4, and evaporated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-70 / 30) to give the title compound. Yield: 55%; 1H NMR (300 MHz, CD2Cl2): δ 1.46 (s, 9H), 1.48 (s, 9H), 3.43-3.47 (m, 4H), 3.60-3.64 (m, 4H), 4.38 (d, J =9.3 Hz, 2H), 5.04 (br s, 1H), [ES+ MS] m / z 553 (MH + ).

[0139] Intermediates 106–107, 120–121, 125–131: tert-Butyl 4-(6-bromo-3-chloro-2-quinolyl)piperazine-1-carboxylate 78 (0.1–0.4 mmol, 1 equiv.), the appropriate amine (1.5–3 equiv.), Cs2CO3 (1.3–1.5 equiv.), Xantphos (0.04–0.10 equiv.), and Pd2dba3 (0.02–0.04 equiv.) were dissolved in 1,4-dioxane (0.7–4.0 mL) under argon. The mixtures were heated at 100 °C overnight, cooled to room temperature, filtered through Celite, dried under vacuum, and purified by flash chromatography. [Table 12] TIFF2024527427000053.tif193165 TIFF2024527427000054.tif202165 TIFF2024527427000055.tif135165

[0140] Intermediate 108: tert-Butyl 4-(3-chloro-1,5-naphthyridin-2-yl)piperazine-1-carboxylate [ka] 2,3-Dichloro-1,5-naphthyridine 77 (0.3 mmol, 1 equiv.), tert-butyl piperazine-1-carboxylate (1.5 equiv.), t-BuONa (1.5 equiv.), SPhos (0.08 equiv.), Pd(OAc)2 (0.04 equiv.) were dissolved in toluene (0.7 mL) under argon. The mixture was heated at 110° C. overnight, cooled to room temperature and dried under vacuum. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-50 / 50) to give the title compound. Yield: 21%; 1 H NMR (300 MHz, CD2Cl2):δ 1.47 (s, 9H), 3.45-3.49 (m, 4H), 3.60-3.64 (m, 4H), 7.28 (dd, J = 4.2, 8.5 Hz, 1H), 8.11 (ddd, J = 0.8, 1.6, [ES+ MS] m / z 349 (MH + ).

[0141] Intermediate 110: tert-Butyl 4-(3-chloro-5-ethynyl-2-pyridyl)piperazine-1-carboxylate [ka] 1M TBAF in THF (1.1 equiv.) was added to a solution of intermediate 109 (0.08-0.61 mmol) in THF (0.3-2.5 mL). The reaction was stirred at room temperature overnight. The reaction was diluted with EtOAc and washed twice with water. The organic layer was then washed with brine, dried over MgSO4, and evaporated under reduced pressure to give the title compound. Yield: 92%; 1H NMR (300 MHz, CD2Cl2):δ 1.46 (s, 9H), 3.21 (s, 1H), 3.32-3.39 (m, 4H), 3.51-3.57 (m, 4H), 7.68 (d, J= 2.0 Hz, 1H), 8.26 (d, J = 2.0 Hz, 1H) ppm;[ES+ MS] m / z 322 (MH + ).

[0142] Intermediates 112-114: In a tube, intermediate 110 (0.23-0.62 mmol), Pd(PPh3)2Cl2 (2-3 mol%), CuI (7-10 mol%) and the corresponding iodo derivative (1.4 equiv.) were added. Then, TEA (14 equiv.) and anhydrous MeCN (0.9-2.5 mL) were added. The reaction was flushed under argon for 30 min and heated at 100 °C in a microwave for 1 h. The reaction was filtered through a plug of Celite. The filtrate was diluted with EtOAc and washed three times with water and once with brine. It was then dried over MgSO4, filtered and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography. [Table 13]

[0143] Intermediate 115: tert-Butyl 4-[3-chloro-6-(2-trimethylsilylethynyl-2-quinolyl]piperazine-1-carboxylate [ka] In a tube, intermediate 79 (1.07-2.01 mmol), Pd(PPh3)2Cl2 (2 mol%) and CuI (6-10 mol%) were added. The tube was purged with argon for 15 min, then ethynyl(trimethyl)silane (1.5 equiv), TEA (14 equiv) and anhydrous MeCN (4-8 mL) were added. The reaction was heated at 100 °C in a microwave for 2 h. The reaction was filtered through a plug of Celite. The filtrate was diluted with EtOAc and washed twice with water. The aqueous layer was extracted once with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent was removed under reduced pressure. The crude product was purified by reverse phase flash chromatography (MeCN / water 10 / 90-100 / 0) to give the title compound. Yield: 78%; 1 H NMR (300 MHz, CD2Cl2):δ 0.27 (s, 9H), 1.47 (s, 9H), 3.42-3.48 (m, 4H), 3.57-3.63 (m, 4H), 7.62 (dd, J= 1.8, 8.7 Hz, 1H), 7.72 (d, J= [ES+ MS] m / z 444 (MH + ).

[0144] Intermediate 116: tert-Butyl 4-(3-chloro-6-ethynyl-2-quinolyl)piperazine-1-carboxylate [ka] 1M TBAF in THF (1.1 equiv.) was added to a solution of intermediate 115 (0.82-1.76 mmol) in THF (4-10 mL). The reaction was stirred at room temperature for 1-3 h. The reaction was diluted with EtOAc and washed twice with water. The aqueous layer was extracted once with EtOAc. The combined organic layers were then washed with brine, dried over MgSO4, and evaporated under reduced pressure to give the title compound. Yield: 100%; 1H NMR (300 MHz, CD2Cl2):δ 1.47 (s, 9H), 3.21 (s, 1H), 3.43-3.49 (m, 4H), 3.58-3.63 (m, 4H), 7.65 (dd, J = 1.8, 8.7 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.81 (d, J = 1.8 Hz, 1H), 8.03 (s, 1H) ppm; + ).

[0145] Intermediate 117: tert-Butyl 4-[6-[1-[3-(tert-butoxycarbonylamino)propyl]triazol-4-yl]-3-chloro-2-quinolyl]piperazine-1-carboxylate [ka] To a tube containing a freshly prepared solution of 1M sodium ascorbate (0.1 equiv.), CuSO4.5H2O (8 mol%), and TBTA (3 mol%) in THF / H2O (3:1, 2.5 mL) was added intermediate 116 (0.40 mmol) and 3-azidopropan-1-amine (1 equiv.). The reaction mixture was stirred at room temperature for 2.5 h. The mixture was then washed twice with saturated K2CO3 solution and extracted three times with EtOAc. The combined organic layers were then washed with brine, dried over MgSO4, and evaporated under reduced pressure. The residue was then dissolved in 1.5 mL of a mixture of 2:1 DCM / MeOH, and Boc2O (2 equiv.) was added at 0 °C. After 48 h, the solvent was evaporated and the residue was purified by reverse phase flash chromatography (water / MeCN 90 / 10-0 / 100) to give the title compound. Yield: 19%; 1H NMR (300 MHz, CD2Cl2):δ 1.43 (s, 9H), 1.47 (s, 9H), 2.13 (p, J = 6.6 Hz, 2H), 3.18 (q, J= 6.4 Hz, 2H), 3.42-3.48 (m, 4H), 3.59-3.65 (m, 4H), 4.48 (t, J = 6.8 Hz, 2H), 4.78 (brs, 1H), 7.86 (d, J = 8.7 Hz, 1H), 8.00 (brs, 1H), 8.05 (dd, J = 2.0, 8.7 Hz, 1H), 8.13 (s, 1H), 8.16 (d, J = 1.9 Hz, 1H) ppm; [ES+ MS] m / z 572 (MH + ).

[0146] Intermediate 118: tert-Butyl 4-[6-[1-[2-(tert-butoxycarbonylamino)ethyl]triazol-4-yl]-3-chloro-2-quinolyl]piperazine-1-carboxylate [ka] To a tube containing a freshly prepared solution of 1M sodium ascorbate (0.1 equiv.), CuSO4.5H2O (9 mol%), and TBTA (tris((1-benzyl-4-triazolyl)methyl)amine, 3 mol%) in THF / H2O (3:1, 2.0 mL) was added intermediate 116 (0.27 mmol), 2-azidoethanamine; hydrochloride (1 equiv.) and TEA (1 equiv.). The reaction mixture was stirred at room temperature for 2 h. Then the mixture was washed twice with saturated K2CO3 solution and extracted once with EtOAc. The combined organic layers were then washed with brine, dried over MgSO4 and evaporated under reduced pressure. The residue was dissolved in DCM (0.6 mL) and Boc2O (1 equiv.) was added at 0 °C. After 4.5 h the solvent was evaporated and the residue was purified by flash chromatography (DCM / EtOAc 100 / 0-70 / 30) to give the title compound. Yield: 87%; 1H NMR (300 MHz, CD2Cl2):δ 1.42 (s, 9H), 1.47 (s, 9H), 3.41-3.48 (m, 4H), 3.58-3.71 (m, 6H), 4.53 (t, J = 5.7 Hz, 2H), 4.98 (brs, 1H), [ES+ MS] m / z 558 (MH + ).

[0147] Intermediate 119: tert-Butyl 4-[3-chloro-6-[1-[2-(dimethylamino)ethyl]triazol-4-yl]-2-quinolyl]piperazine-1-carboxylate [ka] To a tube containing a freshly prepared solution of 1M sodium ascorbate (0.1 equiv.), CuSO4.5H2O (0.14 equiv.), TBTA (3 mol%) and TEA (1 equiv.) in THF / H2O (3:1, 2.0 mL), intermediate 116 (0.22 mmol) and 2-azido-N,N-dimethyl-ethanamine; hydrochloride (1 equiv.) were added. The reaction mixture was stirred at room temperature for 20 h. The mixture was then washed twice with saturated K2CO3 solution and extracted once with EtOAc. The combined organic layers were then washed with brine, dried over MgSO4 and evaporated under reduced pressure. The crude product was then purified by reverse phase chromatography (water 0.1% formic acid / MeCN 0.1% formic acid 10 / 90-0 / 100) to give the title compound. Yield: 61%; 1H NMR (300 MHz, CD2Cl2):δ 1.47 (s, 9H), 2.30 (s, 6H), 2.79 (t, J = 6.1 Hz, 2H), 3.41-3.47 (m, 4H), 3.59-3.64 (m, 4H), 4.49 (t, J = 6.1 [ES+ MS] m / z 486 (MH) + ).

[0148] Intermediates 132-135: tert-Butyl 4-(6-bromo-3-chloro-2-quinolyl)piperazine-1-carboxylate 78 (0.2-0.6 mmol, 1 equiv.), the appropriate phenylboronic acid (1.0 equiv.) and K2CO3 (1.6 equiv.) were dissolved in DME / EtOH / H2O (2 / 1 / 2, 5.0-10.0 mL) under argon. Pd(PPh3)2Cl2 (0.09-0.1 equiv.) was then added and the suspension was heated at 90 °C under argon for 3 h-overnight. The reaction was quenched with water and extracted twice with CHCl2. The organic layer was washed with brine, dried over MgSO4, evaporated under reduced pressure and purified by flash chromatography. [Table 14] TIFF2024527427000065.tif70165

[0149] Intermediate 136-137: Tert-Butyl 4-[3-chloro-6-(3-formylphenyl)-2-quinolyl]piperazine-1-carboxylate 135 (0.13-0.22 mmol) was dissolved in anhydrous MeOH (0.6-0.9 mL) under argon atmosphere and MeNH2 or Me2NH (2 M in THF, 1.1-1.8 equiv.) was added. The solution was stirred at room temperature for 24 h, then NaBH4 (2.0-2.1 equiv.) was added at 0 °C. The suspension was stirred at room temperature overnight and quenched with water at 0 °C. The suspension was stirred at room temperature for 1 h and then extracted twice with CH2Cl2. The organic layer was washed with brine, dried over MgSO4, and evaporated under reduced pressure. [Table 15]

[0150] Intermediate 138: tert-Butyl 4-[6-[3-[(tert-butoxycarbonylamino)methyl]phenyl]-3-chloro-2-quinolyl]piperazine-1-carboxylate [ka] tert-Butyl 4-(6-bromo-3-chloro-2-quinolyl)piperazine-1-carboxylate 78 (2.34 mmol, 1.0 equiv.), bis(pinacolato)diboron (2.52 mmol, 1.1 equiv.), K2CO3 (7.37 mmol, 3.1 equiv.), Pd(dppf)Cl2 (0.07 mmol, 0.03 equiv.) dissolved in dioxane (50 mL) were added to the tube. The mixture was degassed for 40 min and then heated to 100 °C. Overnight, bis(pinacolato)diboron (0.41 mmol, 0.2 equiv.), K2CO3 (2.25 mmol, 1.1 equiv.) and Pd(dppf)Cl2 (0.02 mmol, 0.01 equiv.) were added and the mixture was then stirred for 3 h. The reaction mixture was then washed with water and then extracted three times with dichloromethane. The organic layer was washed with saturated NaCl solution, dried over MgSO4 and evaporated under vacuum. The crude product was purified by flash chromatography (cyclohexane / EtOAc 100 / 0-90 / 10) to give the title compound 138. Yield: 73%; 1 H NMR (300 MHz, CD2Cl2):δ 1.36 (s, 12H), 1.47 (s, 9H), 3.44-3.47(m, 4H), 3.59-3.62 (m, 4H), 7.76 (d, J = 8.4 Hz, 1H), 7.93 (dd, J = 1.4, 8.4 Hz, 1H), 8.08(s, 1H), 8.11 (br s, 1H) ppm.;[ES+ MS] m / z 474 (MH + ).

[0151] Intermediates 139-152, 203-204: LiAlH4 (1M in THF, 2.0 equiv.) was dissolved in THF or Et2O (1.0-5.0 mL) and then a solution of AlCl3 (2.0 equiv.) in THF / Et2O (2:1, 3:1 or 5:1, 3.0-6.0 mL) or Et2O (3.0 mL) was added dropwise. The solution was stirred at room temperature for 20 min. Then, the appropriate benzonitrile (1.2-2.8 mmol, 1.0 equiv.) in THF (1.0-4.0 mL) was added dropwise. The suspension was stirred at room temperature for 1-3 h, then quenched with water at 0 °C and stirred at room temperature for 1 h-overnight. The reaction was quenched with NH3 in H2O and extracted twice with CH2Cl2. The organic layer was washed with brine, dried over MgSO4, and evaporated under reduced pressure. [Table 16] TIFF2024527427000069.tif232165 TIFF2024527427000070.tif193165

[0152] Intermediates 153-168, 205-206: Bromobenzylamine derivatives (0.7-1.9 mmol, 1.0 equiv.) were dissolved in CHCl (1.0-3.0 mL) and then a solution of di-tert-butyl dicarbonate (1.0-3.0 equiv.) in CHCl (2.0-3.0 mL) was added dropwise at 0° C. The reaction was stirred at room temperature for 1 h to 2 days. The crude products were evaporated under reduced pressure and purified by flash or reverse phase chromatography. [Table 17] TIFF2024527427000072.tif241165 TIFF2024527427000073.tif230165 TIFF2024527427000074.tif91165

[0153] Intermediate 169-177: To a solution of bromobenzylamine derivatives (1.0-1.3 mmol, 1.0 equiv.) in THF / H2O (1:1, 1.9-2.2 mL) was added di-tert-butyl dicarbonate (1.5-1.6 equiv.) and NaHCO3 (2.0-2.1 equiv.). The reaction was stirred at room temperature for 1-3 h. The reaction was quenched with water and extracted twice with EtOAc. The organic layer was washed with brine, dried over MgSO4, evaporated under reduced pressure and purified by flash chromatography. [Table 18] TIFF2024527427000076.tif159165

[0154] Intermediates 178-183: tert-Butyl 4-[3-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-quinolyl]piperazine-1-carboxylate 138 (0.25-32 mmol, 1 equiv.), the appropriate phenyl bromide (1.0-1.1 equiv.) and K2CO3 (1.6-1.7 equiv.) were dissolved in DME / EtOH / H2O (2 / 1 / 2, 5.0 mL) under argon. Pd(PPh3)2Cl2 (0.1 equiv.) was then added and the suspension was heated at 90 °C under argon for 3 h. The reaction was quenched with water and extracted twice with CHCl2. The organic layer was then washed with brine, dried over MgSO4, evaporated under reduced pressure and purified by flash chromatography. [Table 19] TIFF2024527427000078.tif246165

[0155] Intermediates 184-202, 207-208: tert-Butyl 4-[3-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-quinolyl]piperazine-1-carboxylate 138 (0.11-0.16 mmol, 1 equiv.) and the appropriate phenyl bromide (1.1-1.7 equiv.) were dissolved in 1,4-dioxane (0.9-1.4 mL). Na2CO3 (2M in water, 0.9-1.4 mL) and Pd(PPh3)4 (0.1 equiv.) were then added and the suspension was heated at 120 °C under microwave irradiation for 30 min. The reaction was filtered through a plug of Celite, quenched with water, and extracted twice with EtOAc. The organic layer was then washed with brine, dried over MgSO4, evaporated under reduced pressure and purified by flash or reverse phase chromatography. [Table 20] TIFF2024527427000080.tif235165 TIFF2024527427000081.tif233165 TIFF2024527427000082.tif240165 TIFF2024527427000083.tif236165 TIFF2024527427000084.tif127165

[0156] Working Example Examples 1-9 were prepared according to Protocol 1. [Table 21] TIFF2024527427000086.tif249165

[0157] Examples 10-11 were prepared according to Protocol 2. [Table 22]

[0158] Examples 12-78, 93-137 were prepared according to Protocol 3. [Table 23] TIFF2024527427000089.tif201169 TIFF2024527427000090.tif232169 TIFF2024527427000091.tif224169 TIFF2024527427000092.tif237169 TIFF2024527427000093.tif241169 TIFF2024527427000094.tif224169 TIFF2024527427000095.tif231169 TIFF2024527427000096.tif209169 TIFF2024527427000097.tif195169 TIFF2024527427000098.tif211169 TIFF2024527427000099.tif219169 TIFF2024527427000100.tif201169 TIFF2024527427000101.tif235169 TIFF2024527427000102.tif213169 TIFF2024527427000103.tif194169 TIFF2024527427000104.tif200169 TIFF2024527427000105.tif221169 TIFF2024527427000106.tif228169 TIFF2024527427000107.tif181169 TIFF2024527427000108.tif198169 TIFF2024527427000109.tif197169 TIFF2024527427000110.tif190169 TIFF2024527427000111.tif218169 TIFF2024527427000112.tif211169 TIFF2024527427000113.tif221169 TIFF2024527427000114.tif222169 TIFF2024527427000115.tif216169 TIFF2024527427000116.tif245169 TIFF2024527427000117.tif205169

[0159] Example 79: 1-(3-chloro-5-iodo-2-pyridyl)piperazine [ka] A dry 10 mL tube was charged with CuI (0.07 equiv), sodium iodide (2.0 equiv), Example 18 (0.10 mmol, 1 equiv). The tube was purged with argon for 30 min, then 1,4-dioxane (2 mL) and (1R,2R)-N1,N2-dimethylcyclohexane-1,2-diamine (0.1 equiv) were added. The mixture was heated at 110° C. for 3 days. The product was purified by normal phase flash chromatography (DCM / MeOH 100 / 0-90 / 10) and reverse phase chromatography (MeOH / H2O 95 / 5-100 / 0) to give the title compound. Yield: 63%; 1 H NMR (300 MHz, CD2Cl2):δ 2.93-2.97 (m, 4H), 3.24-3.28 (m, 4H), 7.85 (d, J = 2.0 Hz, 1H), 8.31 (d, J = 2.0 Hz, 1H) ppm; 13C NMR (75 MHz, CD2Cl2):δ 46.3, 50.7, 81.8, 123.4, 146.1, 151.9, 158.3 ppm;[ES+ MS] m / z 324 (MH + ).

[0160] Example 80: N-[5-chloro-6-(4-methylpiperazin-1-yl)-3-pyridyl]acetamide [ka] Intermediate 17 (0.7 mmol, 1 equiv.) and iron (9.5 equiv.) were dissolved in acetic acid (9.0 mL). The mixture was heated at 50° C. overnight, cooled to room temperature, washed with EtOAc and purified by flash chromatography (DCM / MeOH / NEt3 100 / 0 / 0-90 / 05 / 05) to give the title compound. Yield: 12%; 1 H NMR (300 MHz, CD2Cl2):δ 2.13 (s, 3H), 2.31 (s, 3H), 2.54 (t, J = 4.9 Hz, 4H), 3.28 (t, J = 4.7 Hz, 4H), 7.38 (s, 1H), 8.06 (d, J = 2.4 Hz, 1H), 8.13 (d, J = 2.4 Hz, 1H) ppm; 13 C NMR (75 MHz, CD2Cl2):δ 24.4, 46.2, 49.5, 55.3, 122.7, 130.2, 131.4, 137.6, 155.4, 168.8 ppm;[ES+ MS] m / z 269 (MH + ).

[0161] Example 81: 3-chloro-2-(4-methylpiperazin-1-yl)quinoline [ka] 2,3-Dichloroquinoline (0.25 mmol, 1 equiv.), methylpiperazine (1.5 equiv.) and NEt3 (1.3 equiv.) in DMF (1 mL) were stirred at 110° C. for 2 days. The reaction was purified by flash chromatography (cyclohexane / EtOAc 100 / 0 to 90 / 10) to give the title compound. Yield: 39%; 1 H NMR (300 MHz, CD2Cl2):δ 2.34 (s, 3H), 2.61 (t, J = 4.9 Hz, 4H), 3.50 (t, J = 4.7 Hz, 4H), 7.38 (ddd, J = 1.2, 6.8, 8.1 Hz, 1H), 7.57-7.67 (m, 2H), 7.80 (d, J = 8.1 Hz, 1H),8.05 (s, 1H); 13 C NMR (75 MHz, CD2Cl2):46.3, 49.6, 55.3, 123.0, 125.1, 126.0, 126.8, 127.7, 129.9, 137.8, 145.9, 157.3; + ).

[0162] Example 82: 2-Methoxy-3-piperazin-1-yl-quinoxaline; 2,2,2-trifluoroacetic acid [ka] To a flask containing intermediate 69 (0.08 mmol, 1 equiv.) in dry DCM (2.3 mL) was added 232 μL of TFA (39.5 equiv.). The mixture was stirred at room temperature for 1.5 h. The reaction was evaporated under reduced pressure and the solid was rinsed several times with DCM to give the title compound. Yield: 88%; 1 H NMR (300 MHz, DMSO-d6):δ 3.24-3.32 (m, 4H), 3.84 (t, J = 5.0 Hz, 4H), 4.05 (s, 3H), 7.44-7.54 (m, 2H), 7.67-7.73 (m, 2H), 8.93 (br s, 2H); 13C NMR (75 MHz, DMSO-d6):δ 42.5, 44.2, 53.9, 115.6 (q, J = 291.4 Hz), 125.9, 126.1, 126.3, 126.8, 136.2, 137.4, 146.0, 150.5, 158.4 (q, J = 35.9 Hz);[ES+ MS] m / z 245 (MH + ).

[0163] Example 83: 2-Chloro-3-(3,6-diazabicyclo[3.1.1]heptan-3-yl)quinoxaline; trifluoromethanesulfonic acid [ka] To a solution of intermediate 32 (0.14 mmol, 1 equiv.) in dry DCM (1.5 mL) was added dropwise 2,6-lutidine (6 equiv.) and TMSOTf (3 equiv.) at 0° C. The solution was stirred at room temperature for 3.5 h. The solvent was evaporated under reduced pressure. The crude product was purified by reversed phase flash chromatography (MeCN / H2O 10 / 90-100 / 0) to give the title compound. Yield: 76%; 1 H NMR (300 MHz, DMSO-d6):δ 1.91 (dd, J = 5.2, 10.0 Hz, 1H), 2.79-2.88 (m, 1H), 4.24 (d, J = 13.2 Hz, 2H), 4.46-4.57 (m, 4H), 7.57 (ddd, J = 1.8, 6.6, 8.4 Hz, 1H), 7.70-7.81 (m, 2H), 7.88 (ddd, J = 0.7, 1.4, 8.3 Hz, 1H), 8.12 (br s, 1H), 9.36 (br s, 1H); 13 C NMR (75 MHz, DMSO-d6):δ 27.8, 49.1, 58.2, 126.0, 126.7, 127.2, 130.9, 136.7, 136.8, 139.2, 149.6;[ES+ MS] m / z 261 (MH + ).

[0164] Examples 84 to 92 The appropriate Boc-protected compound (0.10-0.32 mmol, 1 equiv.) was dissolved in dry DCM (2.9-9.4 mL) and TFA (40 equiv.) was added. The mixture was stirred at room temperature for 40 min-2.5 h. The reaction was evaporated under reduced pressure and the solid was rinsed with DCM and diethyl ether to give the desired product. [Table 24] TIFF2024527427000124.tif239165 TIFF2024527427000125.tif59165

[0165] Part B - Biological Activity of the Compounds of the Invention Materials and Methods Strains, media and antibiotics Escherichia coli BW25113 (CGSC 7636) and its derivatives, E. coli ΔtolC (JW5503-1, tolC732::kan, CGSC 11430), E. coli ΔacrA (JW0452-3, ΔacrA748::kan, CGSC 11843), and E. coli ΔacrB (JW0451-2, ΔacrB747::kan, CGSC 8609), were obtained from the E. coli Genetic Stock Center (CGSC, New Haven, Connecticut) and were derived from the Keio Collection (Baba T et al, Mol Sys Biol, 2006). Klebsiella pneumoniae (LMG 2095 / ATCC 13883) and K. pneumoniae (ATCC 43816), Pseudomonas aeruginosa (PAO1), and Acinetobacter baumannii (LMG 1025, ATCC 17978) were obtained from the ATCC or BCCM / LMG Bacteria Collection. All bacteria were grown and tested in cation-adjusted Mueller-Hinton broth (CAMHB; BD Difco) at 37°C. For storage, logarithmic-phase bacteria were frozen (-80°C) in CAMHB supplemented with 15% glycerol.

[0166] Commercially available molecules, including antibiotics and efflux pump inhibitors, were purchased from various suppliers, including Sigma Aldrich, Carbosynth Limited, Fisher Scientific, and Euromedex. Pyridomycin was extracted and purified from Dactylosporangium fulvum as previously described (Hartkoorn RC et al, EMBO Mol Med, 2012).

[0167] Assay 1 Measurement of growth inhibition of E. coli strains by sub-inhibitory concentrations of pyridomycin in combination with Examples 1-137 To assess the dose-dependent activity of Examples 1-137, their ability to enhance the antibacterial activity of subinhibitory concentrations of pyridomycin, an antibiotic that is a good AcrA / B-TolC substrate, was measured. Briefly, E. coli BW25113 was cultured from frozen or grown stocks in CAMHB at OD 600 The bacteria were diluted from 0.0004 to 0.001. The bacterial suspension was then either used as is (no antibiotic control to assess EPI activity) or pyridomycin was added to a final concentration of 8 μg / mL. The bacteria were then added to microplates containing serial dilutions of compounds Examples 1-137 and incubated at 37° C. for 5 hours. The viability of E. coli BW25113 was assessed using a resazurin reduction assay and measured by fluorescence (POLARstar Omega, BMG Labtech: Ex: 530 nm Em: 590 nm). EC 50 was defined as the compound concentration that inhibited resazurin turnover by 50% compared to untreated bacteria. Similar assays were also performed in reverse using a standard dose of EPI (typically 500 μM Compound Example 14' or 100 μM Compound Example 37) and serial dilutions of pyridomycin.

[0168] Assay 2 Measurement of growth inhibition of A. baumannii strains by subinhibitory concentrations of chloramphenicol in combination with Examples 1-137 To assess the dose-dependent activity of Examples 1-137, their ability to enhance the antibacterial activity of sub-inhibitory concentrations of chloramphenicol was measured. Briefly, A. baumannii LMG 1025 (ATCC 17978) was cultured from frozen or grown stocks in CAMHB at OD 6000.001. The bacterial suspension was then used as is (no antibiotic control to assess EPI activity) or had chloramphenicol added to a final concentration of 10 μg / mL. The bacteria were then added to microplates containing serial dilutions of compounds Examples 1-137 and incubated at 37° C. for 5 or 24 hours. Bacterial viability was assessed using a resazurin reduction assay and measured by fluorescence (POLARstar Omega, BMG Labtech: Ex: 530 nm Em: 590 nm). EC 90 was defined as the compound concentration that inhibited resazurin turnover by 90% compared to untreated bacteria.

[0169] Assay 3 Measurement of growth inhibition of A. baumannii strains by subinhibitory concentrations of novobiocin in combination with Examples 1-137 To assess the dose-dependent activity of Examples 1-137, their ability to enhance the antibacterial activity of sub-inhibitory concentrations of novobiocin was measured. Briefly, A. baumannii LMG 1025 (ATCC 17978) was cultured from frozen or growing stocks at OD 2 in CAMHB. 600 0.001. The bacterial suspension was then used as is (no antibiotic control to assess EPI activity) or had novobiocin added to a final concentration of 5 μg / mL. The bacteria were then added to microplates containing serial dilutions of compounds Examples 1-137 and incubated at 37° C. for 5 or 24 hours. Bacterial viability was assessed using a resazurin reduction assay and measured by fluorescence (POLARstar Omega, BMG Labtech: Ex: 530 nm Em: 590 nm). EC 90 was defined as the compound concentration that inhibited resazurin turnover by 90% compared to untreated bacteria.

[0170] Assay 4 Determining the effect of EPI Example 37 on enhancing antibiotic activity in E. coli, A. baumannii, K. pneumoniae, and P. aeruginosa To screen the spectrum of antibiotics potentiated by compound Example 37, a panel of antibiotics (erythromycin (ERY), azithromycin (AZY), tetracycline (TET), novobiocin (NOV), chloramphenicol (CM), fusidic acid (FUS), ciprofloxacin (CIP), linezolid (LIN), triclosan (TRC), pyridomycin (PYR), streptomycin (STP), kanamycin (Cm), genetamycin (Gm), cefepime (CEP), ceftazidime (CAZ), aztreonam (AZT), oxacillin (OXA), piperacillin (PPC), ampicillin (AMP)) were dose-response diluted by acoustic technology (Echo® 550, Labcyte Inc) and added to the microwell plate of interest (typically a 384-well plate). Bacterial suspensions were then prepared in CAMHB from growing precultures (E. coli [OD600=0.001], A. baumannii [OD600=0.001], K. pneumoniae [OD600=0.001] and P. aeruginosa [OD600=0.001]) and added to the microplates using a ViaFill. The microplates containing the bacterial cultures were then incubated (5 or 24 hours at 37°C) and bacterial viability was measured by either resazurin reduction or OD600.

[0171] result MIC of pyridomycin alone against E. coli BW25113 90 The MIC of chloramphenicol alone against A. baumannii LMG 1025 is 12.5-25 μg / mL. 90 The MIC of novobiocin alone against A. baumannii LMG 1025 is 25-100 μg / mL. 90 is 12.5 μg / mL.

[0172] The results of the antibiotic enhancing activity of EPIs (Examples 1-137) are shown in the table below.

[0173] [Table 25] TIFF2024527427000127.tif248165 TIFF2024527427000128.tif249165 TIFF2024527427000129.tif248165 TIFF2024527427000130.tif108165

[0174]

Table 26

Claims

1. Formula (I): 【Chemical 1】 Wherein,[[]] - X is selected from CH; and N and can be selected from; - Y is selected from CH; and N and can be selected from; X and Y are not CH at the same time, - R １ to a halogen atom; -(C １ -C ３ ) alkyl group; -(C １ -C ３ ) halogenoalkyl group; -(C １ -C ３ ) alkoxy group; or a nitrile group and can be selected from; -R ２ with a halogen atom excluding a fluorine atom; An optionally substituted -(C １ -C ６ )alkyl group; An alkenyl group optionally substituted by one heteroatom selected from O, N or S - (C ２ -C ６ ) An optionally substituted -(C ２ -C ６ ) alkynyl group, substituted by one heteroatom selected from O, N or S; -(C １ -C ３ ) alkoxy group; -(C １ -C ３ ) haloalkyl group; -COORa group; -N(H)Rb-Ra group; -(C １ -C ３ ) alkyl group which may be optionally substituted by a -(C ２ -C ６ ) alkynyl-(C ６ -C １０ ) aryl group, wherein the -(C １ -C ３ ) alkyl group may be optionally substituted by a -NRR' group; - (C １ - C ３ ) an alkyl group optionally substituted by a CONH-(C ６ - C １０ ) aryl group, wherein the -(C １ - C ３ ) alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C10)aryl group, where the group is optionally substituted by an -NRR' group (C １ -C ３ )alkyl group and is optionally substituted; -O-(C1-C3)alkyl-(C6-C10)aryl group, where the group is optionally substituted by an -NRR' group (C １ -C ３ )alkyl group and is optionally substituted; A (5- or 6-membered) heteroaryl group having at least one heteroatom selected from O, N or S, which group is optionally substituted by an -NRR' group and optionally substituted by an alkyl group of (C １ -C ３ ) which is optionally substituted; -CONH-(C1-C3)alkyl-(C6-C10)aryl group, and the group is optionally substituted by a halogen atom, a methyl group or a methoxy group; and can be selected from, or -R ２ forms, together with the carbon atom in the 6-position, a fused phenyl or (5- to 6-membered) heteroaryl at the 5- and 6-positions, the fused heteroaryl having at least one heteroatom selected from O, N or S, and the fused phenyl or heteroaryl being as follows: one or more halogen atoms, one or more -(C １ -C ４ ) alkyl groups, One or more -(C １ -C ３ ) haloalkyl groups, One or more —(C optionally substituted by 1 to 3 fluorine atoms １ —C ３ ) alkoxy group, A (4- to 10-membered) heterocycle having at least one N, wherein the heterocycle optionally contains a bridge of 0 to 2 carbon atoms between two members of the heterocycle, and is optionally substituted by one or more of a -(C １ -C ３ )alkyl group, an NRR' group or a carbonyl, and the -(C １ -C ３ )alkyl group is optionally substituted by an NRR' group; an NH-heterocycle containing 4 to 10 members having at least one N, and the heterocycle optionally contains a bridge of 0 to 2 carbon atoms between two members of the heterocycle; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by one or more of -NRR' groups or OH groups, a (C ６ -C １０ ) aryl group; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by a (5- to 12-membered) heteroaryl optionally substituted by an -NRR' group or an OH group; NR ７ R ８ group is optionally substituted by one or more of; - Ra is -(C １ -C ６ ) alkyl group; A halogen atom, optionally substituted by 1 to 3 fluorine atoms, -(C １ -C ４ ) an alkyl group, optionally substituted by 1 to 3 fluorine atoms, -(C １ -C ３ ) an alkoxy group, optionally substituted by, -(C １ -C ３ ) an alkyl-phenyl group; -(C １ -C ３ ), which is a phenyl group optionally substituted by an alkyl group, wherein the -(C １ -C ３ ) alkyl group is substituted by an -NRR' group; or A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, —(C １ —C ３ )alkyl-(5- to 6-membered)heteroaryl selected from - R and R' are the same or different and are selected from -(C １ - C ３ ) alkyl groups and H, - Rb is carbonyl; and SO ２ selected from -R ３ is A heterocyclic ring containing 4 to 10 members having at least one N, the heterocyclic ring optionally containing a bridge of 0 to 2 carbon atoms between two members of the heterocyclic ring, and optionally substituted by a -(C １ -C ３ )alkyl group or -NRR' group; and an -NH-heterocycle containing 4 to 10 members having at least one N, and the heterocycle optionally contains a bridge of 0 to 2 carbon atoms between two members of the heterocycle; selected from -R ７ and R ８ are the same or different and are selected from H, -(C １ -C ６ ) alkyl group and -CO-(C １ -C ６ ) alkyl group, and the -(C １ -C ６ ) alkyl group and -CO-(C １ -C ６ ) alkyl group may be optionally substituted by -NRR' group] a compound represented by, or a pharmaceutically acceptable salt or optical isomer, racemate, diastereoisomer, enantiomer or tautomer thereof (provided that the following compounds are excluded: · 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperazine; · 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; · 1-(5-bromo-3-chloro-2-pyridyl)-4-methyl-piperazine; · 1-[2-chloro-4-(trifluoromethyl)phenyl]piperazine hydrochloride; · 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]piperidin-4-amine; · 1-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-1,4-diazepane; · Methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; · 1-(3-chloro-5-methyl-2-pyridyl)piperazine; · 1-(5-bromo-3-chloro-2-pyridyl)piperazine; · 2-chloro-3-piperazin-1-yl-quinoxaline hydrochloride; · 1-[3-bromo-5-(trifluoromethyl)-2-pyridyl]-4-methyl-piperazine; · 3-methyl-2-piperazin-1-yl-quinoline hydrochloride; ・ 2-Piperazin-1-ylquinoline-3-carbonitrile hydrochloride; ・ 3-[(3R)-3-Methylpiperazin-1-yl]quinoxalin-2-ol hydrochloride; ・ 2-Chloro-3-(4-ethylpiperazin-1-yl)quinoxaline; ・ 3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,2,4-oxadiazole; ・ (1R,5S)-N-[3-Chloro-5-(trifluoromethyl)-2-pyridyl]-3-azabicyclo[3.1.0]hexane-6-amine; ・ 2-Methoxy-3-piperazin-1-yl-quinoxaline hydrochloride; ・ 2-Chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline; ・ 3-Cyano-2-(4-methyl-piperazino)-5-(pyrid-4-yl)-pyridine; ・ Methyl 5-chloro-6-(4-methylpiperazin-1-yl)nicotinate; ・ (1-[3-Chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylpiperazine; ・ 1-(3,5-Dichloro-2-pyridyl)piperazine hydrochloride; ・ 2-Methoxy-3-(4-methylpiperazin-1-yl)quinoxaline; ・ 2-Ethoxy-3-(4-methylpiperazin-1-yl)quinoxaline; ・ 2-Methyl-3-(4-methylpiperazin-1-yl)quinoxaline; ・ 2-Ethyl-3-(4-methylpiperazin-1-yl)quinoxaline; ・ 2-(4-Methylpiperazin-1-yl)-3-(trifluoromethyl)quinoxaline; ・ 2-Bromo-3-(4-methylpiperazin-1-yl)quinoxaline; ・ 2-Chloro-3-(4-methyl-1,4-diazepan-1-yl)quinoxaline; ・ 3,6-Dichloro-2-(4-methylpiperazin-1-yl)quinoxaline; ・ 2,6,7-Trichloro-3-(4-methylpiperazin-1-yl)quinoxaline; ・ 1-(3-Chloroquinoxalin-2-yl)-N-methyl-pyrrolidin-3-amine ・ 2-Chloro-3-[(3S)-3-methylpiperazin-1-yl]quinoxaline hydrochloride; and ・ 4-Bromo-1-piperazin-1-yl-isoquinoline).

2. -R １ be A halogen atom; -(C １ -C ３ ) alkyl group; -(C １ -C ３ ) halogenoalkyl group; or -(C １ -C ３ ) alkoxy group can be selected from; and / or -R ２ to A halogen atom excluding a fluorine atom and a chlorine atom; An optionally substituted -(C １ -C ６ )alkyl group, substituted by one heteroatom selected from O, N or S; An alkenyl group optionally substituted by one heteroatom selected from O, N or S - (C ２ -C ６ ) An optionally substituted -(C ２ -C ６ ) alkynyl group; which is optionally substituted by one heteroatom selected from O, N or S; -(C １ -C ３ ) alkoxy group; -(C ２ ~C ３ ) haloalkyl group; -COORa group; -N(H)Rb-Ra group; -(C １ -C ３ )alkyl group optionally substituted by a -(C ２ -C ６ )alkynyl-(C ６ -C １０ )aryl group, wherein the -(C １ -C ３ )alkyl group is optionally substituted by a -NRR' group; -(C １ -C ３ ) an alkyl group optionally substituted by a CONH-(C ６ -C １０ ) aryl group, wherein the -(C １ -C ３ ) alkyl group is optionally substituted by a -NRR' group; -(C1-C3)alkyl-O-(C6-C10)aryl group, wherein said group is optionally substituted by a -NRR' group and is optionally substituted by a (C １ -C ３ )alkyl group; -O-(C1-C3)alkyl-(C6-C10)aryl group, wherein the group is optionally substituted by an -NRR' group (C １ -C ３ )alkyl group is optionally substituted; A (5- to 6-membered) heteroaryl group having at least one heteroatom selected from O, N or S, wherein the group is optionally substituted by a —NRR′ group and optionally substituted by an alkyl group of (C １ —C ３ ) which is optionally substituted by an alkyl group; -CONH-(C1-C3)alkyl-(C6-C10)aryl group, wherein the group is optionally substituted by a halogen atom, a methyl group or a methoxy group; selected from, or -R ２ together with the carbon atom at the 6-position forms a fused phenyl or (5- to 6-membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, and said fused phenyl or heteroaryl being as follows: one or more halogen atoms, One or more -(C １ -C ４ ) alkyl groups, One or more - (C １ -C ３ ) haloalkyl groups, One or more —(C optionally substituted by 1 to 3 fluorine atoms １ —C ３ ) alkoxy group, A (4- to 10-membered) heterocycle having at least one N, wherein the heterocycle optionally contains a bridge of 0 to 2 carbon atoms between two members of the heterocycle and is optionally substituted by one or more of -(C １ -C ３ )alkyl group, NRR' group or carbonyl, and the -(C １ -C ３ )alkyl group is optionally substituted by an NRR' group; an NH-heterocycle containing 4 to 10 members having at least one N, wherein the heterocycle optionally contains a bridge of 0 to 2 carbon atoms between two members of the heterocycle; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by one or more of -NRR' groups or OH groups, a (C ６ -C １０ ) aryl group; A (5- to 12-membered) heteroaryl optionally substituted by a halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, an -NRR' group or OH, and optionally substituted by an (C １ -C ３ ) alkyl group; NR ７ R ８ group optionally substituted by one or more of, and the other substituents are as defined in claim 1, provided that -R １ where R is a halogen and R ３ is piperazine, X and Y are not simultaneously N -R １ wherein R is halogen, and when ３ R is piperazine, R ２ is not COOCH ３ ​ the compound according to claim 1.

3. -R １ wherein R is a halogen atom, -R ２ with An optionally substituted -(C ２ -C ６ ) alkynyl group, optionally substituted by one heteroatom selected from O, N or S selected from, or -R ２ is, together with the carbon atom at the 6-position, forming a fused phenyl or (5- to 6-membered) heteroaryl at the 5- and 6-positions, the fused heteroaryl having at least one heteroatom selected from O, N or S, and the fused phenyl or heteroaryl being as follows: one or more halogen atoms, One or more -(C １ -C ４ ) alkyl groups, One or more -(C １ -C ３ ) haloalkyl groups, One or more -(C optionally substituted by 1 to 3 fluorine atoms １ -C ３ ) alkoxy group, A (4- to 10-membered) heterocycle having at least one N, the heterocycle optionally containing a bridge of 0 to 2 carbon atoms between two members of the heterocycle, and optionally substituted by one or more of -(C １ -C ３ )alkyl group, NRR' group or carbonyl, and the -(C １ -C ３ )alkyl group is optionally substituted by an NRR' group; an NH-heterocycle containing 4 to 10 members having at least one N, wherein the heterocycle optionally contains a bridge of 0 to 2 carbon atoms between two members of the heterocycle; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, an (C １ -C ３ ) alkyl group optionally substituted by one or more of -NRR' groups or OH groups, an (C ６ -C １０ ) aryl group; A (5- or 6-membered) heteroaryl optionally substituted by a halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, an -NRR' group or OH, and optionally substituted by an (C １ -C ３ ) alkyl group; NR ７ R ８ group optionally substituted by one or more of, and the other substituents are as defined in claim 1, provided that -R １ where R is halogen and R ３ is piperazine, a compound according to claim 1, wherein X and Y are not both N at the same time.

4. -X is CH; and N can be selected from, -Y is CH; and N can be selected from, -X and Y are not simultaneously CH or N, the compound according to claim 1.

5. -R ３ is selected from hetero rings containing 4 to 10 members having at least one N, in particular piperazine, the hetero ring optionally containing a bridge of 0 to 2 carbon atoms between two members of the hetero ring, and -(C １ -C ３ )alkyl group or -NRR' group is optionally substituted, the compound according to claim 1.

6. -X is N and Y is CH; and / or -R １ is selected from chlorine, bromine and iodine; and / or -R ２ is iodine; -NRR' group, optionally substituted by - (C ２ -C ６ ) alkynyl group, especially a pentynyl group; -(C １ -C ３ )alkyl group optionally substituted by a -(C ２ -C ６ )alkynyl-(C ６ -C １０ )aryl group, in particular ethynyl-phenyl, wherein the -(C １ -C ３ )alkyl group is optionally substituted by a -NRR' group; -COORa group; A (5- to 6-membered) heteroaryl group having at least one heteroatom selected from O, N or S, in particular oxadiazole, said group optionally substituted by an -NRR' group, (C １ -C ３ ) alkyl group, in particular optionally substituted by ethyl; selected from, or -R ２ together with the carbon atom in the 6-position halogen atoms, especially chlorine, bromine and iodine; One or more -(C １ -C ４ ) alkyl groups, especially a methyl group; A (4- to 10-membered) heterocycle having at least one N, in particular piperazine, pyrrolidine and imidazolidine, wherein the heterocycle is optionally substituted by a (C １ -C ３ )alkyl group, in particular methyl, an NRR' group or a carbonyl, and the -(C １ -C ３ )alkyl group is optionally substituted by an NRR' group; A (C6-C10)aryl group, in particular phenyl, said group being optionally substituted by a halogen atom, in particular fluorine and chlorine, a methyl group optionally substituted by three fluorine atoms, a methoxy group, an -NRR' group or an OH, and optionally substituted by one or more of the following: １ -C ３ )alkyl groups; an NH-heterocycle containing 4 to 10 members having at least one N, especially piperazine; -NRR' group, optionally substituted by (C １ -C ３ ) an alkyl group, optionally substituted, (5- to 12-membered) heteroaryl, in particular, pyridine and triazole; NR ７ R ８ group forming a condensed phenyl optionally substituted by; and / or -Ra is -C optionally substituted by an NRR' group １ -C ３ phenyl group optionally substituted by an alkyl group selected from, - R and R' are the same or different and are selected from - (C １ - C ３ ) alkyl groups, in particular methyl, and H; and / or -R ３ is piperazine optionally substituted by methyl; and / or -R ７ and R ８ are the same or different and are selected from H, -(C １ -C3) alkyl groups, in particular ethyl, propyl and butyl, and -CO-(C １ -C ３ ) alkyl groups, in particular -CO-CH ２ -, and the -(C １ -C ３ ) alkyl group and the -CO-(C １ -C ３ ) alkyl group are optionally substituted by -NH ２ , the compound according to claim 1.

7. -X is N and Y is CH; and / or -R １ is selected from chlorine, bromine and iodine; and / or -R ２ is iodine; -NRR' group, optionally substituted by - (C ２ -C ６ ) alkynyl group, especially, pentynyl group; -COORa group; a (5- or 6-membered) heteroaryl group having at least one heteroatom selected from O, N or S, in particular oxadiazole, said group being optionally substituted by a -NRR' group (C １ -C ３ ) alkyl group, in particular optionally substituted by ethyl; selected from, or -R ２ together with the carbon atom in the 6-position halogen atoms, especially chlorine, bromine and iodine; one or more -(C １ -C ４ ) alkyl groups, especially a methyl group; a (4 to 10 membered) heterocycle having at least one N, especially piperazine; A (C6-C10) aryl group, in particular phenyl, which group is optionally substituted by an -NRR' group (C １ -C ３ ) alkyl group, in particular methyl, which is optionally substituted; NR ７ R ８ group forming a condensed phenyl optionally substituted by; and / or -Ra is - (C optionally substituted by an NRR' group １ - C ３ ) phenyl group optionally substituted by an alkyl group selected from, -R and R' are H; and / or -R ３ is piperazine optionally substituted by methyl; and / or -R ７ and R ８ are the same or different and are selected from H, -(C １ -C ３ )alkyl groups, especially ethyl and propyl, and -CO-(C １ -C ３ )alkyl groups, especially -CO-CH ２ -, and the -(C １ -C ３ )alkyl group and the -CO-(C １ -C ３ )alkyl group are optionally substituted by -NH ２ , the compound according to claim 1.

8. the compound is as follows: -1-(5-bromo-3-chloro-2-pyridyl)piperazine hydrochloride; -1-(3-chloro-5-iodo-2-pyridyl)piperazine; -1-(3-chloro-5-methyl-2-pyridyl)-4-methyl-piperazine; -1-(3-chloro-5-methyl-2-pyridyl)piperazine hydrochloride; -N-[5-Chloro-6-(4-methylpiperazin-1-yl)-3-pyridyl]acetamide; -N-(5-Chloro-6-piperazin-1-yl-3-pyridyl)acetamide hydrochloride; -N-(5-Chloro-6-piperazin-1-yl-3-pyridyl)methanesulfonamide hydrochloride; -Methyl 5-chloro-6-(4-methylpiperazin-1-yl)pyridine-3-carboxylate; -Ethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -Benzyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -2-Phenylethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -3-Phenylpropyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -p-Tolylmethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -(4-Chlorophenyl)methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -(4-Methoxyphenyl)methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -2-(4-Chlorophenyl)ethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -[4-(2-Aminoethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; -3-Chloro-2-(4-methylpiperazin-1-yl)quinoline; -3-Chloro-2-piperazin-1-yl-quinoline; -3-Chloro-2-piperazin-1-yl-quinoline hydrochloride; -3-Bromo-2-piperazin-1-yl-quinoline hydrochloride; -3-Bromo-2-piperazin-1-yl-6-(trifluoromethyl)quinoline hydrochloride; -3-Bromo-6-chloro-2-piperazin-1-yl-quinoline hydrochloride; -1-[2-Chloro-4-(trifluoromethyl)phenyl]-4-methyl-piperazine; -2-Chloro-3-piperazin-1-yl-quinoline hydrochloride; -1-[3-Bromo-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; -3-Iodo-2-piperazin-1-yl-quinoline hydrochloride; -1-[5-Iodo-3-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; -1-(3-Chloro-5-iodo-2-pyridyl)piperazine; -3-Chloro-2-(1,4-diazepan-1-yl)quinoline; -2-Chloro-3-(3,8-diazabicyclo[3.2.1]octan-3-yl)quinoxaline hydrochloride; -N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinolin-2-amine hydrochloride; -1-[3-Chloro-5-(trifluoromethyl)-2-pyridyl]piperidin-4-amine; -1-(3-Chloro-5-methoxy-2-pyridyl)piperazine hydrochloride; -(1R,5S)-N-[3-Chloro-5-(trifluoromethyl)-2-pyridyl]-3-azabicyclo[3.1.0]hexan-6-amine formate; -3-(4-Chlorophenyl)propyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -[3-(Aminomethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; -5-Chloro-N-[(4-chlorophenyl)methyl]-6-piperazin-1-yl-pyridine-3-carboxamide hydrochloride; -N-[4-(2-Aminoethyl)phenyl]-5-chloro-6-piperazin-1-yl-pyridine-3-carboxamide dihydrochloride; -2,6-Dichloro-3-piperazin-1-yl-quinoline hydrochloride; -2-Chloro-6-methyl-3-piperazin-1-yl-quinoline hydrochloride; -3-Chloro-2-(3,8-diazabicyclo[3.2.1]octan-8-yl)quinoline hydrochloride; -2-Chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline hydrochloride; -N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinoxalin-2-amine hydrochloride; -3-Bromo-6-methyl-2-piperazin-1-yl-quinoline hydrochloride; -3-Chloro-2,6-di(piperazin-1-yl)quinoline dihydrochloride; -2-Methoxy-3-piperazin-1-yl-quinoxaline 2,2,2-trifluoroacetate; -2-Chloro-3-(3,6-diazabicyclo[3.1.1]heptan-3-yl)quinoxaline trifluoromethanesulfonate; - 2-Chloro-3-(4-ethylpiperazin-1-yl)quinoxaline hydrochloride; - 4-(2-Aminoethyl)-N-(5-chloro-6-piperazin-1-yl-3-pyridyl)benzamide dihydrochloride; - Phenyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate 2,2,2-trifluoroacetate; - 2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,3,4-oxadiazole; - 3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,2,4-oxadiazole hydrochloride; - 3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)prop-2-yn-1-amine 2,2,2-trifluoroacetate; - 5-(5-Chloro-6-piperazin-1-yl-3-pyridyl)penta-4-yn-1-amine 2,2,2-trifluoroacetate; - 4-(5-Chloro-6-piperazin-1-yl-3-pyridyl)but-3-yn-1-amine 2,2,2-trifluoroacetate; - 3-Chloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-Chloro-6-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 6-Bromo-3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Chloro-2-piperazin-1-yl-1,5-naphthyridine hydrochloride; - 2-Chloro-6-methoxy-3-piperazin-1-yl-quinoxaline hydrochloride; - N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)ethane-1,2-diamine dihydrochloride; - N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)propane-1,3-diamine dihydrochloride; - 1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)piperazin-2-one dihydrochloride; - 2-Amino-N-(3-chloro-2-piperazin-1-yl-6-quinolyl)acetamide dihydrochloride; - [3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]methanamine dihydrochloride - 2-[3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; -3-[3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]propan-1-amine dihydrochloride; -[3-[(5-chloro-6-piperazin-1-yl-3-pyridyl)methoxy]phenyl]methanamine dihydrochloride; -[3-[(5-chloro-6-piperazin-1-yl-3-pyridyl)oxymethyl]phenyl]methanamine dihydrochloride; -3-chloro-2-piperazin-1-yl-N-(4-piperidyl)quinolin-6-amine dihydrochloride; -1-(3-chloro-2-piperazin-1-yl-6-quinolyl)piperidin-4-amine dihydrochloride; -3-chloro-6-(1,4-diazepan-1-yl)-2-piperazin-1-yl-quinoline dihydrochloride; -(3R)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; -(3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; -3-chloro-2-piperazin-1-yl-N-[(3R)-pyrrolidin-3-yl]quinolin-6-amine dihydrochloride; -1-(3-chloro-2-piperazin-1-yl-6-quinolyl)azetidin-3-amine dihydrochloride; -3-chloro-6-(2,6-diazaspiro[3.3]heptan-2-yl)-2-piperazin-1-yl-quinoline dihydrochloride; -3-chloro-6-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-piperazin-1-yl-quinoline dihydrochloride; -3-chloro-6-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-piperazin-1-yl-quinoline dihydrochloride; -3-chloro-2-piperazin-1-yl-6-(1-piperidyl)quinoline hydrochloride; -4-(3-chloro-2-piperazin-1-yl-6-quinolyl)morpholine hydrochloride; -[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]methanamine dihydrochloride; -2-[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]ethanamine dihydrochloride; -[1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-yl]methanamine dihydrochloride - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-piperidyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - 1-(3-chloro-5-ethynyl-2-pyridyl)piperazine; - 3,7-dichloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-6-phenyl-2-piperazin-1-yl-quinoline hydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanol hydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N-methyl-methanamine dihydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N,N-dimethyl-methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-piperidyl]methanamine dihydrochloride; - [1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-yl]methanamine dihydrochloride; - (3R)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3R)-pyrrolidin-3-yl]quinolin-6-amine dihydrochloride; - 3-chloro-2-piperazin-1-yl-N-[(3S)-3-piperidyl]quinolin-6-amine dihydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)butane-1,4-diamine dihydrochloride; - (1S)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - (1R)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; -2-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; -[5-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-2-fluoro-phenyl]methanamine dihydrochloride; -[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; -[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-4-methoxy-phenyl]methanamine dihydrochloride; -[5-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-3-pyridyl]methanamine dihydrochloride; -3-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]propane-1-amine dihydrochloride; -2-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]ethanamine dihydrochloride; -2-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; -1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; -1-(3,8-Dichloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; -1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one hydrochloride; -1-[3-Chloro-5-(2-phenylethynyl)-2-pyridyl]piperazine 2,2,2-trifluoroacetate; -2-[2-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -2-[3-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -2-[4-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -3-Chloro-2-piperazin-1-yl-6-(1,2,3,4-tetrahydroisoquinolin-5-yl)quinoline dihydrochloride; -3-Chloro-6-isoindolin-4-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 3-Chloro-6-isoindolin-5-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 2-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]propan-2-amine dihydrochloride; - 2-[5-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-2-yl]methanamine dihydrochloride; - 2-[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-2-yl]ethanamine dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]methanamine dihydrochloride; - 2-[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]ethanamine dihydrochloride; - [3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]methanamine dihydrochloride; - 2-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]ethanamine dihydrochloride; - [4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-3-yl]methanamine dihydrochloride; - 2-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-3-yl]ethanamine dihydrochloride; - 3-(2-Aminoethyl)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one dihydrochloride; - 1-(2-Aminoethyl)-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one dihydrochloride; - 1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-3-[2-(dimethylamino)ethyl]pyrrolidin-2-one dihydrochloride; - 1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-3-[2-(dimethylamino)ethyl]imidazolidin-2-one dihydrochloride; - [5-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-3-yl]methanamine dihydrochloride; -2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-3-yl]ethanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-5-yl]methanamine dihydrochloride; -2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,3,4-oxadiazol-2-yl]methanamine dihydrochloride; -2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,3,4-oxadiazol-2-yl]ethanamine dihydrochloride; -[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)oxazol-2-yl]methanamine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)oxazol-2-yl]ethanamine dihydrochloride; -[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)thiazol-2-yl]methanamine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)thiazol-2-yl]ethanamine dihydrochloride; -[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-imidazol-2-yl]methanamine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-imidazol-2-yl]ethanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-1,2,4-triazol-5-yl]methanamine dihydrochloride; -2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-1,2,4-triazol-5-yl]ethanamine dihydrochloride; -6-[3-(aminomethyl)phenyl]-N-[(1S,5R)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinolin-2-amine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methyl-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [2-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [2-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-pyridyl]methanamine dihydrochloride; - [6-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-pyridyl]methanamine dihydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-pyridyl]methanamine dihydrochloride; - [6-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrazin-2-yl]methanamine dihydrochloride; - 3-chloro-6-imidazol-1-yl-2-piperazin-1-yl-quinoline hydrochloride; and - (1S,4S)-2-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-2,5-diazabicyclo[2.2.1]heptane carboxylic acid The compound according to claim 1, selected from the following:

9. The compound is as follows: - 1-(3-chloro-5-iodo-2-pyridyl)piperazine; - [4-(2-aminoethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-chloro-2-(4-methylpiperazin-1-yl)quinoline; - 3-chloro-2-piperazin-1-yl-quinoline; - 3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-bromo-2-piperazin-1-yl-quinoline hydrochloride; - 2-chloro-3-piperazin-1-yl-quinoxaline hydrochloride; - 3-iodo-2-piperazin-1-yl-quinoline hydrochloride; - [3-(aminomethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-bromo-6-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-bromo-6-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2,6-di(piperazin-1-yl)quinoline dihydrochloride; - 3-chloro-6-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 6-bromo-3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 2-[3-(5-chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; - 2-chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline hydrochloride; - 5-(5-chloro-6-piperazin-1-yl-3-pyridyl)penta-4-yn-1-amine 2,2,2-trifluoroacetate; - 3-chloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)ethane-1,2-diamine dihydrochloride; - N'-(3-chloro-2-piperazin-1-yl-6-quinolyl)propane-1,3-diamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - 2-amino-N-(3-chloro-2-piperazin-1-yl-6-quinolyl)acetamide dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]methanamine dihydrochloride; - 2-[2-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; - 2-[3-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; - 2-[4-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; - 3,7-Dichloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)butane-1,4-diamine dihydrochloride; - 3-Chloro-2-piperazin-1-yl-N-[(3S)-3-piperidyl]quinolin-6-amine dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-4-piperidyl]methanamine dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-yl]methanamine dihydrochloride; - (3R)-1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - [2-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanol hydrochloride; - 1-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N-methyl-methanamine dihydrochloride; - 1-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N,N-dimethyl-methanamine dihydrochloride; - 2-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]propane-2-amine dihydrochloride; - (1S)-1-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - (1R)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 3-chloro-2-piperazin-1-yl-6-(1,2,3,4-tetrahydroisoquinolin-5-yl)quinoline dihydrochloride; - 3-chloro-6-isoxindolin-4-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-6-isoxindolin-5-yl-2-piperazin-1-yl-quinoline dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-fluoro-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-pyridyl]methanamine dihydrochloride; - 3-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]propane-1-amine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3,8-dichloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one hydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methyl-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; - [2-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [2-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; and - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-pyridyl]methanamine dihydrochloride The compound according to claim 1, selected from

10. A pharmaceutical composition comprising the compound represented by formula (I) according to any one of claims 1 to 9.

11. Formula (I): [Chemical 2] [Wherein, - X can be selected from CH; and N and - Y can be selected from CH; and N and -R １ with a halogen atom; -(C １ -C ３ ) alkyl group; -(C １ -C ３ ) haloalkyl group; -(C １ -C ３ ) alkoxy group; a nitrile group or can be selected from -R １ Together with Y, it forms a condensed phenyl group at the 3rd and 4th positions, -R ２ with a halogen atom other than a fluorine atom; An optionally substituted -(C １ -C ６ )alkyl group, substituted by one heteroatom selected from O, N or S; An alkenyl group optionally substituted by one heteroatom selected from O, N or S; - (C ２ -C ６ ) An optionally substituted -(C ２ -C ６ ) alkynyl group; which is optionally substituted by one heteroatom selected from O, N or S -(C １ -C ３ ) alkoxy group; -(C １ -C ３ ) halogenoalkyl group; -COORa group; -N(H)Rb-Ra group; -(C １ -C ３ ) an alkyl group optionally substituted by a -(C ２ -C ６ ) alkynyl-(C ６ -C １０ ) aryl group, wherein the -(C １ -C ３ ) alkyl group is optionally substituted by a -NRR' group; -(C １ -C ３ ) an alkyl group optionally substituted by a CONH-(C ６ -C １０ ) aryl group, wherein the -(C １ -C ３ ) alkyl group is optionally substituted by a -NRR' group; -(C1-C3)alkyl-O-(C6-C10)aryl group, where the group is optionally substituted by an -NRR' group (C １ -C ３ )alkyl group; -O-(C1-C3)alkyl-(C6-C10)aryl group, where the group is optionally substituted by an -NRR' group (C １ -C ３ )alkyl group is optionally substituted; A (5- to 6-membered) heteroaryl group having at least one heteroatom selected from O, N or S, which group is optionally substituted by a —NRR′ group and optionally substituted by an alkyl group of (C １ —C ３ ) which is optionally substituted by an alkyl group; -CONH-(C1-C3)alkyl-(C6-C10)aryl group, which group may be optionally substituted by a halogen atom, a methyl group or a methoxy group; or can be selected from -R ２ together with the carbon atom at the 6-position forms a fused phenyl or (5- to 6-membered) heteroaryl at the 5- and 6-positions, the fused heteroaryl having at least one heteroatom selected from O, N or S, and the fused phenyl or heteroaryl being as follows: one or more halogen atoms, one or more -(C １ -C ４ ) alkyl group, One or more —(C １ —C ３ ) haloalkyl group, one or more —(C １ —C ３ ) alkoxy group optionally substituted by 1 to 3 fluorine atoms, A (4- to 10-membered) heterocycle having at least one N, wherein the heterocycle optionally contains a bridge of 0 to 2 carbon atoms between two members of the heterocycle, and is optionally substituted by one or more of -(C １ -C ３ ) alkyl group, NRR' group or carbonyl, and the -(C １ -C ３ ) alkyl group is optionally substituted by an NRR' group; An NH - hetero - ring containing 4 to 10 members having at least one N, wherein the hetero - ring optionally contains a bridge of 0 to 2 carbon atoms between two members of the hetero - ring; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by one or more of -NRR' group or OH, a (C ６ -C １０ ) aryl group; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by a -NRR' group or OH, a (5- to 12-membered) heteroaryl; NR ７ R ８ group Optionally substituted by one or more of the following; - Ra is -(C １ -C ６ ) alkyl group; A halogen atom, optionally substituted by 1 to 3 fluorine atoms, -(C １ -C ４ ) alkyl group, optionally substituted by 1 to 3 fluorine atoms, -(C １ -C ３ ) alkoxy group, optionally substituted by -(C １ -C ３ ) alkyl-phenyl group; -(C １ -C ３ ) an optionally substituted phenyl group substituted by an alkyl group, wherein the -(C １ -C ３ ) alkyl group is substituted by an -NRR' group; or A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, —(C １ —C ３ )alkyl-(5- to 6-membered)heteroaryl selected from - R and R' are the same or different and are selected from -(C １ - C ３ ) alkyl group and H, - Rb is Carbonyl; and SO ２ selected from -R ３ is A heterocyclic ring containing 4 to 10 members having at least one N, the heterocyclic ring optionally containing a bridge of 0 to 2 carbon atoms between two members of the heterocyclic ring, and optionally substituted by a -(C １ -C ３ )alkyl group or -NRR' group; and An NH - hetero - ring containing 4 to 10 members having at least one N, wherein the hetero - ring optionally contains a bridge of 0 to 2 carbon atoms between two members of the hetero - ring; selected from R ７ and R ８ are the same or different and are selected from H, —(C １ —C ６ ) alkyl group and —CO—(C １ —C ６ ) alkyl group, and the —(C １ —C ６ ) alkyl group and —CO—(C １ —C ６ ) alkyl group may be optionally substituted by a —NRR' group]] A pharmaceutical composition comprising a compound represented by or a pharmaceutically acceptable salt or optical isomer, racemate, diastereoisomer, enantiomer or tautomer thereof, for use in treating a disease.

12. -R １ with A halogen atom; -(C １ -C ３ ) alkyl group; -(C １ -C ３ ) haloalkyl group; -(C １ -C ３ ) alkoxy group; or A nitrile group can be selected from -R ２ with A halogen atom other than a fluorine atom; An optionally substituted -(C １ -C ６ )alkyl group, substituted by one heteroatom selected from O, N or S; An optionally substituted -(C ２ -C ６ ) alkenyl group, substituted by one heteroatom selected from O, N or S; An optionally substituted -(C ２ -C ６ ) alkynyl group; which is optionally substituted by one heteroatom selected from O, N or S -(C １ -C ３ ) alkoxy group; -(C １ -C ３ ) haloalkyl group; - COORa group; - N(H)Rb - Ra group; -(C １ -C ３ ) an alkyl group optionally substituted by a -(C ２ -C ６ ) alkynyl-(C ６ -C １０ ) aryl group, wherein the -(C １ -C ３ ) alkyl group is optionally substituted by a -NRR' group; -(C １ -C ３ ) an alkyl group optionally substituted by a CONH-(C ６ -C １０ ) aryl group, wherein the -(C １ -C ３ ) alkyl group is optionally substituted by an -NRR' group; -(C1-C3)alkyl-O-(C6-C10)aryl group, wherein the group is optionally substituted by an -NRR' group and is optionally substituted by a (C １ -C ３ )alkyl group; -O-(C1-C3)alkyl-(C6-C10)aryl group, wherein the group is optionally substituted by an -NRR' group and is optionally substituted by a (C １ -C ３ )alkyl group; A (5- to 6-membered) heteroaryl group having at least one heteroatom selected from O, N or S, said group optionally substituted by an -NRR' group and optionally substituted by an alkyl group of (C １ -C ３ ) which is optionally substituted; - CONH - (C1 - C3)alkyl - (C6 - C10)aryl group, wherein the group is optionally substituted by a halogen atom, a methyl group or a methoxy group; can be selected from or -R ２ is, together with the carbon atom at the 6-position, forming a fused phenyl or (5- to 6-membered) heteroaryl at the 5- and 6-positions, the fused heteroaryl having at least one heteroatom selected from O, N or S, and the fused phenyl or heteroaryl being as follows: One or more halogen atoms, one or more - (C １ -C ４ ) alkyl groups, One or more -(C １ -C ３ ) haloalkyl groups, One or more —(C optionally substituted by 1 to 3 fluorine atoms １ —C ３ ) alkoxy group, A (4- to 10-membered) heterocycle having at least one N, the heterocycle optionally containing a bridge of 0 to 2 carbon atoms between two members of the heterocycle, and optionally substituted by one or more of -(C １ -C ３ ) alkyl group, NRR' group or carbonyl, and the -(C １ -C ３ ) alkyl group is optionally substituted by an NRR' group; An NH - hetero - ring containing 4 to 10 members having at least one N, wherein the hetero - ring optionally contains a bridge of 0 to 2 carbon atoms between two members of the hetero - ring; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by one or more of -NRR' groups or OH groups, a (C ６ -C １０ ) aryl group; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by an -NRR' group or OH, a (5- to 12-membered) heteroaryl; NR ７ R ８ group Optionally substituted by one or more of the following; - Ra is -(C １ -C ６ ) alkyl group; a halogen atom, a -(C １ -C ４ ) alkyl group optionally substituted by 1 to 3 fluorine atoms, a -(C １ -C ３ ) alkoxy group optionally substituted by 1 to 3 fluorine atoms, a -(C １ -C ３ ) alkyl-phenyl group; -(C １ -C ３ ) an optionally substituted phenyl group with an alkyl group, wherein the -(C １ -C ３ ) alkyl group is substituted with an -NRR' group; or A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, —(C １ —C ３ )alkyl-(5- to 6-membered)heteroaryl selected from - R and R' are the same or different and are selected from - (C １ - C ３ ) alkyl groups and H - Rb is Carbonyl; and SO ２ selected from -R ３ is A heterocyclic ring containing 4 to 10 members having at least one N, the heterocyclic ring optionally containing a bridge of 0 to 2 carbon atoms between two members of the heterocyclic ring, and optionally substituted by a -(C １ -C ３ )alkyl group or -NRR' group; and An NH - hetero - ring containing 4 to 10 members having at least one N, wherein the hetero - ring optionally contains a bridge of 0 to 2 carbon atoms between two members of the hetero - ring; selected from -R ７ and R ８ are the same or different and are selected from H, -(C １ -C ６ -alkyl group and -CO-(C １ -C ６ -alkyl group, and the -(C １ -C ６ -alkyl group and -CO-(C １ -C ６ -alkyl group may be optionally substituted by an -NRR' group, the pharmaceutical composition for use according to claim 11.

13. -R １ is a halogen atom; and / or -R ２ with Optionally substituted by one heteroatom selected from O, N or S—(C ２ —C ６ ) alkynyl group can be selected from or -R ２ is, together with the carbon atom at the 6-position, forming a fused phenyl or (5- to 6-membered) heteroaryl at the 5- and 6-positions, said fused heteroaryl having at least one heteroatom selected from O, N or S, and said fused phenyl or heteroaryl being as follows: One or more halogen atoms, One or more -(C １ -C ４ ) alkyl groups, One or more -(C １ -C ３ ) haloalkyl groups, One or more —(C optionally substituted by 1 to 3 fluorine atoms １ —C ３ ) alkoxy group, A (4- to 10-membered) heterocycle having at least one N, wherein the heterocycle optionally contains a bridge of 0 to 2 carbon atoms between two members of the heterocycle, and is optionally substituted by one or more of -(C １ -C ３ ) alkyl group, NRR' group or carbonyl, and the -(C １ -C ３ ) alkyl group is optionally substituted by an NRR' group; An NH - hetero - ring containing 4 to 10 members having at least one N, wherein the hetero - ring optionally contains a bridge of 0 to 2 carbon atoms between two members of the hetero - ring; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by one or more of -NRR' group or OH, a (C ６ -C １０ ) aryl group; A halogen atom, a methyl group optionally substituted by 1 to 3 fluorine atoms, a methoxy group optionally substituted by 1 to 3 fluorine atoms, a (C １ -C ３ ) alkyl group optionally substituted by an -NRR' group or OH, a (5- or 6-membered) heteroaryl; NR ７ R ８ group Optionally substituted by one or more of the following; and / or, - X is CH; and N can be selected from - Y is CH; and N can be selected from - X and Y are not simultaneously CH or N, and / or -R ３ is selected from hetero rings containing 4 to 10 members having at least one N, in particular piperazine, the hetero ring optionally containing a bridge of 0 to 2 carbon atoms between two members of the hetero ring, and -(C １ -C ３ )alkyl group or -NRR' group is optionally substituted, the pharmaceutical composition for use according to claim 11.

14. The compound is as follows: - 1 - [3 - chloro - 5 - (trifluoromethyl)-2 - pyridyl]-4 - methyl - piperazine; -1-[3-Chloro-5-(trifluoromethyl)-2-pyridyl]piperazine; -1-[3-Chloro-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; -1-(5-Bromo-3-chloro-2-pyridyl)-4-methyl-piperazine; -1-(5-Bromo-3-chloro-2-pyridyl)piperazine hydrochloride; -1-(3-Chloro-5-iodo-2-pyridyl)piperazine; -1-(3-Chloro-5-methyl-2-pyridyl)-4-methyl-piperazine; -1-(3-Chloro-5-methyl-2-pyridyl)piperazine hydrochloride; -N-[5-Chloro-6-(4-methylpiperazin-1-yl)-3-pyridyl]acetamide; -N-(5-Chloro-6-piperazin-1-yl-3-pyridyl)acetamide hydrochloride; -N-(5-Chloro-6-piperazin-1-yl-3-pyridyl)methanesulfonamide hydrochloride; -Methyl 5-chloro-6-(4-methylpiperazin-1-yl)pyridine-3-carboxylate; -Methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -Ethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -Benzyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -2-Phenylethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -3-Phenylpropyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -p-Tolylmethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -(4-Chlorophenyl)methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -(4-Methoxyphenyl)methyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -2-(4-Chlorophenyl)ethyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; -[4-(2-Aminoethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; -3-Chloro-2-(4-methylpiperazin-1-yl)quinoline; -3-Chloro-2-piperazin-1-yl-quinoline; - 3-Chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Bromo-2-piperazin-1-yl-quinoline hydrochloride; - 3-Bromo-2-piperazin-1-yl-6-(trifluoromethyl)quinoline hydrochloride; - 3-Bromo-6-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 1-[2-Chloro-4-(trifluoromethyl)phenyl]-4-methyl-piperazine; - 1-[2-Chloro-4-(trifluoromethyl)phenyl]piperazine hydrochloride; - 2-Chloro-3-piperazin-1-yl-quinoline hydrochloride; - 2-Chloro-3-piperazin-1-yl-quinoxaline hydrochloride; - 1-[3-Bromo-5-(trifluoromethyl)-2-pyridyl]-4-methyl-piperazine; - 1-[3-Bromo-5-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; - 3-Iodo-2-piperazin-1-yl-quinoline hydrochloride; - 3-Methyl-2-piperazin-1-yl-quinoline hydrochloride; - 2-Piperazin-1-ylquinoline-3-carbonitrile hydrochloride; - 1-[5-Iodo-3-(trifluoromethyl)-2-pyridyl]piperazine hydrochloride; - 1-(3-Chloro-5-iodo-2-pyridyl)piperazine; - 1-[3-Chloro-5-(trifluoromethyl)-2-pyridyl]-1,4-diazepane; - 3-Chloro-2-(1,4-diazepan-1-yl)quinoline; - 2-Chloro-3-(3,8-diazabicyclo[3.2.1]octan-3-yl)quinoxaline hydrochloride; - 3-[(3R)-3-Methylpiperazin-1-yl]quinoxalin-2-ol hydrochloride; - 2-Chloro-3-[(3S)-3-methylpiperazin-1-yl]quinoxaline hydrochloride; - N-[(1R,5S)-3-Azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinolin-2-amine hydrochloride; - 1-[3-Chloro-5-(trifluoromethyl)-2-pyridyl]piperidin-4-amine; - 1-(3-Chloro-5-methoxy-2-pyridyl)piperazine hydrochloride; - (1R,5S)-N-[3-Chloro-5-(trifluoromethyl)-2-pyridyl]-3-azabicyclo[3.1.0]hexane-6-amine formate; - 3-(4-Chlorophenyl)propyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate hydrochloride; - [3-(Aminomethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 5-Chloro-N-[(4-chlorophenyl)methyl]-6-piperazin-1-yl-pyridine-3-carboxamide hydrochloride; - N-[4-(2-Aminoethyl)phenyl]-5-chloro-6-piperazin-1-yl-pyridine-3-carboxamide dihydrochloride; - 2,6-Dichloro-3-piperazin-1-yl-quinoline hydrochloride; - 2-Chloro-6-methyl-3-piperazin-1-yl-quinoline hydrochloride; - 3-Chloro-2-(3,8-diazabicyclo[3.2.1]octan-8-yl)quinoline hydrochloride; - 2-Chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline hydrochloride; - N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinoxalin-2-amine hydrochloride; - 3-Bromo-6-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-Chloro-2,6-di(piperazin-1-yl)quinoline dihydrochloride; - 2-Methoxy-3-piperazin-1-yl-quinoxaline 2,2,2-trifluoroacetate; - 2-Chloro-3-(3,6-diazabicyclo[3.1.1]heptan-3-yl)quinoxaline trifluoromethanesulfonate; - 2-Chloro-3-(4-ethylpiperazin-1-yl)quinoxaline hydrochloride; - 4-(2-Aminoethyl)-N-(5-chloro-6-piperazin-1-yl-3-pyridyl)benzamide dihydrochloride; - Phenyl 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate 2,2,2-trifluoroacetate; - 3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-5-methyl-1,2,4-oxadiazole hydrochloride; - 3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)prop-2-yn-1-amine 2,2,2-trifluoroacetate; - 5-(5-Chloro-6-piperazin-1-yl-3-pyridyl)penta-4-yn-1-amine 2,2,2-trifluoroacetate; - 4-(5-Chloro-6-piperazin-1-yl-3-pyridyl)but-3-yn-1-amine 2,2,2-trifluoroacetate; - 3-Chloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-Chloro-6-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 6-Bromo-3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-Chloro-2-piperazin-1-yl-1,5-naphthyridine hydrochloride; - 2-Chloro-6-methoxy-3-piperazin-1-yl-quinoxaline hydrochloride; - N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)ethane-1,2-diamine dihydrochloride; - N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)propane-1,3-diamine dihydrochloride; - 1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)piperazin-2-one dihydrochloride; - 2-Amino-N-(3-chloro-2-piperazin-1-yl-6-quinolyl)acetamide dihydrochloride; - [3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]methanamine dihydrochloride; - 2-[3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; - 3-[3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]propan-1-amine dihydrochloride; - [3-[(5-Chloro-6-piperazin-1-yl-3-pyridyl)methoxy]phenyl]methanamine dihydrochloride; - [3-[(5-Chloro-6-piperazin-1-yl-3-pyridyl)oxymethyl]phenyl]methanamine dihydrochloride; - 3-Chloro-2-piperazin-1-yl-N-(4-piperidyl)quinoline-6-amine dihydrochloride; - 1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)piperidin-4-amine dihydrochloride; - 3-Chloro-6-(1,4-diazepan-1-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - (3R)-1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - 3-Chloro-2-piperazin-1-yl-N-[(3R)-pyrrolidin-3-yl]quinoline-6-amine dihydrochloride; - 1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)azetidin-3-amine dihydrochloride; - 3-Chloro-6-(2,6-diazaspiro[3.3]heptan-2-yl)-2-piperazin-1-yl-quinoline dihydrochloride - 3-Chloro-6-(3,8-diazabicyclo[3.2.1]octan-8-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - 3-Chloro-6-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-piperazin-1-yl-quinoline dihydrochloride; - 3-Chloro-2-piperazin-1-yl-6-(1-piperidyl)quinoline hydrochloride; - 4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)morpholine hydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]methanamine dihydrochloride; - 2-[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]ethanamine dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-yl]methanamine dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-2-piperidyl]methanamine dihydrochloride; - [3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - 1-(3-Chloro-5-ethynyl-2-pyridyl)piperazine; - 3,7-Dichloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-Chloro-6-phenyl-2-piperazin-1-yl-quinoline hydrochloride; - [2-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanol hydrochloride; - 1-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N-methyl-methanamine dihydrochloride; - 1-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N,N-dimethyl-methanamine dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-4-piperidyl]methanamine dihydrochloride; - [1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-yl]methanamine dihydrochloride; - (3R)-1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - 3-Chloro-2-piperazin-1-yl-N-[(3R)-pyrrolidin-3-yl]quinolin-6-amine dihydrochloride; - 3-Chloro-2-piperazin-1-yl-N-[(3S)-3-piperidyl]quinolin-6-amine dihydrochloride; - N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)butane-1,4-diamine dihydrochloride; - (1S)-1-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - (1R)-1-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - [5-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-2-fluoro-phenyl]methanamine dihydrochloride; - [3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-4-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-3-pyridyl]methanamine dihydrochloride; - 3-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-1-yl]propane-1-amine dihydrochloride; - 2-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-1-yl]ethanamine dihydrochloride; - 2-[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; - 1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; - 1-(3,8-Dichloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; -1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one hydrochloride; -1-[3-Chloro-5-(2-phenylethynyl)-2-pyridyl]piperazine 2,2,2-trifluoroacetate; -2-[2-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -2-[3-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -2-[4-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -3-Chloro-2-piperazin-1-yl-6-(1,2,3,4-tetrahydroisoquinolin-5-yl)quinoline dihydrochloride; -3-Chloro-6-isoindolin-4-yl-2-piperazin-1-yl-quinoline dihydrochloride; -3-Chloro-6-isoindolin-5-yl-2-piperazin-1-yl-quinoline dihydrochloride; -2-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]propan-2-amine dihydrochloride; -2-[5-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,3-triazol-1-yl]-N,N-dimethyl-ethanamine dihydrochloride; -[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-2-yl]methanamine dihydrochloride; -2-[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-2-yl]ethanamine dihydrochloride; -[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]methanamine dihydrochloride; -2-[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]ethanamine dihydrochloride; -[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]methanamine dihydrochloride; -2-[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)imidazol-4-yl]ethanamine dihydrochloride; -[4-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-3-yl]methanamine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-triazol-3-yl]ethanamine dihydrochloride; -3-(2-aminoethyl)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one dihydrochloride; -1-(2-aminoethyl)-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one dihydrochloride; -1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-[2-(dimethylamino)ethyl]pyrrolidin-2-one dihydrochloride; -1-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-[2-(dimethylamino)ethyl]imidazolidin-2-one dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-3-yl]methanamine dihydrochloride; -2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-3-yl]ethanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-5-yl]methanamine dihydrochloride; -2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,3,4-oxadiazol-2-yl]methanamine dihydrochloride; -2-[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,3,4-oxadiazol-2-yl]ethanamine dihydrochloride; -[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)oxazol-2-yl]methanamine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)oxazol-2-yl]ethanamine dihydrochloride; -[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)thiazol-2-yl]methanamine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)thiazol-2-yl]ethanamine dihydrochloride; -[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-imidazol-2-yl]methanamine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-imidazol-2-yl]ethanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-1,2,4-triazol-5-yl]methanamine dihydrochloride; -2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1H-1,2,4-triazol-5-yl]ethanamine dihydrochloride; -6-[3-(aminomethyl)phenyl]-N-[(1S,5R)-3-azabicyclo[3.1.0]hexan-6-yl]-3-chloro-quinolin-2-amine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-(trifluoromethyl)phenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-(trifluoromethyl)phenyl]methanamine dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methyl-phenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methyl-phenyl]methanamine dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methoxy-phenyl]methanamine dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxy-phenyl]methanamine dihydrochloride; -[2-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; -[4-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [2-chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-pyridyl]methanamine dihydrochloride; - [6-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-pyridyl]methanamine dihydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-pyridyl]methanamine dihydrochloride; - [6-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrazin-2-yl]methanamine dihydrochloride; - 3-chloro-6-imidazol-1-yl-2-piperazin-1-yl-quinoline hydrochloride; and - (1S,4S)-2-[3-chloro-5-(trifluoromethyl)-2-pyridyl]-2,5-diazabicyclo[2.2.1]heptane formate A pharmaceutical composition for use according to claim 11, selected from

15. wherein the compound is as follows: - 1-(3-chloro-5-iodo-2-pyridyl)piperazine; - [4-(2-aminoethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-chloro-2-(4-methylpiperazin-1-yl)quinoline; - 3-chloro-2-piperazin-1-yl-quinoline; - 3-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-bromo-2-piperazin-1-yl-quinoline hydrochloride; - 2-chloro-3-piperazin-1-yl-quinoxaline hydrochloride; - 3-iodo-2-piperazin-1-yl-quinoline hydrochloride; - [3-(aminomethyl)phenyl] 5-chloro-6-piperazin-1-yl-pyridine-3-carboxylate dihydrochloride; - 3-bromo-6-chloro-2-piperazin-1-yl-quinoline hydrochloride; - 3-bromo-6-methyl-2-piperazin-1-yl-quinoline hydrochloride; - 3-chloro-2,6-di(piperazin-1-yl)quinoline dihydrochloride; - 3-chloro-6-iodo-2-piperazin-1-yl-quinoline hydrochloride; - 6-bromo-3-chloro-2-piperazin-1-yl-quinoline hydrochloride; -2-[3-(5-Chloro-6-piperazin-1-yl-3-pyridyl)-1,2,4-oxadiazol-5-yl]ethanamine dihydrochloride; -2-Chloro-6,7-dimethyl-3-piperazin-1-yl-quinoxaline hydrochloride; -5-(5-Chloro-6-piperazin-1-yl-3-pyridyl)penta-4-yn-1-amine 2,2,2-trifluoroacetate; -3-Chloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; -N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)ethane-1,2-diamine dihydrochloride; -N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)propane-1,3-diamine dihydrochloride; -[3-(3-Chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; -2-Amino-N-(3-chloro-2-piperazin-1-yl-6-quinolyl)acetamide dihydrochloride; -[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-3-piperidyl]methanamine dihydrochloride; -2-[2-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -2-[3-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -2-[4-[2-(5-Chloro-6-piperazin-1-yl-3-pyridyl)ethynyl]phenyl]ethanamine 2,2,2-trifluoroacetate; -3,7-Dichloro-8-methyl-2-piperazin-1-yl-quinoline hydrochloride; -N'-(3-Chloro-2-piperazin-1-yl-6-quinolyl)butane-1,4-diamine dihydrochloride; -3-Chloro-2-piperazin-1-yl-N-[(3S)-3-piperidyl]quinolin-6-amine dihydrochloride; -[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-4-piperidyl]methanamine dihydrochloride; -[1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-yl]methanamine dihydrochloride; -(3R)-1-(3-Chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - (3S)-1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-3-amine dihydrochloride; - [2-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanol hydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N-methyl-methanamine dihydrochloride; - 1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]-N,N-dimethyl-methanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]propane-2-amine dihydrochloride; - (1S)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - (1R)-1-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]ethanamine dihydrochloride; - 3-chloro-2-piperazin-1-yl-6-(1,2,3,4-tetrahydroisoquinolin-5-yl)quinoline dihydrochloride; - 3-chloro-6-isoindolin-4-yl-2-piperazin-1-yl-quinoline dihydrochloride; - 3-chloro-6-isoindolin-5-yl-2-piperazin-1-yl-quinoline dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-fluoro-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methyl-phenyl]methanamine dihydrochloride; - [3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methoxy-phenyl]methanamine dihydrochloride; - [5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-3-pyridyl]methanamine dihydrochloride; -3-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,3-triazol-1-yl]propan-1-amine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,3-triazol-1-yl]ethanamine dihydrochloride; -2-[4-(3-chloro-2-piperazin-1-yl-6-quinolyl)-1,2,3-triazol-1-yl]-N,N-dimethylethanamine dihydrochloride; -1-(3-chloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; -1-(3,8-dichloro-2-piperazin-1-yl-6-quinolyl)pyrrolidin-2-one hydrochloride; -1-(3-chloro-2-piperazin-1-yl-6-quinolyl)imidazolidin-2-one hydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-(trifluoromethyl)phenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-(trifluoromethyl)phenyl]methanamine dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-(trifluoromethyl)phenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-4-methylphenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methylphenyl]methanamine dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methylphenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxyphenyl]methanamine dihydrochloride; -[3-(3-chloro-2-piperazin-1-yl-6-quinolyl)-5-methoxyphenyl]methanamine dihydrochloride; -[5-(3-chloro-2-piperazin-1-yl-6-quinolyl)-2-methoxyphenyl]methanamine dihydrochloride; -[2-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; -[4-chloro-3-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [3-Chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; - [2-Chloro-5-(3-chloro-2-piperazin-1-yl-6-quinolyl)phenyl]methanamine dihydrochloride; and - [2-(3-Chloro-2-piperazin-1-yl-6-quinolyl)-4-pyridyl]methanamine dihydrochloride The pharmaceutical composition for use according to claim 11, selected from:

16. The pharmaceutical composition according to any one of claims 11 to 15, wherein the pharmaceutical composition is for treating a bacterial infectious disease and is administered in combination with an antibiotic.

17. The pharmaceutical composition according to claim 16, wherein the compound represented by formula (I) is a Gram-negative bacterial efflux pump inhibitor.

18. The pharmaceutical composition according to claim 16, for preventing and / or treating an antibiotic-resistant (innate or acquired) Gram-negative bacterial infection.

19. The pharmaceutical composition according to claim 18, wherein the Gram-negative bacteria are selected from E. coli, K. pneumoniae and other enterobacteria, A. baumannii, P. aeruginosa, Neisseria gonorrhoeae and Shigella species.

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