Pharmaceutical uses of piperazine-substituted benzothiophenes for the treatment of mental disorders

Abstract

This application relates to the pharmaceutical applications of a novel compound that is a prodrug of brexpiprazole. [Solution] When administered to a subject, the novel compound of the present invention undergoes chemical transformation through one or more metabolic processes in vivo, releasing a pharmacologically active substance. Brexpiprazole, marketed as Rexulti®, is an atypical antipsychotic indicated for the treatment of major depressive disorder (MDD) in adults and as adjunctive therapy to antidepressants for the treatment of schizophrenia in adult and pediatric patients aged 13 years and older.

Description

[Technical Field]

[0001] This application relates to the pharmaceutical use of a novel compound that is a prodrug of brexpiprazole. The novel compound of the present invention, when administered to a subject, undergoes one or more metabolic processes in vivo to undergo chemical transformation and release a pharmacologically active substance. Brexpiprazole, marketed as Rexulti®, is an atypical antipsychotic indicated for the treatment of major depressive disorder (MDD) in adults and as adjunctive therapy to antidepressants for the treatment of schizophrenia in adult and pediatric patients aged 13 years and older. [Background technology]

[0002] Brexpiprazole (7-[4-(4-benzo[b]thiophen-4-ylpiperazine-1-yl)butoxy]-1H-quinoline-2-one) or its salts have dopamine D2 receptor partial agonist activity and serotonin 5-HT receptor activity. 2A It possesses receptor antagonist activity and adrenaline α1 receptor antagonist activity. Furthermore, brexpiprazole or its salts are known to possess serotonin uptake inhibitory activity or serotonin reuptake inhibitory activity in addition to these activities, and have broad therapeutic potential for neurological diseases (Patent Documents 1 and 2).

[0003] One method of drug design in the pharmaceutical field involves chemically transforming or modifying one or more functional groups of a known drug molecule to improve its pharmacokinetic properties, for example, by enhancing its efficacy or slowing its metabolism in the body. Such chemical transformations or modifications include the formation of conjugates between multiple active ingredient molecules and carrier moieties (Patent Document 3). There is a need for novel compounds that can be converted to brexpiprazole in vivo, exhibit improved pharmacokinetic properties, have fewer side effects, and possess improved tolerability and safety. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] International Publication No. WO2006 / 112464 [Patent Document 2] International Publication No. WO2013 / 035892 [Patent Document 3] International Publication No. WO2012 / 088441 [Overview of the project] [Problems that the invention aims to solve]

[0005] One of the objectives of the present invention is to provide pharmaceutical applications for novel compounds that possess antipsychotic activity and exhibit acceptable pharmacokinetic properties, side effects, tolerability, and safety compared to known typical and atypical antipsychotics such as brexpiprazole. [Means for solving the problem]

[0006] This invention describes the pharmaceutical uses of compounds having antipsychotic activity or pharmaceutically acceptable salts thereof. Accordingly, the compounds or pharmaceutically acceptable salts thereof according to the present invention are useful for pharmaceuticals, for example, in the treatment and / or prevention of human beings having related antipsychotic diseases and conditions.

[0007] In one embodiment, the present invention is based on formula (I): [ka] [In the formula, a is either 2 or 3; R 1 C may be a linear or branched chain that is substituted as appropriate. 1-20 Alkylene; C may be substituted as appropriate. 2-10 Alkenylene; divalent carbon may be substituted as appropriate. 3-8 Cycloalkyl group; optionally substituted divalent heterocyclic group; optionally substituted divalent C 6-10 Aryl;-NH(linear or branched chain C, which may be substituted as appropriate) 1-20 Alkylene); or divalent carbon which may be appropriately substituted.3-8 is cycloalkenyl; R 2 is -C(O)-, -O-C(O)-, -C(O)-NR a -CH2-, -O-, -CH2-, -NR a -C(O)-, or a direct bond; R 3 is an optionally substituted non-aromatic divalent or trivalent heterocyclic group, an optionally substituted aromatic divalent or trivalent heterocyclic group, or an optionally substituted straight-chain or branched-chain C 1-20 alkylene; R a is hydrogen or an optionally substituted straight-chain or branched-chain C 1-20 alkyl; When a is 2, R 3 is divalent; When a is 3, R 3 is trivalent; [[ID=3I]]R 2 and R 3 are linked by a covalent bond; However, when R 1 is straight-chain alkylene and R 2 is -CH2- or a direct bond, R 3 is not straight-chain alkylene]<00003IE>To provide a medicament containing a compound represented by, each geometric isomer thereof, each enantiomer thereof, each diastereoisomer thereof, each tautomer thereof, each zwitterion thereof, or a pharmaceutically acceptable salt thereof.

Advantages of the Invention

[0008] The compound of formula (I) or a pharmaceutically acceptable salt thereof includes a structure in which brexpiprazole is chemically modified, for example, a structure in which a plurality of brexpiprazole molecules are covalently bonded to each other via a chemical linker. When the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered to a subject, it may be chemically converted to brexpiprazole, which is a pharmacologically active substance, under physiological conditions such as one or more metabolic processes, and release brexpiprazole in vivo.

[0009] A compound of formula (I) or a pharmaceutically acceptable salt thereof may have at least one pharmacological activity selected from at least the following: - Stability in subcutaneous tissue, for example, low conversion to the parent drug brexpiprazole in subcutaneous tissue; - Rapid conversion to brexpiprazole in systemic circulation; - A pharmacokinetic profile suitable for a sustained-release injectable (LAI), e.g., a longer duration of action per dose than the parent drug; - Low irritation at the injection site. [Brief explanation of the drawing]

[0010] [Figure 1] Figure 1 shows the XRPD pattern of crystalline form A of the compound from Example 10. [Figure 2] Figure 2 shows the DSC thermogram of crystalline form A of the compound from Example 10. [Figure 3] Figure 3 shows the XRPD pattern of crystalline form B of the compound from Example 10. [Figure 4] Figure 4 shows the DSC thermogram of crystalline form B of the compound from Example 10. [Figure 5] Figure 5 shows the XRPD pattern of crystalline form 1 of the compound from Example 19. [Figure 6] Figure 6 shows the TGA profile of crystalline form 1 of the compound from Example 19. [Figure 7] Figure 7 shows the DSC thermogram of crystalline form 1 of the compound from Example 19. [Figure 8] Figure 8 shows the PK profile (plasma concentration-time of brexpiprazole) when the compound of Example 10 was administered to rats via SC according to Test Example 4 (mean ± SD; N=3). The upper line shows the PK profile of the aqueous suspension (1.9 μm) of Example 10. The lower line shows the PK profile of the aqueous suspension (3.4 μm) of Example 10. [Figure 9]Figure 9 shows the PK profile (plasma concentration-time of brexpiprazole) when the compound of Example 19 was administered to rats via SC according to Test Example 4 (mean ± SD; N=3). The upper line shows the PK profile of the aqueous suspension (0.8 μm) of Example 19. The lower line shows the PK profile of the aqueous suspension (1.5 μm) of Example 19. [Modes for carrying out the invention]

[0011] Depending on the value of "a", equation (I) can be expressed as equation (IA) or equation (IB). For clarity, equations (IA) and (IB) are shown below. When a = 2, equation (I) is given by equation (IA) as shown below: [ka] When a = 3, equation (I) is given by equation (IB) as shown below: [ka]

[0012] In another embodiment, the present invention is formulated by formula (II): [ka] [In the formula, b is either 2 or 3; R 4 C may be a linear or branched chain that is substituted as appropriate. 1-20 Alkylene; C may be substituted as appropriate. 2-10 Alkenylene; divalent carbon may be substituted as appropriate. 3-8 Cycloalkyl group; optionally substituted divalent heterocyclic group; optionally substituted divalent C 6-10 Aryl;-NH(linear or branched chain C, which may be substituted as appropriate) 1-20 Alkylene); or divalent carbon which may be appropriately substituted. 3-8 It is a cycloalkenyl; R 5-C(O)-, -OC(O)-, -C(O)-NR b -CH2-, -O-, -CH2-, -NR b -C(O)-, or a direct bond; R 6 C is a non-aromatic divalent or trivalent heterocyclic group which may be substituted as appropriate, an aromatic divalent or trivalent heterocyclic group which may be substituted as appropriate, or a linear or branched chain which may be substituted as appropriate. 1-20 It is alkylene; R b C is a straight or branched chain that may be substituted with hydrogen as appropriate. 1-20 It is alkyl; If b is 2, R 6 It is divalent; If b is 3, R 6 It is trivalent; R 5 and R 6 [They are connected by a covalent bond.] The present invention provides the compounds represented by [formula], their geometric isomers, their enantiomers, their diastereoisomers, their tautomers, their zwitterions, or pharmaceutically acceptable salts thereof.

[0013] Depending on the value of "b", equation (II) can be expressed as equation (IIA) or equation (IIB). For clarity, equations (IIA) and (IIB) are shown below. When b = 2, equation (II) is given by equation (IIA) shown below: [ka] When b = 3, equation (II) is given by equation (IIB) as shown below: [ka]

[0014] In one embodiment, the present invention is a is 2 or 3; R 1 Linear or branched chain C may be appropriately substituted. 2-16The alkylene, where one or more methylene groups may be replaced with functional groups selected from -O- or -NH-, or one or more methylene groups may be replaced with spirocyclopentane or divalent piperidine, or one or more methylene groups may be replaced with a divalent 1,3,5-triazole ring group; ethylene; optionally substituted divalent cyclohexyl; optionally substituted divalent azetidine; or optionally substituted divalent piperidine; R 2 is -C(O)-, -OC(O)-, -C(O)-N(CH3)-CH2-, -C(O)-NH-CH2-, -O-, -NH-C(O)-, -CH2-, or a direct bond; R 3 Divalent or trivalent piperazines, divalent or trivalent 2,5-diazabicyclo[2.2.2]octane, divalent or trivalent 2,5-diazabicyclo[2.2.1]heptane, divalent or trivalent octahydropyrrolo[3,4-c]pyrrole, divalent or trivalent pyrazine, divalent or trivalent 3,9-diazaspiro[5,5]undecane, divalent or trivalent 1,4,7-triazonane, divalent or trivalent 2,6-diazaspiro[3.3]heptane, divalent or trivalent 1,3,5-triazine, divalent or trivalent 1,3-thiazole, or linear or branched chain C 2-6 It is alkylene; If a is 2, then R 3 It is divalent; If a is 3, R 3 It is trivalent; R 2 and R 3 The present invention provides a compound represented by formula (I), in which the elements are linked by covalent bonds.

[0015] In one embodiment, the present invention is a is 2; R1 Linear or branched chain C may be appropriately substituted. 2-16 It is an alkylene, where one or more methylene groups may be replaced by oxygen or amino groups, or one or more methylene groups may be replaced by spirocyclopentane or divalent piperidine, or one or more methylene groups may be replaced by a divalent 1,3,5-triazole ring; ethylene; optionally substituted divalent cyclohexyl; optionally substituted divalent azetidine; or optionally substituted divalent piperidine; R 2 is -C(O)-, -OC(O)-, -C(O)-N(CH3)-CH2-, -C(O)-NH-CH2-, -CH2-, -NH-C(O)-, or a direct bond; R 3 Divalent piperazines, divalent 2,5-diazabicyclo[2.2.2]octane, divalent 2,5-diazabicyclo[2.2.1]heptane, divalent octahydropyrrolo[3,4-c]pyrrole, divalent pyrazines, divalent 3,9-diazaspiro[5,5]undecane, divalent 2,6-diazaspiro[3.3]heptane, divalent 1,3-thiazole, or linear or branched C33s, which may be substituted as appropriate. 2-6 The present invention provides a compound represented by formula (I), which is an alkylene.

[0016] In one embodiment, the present invention is a is 3; R 1 Linear or branched chain C may be appropriately substituted. 2-6 It is an alkylene, where one or more methylene groups can be replaced by divalent piperidine; R 2 is -C(O)-, -O-, or a direct bond; R 3The present invention provides a compound represented by formula (I), wherein the compound is a trivalent 1,4,7-triazonane or a trivalent 1,3,5-triazine, which may be optionally substituted.

[0017] In one embodiment, the present invention is a is 2; R 1 is -CH=CH-, -(CH2)2-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -NH-(CH2)7-, -(CH2)8-, -(CH2)9-, -(CH2) 12 -,-(CH2) 16 -, [ka] and; R 2 is -C(O)-, -OC(O)-, -C(O)-N(CH3)-CH2-, -C(O)-NH-CH2-, -CH2-, -NH-C(O)-, or a direct bond; R 3 ga-(CH2)4-, [ka] The present invention provides a compound represented by formula (I).

[0018] In one embodiment, the present invention is a is 3; R 1 or -(CH2)2-, -(CH2)5-, [ka] and; R 2 is -C(O)-, -O-, or a direct bond; R 3 but [ka] The present invention provides a compound represented by formula (I).

[0019] In one embodiment, the present invention is a is 2; R 1 Linear or branched chain C may be appropriately substituted. 1-20 It is alkylene; R 2 is -C(O)-; R 3 The present invention provides a compound represented by formula (I), which is a divalent piperazine in which may be appropriately substituted.

[0020] In another embodiment, the present invention is: a is 2; R 1 Linear or branched chain C may be appropriately substituted. 1-20 It is alkylene; R 2 is -C(O)-; R 3 but [ka] The present invention provides a compound represented by formula (I).

[0021] In this specification, the term "alkyl" means a saturated hydrocarbon portion having a linear or branched chain portion or a combination thereof, and containing 1 to 20 carbon atoms. One or more methylene (-CH2-) groups of an alkyl group may be oxygen, sulfur, sulfoxide, amino group, carbonyl, carboxyl, sulfonyl, sulfate, sulfonate, amide, sulfonamide, or divalent C 3-8 Alkyl groups can be replaced with cycloalkyl groups, divalent heterocyclic groups, or divalent aryl groups. Alkyl groups may have one or more chiral centers. Alkyl groups can be independently substituted with halogen atoms, hydroxyl groups, cycloalkyl groups, amino groups, heterocyclic groups, aryl groups, carboxylic acid groups, phosphonic acid groups, sulfonic acid groups, phosphoric acid groups, nitro groups, amide groups, or sulfonamide groups. Monovalent alkyl groups can be independently substituted with their formula -C n H 2n+1 Alternatively, it may be indicated by its abbreviated common name.

[0022] In this specification, the term "alkylene" means a saturated divalent hydrocarbon portion having a straight-chain or branched-chain portion or a combination thereof, and containing 1 to 20 carbon atoms. One or more methylene (-CH2-) groups of the alkylene group are oxygen, sulfur, sulfoxide, amino group, carbonyl, carboxyl, sulfonyl, sulfate, sulfonate, amide, sulfonamide, divalent C 3-8 It can be replaced by a cycloalkyl, divalent heterocyclic, or divalent aryl group. The alkylene group may have one or more chiral centers. The alkylene group can be independently substituted with a halogen atom, a hydroxyl group, a cycloalkyl group, an amino group, a heterocyclic group, an aryl group, a carboxylic acid group, a phosphonic acid group, a sulfonic acid group, a phosphoric acid group, a nitro group, an amide group, or a sulfonamide group. The alkylene group can be independently substituted with its formula -C n H 2n - This can be shown by:

[0023] In this specification, the term "halogen" refers to chlorine, bromine, fluorine, and iodine atoms.

[0024] In this specification, the term "alkenyl" means a hydrocarbon group having 2 to 10 carbon atoms derived from a saturated alkyl group having at least one double bond. One or more methylene (-CH2-) groups of an alkenyl are oxygen, sulfur, sulfoxide, amino group, carbonyl, carboxyl, sulfonyl, sulfate, sulfonate, amide, sulfonamide, divalent C 3-8 It can be replaced by a cycloalkyl group, a divalent heterocyclic group, or a divalent aryl group. 2-10 The alkenyl group may have an E or Z stereoconfiguration. The alkenyl group may be substituted with an alkyl group or halogen atom as defined above.

[0025] In this specification, the term "alkenylene" means a divalent hydrocarbon group having 2 to 10 carbon atoms derived from saturated alkylene, having at least one double bond. One or more methylene (-CH2-) groups of alkenylene are oxygen, sulfur, sulfoxide, amino group, carbonyl, carboxyl, sulfonyl, sulfate, sulfonate, amide, sulfonamide, divalent C3-8 It may be replaced by a cycloalkyl group, a divalent heterocyclic group, or a divalent aryl group. C 2-10 The alkenylene may be in the E or Z configuration. The alkenylene group may be substituted with an alkyl group or a halogen atom as defined above.

[0026] As used herein, the term "heterocycle" means a 3- to 12-membered ring that contains at least one heteroatom selected from oxygen, an amino group, sulfur, or at least two combinations thereof within a carbocyclic structure and may be aromatic or non-aromatic, saturated or unsaturated. The heterocycle can incorporate C=O and the S and N heteroatoms can be oxidized. The heterocycle can be monocyclic or polycyclic, trivalent, divalent or monovalent, or spiro. The heterocyclic moiety can be substituted with a halogen atom, a sulfonyl group, a sulfoxide group, a nitro group, a cyano group, -OC 1-6 alkyl group, -SC 1-6 alkyl group, -C 1-8 alkyl group, -C 2-6 alkenyl group, -C 2-6 alkynyl group, a ketone group, an alkylamino group, an amino group, an aryl group, C 3-8 cycloalkyl group, or a hydroxyl group. Examples of heterocycles are 1,3,5-triazole, azetidine, piperidine, piperazine, 2,5-diazabicyclo[2.2.2]octane, 2,5-diazabicyclo[2.2.1]heptane, octahydropyrrolo[3,4-c]pyrrole, pyrazine, 3,9-diazaspiro[5,5]undecane, 1,4,7-triazonane, 2,6-diazaspiro[3.3]heptane, 1,3,5-triazine, and 1,3-thiazole. The heterocyclic groups can be independently substituted with a halogen atom or a hydroxyl group.

[0027] As used herein, the term "aryl" means an organic moiety derived from an aromatic hydrocarbon consisting of a ring containing 6 to 10 carbon atoms from which one hydrogen atom has been removed. Aryl can be substituted with a halogen atom, sulfonyl C 1-6 alkyl group, sulfoxide C 1-6 alkyl group, a sulfonamide group, a carboxyl group, C 1-6an alkyl carboxylate (ester) group, an amide group, a nitro group, a cyano group, -OC 1-6 an alkyl group, -SC 1-6 an alkyl group, -C 1-6 an alkyl group, -C 2-6 an alkenyl group, -C 2-6 an alkynyl group, a ketone group, an aldehyde, an alkylamino group, an amino group, an aryl group, C 3-8 a cycloalkyl group, or a hydroxyl group. The aryl can be monocyclic or polycyclic. The aryl moiety can be divalent or monovalent.

[0028] As used herein, the term "cycloalkyl" means a monovalent or divalent saturated carbocyclic group of 3 to 8 carbon atoms. The cycloalkyl group can be spiro, monocyclic, or polycyclic. The cycloalkyl group is independently substituted with a halogen atom, a sulfonyl group, a sulfoxide group, a sulfonyl C 1-8 an alkyl group, a sulfoxide C 1-8 an alkyl group, a sulfonamide group, a nitro group, a cyano group, -OC 1-8 an alkyl group, -SC 1-8 an alkyl group, -C 1-8 an alkyl group, -C 2-6 an alkenyl group, -C 2-6 an alkynyl group, a ketone group, an alkylamino group, an amino group, an aryl group, C 3-8 a cycloalkyl group, or a hydroxyl group.

[0029] As used herein, the term "cycloalkenyl" means a monovalent or divalent group of 3 to 8 carbon atoms derived from a saturated cycloalkyl having at least one double bond. The cycloalkenyl group can be monocyclic or polycyclic. The cycloalkenyl group is independently substituted with a halogen atom, a sulfonyl group, a sulfoxide group, a sulfonyl C 1-8 an alkyl group, a sulfoxide C 1-8 an alkyl group, a sulfonamide group, a nitro group, a cyano group, -OC 1-8 an alkyl group, -SC 1-8 an alkyl group, -C 1-8 an alkyl group, -C 2-6 an alkenyl group, -C 2-6Alkynyl group, ketone group, alkylamino group, amino group, aryl group, C 3-8 It may be substituted with a cycloalkyl group or a hydroxyl group.

[0030] In this specification, the term "hydroxyl" refers to the group of the formula "-OH".

[0031] In this specification, the term "carbonyl" refers to the group of the formula "-C(O)-".

[0032] In this specification, the term "ketone" is defined as -(CO)R x (Here, R x This refers to organic compounds having a carbonyl group linked to a carbon atom (which may be an alkyl, aryl, cycloalkyl, cycloalkenyl, or heterocyclic compound) as defined above.

[0033] In this specification, the terms "amine" or "amino" refer to the formula "-NR" x R y (Here, R x and R y These terms, either identically or independently, represent H, which may be an alkyl, aryl, cycloalkyl, cycloalkenyl, or heterocyclic group as defined above.

[0034] In this specification, the term "carboxyl" refers to the base of the formula "-C(O)O-".

[0035] In this specification, the term "sulfonyl" refers to the group of the formula "-SO2-".

[0036] In this specification, the term "sulfate" refers to the base of the formula "-OS(O)2-O-".

[0037] In this specification, the term "sulfonate" refers to the group of the formula "-S(O)2-O-".

[0038] In this specification, the term "carboxylic acid" refers to the group of the formula "-C(O)OH".

[0039] In this specification, the term "nitro" refers to the base of the formula "-NO2".

[0040] In this specification, the term "cyano" refers to the base of the formula "-CN".

[0041] In this specification, the term "amide" refers to the formula "-C(O)NR x R y The basis of " (where R x and R y These elements, either identically or independently, represent H (which may be an alkyl, aryl, cycloalkyl, cycloalkenyl, or heterocycle as defined above).

[0042] In this specification, the term "sulfonamide" refers to the formula "-S(O)2NR" x R y The basis of " (where R x and R y These elements, either identically or independently, represent H (which may be an alkyl, aryl, cycloalkyl, cycloalkenyl, or heterocycle as defined above).

[0043] In this specification, the term "azid" is defined in the formula "-N=N + This indicates the base "=N-" or "-N3".

[0044] In this specification, the term "sulfoxide" refers to the base of the formula "-S(O)-".

[0045] In this specification, the term "phosphonic acid" refers to the group of the formula "-P(O)(OH)2".

[0046] In this specification, the term "phosphoric acid" refers to the group of the formula "-OP(O)(OH)2".

[0047] In this specification, the term "sulfonic acid" refers to the group of the formula "-S(O)2OH".

[0048] In this specification, "H" in the formula represents a hydrogen atom.

[0049] In this specification, the "O" in formula represents an oxygen atom.

[0050] In this specification, "N" in the formula represents a nitrogen atom.

[0051] In this specification, the "S" in formula represents a sulfur atom.

[0052] In this specification, the term "1,3,5-triazole" refers to the structure: [ka] This indicates.

[0053] In this specification, the term "azetidine" refers to its structure: [ka] This indicates.

[0054] In this specification, the term "piperidine" refers to the structure: [ka] This indicates.

[0055] In this specification, the term "piperazine" refers to the structure: [ka] This indicates.

[0056] In this specification, the term "2,5-diazabicyclo[2.2.2]octane" refers to the structure: [ka] This indicates.

[0057] In this specification, the term "2,5-diazabicyclo[2.2.1]heptane" refers to the structure: [ka] This indicates.

[0058] In this specification, the term "octahydropyrrolo[3,4-c]pyrrole" refers to the structure: [ka] This indicates.

[0059] In this specification, the term "pyrazine" refers to the structure: [ka] This indicates.

[0060] In this specification, the term "3,9-diazaspiro[5,5]undecane" refers to the structure: [ka] This indicates.

[0061] In this specification, the term "1,4,7-triazonane" refers to the structure: [ka] This indicates.

[0062] In this specification, the term "2,6-diazaspiro[3.3]heptane" is defined by formula: [ka] This shows the basis.

[0063] In this specification, the term "1,3,5-triazine" is defined by formula: [ka] This shows the basis.

[0064] In this specification, the term "1,3-thiazole" is defined by formula: [ka] This shows the basis.

[0065] In this specification, the term "(2S)-2-ethylpiperazine" is defined by the formula: [ka] This shows the basis.

[0066] In this specification, the term "1,4-diazidobutane" is defined by formula: [ka] This shows the basis.

[0067] In this specification, the term "pyrazine-2,5-dicarbonyl dichloride" is defined by formula: [ka] This shows the basis.

[0068] The above names, formulas, and structures are used interchangeably and may refer to the same items herein. In the formulas described throughout the specification (I, IA, IB, II, IIA, and IIB), the "R" group and its value, according to the permissible valency, should be apparent to those skilled in the art that substitutions result in the stable compounds represented by these formulas.

[0069] In another aspect, the present invention is -R 1 -, -R 2 -, R 3 The present invention provides a compound of formula (I) in which the value of "a" is as shown in Table 1. [Table 1] TIFF2026047308000029.tif243166 TIFF2026047308000030.tif241164 TIFF2026047308000031.tif250169 TIFF2026047308000032.tif247163 TIFF2026047308000033.tif244169 TIFF2026047308000034.tif224163 TIFF2026047308000035.tif82163

[0070] In yet another aspect, the present invention also relates to formula (X): [ka] [In the formula, R 7 , R 8 , R 9 , and R 10 Typical and exemplary values ​​are shown in Table 2. The compound shown is provided. [Table 2] TIFF2026047308000038.tif177170

[0071] Some compounds of formulas (I) and (II), as well as their intermediates, have at least one chiral center in their structure. This chiral center may be in an R or S configuration, and the notation R and S is used in accordance with the rules described in Pure Appli. Chem. (1976), 45, 11-13.

[0072] In this specification, the term “pharmaceutically acceptable salt” means a salt or complex that retains the desired biological activity of the compound identified above. Examples of “pharmaceutically acceptable salts” in the present invention include therapeutically active salt forms of bases or acids that can form the compounds of formulas (I) and (II).

[0073] The acid addition salt forms of the compounds of formulas (I) and (II), in which the free form is produced as a base, can be obtained by treating the free base with an inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, etc.; or with an organic acid, such as acetic acid, hydroxyacetic acid, propanoic acid, lactic acid, pyruvic acid, malonic acid, fumaric acid, maleic acid, oxalic acid, tartaric acid, succinic acid, malic acid, ascorbic acid, benzoic acid, tannic acid, pamoic acid, citric acid, methylsulfonic acid, ethanesulfonic acid, benzenesulfonic acid, formic acid, etc. (Handbook of Pharmaceutical Salts, P. Heinrich Stahal & Camille G. Wermuth (Eds), Verlag Helvetica Chemica Acta- Zurich, 2002, 329-345).

[0074] The base addition salt forms of the compounds of formulas (I) and (II) that arise as acids can be obtained by treating the acid with a suitable base, such as an inorganic base like sodium hydroxide, magnesium hydroxide, potassium hydroxide, calcium hydroxide, or ammonia; or an organic base like L-arginine, ethanolamine, betaine, benzathine, or morpholine (Handbook of Pharmaceutical Salts, P. Heinrich Stahl & Camille G. Wermuth (Eds), Verlag Helvetica Chemica Acta-Zurich, 2002, 329-345).

[0075] The compounds of formula (I) and formula (II) and their salts may be in the form of solvates, which are within the scope of the present invention. Examples of such solvates include hydrates and alcoholic dihydrates.

[0076] The compounds of formula (I) and formula (II) may be the compounds themselves or any crystalline polymorph thereof.

[0077] The compounds provided herein can be synthesized according to the procedures described herein. The synthesis methods described herein are merely illustrative, and the compounds disclosed herein may also be synthesized by alternative routes using alternative synthetic strategies recognized by those skilled in the art. At this stage, many additional compounds within the scope of the invention may be prepared by using a variety of common chemical reactions. Details of some specific chemical transformations are provided in the Examples. Those skilled in the art can usually synthesize any compound of the invention contained in formula (I), formula (IA), or formula (IB), respectively, by modifying and / or adapting the following schemes. In general, each compound of formula (I), formula (IA), or formula (IB) can be synthesized according to the following schemes. Any variable ("R" group) used in the following schemes is the variable defined in formula (I) unless otherwise specified. All starting materials are commercially available, known in the art, or may be synthesized using known procedures using the ordinary art. Starting materials may also be synthesized by procedures disclosed herein. Suitable reaction conditions for the schemes discussed in this section, such as solvents, reaction temperatures, and reagents, may also be found in the Experimental section.

[0078] Scheme 1: Reaction for compound of formula (IA) [ka] Here, R 1 , R 2 , and R 3 The compounds of general formula (IA) can be prepared from intermediates of formulas (IX) and (IY) through the coupling reaction shown in Scheme 1.

[0079] Examples of the reactive group "X" in formula (IX) involved in the coupling reaction can be alkylcarboxylates, carboxylic acids, alkynes, alkyl ethers, amines, alkyl sulfonates, nitro groups, or alcohols.

[0080] Examples of the reactive group "Y" in formula (IY) involved in the coupling reaction can be an azide, amine, acylchloride, alkyl halide, or halogenated cyclic moiety. The intermediate in which "Y" is an azide is Int78, which is an intermediate listed in Table 7. Other intermediates included in formula (IY) are Int04, Int05, Int08, Int09, piperazine, (2R,5S)-2,5-dimethylpiperazine, 2,5-diazabicyclo[2.2.2]octane, octahydropyrrolo[3,4-c]pyrrole, 2,6-diazaspiro[3.3]heptane, 3,9-diazaspiro[5,5]undecane, and 1-[5-(aminomethyl)pyrazine-2-yl]meth These are amine, methyl({5-[(methylamino)methyl]pyrazine-2-yl}methyl)amine, (2S)-2-ethylpiperazine, pyrazine-2,5-dicarbonyl dichloride, 2,4-dichloro-1,3,5-triazine, 2,5-bis(bromomethyl)pyrazine, 1,3-thiazole-2,5-dicarbonyl dichloride, 1,4-diazidobutane, and (2S)-2-ethylpiperazine. Several intermediates included in formula (IY) are commercially available.

[0081] The reaction in Scheme 1 may be an amide coupling reaction using a suitable amide coupling reagent (e.g., TBTU) and an organic base (e.g., TEA), or an aromatic or non-aromatic nucleophilic substitution, or a copper-catalyzed hysgencycloaddition reaction, according to a method described in the literature or known to those skilled in the art. The amount of amide coupling reagent used may generally correspond to at least equimolar amounts, preferably 1.5 times the molar amount, relative to the compound of formula (IX).

[0082] The reaction in Scheme 1 can be carried out in a solvent-free (neat) or suitable solvent. Examples of suitable solvents include water; ethers, e.g., dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, ethylene glycol dimethyl ether, etc.; aromatic hydrocarbons, e.g., benzene, toluene, xylene, etc.; lower alcohols, e.g., methanol, ethanol, isopropanol, etc.; ketones, e.g., acetone, methyl ethyl ketone, etc.; and polar solvents, e.g., N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), hexamethyl phosphate triamide, acetonitrile, etc.

[0083] In Scheme 1, the proportions of compounds of formula (IX) and formula (IY) are generally such that the ratio of the latter to the former is at least 1.5 times the molars, preferably about 1.5 to 3 times the molars. The above reaction is generally carried out at room temperature to 200°C, preferably room temperature to 150°C, and is completed in about 1 to 72 hours.

[0084] As described in intermediate Int77, when group "X" is a terminal alkyne, compounds of general formula (IA) can be prepared by a copper-catalyzed hysgencycloaddition reaction. Group "Y" is the azide in the intermediate of formula (IY) involved in this reaction. The examples described in Example 58 and Table 11 were synthesized by this reaction.

[0085] Several intermediates of formula (IX) can be prepared according to the reactions described in Scheme 2. Such intermediates are Int02, Int03, Int39, Int42, Int47, Int48, Int49, Int50, Int52, Int57, Int59, Int60, Int68, Int69, Int70, Int73, Int74, and the intermediates listed in Tables 4, 5, and 6. Int26 is represented by formula (IPG). Several intermediates of formula (ILG) are Int01 and the intermediates listed in Table 3.

[0086] Scheme 2: Reaction for the intermediate of equation (IX) [ka] a) Protection of the functional group "X", where suitable protecting groups can be tert-butyl (t-Bu), tert-butyloxycarbonyl (Boc), or tert-butyldimethylsilyl (TBDMS). b) Alkylation in the presence of a quaternary ammonium salt (TBA-HSO4) and an alkylating agent such as chloromethyl chlorosulfate. c) Alkylation in the presence of a base such as NaH and heat. d) Deprotection of the functional group "X", where a suitable deprotecting agent may be TFA, HCl, or TBAF.

[0087] Several intermediates of formula (IY) can be prepared according to the reaction described in Scheme 3. Int05 is such an intermediate. Scheme 3: Reaction for the intermediate of equation (IY) [ka] a) Protection of alcohol functional groups; suitable protecting groups are Boc and phthalimide. b) Deprotection in the presence of a known reagent (hydrazine).

[0088] Several intermediates of formula (IY), where Y is an azide, can be prepared by amide coupling reactions, where the starting material is an alkylcarboxylic acid. The amide coupling reagent, e.g., HATU or TBTU, and the organic base, e.g., TEA or DIPEA, can be used according to methods described in the literature or known to those skilled in the art.

[0089] The compound of formula (IB) can be prepared according to the general reaction described in Scheme 4. Scheme 4: Reaction for compound of formula (IB) [ka] The reaction product of formula (IBY) is generally available commercially, or can be prepared by a reaction described in literature familiar to those skilled in the art.

[0090] The general synthesis procedures and specific examples provided herein are illustrative only and should not be construed as limiting the scope of this disclosure in any way.

[0091] Detailed description of the invention It should be understood that the following general and detailed descriptions are illustrative and descriptive only, and not limitations on the claimed invention. As used herein, singular forms include plural forms unless otherwise specified.

[0092] It will be readily apparent to those skilled in the art that some of the compounds of the present invention may contain one or more chiral centers, and that the compounds may exist as enantiomers and diastereomers. Unless otherwise specified, the scope of the present invention includes all enantiomers, diastereomers, and racemic mixtures. Some of the compounds of the present invention may form salts with pharmaceutically acceptable acids or bases, and such pharmaceutically acceptable salts of the compounds described herein are also within the scope of the present invention.

[0093] The present invention includes all pharmaceutically acceptable isotope-rich compounds. Any compound and intermediate of the present invention may contain one or more isotope-rich elements or hydrogen 1 Replace H (or H) with deuterium 2 H (or D) or 12 Replace C 13 The ratio may differ from that of the natural elements, such as using a C-rich material. Similar substitutions can be used for N, O, and S, etc. Examples of isotopic elements include deuterium ( 2 H or D), tritium ( 3 H), 13 C, 14 C, 13 N, 15 N, 15 O,17 O, 18 O, 32 P, 35 S, 36 Cl, 37 Cl, 18 F, 123 I, 125 Examples include I. The use of isotopes may be useful not only for the therapeutic aspects of the present invention but also for the analytical aspects. For example, the use of deuterium may alter the metabolism (rate) of the compounds of the present invention to increase their in vivo half-life. These compounds can be prepared using isotope-rich reagents according to the preparation methods described.

[0094] In some embodiments, compounds of formula (I) and formula (II) or pharmaceutically acceptable salts thereof may have an average particle diameter in the range of 0.05–10 μm, e.g., 0.1–10 μm, e.g., 0.1–5 μm, e.g., 0.1–3.4 μm, e.g., 0.2–1.9 μm, e.g., 0.2–0.4 μm, measured by laser diffraction, e.g., using a laser diffraction particle size distribution analyzer. A suitable average particle diameter may be advantageous in providing a desired absorption rate and / or acceptable irritation at the injection site. In this specification, the term “average particle diameter” means the volume-average diameter measured by laser light scattering (LLS). The particle size distribution is measured by LLS, and the corresponding average particle diameter is calculated from the particle size distribution.

[0095] Pharmaceutical use Compounds of formula (I) and formula (II) or pharmaceutically acceptable salts thereof may be converted to brexpiprazole in systemic circulation upon administration to a subject. Polyvalent brexpiprazole molecules may be bioconverted in vivo, such as in plasma, to intermediates such as N-hydroxymethylbrexpiprazole, and then hydrolyzed to brexpiprazole by enzymatic hydrolysis. Brexpiprazole is used for schizophrenia; treatment-resistant, refractory or chronic schizophrenia; affective disorders; psychotic disorders; mood disorders; bipolar disorder type I; bipolar disorder type II; depression; endogenous depression; major depressive disorder (MDD); melancholic and treatment-resistant depression; dysthymia; cyclothymic disorder; panic attacks; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorders; conversion disorders; pain disorders; hypochondriasis; factitious disorder; dissociative disorders; sexual dysfunction; libido disorders; sexual arousal disorders; erectile dysfunction; anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia; iatrogenic anhedonia. It is useful for treating and / or preventing antipsychotic-related central nervous system disorders such as: anhedonia due to psychogenic or mental causes; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment due to Alzheimer's disease; Parkinson's disease and related neurodegenerative diseases; cognitive impairment in schizophrenia; cognitive impairment due to treatment-resistant, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autism; Tourette's disorder; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder. Therefore, compounds of formula (I) and formula (II) may also be useful for treating and / or preventing central nervous system disorders.

[0096] In this specification, the terms “prophylaxis,” “prevention,” or “to prevent” mean prior presentation and may relate to, as such, the prevention of symptoms of a disease or disorder in a subject, or the prevention of recurrence of symptoms of a disease or disorder in an affected subject, but are not limited to the complete prevention of the disease. In this specification, the terms “treatment” or “to treat” include the control, mitigation, reduction, or regulation of a disease condition or its symptoms. The subject would typically be one that requires treatment or prevention in the present invention. The subject would typically be a mammal. The subject would appropriately be a human.

[0097] Pharmaceutical composition In one embodiment of the present invention, a pharmaceutical preparation (hereinafter also referred to as a "pharmaceutical composition") is provided, comprising a compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof as an active ingredient.

[0098] The pharmaceutical preparations described herein may be selected from various forms depending on the therapeutic purpose. Any route of administration of the pharmaceutical preparation may be selected depending on the dosage form, the age and sex of the patient to be administered, the disease state, and other conditions. The pharmaceutical preparation may be administered orally, intravenously, intramuscularly, intradermally, subcutaneously, intraperitoneally, or rectally, as necessary. Examples of pharmaceutical preparations include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, and injections (liquids, suspensions, etc.). Examples of tablets include coated tablets such as sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, bilayer tablets, and multilayer tablets.

[0099] Compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof may be formulated in combination with pharmaceutically acceptable carriers into any form of pharmaceutical preparation. Examples of carriers include substances commonly used for components of pharmaceutical preparations, such as excipients such as lactose; binders such as polyvinylpyrrolidone; disintegrants such as starch; absorption adjuvants such as sodium lauryl sulfate; humectants such as glycerin and starch; adsorbents such as colloidal silicic acid; lubricants such as magnesium stearate and polyethylene glycol; diluents; fillers; bulking agents; and surfactants.

[0100] Pharmaceutically acceptable carriers used in the formulation of tablets include excipients such as lactose; binders such as polyvinylpyrrolidone; disintegrants such as starch; absorption aids such as sodium lauryl sulfate; humectants such as glycerin and starch; adsorbents such as colloidal silicic acid; and lubricants such as magnesium stearate and polyethylene glycol.

[0101] Pharmaceutically acceptable carriers used in formulation into pills include excipients such as glucose; binders such as gum arabic powder; and disintegrants such as laminaran.

[0102] Water is a pharmaceutically acceptable diluent used in formulations into liquids, emulsions, or suspensions. Any common solubilizers and / or buffers, as well as colorants, preservatives, fragrances, flavorings, and sweeteners, may also be included in the formulations, and other drugs may also be included as needed.

[0103] Cocoa butter is a specific example of a pharmaceutically acceptable carrier used in the formulation of suppositories.

[0104] In some embodiments, the compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof may be formulated into a solution, emulsion, or suspension for preparation of an injectable preparation. In some embodiments, the injectable preparation is preferably sterile and preferably isotonic with blood. The injectable preparation may be formulated with conventional diluents, such as water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid esters. The injectable preparation may also contain stabilizers such as polymeric stabilizers, such as poloxamer 188, 338; PEG200, 1000, 4000; PPG 4000, and surfactants, such as PS20, 80; sodium deoxycholate, sodium cholate, and sodium dodecyl sulfate. The isotonic injectable preparation may also contain a sufficient amount of sodium chloride and analgesics, such as glucose, amino acids, and glycerin, and may also contain other components such as colorants, preservatives, flavorings, and sweeteners. Preferably, the injectable preparation is an intramuscular or subcutaneous injection preparation.

[0105] The amount of compound (I) or (II) or a pharmaceutically acceptable salt thereof contained in the pharmaceutical preparation (hereinafter also referred to as the "effective amount") may be any amount commonly used in the art, but is not limited thereto, and preferably includes any amount between 1% and 70% of the pharmaceutical preparation. The dose administered of compound (I) or (II) or a pharmaceutically acceptable salt thereof may be any dose selected according to the route of administration, the age and sex of the patient being administered, the severity of the disease, and other conditions, and may be 0.01 to 100 mg per kg of body weight per day, preferably 0.1 to 50 mg. The dose may be administered in one dose or in several divided doses, for example, 2 to 4 times.

[0106] The compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof may be used or administered in combination with at least one therapeutic or prophylactic agent or standard therapeutic agent useful for one of the above diseases, which is also referred to herein as a concomitant agent. When the compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof is used in combination with a concomitant agent, the compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof and the concomitant agent may be administered simultaneously or together, nearly simultaneously, separately or consecutively, or separately or consecutively at different times at appropriate intervals. The compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof and the concomitant agent may be formulated into separate formulations, or mixed or formulated into a single formulation.

[0107] Embodiment Term 1: Formula (I): [ka] [In the formula, a is either 2 or 3; R 1 C may be a linear or branched chain that is substituted as appropriate. 1-20 Alkylene; C may be substituted as appropriate. 2-10 Alkenylene; divalent carbon may be substituted as appropriate. 3-8 Cycloalkyl group; optionally substituted divalent heterocyclic group; optionally substituted divalent C 6-10 Aryl;-NH(linear or branched chain C, which may be substituted as appropriate) 1-20 Alkylene); or divalent carbon which may be appropriately substituted. 3-8 It is a cycloalkenyl; R 2 -C(O)-, -OC(O)-, -C(O)-NR a -CH2-, -O-, -CH2-, -NR a -C(O)-, or a direct bond; R 3C is a non-aromatic divalent or trivalent heterocyclic group which may be substituted as appropriate, an aromatic divalent or trivalent heterocyclic group which may be substituted as appropriate, or a linear or branched chain which may be substituted as appropriate. 1-20 It is alkylene; R a C is a straight or branched chain that may be substituted with hydrogen as appropriate. 1-20 It is alkyl; If a is 2, then R 3 It is divalent; If a is 3, R 3 It is trivalent; R 2 and R 3 They are joined by a covalent bond; However, R 1 It is a linear alkylene, and R 2 If R is -CH2- or a direct bond, 3 [It is not a linear alkylene] A pharmaceutical product containing the compound indicated by or a pharmaceutically acceptable salt thereof.

[0108] Item 2: a is 2 or 3; R 1 Linear or branched chain C may be appropriately substituted. 2-16 The alkylene, where one or more methylene groups may be replaced with functional groups selected from -O- or -NH-, or one or more methylene groups may be replaced with spirocyclopentane or divalent piperidine, or one or more methylene groups may be replaced with a divalent 1,3,5-triazole ring group; ethylene; optionally substituted divalent cyclohexyl; optionally substituted divalent azetidine; or optionally substituted divalent piperidine; R 2 is -C(O)-, -OC(O)-, -C(O)-N(CH3)-CH2-, -C(O)-NH-CH2-, -O-, -NH-C(O)-, -CH2-, or a direct bond; R 3Divalent or trivalent piperazines, divalent or trivalent 2,5-diazabicyclo[2.2.2]octane, divalent or trivalent 2,5-diazabicyclo[2.2.1]heptane, divalent or trivalent octahydropyrrolo[3,4-c]pyrrole, divalent or trivalent pyrazine, divalent or trivalent 3,9-diazaspiro[5,5]undecane, divalent or trivalent 1,4,7-triazonane, divalent or trivalent 2,6-diazaspiro[3.3]heptane, divalent or trivalent 1,3,5-triazine, divalent or trivalent 1,3-thiazole, or linear or branched chain C 2-6 It is alkylene; If a is 2, then R 3 It is divalent; If a is 3, R 3 It is a trivalent drug as described in item 1.

[0109] Item 3: a is 2; R 1 Linear or branched chain C may be appropriately substituted. 2-16 It is an alkylene, where one or more methylene groups may be replaced by oxygen or amino groups, or one or more methylene groups may be replaced by spirocyclopentane or divalent piperidine, or one or more methylene groups may be replaced by a divalent 1,3,5-triazole ring group; ethylene; optionally substituted divalent cyclohexyl; optionally substituted divalent azetidine; or optionally substituted divalent piperidine; R 2 is -C(O)-, -OC(O)-, -C(O)-N(CH3)-CH2-, -C(O)-NH-CH2-, -CH2-, -NH-C(O)-, or a direct bond; R 3A divalent piperazine which may be appropriately substituted, a divalent 2,5-diazabicyclo[2.2.2]octane which may be appropriately substituted, a divalent 2,5-diazabicyclo[2.2.1]heptane which may be appropriately substituted, a divalent octahydropyrrolo[3,4-c]pyrrole which may be appropriately substituted, a divalent pyrazine which may be appropriately substituted, a divalent 3,9-diazaspiro[5,5]undecane which may be appropriately substituted, a divalent 2,6-diazaspiro[3.3]heptane which may be appropriately substituted, a divalent 1,3-thiazole which may be appropriately substituted, or a linear or branched C 2-6 The pharmaceutical according to item 1 or 2, which is an alkylene.

[0110] Item 4: a is 3; R 1 is a linear or branched C 2-6 alkylene, where one or more methylene groups can be replaced by divalent piperidine; R 2 is -C(O)-, -O-, or a direct bond; R 3 The pharmaceutical according to item 1 or 2, which is a trivalent 1,4,7-triazonane which may be appropriately substituted or a trivalent 1,3,5-triazine which may be appropriately substituted.

[0111] Item 5: a is 2; R 1 is -CH=CH-, -(CH2)2-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9-, -(CH2) 12 -, -(CH2) 16 -, -NH-(CH2)7-,

Chemical formula

[0112] Item 6: a is 3; R 1 or -(CH2)2-, -(CH2)5-, [ka] and; R 2 is -C(O)-, -O-, or a direct bond; R 3 but [ka] The pharmaceutical product described in item 1 or 2.

[0113] Item 7: Compounds that are the following: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}piperazine-1-yl)-6-oxohexanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-[(2R,5S)-4-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-dimethylpiperazine-1-yl]-8-oxooctanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(5-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.1]heptan-2-yl]-8-oxooctanoate; Tris(trifluoroacetic acid); (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(6-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(9-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanaamide}methyl)pyrazine-2-yl]methyl}carbamoyl)heptanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-N-methyl-8-oxooctanaamide}methyl)pyrazine-2-yl]methyl}(methyl)carbamoyl)heptanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazine-1-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[(2S,5R)-4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-2,5-dimethylpiperazine-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-[(3ar,6ar)-5-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[4,7-bis({4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl})-1,4,7-triazonan-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-(4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}piperazine-1-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-[(2R,5S)-4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}-2,5-dimethylpiperazine-1-yl]-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-(5-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-9-({[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-N-methyl-10-oxodecanamide}methyl)pyrazine-2-yl]methyl}(methyl)carbamoyl)nonanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}piperazine-1-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-[(2S,5R)-4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-2,5-dimethylpiperazine-1-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(6-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-[(3ar,6ar)-5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-N-methyl-6-oxohexanamide}methyl)pyrazine-2-yl]methyl}(methyl)carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanamide}methyl)pyrazine-2-yl]methyl}carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(2E)-4-{4-[(2E)-4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobuta-2-enoyl]piperazine-1-yl}-4-oxobuta-2-enoate; (7-{4-[4-(1-Benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 14-(4-{14-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-14-oxotetradecanoyl}piperazin-1-yl)-14-oxotetradecanoate; (7-{4-[4-(1-Benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 14-[(2S,5R)-4-{14-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-14-oxotetradecanoyl}-2,5-dimethylpiperazin-1-yl]-14-oxotetradecanoate; (7-{4-[4-(1-Benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 18-(4-{18-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-18-oxooctadecanoyl}piperazin-1-yl)-18-oxooctadecanoate; (7-{4-[4-(1-Benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 18-[(2S,5R)-4-{18-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-18-octadecanoyl}-2,5-dimethylpiperazin-1-yl]-18-oxooctadecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-{4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-[(2S,5R)-2,5-dimethyl-4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1s,4s)-4-{4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1s,4s)-4-[(2S,5R)-2,5-dimethyl-4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 1-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)piperazine-1-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[(3ar,6ar)-5-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)-octahydropyrrolo[3,4-c]pyrrole-2-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2,2-dimethyl-3-oxopropanoyl}piperazin-1-yl)-2,2-dimethyl-3-oxopropanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2,2-dimethyl-4-oxobutanoyl}piperazin-1-yl)-3,3-dimethyl-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3,3-dimethyl-4-oxobutanoyl}piperazin-1-yl)-2,2-dimethyl-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3,3-dimethyl-5-oxopentanoyl}piperazin-1-yl)-3,3-dimethyl-5-oxopentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-2-{2-[4-(2-{2-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2-oxoethoxy}acetyl)piperazine-1-yl]-2-oxoethoxy}acetate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-N-(8-{4-[8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)octanoyl]piperazine-1-yl}-8-oxooctyl)carbamate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-N-[(2S)-1-{4-[(2S)-2-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]piperazine-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-4-carbonyl)piperazine-1-carbonyl]piperidine-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4,6-bis(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)methyl]pyrazine-2-yl}methyl)piperidine-4-yl]propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazole-2-yl]formamide}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)pyrazine-2-yl]formamide}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-{[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecyl}carbamoyl)pyrazine-2-yl]formamide}decanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}piperazine-1-yl)hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-{4-[({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}oxy)carbonyl]piperazine-1-carbonyloxy}hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-[(4-{[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexyl]methyl}piperazine-1-yl)methyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazine-2-yl]oxy}hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-{1-[4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(5-{4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]piperazine-1-yl}-5-oxopentyl)-1H-1,2,3-triazole-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(1-{5-[(2S,5R)-4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]-2,5-dimethylpiperazine-1-yl]-5-oxopentyl}-1H-1,2,3-triazole-4-yl)butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(5-{5-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]-2,5-diazabicyclo[2.2.2]octan-2-yl}-5-oxopentyl)-1H-1,2,3-triazole-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(6-{4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)hexanoyl]piperazine-1-yl}-6-oxohexyl)-1H-1,2,3-triazole-4-yl]butanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(1-{6-[(2S,5R)-4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)hexanoyl]-2,5-dimethylpiperazine-1-yl]-6-oxohexyl}-1H-1,2,3-triazole-4-yl)butanoate A pharmaceutical product as described in item 1, selected from the group consisting of the following.

[0114] Item 8: Compounds that are the following: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[4,7-bis({4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl})-1,4,7-triazonan-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4,6-bis(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazine-2-yl]oxy}hexanoate A pharmaceutical product as described in item 1, selected from the group consisting of the following.

[0115] Item 9: a is 2; R 1 -(CH2)2-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9-, -(CH2) 12 -, or -(CH2) 16 -and; R 2 is -C(O)-, -CH2-, or a direct bond; R 3 but [ka] The pharmaceutical product described in item 1.

[0116] Item 10: Compounds that are the following: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}piperazine-1-yl)-6-oxohexanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-[(2R,5S)-4-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-dimethylpiperazine-1-yl]-8-oxooctanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(5-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.1]heptan-2-yl]-8-oxooctanoate; Tris(trifluoroacetic acid); (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazine-1-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[(2S,5R)-4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-2,5-dimethylpiperazine-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-(4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}piperazine-1-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-[(2R,5S)-4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}-2,5-dimethylpiperazine-1-yl]-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-(5-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}piperazine-1-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-[(2S,5R)-4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-2,5-dimethylpiperazine-1-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-14-(4-{14-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-14-oxotetradecanoyl}piperazine-1-yl)-14-oxotetradecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-14-[(2S,5R)-4-{14-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-14-oxotetradecanoyl}-2,5-dimethylpiperazine-1-yl]-14-oxotetradecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-18-(4-{18-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-18-oxooctadecanoyl}piperazine-1-yl)-18-oxooctadecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-18-[(2S,5R)-4-{18-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-18-octadecanoyl}-2,5-dimethylpiperazine-1-yl]-18-oxooctadecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-N-(8-{4-[8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)octanoyl]piperazine-1-yl}-8-oxooctyl)carbamate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}piperazine-1-yl)hexanoate A pharmaceutical product as described in item 9, selected from the group consisting of the following.

[0117] Item 11: a is 2; R 1 but [ka] and; R 2 is -C(O)-, -CH2-, or a direct bond; R 3 ga-(CH2)4-, [ka] The pharmaceutical product described in item 1.

[0118] Item 12: Compounds that are the following: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-{4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-[(2S,5R)-2,5-dimethyl-4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1s,4s)-4-{4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1s,4s)-4-[(2S,5R)-2,5-dimethyl-4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 1-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)piperazine-1-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[(3ar,6ar)-5-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)-octahydropyrrolo[3,4-c]pyrrole-2-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2,2-dimethyl-3-oxopropanoyl}piperazin-1-yl)-2,2-dimethyl-3-oxopropanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2,2-dimethyl-4-oxobutanoyl}piperazin-1-yl)-3,3-dimethyl-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3,3-dimethyl-4-oxobutanoyl}piperazin-1-yl)-2,2-dimethyl-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3,3-dimethyl-5-oxopentanoyl}piperazin-1-yl)-3,3-dimethyl-5-oxopentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-2-{2-[4-(2-{2-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2-oxoethoxy}acetyl)piperazine-1-yl]-2-oxoethoxy}acetate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-N-[(2S)-1-{4-[(2S)-2-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]piperazine-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-4-carbonyl)piperazine-1-carbonyl]piperidine-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)methyl]pyrazine-2-yl}methyl)piperidine-4-yl]propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-[(4-{[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexyl]methyl}piperazine-1-yl)methyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-{1-[4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(5-{4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]piperazine-1-yl}-5-oxopentyl)-1H-1,2,3-triazole-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(1-{5-[(2S,5R)-4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]-2,5-dimethylpiperazine-1-yl]-5-oxopentyl}-1H-1,2,3-triazole-4-yl)butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(5-{5-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]-2,5-diazabicyclo[2.2.2]octan-2-yl}-5-oxopentyl)-1H-1,2,3-triazole-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(6-{4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)hexanoyl]piperazine-1-yl}-6-oxohexyl)-1H-1,2,3-triazole-4-yl]butanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(1-{6-[(2S,5R)-4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)hexanoyl]-2,5-dimethylpiperazine-1-yl]-6-oxohexyl}-1H-1,2,3-triazole-4-yl)butanoate A pharmaceutical product as described in item 11, selected from the group consisting of the following.

[0119] Item 13: a is 2; R 1 is -(CH2)2-, -(CH2)4-, -(CH2)6-, or -(CH2)9-; R 2 is -C(O)-, -C(O)-N(CH3)-CH2-, -C(O)-NH-CH2-, or -NH-C(O)-; R 3 but [ka] The pharmaceutical product described in item 1.

[0120] Item 14: Compounds that are the following: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(6-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(9-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-[(3ar,6ar)-5-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(6-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-[(3ar,6ar)-5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-N-methyl-6-oxohexanamide}methyl)pyrazine-2-yl]methyl}(methyl)carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanamide}methyl)pyrazine-2-yl]methyl}carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazole-2-yl]formamide}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)pyrazine-2-yl]formamide}pentanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-{[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecyl}carbamoyl)pyrazine-2-yl]formamide}decanoate A pharmaceutical product as described in item 13, selected from the group consisting of the following.

[0121] Item 15: A pharmaceutical product according to any one of items 1 to 14, wherein the compound is any of all example compounds described herein, having an average particle size in the range of 0.05 to 10 μm as measured by laser diffraction.

[0122] Item 16: A pharmaceutical composition comprising a pharmaceutically acceptable carrier as described in any one of items 1 to 15.

[0123] Item 17: A medicine described in any one of items 1 to 15 for the treatment and / or prevention of central nervous system disorders.

[0124] Item 18: Central nervous system disorders including schizophrenia; treatment-resistant, intractable or chronic schizophrenia; affective disorders; psychotic disorders; mood disorders; bipolar disorder type I; bipolar disorder type II; depression; endogenous depression; major depressive disorder (MDD); melancholic and treatment-resistant depression; dysthymia; cyclothymic disorder; panic attacks; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorders; conversion disorders; pain disorders; hypochondriasis; factitious disorder; dissociative disorders; sexual dysfunction; libido disorders; sexual arousal disorders; erectile dysfunction; anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia ; Iatrogenic anhedonia; psychogenic or psychiatric anhedonia; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment due to Alzheimer's disease; Parkinson's disease and related neurodegenerative diseases; cognitive impairment in schizophrenia; cognitive impairment due to treatment-resistant, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autism; Tourette's disorder; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder, as described in paragraph 17.

[0125] Item 19: Use of any one of items 1 to 15 in the manufacture of a drug for the treatment and / or prevention of central nervous system disorders.

[0126] Item 20: Central nervous system disorders including schizophrenia; treatment-resistant, intractable or chronic schizophrenia; affective disorders; psychotic disorders; mood disorders; bipolar disorder type I; bipolar disorder type II; depression; endogenous depression; major depressive disorder (MDD); melancholic and treatment-resistant depression; dysthymia; cyclothymic disorder; panic attacks; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorders; conversion disorders; pain disorders; hypochondriasis; factitious disorder; dissociative disorders; sexual dysfunction; libido disorders; sexual arousal disorders; erectile dysfunction; anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia Uses as described in paragraph 19, selected from the group consisting of: iatrogenic anhedonia; psychogenic or psychiatric anhedonia; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment due to Alzheimer's disease; Parkinson's disease and related neurodegenerative diseases; cognitive impairment in schizophrenia; cognitive impairment due to treatment-resistant, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autism; Tourette's disorder; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

[0127] Article 21: A method for treating and / or preventing a central nervous system disorder, comprising administering a medicament described in any one of Articles 1 to 15 to a person in need thereof.

[0128] Section 22: Central nervous system disorders including schizophrenia; treatment-resistant, intractable or chronic schizophrenia; affective disorders; psychotic disorders; mood disorders; bipolar disorder type I; bipolar disorder type II; depression; endogenous depression; major depressive disorder (MDD); melancholic and treatment-resistant depression; dysthymia; cyclothymic disorder; panic attacks; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorders; conversion disorders; pain disorders; hypochondriasis; factitious disorder; dissociative disorders; sexual dysfunction; libido disorders; sexual arousal disorders; erectile dysfunction; anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia The method according to item 21, selected from the group consisting of: iatrogenic anhedonia; psychogenic or psychiatric anhedonia; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment due to Alzheimer's disease; Parkinson's disease and related neurodegenerative diseases; cognitive impairment in schizophrenia; cognitive impairment due to treatment-resistant, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autism; Tourette's disorder; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

[0129] Item 23: A compound or pharmaceutically acceptable salt thereof, as described in any one of items 1 to 15, for use in the treatment and / or prevention of central nervous system disorders.

[0130] Section 24: Central nervous system disorders including schizophrenia; treatment-resistant, intractable or chronic schizophrenia; affective disorders; psychotic disorders; mood disorders; bipolar disorder type I; bipolar disorder type II; depression; endogenous depression; major depressive disorder (MDD); melancholic and treatment-resistant depression; dysthymia; cyclothymic disorder; panic attacks; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorders; conversion disorders; pain disorders; hypochondriasis; factitious disorder; dissociative disorders; sexual dysfunction; libido disorders; sexual arousal disorders; erectile dysfunction; anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia; Compounds as described in item 23, selected from the group consisting of iatrogenic anhedonia; psychogenic or psychiatric anhedonia; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment due to Alzheimer's disease; Parkinson's disease and related neurodegenerative diseases; cognitive impairment of schizophrenia; cognitive impairment due to treatment-resistant, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autism; Tourette's disorder; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

[0131] Section 25: A method for producing any of the compounds described in Sections 1 to 15 or a pharmaceutically acceptable salt thereof, as described herein.

[0132] Item 26: Intermediate compounds in a method for producing any one of the compounds described in items 1 to 15 or a pharmaceutically acceptable salt thereof, as described herein.

[0133] Term 27: Formula (X): [ka] [In the formula, R 7-CH=CH-, -(CH2)2-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9-, -(CH2) 12 -,-(CH2) 16 -, [ka] and; R 8 is -C(O)-, -C(O)-N(CH3)-CH2-, -C(O)-NH-CH2-, -CH2-, -NH-C(O)-, or a direct bond; R 9 ha-(CH2)4-, [ka] and; R 10 -(CH2)2-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9-, H, -COOH, -C(O)-(CH2) 2-10 -C(O)H, -C(O)-(CH2) 2-10 -C(O)(tBu), or -C(O)(tBu)] The compound or salt thereof indicated by [the symbol].

[0134] The following examples are merely illustrative and should not be construed as limiting the invention in any way. Those skilled in the art will understand that variations and modifications of the following examples can be made without exceeding the spirit or scope of the invention. As will be apparent to those skilled in the art, individual isomers can be obtained by conventional methods of separating their mixture. For example, in the case of diastereomer isomers, chromatographic separation may be used. [Examples]

[0135] Details and methods of general experiments Analysis method Apparatus, substances, and methods used in the analysis 1H-NMR spectra were measured using a 400 Agilent INOVA, 500 Agilent VNMRS, 600 Agilent INOVA spectrometer, or Bruker Avance III 400 spectrometer operating at 400, 500, and 600 MHz (proton frequencies). Chemical shifts are reported as δ values ​​in ppm, using the residual solvent peak as an internal standard. The coupling constant (J value) is expressed in Hertz (Hz), and the multiplicity is reported using the following abbreviations: (s = singlet, d = doublet, t = triplet, q = quartet, p = quintet, h = heptet, m = multiplet, br. s = broad singlet, nd = undetermined, dd = double doublet, ddd = double double doublet, quin = quintuplet, td = triple doublet, tt = triple triplet, qd = quadruple doublet).

[0136] LC / UV / MS analysis method LC / MS retention times are estimated with an experimental error of +0.5 minutes. LC / MS may be recorded under the following conditions: diode array DAD chromatograph traces, mass chromatograms, and mass spectra may be measured using a UPLC / PDA / MS Acquity™ system connected to a Micromass ZQ™ or Waters SQD single quadrupole mass spectrometer operated in positive and / or negative electron spray ES ionization mode, and / or a Fractionlynx system used in analytical mode connected to a ZQ™ single quadrupole operated in positive and / or negative ES ionization mode. The quality control methods used were performed under low or high pH conditions: Method 1, Low pH conditions column: Acquity CSH C18 2.1 x 50 mm 1.7 μm, column temperature 40°C; mobile phase solvent A is milliQ water + 0.1% HCOOH, mobile phase solvent B is MeCN + 0.1% HCOOH. Flow rate is 1 mL / min. Gradient table is t = 0 min 97% A 3% B, t = 1.5 min 0.1% A 99.9% B, t = 1.9 min 0.1% A 99.9% B, and t = 2 min 97% A 3% B. UV detection range is 210-350 nm, ES+ / ES- range is 100-1900 AMU. Method 2, High pH column: Kinetex EVO C18 2.1 x 50 mm 1.7 μm, column temperature 40°C; mobile phase solvent A is a 10 mM aqueous solution of NH4HCO3 adjusted to pH = 10 with ammonia, mobile phase solvent B is MeCN. Flow rate is 1 mL / min. Gradient tables are t = 0 min 97% A 3% B, t = 1.5 min 0.1% A 99.9% B, t = 1.9 min 0.1% A 99.9% B, and t = 2 min 97% A 3% B. UV detection range is 210-350 nm, ES+ / ES- range is 100-1200 AMU. Method 3, Low pH column: Acquity Peptide BEH C18 2.1 x 50 mm 1.7 μm, column temperature 40°C; mobile phase solvent A is milliQ water + 0.05% TFA, mobile phase solvent B is MeCN + 0.05% TFA. Flow rate is 0.7 mL / min. Gradient table is t = 0 min 97% A 3% B, t = 3.0 min 20% A 80% B, t = 3.5 min 5% A 95% B, t = 3.9 min 5% A 95% B, and t = 4 min 97% A 3% B. UV detection range is 210-350 nm, ES+ / ES- range is 100-1900 AMU. Method 4, Low pH column: Acquity Peptide BEH C18 2.1 x 50 mm 1.7 μm, column temperature 40°C; mobile phase solvent A is milliQ water + 0.05% TFA, mobile phase solvent B is MeCN + 0.05% TFA. Flow rate is 0.7 mL / min. Gradient table is t = 0 min 97% A 3% B, t = 0.5 min 97% A 3% B, t = 3.0 min 40% A 60% B, t = 3.5 min 5% A 95% B, t = 3.9 min 5% A 95% B, and t = 4 min 97% A 3% B. UV detection range is 210-350 nm, ES+ / ES- range is 100-1900 AMU.

[0137] HPLC semi-preparative method Semi-preparative HPLC was performed using an MDAP Waters instrument equipped with a CSH C18 (30 x 100 mm, 5 μm) column and a 1 mL injection loop, along with a mass spectrometer (MS: ZQ2000) and a DAD detector 220. A gradient of MeCN + HCOOH in H2O was used as the mobile phase, with a flow rate of 40.00 mL / min and a 50% to 70% gradient over 10 minutes.

[0138] The chemical names of the compounds were generated using Structure To Name ChemAxon MarvinSketch software.

[0139] All reagents whose synthesis method is not described in the experimental section are either commercially available, known compounds, or may be formed from known compounds by methods known to those skilled in the art.

[0140] The following abbreviations are used in the examples. 2-MeTHF = 2-methyltetrahydrofuran atm = atmospheric pressure Boc = tert-butyloxycarbonyl Boc2O = di-tert-butyldicarbonate cHex = Cyclohexane CuI = Copper(I) iodide DCM = Dichloromethane DIAD = Diisopropyl azodicarboxylate DIPEA = N,N-diisopropylethylamine DMAP = 4-(dimethylamino)pyridine DMF = Dimethylformamide DMSO = Dimethyl sulfoxide HCl = ethyl acetate HCOOH = Formic acid h = time HATU = 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate HCl = hydrochloric acid HBTU = [(1H-1,2,3-benzotriazole-1-yl-oxy)(dimethylamino)methylidene]dimethylazanium; hexafluoro-lambda-5-phosphanide H2O = Water IPA = Propane-2-ol K2CO3 = Potassium Carbonate LC-MS = Liquid Chromatography / Mass Spectrometry MeCN = Acetonitrile MeOH = methanol MsCl = Methanesulfonyl chloride N2 = Nitrogen NaH = Sodium hydride NaOH = Sodium hydroxide Na2SO4 = Sodium sulfate NaHCO3 = Sodium Bicarbonate Na2CO3 = Sodium carbonate NH4Cl = Ammonium chloride nHex = n-hexane Pd / C = Palladium Carbon Pd(OAc)2 = Palladium(II) acetate PPh3 = Triphenylphosphine Py = pyridine quant. = quantitative Rt = retention time RT = room temperature Sec. = seconds ss = saturated solution TBA-HSO4 = Tetrabutylammonium hydrogen sulfate TBTU = O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate TEA = Triethylamine TFA = Trifluoroacetic acid THF = Tetrahydrofuran

[0141] Production of intermediates Int01: 1-tert-butyl 8-chloromethyl octanedioate [ka] To a mixture of 8-[(2-methylpropan-2-yl)oxy]-8-oxooctanoic acid (3.7 g) in DCM (35 mL) and H2O (44 mL), NaHCO3 (5.4 g) and TBA-HSO4 (5.5 g) were added. The mixture was cooled to 0°C, and an 8 mL solution of chloromethyl chlorosulfonate (1.6 mL) in DCM was added dropwise. The reaction mixture was then stirred at room temperature for 3 hours. The mixture was diluted with DCM and washed with H2O. The organic layer was dried over Na2SO4, filtered, and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~10% siRNA / cHex) to obtain IntO1 (2.76 g). 1 H NMR (400 MHz, CHLOROFORM-d) δ 5.70 (s, 2H), 2.38 (t, J = 7.45 Hz, 2H), 2.20 (t, J = 7.45 Hz, 2H), 1.72 - 1.55 (m, 4H), 1.44 (s, 9H), 1.40 - 1.26 (m, 4H).

[0142] Int02: 1-(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 8-tert-butyl octanedioate [ka] Under an N2 atmosphere, NaH (60% in mineral oil, 0.14 g) was added to 1,4-dioxane (30 mL), followed by the addition of 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinoline-2-one (1.4 g). The reaction mixture was stirred at room temperature for 15 minutes. Then, a solution of Int01 (1.35 g) in 1,4-dioxane (7 mL) was added dropwise. The reaction mixture was stirred at 60°C (ambient temperature) for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and quenched with a saturated NH4Cl solution. The resulting mixture was extracted with ethyl acetate (twice). The combined organic layers were dried using a phase separator, and the solvent was concentrated under vacuum. The crude product was purified by silica gel cartridge chromatography (eluent = 10%~100% ethyl acetate / cHex) to obtain Int02 (2.9 g). LC-MS (ESI): m / z (M+1): 676.4, Rt= 0.98 min. (Method 1).

[0143] Int03: 8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoate [ka] To a solution of IntO2 (2.9 g) in DCM (91 mL), TFA (5.25 mL) was added dropwise at room temperature. The mixture was stirred at room temperature for 48 hours. The solvent was removed by distillation, and the residual TFA was partially azeotropically dissolved in toluene. Then, 1,4-dioxane (10 mL) and HCl 4N / 1,4-dioxane (15 mL) were added, and the mixture was evaporated under high vacuum to obtain a yellow oily substance. This was collected by DCM, washed twice with saturated NaHCO3 solution, the organic phase was filtered through a phase separator, and acidified with 1.8 mL of aqueous HCl (1 M) (pH=3-4). The organic phase was washed twice with H2O, dried over Na2SO4, filtered, and concentrated under vacuum to obtain IntO3 (2.0 g). LC-MS (ESI): m / z (M+1): 620.0, Rt= 0.68 min. (Method 1).

[0144] Int04: Methyl({5-[(methylamino)methyl]pyrazine-2-yl}methyl)amine [ka] A 2M THF solution of methanamine (8 mL) was diluted with an additional 10 mL of THF and cooled to 0°C. 2,5-bis(bromomethyl)pyrazine (0.28 g) in 3 mL of THF was added dropwise at 0°C. The reaction mixture was placed in a vial and stirred at room temperature for 5 hours. The solvent was then removed under high vacuum, and the residue was purified using an SCX column (eluent = MeOH, then 2M ammonia / MeOH) to obtain the crude product Int04 (174 mg). 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.53 (s, 2H), 3.89 (d, J = 2.32 Hz, 4H), 2.49 (d, J = 1.63 Hz, 6H).

[0145] Int05: 1-[5-(aminomethyl)pyrazine-2-yl]methanamine dihydrochloride [ka] Step A: To a solution of [5-(hydroxymethyl)pyrazine-2-yl]methanol (50 mg) in dry THF (3.5 mL), PPh3 (206 mg) and phthalimide (105 mg) were added at room temperature. The mixture was cooled to 0°C and DIAD (0.16 mL) was added dropwise. The mixture was stirred at room temperature for 3 hours. The reaction mixture was filtered through a phase separator and washed with MeCN. The solid residue was dried under vacuum to obtain 2-({5-[(1,3-dioxo-2,3-dihydro-1H-isoindole-2-yl)methyl]pyrazine-2-yl}methyl)-2,3-dihydro-1H-isoindole-1,3-dione (127 mg). LC-MS (ESI): m / z (M+1): 399.1, Rt= 0.96 min. (Method 1). Step B: Hydrazine (0.04 mL) was added to a suspension of 2-({5-[(1,3-dioxo-2,3-dihydro-1H-isoindole-2-yl)methyl]pyrazine-2-yl}methyl)-2,3-dihydro-1H-isoindole-1,3-dione (127 mg) in DCM (4 mL), and the mixture was refluxed for 3 hours. The mixture was cooled to room temperature, TEA (0.2 mL) and Boc2O (0.21 g) were added, and the resulting mixture was stirred at 35°C for 24 hours. The mixture was cooled to room temperature, and the solid was filtered off. The organic layer was washed with H2O, the organic phase was filtered through a phase separator, and evaporated under high vacuum. The crude product obtained was purified by silica gel cartridge chromatography (eluent = 0%~40% SiO / cHex) to obtain tert-butyl N-{[5-({[(tert-butoxy)carbonyl]amino}methyl)pyrazine-2-yl]methyl}carbamate (48 mg). LC-MS (ESI): m / z (M+1): 399.2, Rt= 0.90 min. (Method 1). Step C: To a solution of tert-butyl N-[[5-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyrazine-2-yl]methyl]carbamate (48 mg) in 1,4-dioxane (2 mL), HCl 4M / 1,4-dioxane (0.57 mL) was added, and the reaction mixture was stirred overnight at room temperature. Then, HCl 4M / 1,4-dioxane (0.2 mL) was added, and the mixture was stirred for a further 6 hours at room temperature. The mixture was evaporated under high vacuum to obtain the crude product Int05 (31 mg). 1 H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 2H), 8.47 (s, 6H), 4.31 (s, 4H).

[0146] Int08: 2,6-diazaspiro[3.3]heptane bis(trifluoroacetic acid) salt [ka] To a solution of tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate (100 mg) in DCM (4 mL), TFA (0.6 mL) was added dropwise at 0°C. After stirring at room temperature for 3 hours, the mixture was evaporated under high vacuum to obtain Int08 (197 mg). 1 H NMR (400 MHz, CHLOROFORM-d) δ 4.07 (s, 8H), 2.25 (s, 2H).

[0147] Int09: 3,9-diazaspiro[5.5]undecane bis(trifluoroacetic acid) salt [ka]

[0148] Int09 was prepared from tert-butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (0.10 g) according to the procedure described for Int08, and Int09 (0.197 g) was obtained. 1H NMR (400 MHz, DMSO-d6) δ 8.47 (brs, 4H), 3.05 (dq, J = 8.63, 4.88 Hz, 8H), 1.63 (t, J = 5.92 Hz, 8H). Intermediates Int10, Int13, Int18, Int21, Int27, Int30, Int33, Int36, Int39, Int41, Int44, Int55, Int58, Int61, Int63, Int66, Int71, and Int75 were synthesized according to the method used for the synthesis of Int01.

[0149] Table 3 lists the starting materials used in the synthesis of each compound and their characteristics. [Table 3] TIFF2026047308000063.tif249165 TIFF2026047308000064.tif249164 TIFF2026047308000065.tif244170 TIFF2026047308000066.tif225169

[0150] Intermediates Int06, Int11, Int14, Int16, Int19, Int22, Int24, Int28, Int31, Int32, Int34, Int37, Int45, Int53, Int72, Int76, and Int77 were synthesized according to the method used for the synthesis of Int02.

[0151] Table 4 lists the starting materials used in the synthesis of each compound and their characteristics. [Table 4] TIFF2026047308000068.tif252170 TIFF2026047308000069.tif250166 TIFF2026047308000070.tif248164 TIFF2026047308000071.tif206170 TIFF2026047308000072.tif203170 TIFF2026047308000073.tif218170 TIFF2026047308000074.tif170170

[0152] Intermediates Int07, Int12, Int15, Int17, Int20, Int23, Int25, Int29, Int35, Int38, Int40, Int43, Int46, Int54, and Int65 were synthesized according to the method used for the synthesis of Int03.

[0153] Table 5 lists the starting materials used in the synthesis of each compound and their characteristics. [Table 5] TIFF2026047308000076.tif249164 TIFF2026047308000077.tif248170 TIFF2026047308000078.tif224170 TIFF2026047308000079.tif254170 TIFF2026047308000080.tif166169

[0154] Int26: (1s,4s)-4-[(tert-butoxy)carbonyl]cyclohexane-1-carboxylic acid [ka] A suspension of (1s,4s)-cyclohexane-1,4-dicarboxylic acid (4.0 g) in toluene (30 mL) was refluxed for 10 minutes to obtain a clear solution. The temperature was then raised to 100°C, and N,N-dimethylformamide di-tert-butylacetal (11.1 mL) was added dropwise over 5 minutes. The mixture was refluxed for 5 hours, then cooled to room temperature, and the solvent was removed under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 20%~50% SiO₂ / cHex) to obtain Int26 (2.1 g). 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.51 (tt, J = 7.5, 4.3 Hz, 1H), 2.36 (tt, J = 7.5, 4.2 Hz, 1H), 2.01 - 1.80 (m, 4H), 1.67 (dddd, J = 16.9, 12.5, 7.8, 4.3 Hz, 5H), 1.44 (d, J = 2.7 Hz, 9H).

[0155] Int39: 1-(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-tert-butyl 2,2-dimethylbutanediole [ka] Step A: Int39 was prepared from a mixture of 4-(tert-butoxy)-2,2-dimethyl-4-oxobutanoic acid and 4-(tert-butoxy)-3,3-dimethyl-4-oxobutanoic acid (0.97 g) according to the procedure described for Int01, to obtain a mixture of 4-tert-butyl 1-chloromethyl 2,2-dimethylbutanediate and 1-tert-butyl 4-chloromethyl 2,2-dimethylbutanediate (0.45 g). Step B: The obtained mixture was reacted with 7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinoline-2-one (0.45 g) according to the procedure described for Int02. The obtained mixture was further purified by chiral semi-preparative HPLC Column Chiralcel OJ-H (eluent = nHex / EtOH: 80 / 20) to obtain Int39 (120 mg). 1 H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.62 (d, J=9.6 Hz, 1 H), 7.56 (d, J=7.9 Hz, 1 H), 7.37 - 7.46 (m, 3 H), 7.26 - 7.31 (m, 1 H), 6.94 (d, J=2.0 Hz, 1 H), 6.90 (d, J=7.7 Hz, 1 H), 6.84 (dd, J=8.6, 2.0 Hz, 1 H), 6.52 (d, J=9.6 Hz, 1 H), 6.35 (br s, 2 H), 4.14 (t, J=6.2 Hz, 2 H), 3.20 (br s, 4 H), 2.73 (br s, 4 H), 2.52 - 2.57 (m, 2 H), 2.51 (s, 2 H), 1.85 - 1.98 (m, 2 H), 1.70 - 1.83 (m, 2 H), 1.38 (s, 9 H), 1.26 (s, 6 H).

[0156] Int42: 1-(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 5-tert-butyl 3,3-dimethylpentanediole [ka] Under an N2 atmosphere, NaH (60% in mineral oil, 0.154 g) was added at room temperature to a suspension of 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinoline-2-one (1.67 g) in 2-MeTHF (20 mL). The reaction mixture was stirred at 70°C (ambient temperature) for 30 minutes, then cooled to room temperature, and a solution of Int41 (1.0 g) in 2-MeTHF (10 mL) was added dropwise. The reaction mixture was stirred at 70°C (ambient temperature) for 3 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and quenched with a saturated NH4Cl solution. The resulting mixture was extracted with ethyl acetate (twice). The combined organic layers were dried on a phase separator, and the solvent was removed under vacuum. The crude product obtained was purified by silica gel cartridge chromatography (eluent = 10%~100% acetone / cHex) to obtain Int42 (610 mg). LC-MS (ESI): m / z (M+1): 662.6, Rt= 2.91 min. (Method 4).

[0157] Int47: tert-butyl 8-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)octanoate [ka] Under an N2 atmosphere, NaH (60% of mineral oil, 24 mg) was added to DMF (2 mL) and 2-MeTHF (2 mL) at room temperature. Then, 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinoline-2-one (220 mg) was added, and the reaction mixture was stirred at 60°C for 5 minutes, then cooled to -18°C. A solution of chloromethyl 4-nitrophenyl carbonate (153 mg) in DMF (2 mL) was added dropwise. The reaction mixture was stirred at -18°C for 18 hours. A saturated solution of cold NH4Cl was added, and the mixture was extracted by DCM (twice). The combined organic layers were dried using a phase separator, and the solvent was removed under vacuum to obtain a DMF solution of [7-[4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy]-2-oxoquinoline-1-yl]methyl (4-nitrophenyl) carbonate. To this, a DCM solution (5 mL) of tert-butyl 8-aminooctanoate (109 mg) and TEA (0.35 mL) were added at room temperature, and the reaction mixture was stirred at room temperature for 16 hours. Volatile substances were removed under vacuum, and the resulting crude product was purified by C-18 cartridge chromatography (eluent = 0.1% TFA / H2O with 0%~100% MeCN) to obtain Int47 (98 mg). LC-MS (ESI): m / z (M+1): 705,7, Rt = 3.0 min (Method 3).

[0158] Int48: 8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)octanoic acid trifluoroacetate [ka] To a solution of tert-butyl Int47 (98 mg) in DCM (4 mL), TFA (0.24 mL) was added dropwise at room temperature. The reaction mixture was stirred at room temperature for 16 hours. Toluene (10 mL) was added, and volatile matter was removed under vacuum to obtain Int48 (100 mg). LC-MS (ESI): m / z (M+1): 649.6, Rt= 2.52 min. (Method 3).

[0159] Int49: tert-butyl (2S)-2-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)-3-methylbutanoate [ka] Int49 was prepared from 7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-1,2-dihydroquinoline-2-one (500 mg), tert-butyl (2S)-2-amino-3-methylbutanoate hydrochloride (360 mg), and chloromethyl 4-nitrophenyl carbonate (350 mg) according to the procedure described for Int47 to obtain Int49 (570 mg). LC-MS (ESI): m / z (M+1): 663.3, Rt= 0.88 min. (Method 1).

[0160] Int50: (2S)-2-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)-3-methylbutanoic acid trifluoroacetate [ka] Int50 was prepared according to the procedure described for Int49 (570 mg) to Int48, and Int50 (370 mg) was obtained. LC-MS (ESI): m / z (M+1): 607.2, Rt= 0.75 min. (Method 1).

[0161] Intermediates Int51, Int56, Int62, Int64, and Int67 were synthesized using the same method as that used for the synthesis of Int49. Table 6 lists the starting materials used in the synthesis of each compound and their characteristics. [Table 6] TIFF2026047308000089.tif250169 TIFF2026047308000090.tif86169

[0162] Int52: 1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-4-carboxylic acid trifluoroacetate [ka] Int52 was prepared from Int51 (800 mg) according to the procedure described for Int48, and Int52 (545 mg, 63% yield) was obtained. LC-MS (ESI): m / z (M+1): 619.5, Rt= 2.35 min. (Method 3).

[0163] Int57: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 3-(piperidine-4-yl)propanoate [ka] Int57 was prepared from Int56 (1.28 g) according to the procedure described for Int54, and Int57 (1.24 g) was obtained. LC-MS (ESI): m / z (M+1): 603.3, Rt= 0.55 min. (Method 1).

[0164] Int59: 3-(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 1-tert-butyl azetidine-1,3-dicarboxylate [ka] Int59 was prepared from 7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-1,2-dihydroquinoline-2-one (1.6 g) and Int58 (1.4 g) according to the procedure described for Int49, and Int59 (1.9 g) was obtained. LC-MS (ESI): m / z (M+1): 647.5, Rt= 0.83 min. (Method 1).

[0165] Int60: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl azetidine-3-carboxylate [ka] Int60 was prepared from Int59 (1.9 g) according to the procedure described for Int54, and Int60 (1.6 g) was obtained. LC-MS (ESI): m / z (M+1): 547.3, Rt= 0.53 min. (Method 1).

[0166] Int68: 4-(1-benzothiophen-4-yl)-1-{4-[(1-{[(6-hydroxyhexanoyl)oxy]methyl}-2-oxo-1,2-dihydroquinoline-7-yl)oxy]butyl}piperazine-1-ium fluoride [ka] N-ethyldiisopropylamine hydrofluoride (1.5 mL) was added to a solution of Int67 (1 g) in THF (8 mL) at 0°C. The reaction mixture was stirred at room temperature for 7 hours. A saturated solution of NaHCO3 was added, and the mixture was extracted with  (twice). The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered, and evaporated under vacuum. The resulting crude product was triturated with ether: 90:10 to obtain Int68 (775 mg). LC-MS (ESI): m / z (M+1): 578.2, Rt= 0.73 min. (Method 1)

[0167] Int69: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 6-(methanesulfonyloxy)hexanoate [ka] MsCl (0.06 mL) was added at 0°C to a mixture of Int68 (250 mg), TEA (0.16 mL), and DMAP (4.8 mg) in DCM (4.3 mL). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with DCM and washed with H2O (twice) and saturated brine. The organic phase was dried over Na2SO4, filtered, and the solvent was removed under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~10% MeOH / DCM) to obtain Int69 (223 mg). LC-MS (ESI): m / z (M+1): 656.4, Rt= 0.8 min. (Method 1).

[0168] Int70: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 6-{[(4-nitrophenoxy)carbonyl]oxy}hexanoate [ka] Py (0.01 mL) was added to a solution of Int68 (32.0 mg) in DCM (1 mL) at 0°C, followed by the addition of 4-nitrophenyl chloroformate (11 mg). The reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with DCM and washed five times with saturated NaHCO3 solution. The organic phase was dried using a phase separator and evaporated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~100% MeOH / MeCN) to obtain Int70 (20 mg). LC-MS (ESI): m / z (M+1): 743.4, Rt= 0.96 min. (Method 1).

[0169] Int73: 4-(1-benzothiophen-4-yl)-1-{4-[(2-oxo-1-{[(1r,4r)-4-(hydroxymethyl)cyclohexanecarbonyloxy]methyl}-1,2-dihydroquinoline-7-yl)oxy]butyl}piperazine-1-ium fluoride [ka] Int73 was prepared from Int72 (970 mg) according to the procedure described for Int68, and Int73 (744 mg) was obtained. LC-MS (ESI): m / z (M+1): 604.2, Rt= 0.75 min. (Method 1).

[0170] Int74: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl (1r,4r)-4-[(methanesulfonyloxy)methyl]cyclohexane-1-carboxylate [ka] Int74 was prepared according to the procedure described for Int73 (250 mg) to Int69, and Int74 (237 mg, 87% yield) was obtained. LC-MS (ESI): m / z (M+1): 682.1, Rt= 0.82 min. (Method 1).

[0171] Int78: 5-azido-1-[4-(5-azidopentanoyl)piperazine-1-yl]pentan-1-one [ka] DIPEA (0.36 mL) and HBTU (660 mg) were added to a solution of 5-azidopentanoic acid (0.350 mL) and piperazine (60 mg) in THF (5 mL), and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed twice with a saturated solution of NaHCO3. The organic phase was dried using a phase separator, and the solvent was removed under vacuum at 37°C. The resulting crude product was purified by C18 cartridge chromatography (eluent = 5%~50% MeCN / H2O) to obtain Int78 (170 mg). LC-MS (ESI): m / z (M+1): 337.2, Rt= 0.82 min. (Method 1).

[0172] Intermediates Int79, Int80, Int81, and Int82 were synthesized using the same method as that used for the synthesis of Int78.

[0173] Table 7 lists the starting materials used in the synthesis of each compound and their characteristics. [Table 7] TIFF2026047308000102.tif69170

[0174] Int83 : 4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoic acid trifluoroacetic acid [ka] TFA (6.1 mL, 80 mmol) was added dropwise to a solution of Int06 (6.2 g, 10 mmol) in DCM (85 mL) at room temperature. The mixture was stirred at room temperature for 20 hours. Then, an additional TFA (6.1 mL, 80 mmol) was added, and the mixture was stirred at room temperature for a further 8 hours. The solvent was removed by distillation, and the TFA residue was partially azeotropically removed with toluene. The residue was concentrated under vacuum to obtain 4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoic acid trifluoroacetic acid (6.9 g, 10.2 mmol, quantitative yield). LC-MS (ESI): m / z (M+1): 564.5, Rt = 2.28 min. (Method 4).

[0175] Int84 : tert-butyl 4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazine-1-carboxylate [ka] TBTU (405 mg, 1.26 mmol) was added to a solution of Int83 (710 mg, 1.05 mmol) in dry DMF (5 mL). After 5 minutes, TEA (0.58 mL, 4.2 mmol) and tert-butylpiperazine-1-carboxylate (215 mg, 1.16 mmol) / DMF (10 mL) were added, and the reaction mixture was stirred at room temperature for 3 hours. H2O and DCM were added to the reaction mixture, the mixed phase was separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with saturated brine, dried over Na2SO4, filtered, and concentrated under vacuum. The crude product obtained was purified by silica gel cartridge chromatography (eluent = DCM ~ 6% MeOH / DCM) to obtain tert-butyl 4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazin-1 carboxylate (0.50 g, 0.68 mmol, 64% yield). LC-MS (ESI): m / z (M+1): 732.6, Rt = 2.05 min. (Method 4).

[0176] Int85: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-oxo-4-(piperazine-1-yl)butanoate [ka] Int85 was prepared from Int84 (150 mg, 0.156 mmol) according to the procedure described for Int03, to obtain (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-oxo-4-(piperazin-1-yl)butanoate (93 mg, 0.147 mmol, 95% yield). LC-MS (ESI): m / z (M+1): 632.4, Rt = 1.40-1.50 min. (Method 4).

[0177] Int86: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-{4-[4-(tert-butoxy)-4-oxobutanoyl]piperazine-1-yl}-4-oxobutanoate trifluoroacetic acid [ka] Int86 was prepared from Int85 (90 mg, 0.142 mmol) and 4-tert-butoxy-4-oxo-butanoic acid (30 mg, 0.17 mmol) according to the procedure described for Int6, to obtain (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-{4-[4-(tert-butoxy)-4-oxobutanoyl]piperazin-1-yl}-4-oxobutanoate trifluoroacetic acid (70 mg, 55% yield). LC-MS (ESI): m / z (M+1): m / z (M+1): 788.6, Rt = 2.02 min. (Method 4).

[0178] Int87: 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazine-1-yl)-4-oxobutanoic acid [ka] Int87 was prepared from Int86 (70 mg, 0.089 mmol) according to the procedure described for Int03 to obtain 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazin-1-yl)-4-oxobutanoic acid (12 mg, 0.016 mmol, 17% yield). LC-MS (ESI): m / z (M+1): 732.5, Rt = 1.66 min. (Method 4). 1 H NMR (500 MHz, DMSO-d6) δ ppm 10.44 - 13.97 (m, 2 H), 8.13 (s, 1 H), 7.89 (d, J=9.5 Hz, 1 H), 7.69 (d, J=5.5 Hz, 1 H), 7.66 (d, J=9.1 Hz, 1 H), 7.61 (d, J=8.1 Hz, 1 H), 7.40 (d, J=5.4 Hz, 1 H), 7.27 (t, J=7.8 Hz, 1 H), 6.92 - 6.97 (m, 2 H), 6.89 (br d, J=7.5 Hz, 1 H), 6.43 (d, J=9.5 Hz, 1 H), 6.16 - 6.29 (m, 2 H), 4.16 (t, J=6.4 Hz, 2 H), 3.23 - 3.53 (m, 8 H), 3.07 (br s, 4 H), 2.59 - 2.74 (m, 4 H), 2.47 - 2.53 (m, 2 H), 2.31 - 2.81 (m, 8 H), 1.76 - 1.87 (m, 2H), 1.62 - 1.72 (m, 2H).

[0179] Int88: 4-[4-(3-carboxypropanoyl)piperazine-1-yl]-4-oxobutanoic acid [ka] A suspension of piperazine (1.0 g, 11.6 mmol) and oxolan-2,5-dione (2.3 g, 23.2 mmol) in toluene (15 mL) was stirred at 110°C for 1 hour. Then, DMF (5 mL) was added and the suspension was stirred at 110°C for a further 4 hours. The solvent was removed by distillation under reduced pressure. The solid residue was collected with EtOH, filtered, and washed with EtOH. The solid residue was vacuum dried to obtain 4-[4-(3-carboxypropanoyl)piperazin-1-yl]-4-oxobutanoic acid (2.51 g, 8.8 mmol, 76% yield). LC-MS (ESI): m / z (M+1): 287.2, Rt = 0.39 min. (Method 1). 1 H NMR (400 MHz, DMSO-d6) δ ppm 12.05 (s, 2H), 3.52 - 3.39 (m, 8H), 2.56 (t, J = 6.6 Hz, 4H), 2.44 (dd, J = 7.3, 5.6 Hz, 4H).

[0180] Int89: 8,8'-(piperazine-1,4-diyl)bis(8-oxooctanoic acid) [ka] Int89 is prepared in the same manner as described herein.

[0181] Manufacturing of the final compound Example 01: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}piperazine-1-yl)-6-oxohexanoate [ka] TBTU (543 mg) was added to a solution of Int15 (0.19 g) in dry DMF (13 mL). After 5 minutes, TEA (0.54 mL) and piperazine (50 mg) were added, and the reaction mixture was stirred overnight at room temperature. Further addition of piperazine (17 mg) and TEA (0.15 mL) was made, and the reaction mixture was stirred for another hour at room temperature. H2O and DCM were added to the reaction mixture, the mixed phase was separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with saturated brine, dried over Na2SO4, filtered, and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM ~ 3% MeOH / DCM) to obtain Example 01 (660 mg). LC-MS (ESI): m / z (M+1): 1233.7, Rt= 2.72 min. (Method 4). 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.49 (s, 2 H), 7.63 (d, J=9.6 Hz, 2 H), 7.55 (d, J=8.1 Hz, 2 H), 7.46 (d, J=8.6 Hz, 2 H), 7.37 - 7.43 (m, 4 H), 7.18 - 7.34 (m, 2 H), 6.82 - 6.94 (m, 6 H), 6.68 (br t, J=5.0 Hz, 2 H), 6.50 (d, J=9.4 Hz, 2 H), 6.32 (br s, 4 H), 4.56 (d, J=5.5 Hz, 4 H), 4.09 (t, J=6.1 Hz, 4 H), 3.21 (br s, 8 H), 2.75 (br s, 8 H), 2.56 (br t, J=7.3 Hz, 4 H), 2.36 (t, J=7.3 Hz, 4 H), 2.22 (t, J=7.6 Hz, 4 H), 1.87 - 1.98 (m, 4 H), 1.78 (quin, J=7.3 Hz, 4 H), 1.51 - 1.69 (m, 8 H), 1.28 - 1.43 (m, 8 H).

[0182] Examples 02, 03, 05, 06, 07, 09, 11, 13, 14, 15, 16, 17, 18, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 were synthesized according to the method used for the synthesis of Example 01.

[0183] Table 8 lists the starting materials used in the synthesis of each compound and their characteristics. [Table 8] TIFF2026047308000112.tif200170 TIFF2026047308000113.tif229169 TIFF2026047308000114.tif202168 TIFF2026047308000115.tif210169 TIFF2026047308000116.tif218170 TIFF2026047308000117.tif200170 TIFF2026047308000118.tif210170 TIFF2026047308000119.tif207169 TIFF2026047308000120.tif194170 TIFF2026047308000121.tif200170 TIFF2026047308000122.tif212170 TIFF2026047308000123.tif213169 TIFF2026047308000124.tif206170 TIFF2026047308000125.tif217169 TIFF2026047308000126.tif201170 TIFF2026047308000127.tif218170 TIFF2026047308000128.tif217169 TIFF2026047308000129.tif212169 TIFF2026047308000130.tif207170 TIFF2026047308000131.tif246169 TIFF2026047308000132.tif245170 TIFF2026047308000133.tif242169 TIFF2026047308000134.tif195170 TIFF2026047308000135.tif199169 TIFF2026047308000136.tif209170 TIFF2026047308000137.tif206170 TIFF2026047308000138.tif212170 TIFF2026047308000139.tif249164 TIFF2026047308000140.tif249165 TIFF2026047308000141.tif224170 TIFF2026047308000142.tif193170 TIFF2026047308000143.tif254170 TIFF2026047308000144.tif253170 TIFF2026047308000145.tif254170 TIFF2026047308000146.tif188170

[0184] Example 04: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.1]heptan-2-yl]-8-oxooctanoate; Tris(trifluoroacetic acid) [ka] TBTU (543 mg) was added to a solution of Int03 (90 mg) and (2S)-2-ethylpiperazine dihydrochloride (12 mg) in dried DMF (13 mL). The final compound was purified by C18 cartridge chromatography (eluent = 0.1% TFA / H2O with 5%-50% MeCN) to obtain Example 04 (12 mg). LC-MS (ESI): m / z (M+1): 1302.8, Rt= 2.91 min. (Method 4). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 11.83 - 12.91 (m, 2 H), 7.65 (d, J=7.9 Hz, 4 H), 7.43 - 7.51 (m, 4 H), 7.28 - 7.34 (m, 4 H), 6.96 (d, J=7.5 Hz, 2 H), 6.90 (d, J=0.9 Hz, 2 H), 6.78 - 6.87 (m, 2 H), 6.55 (d, J=9.4 Hz, 2 H), 6.33 (br s, 4 H), 4.42 - 5.01 (m, 2 H), 4.09 (t, J=5.4 Hz, 4 H), 3.77 - 3.93 (m, 4 H), 3.35 - 3.65 (m, 12 H), 3.25 - 3.34 (m, 4 H), 3.10 - 3.24 (m, 4 H), 2.33 - 2.42 (m, 4 H), 2.03 - 2.31 (m, 8 H), 1.74 - 2.03 (m, 6 H), 1.46 - 1.70 (m, 8 H), 1.18 - 1.42 (m, 8 H).

[0185] Example 08: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanaamide}methyl)pyrazine-2-yl]methyl}carbamoyl)heptanoate [ka] TBTU (543 mg) was added to a solution of Int03 (110 mg) and Int05 (16 mg) in dry DMF (13 mL). After 5 minutes, TEA (0.54 mL) and piperazine (50 mg) were added, and the reaction mixture was stirred overnight at room temperature. Further addition of piperazine (17 mg) and TEA (0.15 mL) was made, and the reaction mixture was stirred for another hour at room temperature. H2O and DCM were added to the reaction mixture, the mixed phase was separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with saturated brine, dried over Na2SO4, filtered, and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM ~ 3% MeOH / DCM) to obtain Example 08 (30 mg). LC-MS (ESI): m / z (M+1): 1342.9, Rt= 2.09 min. (Method 3). 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.49 (s, 2 H), 7.63 (d, J=9.6 Hz, 2 H), 7.55 (d, J=8.1 Hz, 2 H), 7.46 (d, J=8.6 Hz, 2 H), 7.37 - 7.43 (m, 4 H), 7.18 - 7.34 (m, 2 H), 6.82 - 6.94 (m, 6 H), 6.68 (br t, J=5.0 Hz, 2 H), 6.50 (d, J=9.4 Hz, 2 H), 6.32 (br s, 4 H), 4.56 (d, J=5.5 Hz, 4 H), 4.09 (t, J=6.1 Hz, 4 H), 3.21 (br s, 8 H), 2.75 (br s, 8 H), 2.56 (br t, J=7.3 Hz, 4 H), 2.36 (t, J=7.3 Hz, 4 H), 2.22 (t, J=7.6 Hz, 4 H), 1.87 - 1.98 (m, 4 H), 1.78 (quin, J=7.3 Hz, 4 H), 1.51 - 1.69 (m, 8 H), 1.28 - 1.43 (m, 8 H).

[0186] Example 10: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazin-1-yl)-4-oxobutanoate [ka] TBTU (395 mg) was added to a solution of Int07 (568 mg) in dried DMF (7.73 mL). After 5 minutes, piperazine (37 mg) and TEA (0.26 mL) were added. The mixture was stirred at room temperature for 16 hours. Water and DCM were added to the reaction mixture and extracted with DCM (3 times). The combined organic layer was dried over Na2SO4, filtered, and concentrated under high vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0-6% MeOH / DCM) to obtain Example 10 (250 mg). LC-MS (ESI): m / z (M+1): 1177.9, Rt= 1.99 min. (Method 3). 1 H NMR (600 MHz, CHLOROFORM-d) δ ppm 7.63 (d, J=9.6 Hz, 2 H), 7.55 (d, J=7.9 Hz, 2 H), 7.45 (d, J=8.6 Hz, 2 H), 7.40 (q, J=5.6 Hz, 4 H), 7.21 - 7.31 (m, 2 H), 6.87 - 6.92 (m, 4 H), 6.85 (dd, J=8.6, 2.3 Hz, 2 H), 6.51 (d, J=9.6 Hz, 2 H), 6.34 (br s, 4 H), 4.14 (t, J=6.1 Hz, 4 H), 3.28 - 3.62 (m, 8 H), 3.22 (br s, 8 H), 2.67 - 2.89 (m, 12 H), 2.51 - 2.66 (m, 8 H), 1.88 - 1.96 (m, 4 H), 1.80 (br d, J=6.6 Hz, 4 H).

[0187] Example 12: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-4-oxobutanoate [ka] TBTU (543 mg) was added to a solution of Int07 (200 mg) and Int09 (57 mg) in dry DMF (13 mL). After 5 minutes, TEA (0.54 mL) and piperazine (50 mg) were added, and the reaction mixture was stirred overnight at room temperature. Further addition of piperazine (17 mg) and TEA (0.15 mL) was made, and the reaction mixture was stirred for another hour at room temperature. H2O and DCM were added to the reaction mixture, the mixed phase was separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with saturated brine, dried over Na2SO4, filtered, and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM ~ 3% MeOH / DCM) to obtain Example 12 (41 mg). LC-MS (ESI): m / z (M+1): 1245.7, Rt= 2.03 min. (Method 3). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.63 (d, J=9.5 Hz, 2 H), 7.56 (d, J=8.1 Hz, 2 H), 7.44 (d, J=8.6 Hz, 2 H), 7.36 - 7.42 (m, 4 H), 7.23 - 7.31 (m, 2 H), 6.87 - 6.94 (m, 4 H), 6.85 (dd, J=8.6, 2.2 Hz, 2 H), 6.52 (d, J=9.5 Hz, 2 H), 6.34 (br s, 4 H), 4.16 (t, J=5.9 Hz, 4 H), 3.31 - 3.63 (m, 8 H), 3.16 - 3.31 (m, 8 H), 2.78 - 3.10 (m, 8 H), 2.59 - 2.77 (m, 12 H), 1.82 - 1.96 (m, 8 H), 1.29 - 1.51 (m, 8 H).

[0188] Example 19: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}piperazine-1-yl)-8-oxooctanoate [ka] TBTU (543 mg) was added to a solution of Int03 (890 mg) in dried DMF (13 mL). After 5 minutes, TEA (0.54 mL) and piperazine (50 mg) were added, and the reaction mixture was stirred overnight at room temperature. Further addition of piperazine (17 mg) and TEA (0.15 mL) was made, and the reaction mixture was stirred for another hour at room temperature. H2O and DCM were added to the reaction mixture, the mixed phase was separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with saturated brine, dried over Na2SO4, filtered, and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM ~ 3% MeOH / DCM) to obtain Example 19 (660 mg). LC-MS (ESI): m / z (M+1): 1290.0, Rt= 2.17 min. (Method 3). 1 H NMR (400 MHz, DMSO-d6) δ ppm 7.88 (d, J=9.6 Hz, 2 H), 7.63 - 7.72 (m, 4 H), 7.59 (d, J=8.1 Hz, 2 H), 7.38 (d, J=5.7 Hz, 2 H), 7.25 (t, J=7.8 Hz, 2 H), 6.91 - 7.00 (m, 4 H), 6.86 (d, J=7.7 Hz, 2 H), 6.42 (d, J=9.4 Hz, 2 H), 6.27 (br s, 4 H), 4.13 (t, J=6.2 Hz, 4 H), 3.23 - 3.48 (m, 8 H), 3.04 (br s, 8 H), 2.60 (br s, 8 H), 2.43 (br t, J=7.0 Hz, 4 H), 2.28 - 2.37 (m, 4 H), 2.21 (t, J=7.3 Hz, 4 H), 1.75 - 1.86 (m, 4 H), 1.58 - 1.71 (m, 4 H), 1.50 (quin, J=7.2 Hz, 4 H), 1.34 - 1.44 (m, 4 H), 1.16 - 1.29 (m, 8 H).

[0189] Example 45: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate [ka] Pyrazine-2,5-dicarbonyl dichloride (36 mg) was added at 0°C to a solution of Int54 (200 mg) and TEA (0.24 mL) in DCM (6 mL). The reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with DCM and washed with H2O and saturated brine. The organic phase was dried over Na2SO4, filtered, and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~10% MeOH / DCM) to obtain Example 45 (6 mg). LC-MS (ESI): m / z (M+1): 1282.0, Rt= 2.72 min. (Method 3). 1H NMR (600 MHz, DMSO-d6 ) δ ppm 9.59 (br s, 2 H), 8.78 (s, 2 H), 7.91 (d, J=9.6 Hz, 2 H), 7.75 (d, J=5.6 Hz, 2 H), 7.64 - 7.73 (m, 4 H), 7.49 (d, J=5.6 Hz, 2 H), 7.31 (t, J=7.9 Hz, 2 H), 6.90 - 7.06 (m, 6 H), 6.45 (d, J=9.6 Hz, 2 H), 6.09 - 6.42 (m, 4 H), 4.16 (br t, J=5.4 Hz, 4 H), 3.64 - 4.40 (m, 4 H), 3.33 - 3.71 (m, 8 H), 3.30 (br d, J=3.0 Hz, 4 H), 3.04 - 3.60 (m, 8 H), 2.94 - 3.18 (m, 4 H), 2.77 (td, J=10.5, 4.1 Hz, 2 H), 1.70 - 2.02 (m, 12 H), 1.46 - 1.67 (m, 4 H).

[0190] Example 46: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate [ka] DIPEA (32 mg) was added to a solution of 2,4-dichloro-1,3,5-triazine (6.2 mg) and Int57 (49 mg) in DMF (1.2 mL). The reaction mixture was stirred at room temperature for 16 hours. The mixture was diluted with siRNA and washed with H2O (twice) and saturated brine (twice). The organic phase was dried over Na2SO4, filtered, and evaporated under vacuum. The crude product was purified by silica gel cartridge chromatography (eluent = 0%~10% MeOH / DCM), then by C-18 cartridge chromatography (eluent = 0.1% HCOOH / H2O with 5%~50% MeCN). The product was diluted with DCM and desalted with excess K2CO3. After 10 minutes of stirring, the solid was filtered off, and the solution was concentrated under vacuum to obtain Example 46 (17 mg). LC-MS (ESI): m / z (M+1): 1293.0, Rt= 1.98 min. (Method 3). 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.13 (s, 1 H), 7.63 (d, J=9.5 Hz, 2 H), 7.55 (d, J=8.0 Hz, 2 H), 7.46 (d, J=8.7 Hz, 2 H), 7.36 - 7.43 (m, 4 H), 7.23 - 7.32 (m, 2 H), 6.82 - 6.92 (m, 6 H), 6.53 (d, J=9.4 Hz, 2 H), 6.35 (br s, 4 H), 4.67 (br d, J=13.4 Hz, 4 H), 4.09 (t, J=6.1 Hz, 4 H), 3.20 (br s, 8 H), 2.72 (br s, 8 H), 2.61 - 2.70 (m, 4 H), 2.54 (t, J=7.4 Hz, 4 H), 2.41 (t, J=7.6 Hz, 4 H), 1.86 - 1.96 (m, 4 H), 1.72 - 1.82 (m, 4 H), 1.63 - 1.71 (m, 4 H), 1.42 - 1.64 (m, 6 H), 1.00 - 1.15 (m, 4 H).

[0191] Example 47: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4,6-bis(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate hexakis(trifluoroacetic acid) salt [ka] DIPEA (0.12 mL) was added to a solution of Int57 (199 mg) and 2,4,6-trichloro-1,3,5-triazine (20 mg) in DMF (4 mL), and the reaction was stirred at 60°C for 16 hours. The mixture was cooled to room temperature, diluted with ethyl acetate, and washed with H2O (twice) and saturated brine (twice). The organic phase was dried over Na2SO4, filtered, and concentrated under vacuum. The crude product was purified by silica gel cartridge chromatography (eluent = 0%~10% MeOH / DCM). The product was further purified by C-18 cartridge chromatography (eluent = 0.1% HCOOH / H2O with 5%~50% MeCN) to obtain Example 47 (51 mg). LC-MS (ESI): m / z (M+1): 1885, Rt= 2.22 min. (Method 3). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.92 - 13.62 (m, 3 H), 7.64 (dd, J=8.9, 5.4 Hz, 6 H), 7.42 - 7.51 (m, 6 H), 7.28 - 7.34 (m, 6 H), 6.94 (d, J=7.5 Hz, 3 H), 6.90 (s, 3 H), 6.84 (br d, J=8.6 Hz, 3 H), 6.54 (d, J=9.6 Hz, 3 H), 6.35 (br s, 6 H), 4.46 (br d, J=12.7 Hz, 6 H), 4.08 (br t, J=5.6 Hz, 6 H), 3.79 (br d, J=11.0 Hz, 6 H), 3.47 - 3.61 (m, 6 H), 3.34 - 3.45 (m, 6 H), 3.07 - 3.30 (m, 12 H), 2.75 (br t, J=12.5 Hz, 6 H), 2.38 (br t, J=7.3 Hz, 6 H), 2.01 - 2.18 (m, 6 H), 1.64 - 1.99 (m, 12 H), 1.35 - 1.63 (m, 9 H), 1.09 (q, J=11.0 Hz, 6 H).

[0192] Example 48: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)methyl]pyrazine-2-yl}methyl)piperidine-4-yl]propanoate [ka] Example 48 was prepared using Int57 (150 mg) and 2,5-bis(bromomethyl)pyrazine (33 mg) according to the procedure described for Example 46. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~4% MeOH / DCM) to obtain Example 48 (15 mg). LC-MS (ESI): m / z (M+1): 1309, Rt= 1.77 min. (Method 3). 1 H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.54 (s, 2 H), 7.63 (d, J=9.5 Hz, 2 H), 7.55 (d, J=8.2 Hz, 2 H), 7.46 (d, J=8.6 Hz, 2 H), 7.37 - 7.43 (m, 4 H), 7.23 - 7.31 (m, 2 H), 6.87 - 6.92 (m, 4 H), 6.85 (dd, J=8.5, 2.1 Hz, 2 H), 6.52 (d, J=9.5 Hz, 2 H), 6.34 (br s, 4 H), 4.09 (t, J=6.2 Hz, 4 H), 3.59 (s, 4 H), 3.01 - 3.36 (m, 8 H), 2.79 - 2.87 (m, 4 H), 2.62 - 2.79 (m, 8 H), 2.54 (br t, J=7.2 Hz, 4 H), 2.38 (t, J=7.8 Hz, 4 H), 1.87 - 2.01 (m, 8 H), 1.73 - 1.83 (m, 4 H), 1.46 - 1.64 (m, 8 H), 1.17 - 1.29 (m, 6 H).

[0193] Example 49: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-yl}propanoate [ka] Pyrazine-2,5-dicarbonyl dichloride (43 mg) was added at 0°C to a solution of Int57 (250 mg) and TEA (0.58 mL) in DMF (8 mL). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate and washed with H2O and saturated brine (twice). The organic phase was dried over Na2SO4, filtered, and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~10% MeOH / DCM) to obtain Example 49 (35 mg). LC-MS (ESI): m / z (M+1): 1338, Rt= 2.11 min. (Method 3). 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.79 (s, 2 H), 7.64 (d, J=9.4 Hz, 2 H), 7.55 (d, J=7.9 Hz, 2 H), 7.47 (d, J=8.6 Hz, 2 H), 7.37 - 7.44 (m, 4 H), 7.20 - 7.31 (m, 2 H), 6.82 - 6.93 (m, 6 H), 6.53 (d, J=9.4 Hz, 2 H), 6.35 (br s, 4 H), 4.10 (t, J=6.2 Hz, 4 H), 3.73 - 4.80 (m, 4 H), 3.20 (br s, 8 H), 2.74 (br s, 8 H), 2.64 - 3.05 (m, 4 H), 2.55 (t, J=7.5 Hz, 4 H), 2.42 (t, J=7.5 Hz, 4 H), 1.86 - 1.98 (m, 4 H), 1.11 - 1.85 (m, 18 H).

[0194] Example 50: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate bis(trifluoroacetic acid) salt [ka] Example 50 was prepared from Int60 (350 mg) and pyrazine-2,5-dicarbonyl dichloride (66 mg) according to the procedure described for Example 49, and Example 50 (8.2 mg) was obtained. LC-MS (ESI): m / z (M+1): 1225.9, Rt= 2.64 min. (Method 3). 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 11.32 - 13.18 (m, 3 H), 9.13 - 9.17 (m, 2 H), 7.59 - 7.73 (m, 4 H), 7.41 - 7.52 (m, 4 H), 7.27 - 7.36 (m, 4 H), 6.95 (dd, J=7.6, 3.0 Hz, 2 H), 6.89 (br d, J=4.6 Hz, 2 H), 6.85 (br d, J=8.6 Hz, 2 H), 6.56 (d, J=9.4 Hz, 2 H), 6.34 - 6.51 (m, 4 H), 4.85 (brd, J=7.0Hz, 4H), 4.33 - 4.46 (m, 4 H), 4.09 (br t, J=5.5 Hz, 4 H), 3.83 (br d, J=10.7 Hz, 4 H), 3.48 - 3.68 (m, 6 H), 3.40 (br t, J=12.3 Hz, 4 H), 3.09 - 3.32 (m, 8 H), 1.80 - 2.11 (m, 8 H).

[0195] Example 51: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazole-2-yl]formamide}pentanoate [ka] Step A: TFA (1.12 mL) was added dropwise to a solution of Int62 (0.68 g) in DCM (10 mL) at room temperature. The reaction mixture was stirred at room temperature for 4 hours. Toluene (20 mL) was added, and the volatiles were evaporated under vacuum. The residue was dissolved in THF (10 mL) and toluene (20 mL) at room temperature, and 4M HCl / 1,4-dioxane (1.2 mL) was added dropwise. After stirring for 10 minutes, the mixture was concentrated under vacuum to obtain Example 51-Step A: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 5-aminopentanoate dihydrochloride (658 mg, quantitative yield). Step B: 1,3-Thiazole-2,5-Dicarbonyl Dichloride (33 mg) was added at room temperature to a solution of crude product (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 5-aminopentanoate dihydrochloride (0.20 g) in DMF (6 mL), followed by the addition of TEA (0.6 mL). The reaction mixture was stirred at 100°C for 3 hours. The reaction mixture was cooled to room temperature, diluted in a cold NH4Cl saturated solution, and extracted by DCM (twice). The combined organic layers were dried using a phase separator and concentrated under vacuum. The crude product obtained was purified by C-18 cartridge chromatography (eluent = 0.1% TFA / H2O with 0%-100% MeCN), followed by silica gel cartridge chromatography (eluent = 0%-10% MeOH / DCM) to obtain Example 51 (3.3 mg). LC-MS (ESI): m / z (M+1): 1257.7, Rt= 2.09 min. (Method 3). 1 H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.23 ​​(s, 1 H), 7.61 - 7.69 (m, 2 H), 7.52 - 7.58 (m, 2 H), 7.44 - 7.50 (m, 2 H), 7.36 - 7.43 (m, 4 H), 7.32 (t, J=6.0 Hz, 1 H), 7.23 - 7.29 (m, 2 H), 6.83 - 6.93 (m, 6 H), 6.61 (br s, 1 H), 6.47 - 6.55 (m, 2 H), 6.23 - 6.39 (m, 4 H), 4.04 - 4.15 (m, 4 H), 3.37 - 3.49 (m, 4 H), 3.19 (br s, 8 H), 2.73 (br s, 8 H), 2.49 - 2.59 (m, 4 H), 2.40 - 2.48 (m, 4 H), 1.86 - 1.95 (m, 4 H), 1.71 - 1.81 (m, 8 H), 1.63 - 1.70 (m, 4H)

[0196] Examples 52 and 53 were prepared according to the procedure described for Example 51. The reactants used in the synthesis of each compound and their characteristics are listed in Table 9. [Table 9] TIFF2026047308000160.tif155169

[0197] Example 54: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}piperazine-1-yl)hexanoate [ka] TEA (0.04 mL) and piperazine (9 mg) were added to a suspension of Int69 (140 mg) in DMF (1 mL). The mixture was stirred at 100°C for 5 hours. The solution was cooled to room temperature, diluted with EtOA, and washed with H2O (twice) and saturated brine. The organic phase was dried over Na2SO4, filtered, and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~10% MeOH / DCM) to obtain Example 54 (40 mg). LC-MS (ESI): m / z (M+1): 1207.0, Rt= 1.78 min. (Method 3). 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.63 (d, J=9.5 Hz, 2 H), 7.55 (d, J=7.9 Hz, 2 H), 7.45 (d, J=8.4 Hz, 2 H), 7.37 - 7.43 (m, 4 H), 7.23 - 7.32 (m, 2 H), 6.80 - 6.93 (m, 6 H), 6.52 (d, J=9.5 Hz, 2 H), 6.34 (s, 4 H), 4.09 (t, J=6.2 Hz, 4 H), 3.20 (br s, 8 H), 2.65 - 2.91 (m, 8 H), 2.51 - 2.59 (m, 4H), 2.34 - 2.40 (m, 4 H), 2.20 - 2.29 (m, 4 H), 2.16 - 2.64 (m, 8 H), 1.85 - 1.96 (m, 4 H), 1.73 - 1.82 (m, 4 H), 1.55 - 1.71 (m, 4 H), 1.40 - 1.50 (m, 4 H), 1.27 - 1.35 (m, 4 H).

[0198] Example 55: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-{4-[({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}oxy)carbonyl]piperazine-1-carbonyloxy}hexanoate [ka] DIPEA (0.02 mL) was added to a solution of Int70 (20 mg) in DCM (1 mL) at 0°C, followed by piperazine (0.9 mg). The reaction mixture was stirred at room temperature for 6 hours. The reaction mixture was diluted with DCM and washed twice with Na2CO3. The organic phase was filtered through a phase separator and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~10% MeOH / DCM) to obtain Example 55 (7 mg). LC-MS (ESI): m / z (M+1): 1293.7, Rt= 2.23 min. (Method 3). 1H NMR (600 MHz, CHLOROFORM-d) δ ppm 7.61 (d, J=9.6 Hz, 2 H), 7.54 (d, J=8.1 Hz, 2 H), 7.44 (d, J=8.6 Hz, 2 H), 7.39 - 7.41 (m, 2 H), 7.36 - 7.38 (m, 2 H), 7.25 - 7.28 (m, 2 H), 6.88 (d, J=7.6 Hz, 2 H), 6.86 (d, J=2.0 Hz, 2 H), 6.83 (dd, J=8.6, 2.1 Hz, 2 H), 6.50 (d, J=9.6 Hz, 2 H), 6.31 (br s, 4 H), 4.07 (t, J=6.3 Hz, 4 H), 4.03 (t, J=6.7 Hz, 4 H), 3.40 (br s, 8 H), 3.18 (br s, 8 H), 2.71 (br s, 8 H), 2.53 (br t, J=7.3 Hz, 4 H), 2.36 (t, J=7.5 Hz, 4 H), 1.85 - 1.94 (m, 4 H), 1.72 - 1.79 (m, 4 H), 1.66 (quin, J=7.7 Hz, 4 H), 1.58 - 1.64 (m, 4 H), 1.32 - 1.40 (m, 4 H).

[0199] Example 56 was prepared according to the procedure described for Example 54. The reactants used in the synthesis of Example 56 and their characteristics are listed in Table 10. [Table 10]

[0200] Example 57: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazine-2-yl]oxy}hexanoate tetrakis(trifluoroacetic acid) salt DIPEA (0.11 mL) was added dropwise at 0°C to a solution of 2,4,6-trichloro-1,3,5-triazine (16 mg) and Int68 (150 mg) in MeCN (1 mL). The reaction mixture was stirred at room temperature for 5 days. The reaction mixture was diluted with DCM (10 mL) and washed with H2O (3 mL). The organic phase was dried using a phase separator and concentrated under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0%~7% MeOH / DCM), followed by C-18 cartridge chromatography (eluent = 0.1% TFA / H2O with 5%~95% MeCN) to obtain Example 57 (7 mg). [ka] LC-MS (ESI): m / z (M+1): 1808.3, Rt= 2.32 min. (Method 3). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.61 - 7.65 (m, 6 H), 7.41 - 7.49 (m, 6 H), 7.28 - 7.35 (m, 6 H), 6.94 (d, J=7.5 Hz, 3 H), 6.90 (d, J=1.8 Hz, 3 H), 6.83 (dd, J=8.6, 2.1 Hz, 3 H), 6.54 (d, J=9.5 Hz, 3 H), 6.32 (br s, 6 H), 4.30 (br t, J=6.6 Hz, 6 H), 4.06 - 4.13 (m, 6 H), 3.83 (br d, J=11.4 Hz, 6 H), 3.55 (br d, J=12.5 Hz, 6 H), 3.40 (br t, J=12.3 Hz, 6 H), 3.24 - 3.33 (m, 6 H), 3.19 (br t, J=10.4 Hz, 6 H), 2.37 (br t, J=7.5 Hz, 6 H), 2.06 - 2.13 (m, 6 H), 1.95 (br dd, J=13.0, 6.2 Hz, 6 H), 1.70 - 1.77 (m, 6 H), 1.67 (dt, J=15.3, 7.7 Hz, 6 H), 1.36 - 1.50 (m, 6 H).

[0201] Example 58: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}pentanoate formate [ka] DIPEA (0.04 mL) and CuI (48 mg) were dissolved in degassed DMF (1.5 mL). Then, Int76 (357 mg) and 1,4-diazidobutane (35.0 mg) were added at room temperature, and the reaction mixture was stirred overnight at 40°C. The reaction mixture was cooled to room temperature and purified directly by C18 cartridge chromatography (eluent = 0.1% HCOOH / H2O with 3%~40% MeCN) to obtain Example 58 (24 mg). LC-MS (ESI): m / z (M / 2+H): 642.6, Rt= 1.93 min. (Method 4). 1 H NMR (500 MHz, DMSO-d6) δ ppm 7.88 (d, J=9.6 Hz, 2 H), 7.71 (s, 2 H), 7.67 (d, J=5.5 Hz, 2 H), 7.65 (d, J=8.6 Hz, 2 H), 7.59 (d, J=8.0 Hz, 2 H), 7.37 (d, J=5.4 Hz, 2 H), 7.25 (t, J=7.9 Hz, 2 H), 6.96 (d, J=1.8 Hz, 2 H), 6.94 (dd, J=8.6, 2.1 Hz, 2 H), 6.85 (d, J=7.5 Hz, 2 H), 6.42 (d, J=9.5 Hz, 2 H), 6.26 (br s, 4 H), 4.26 (br s, 4 H), 4.11 (t, J=6.4 Hz, 4 H), 3.03 (br s, 8 H), 2.59 (br s, 8 H), 2.55 (br t, J=6.9 Hz, 4 H), 2.42 (br t, J=7.1 Hz, 4 H), 2.33 - 2.37 (m, 4 H), 1.74 - 1.83 (m, 4 H), 1.69 (br s, 4 H), 1.62 (dt, J=14.5, 7.2 Hz, 4 H), 1.51 - 1.58 (m, 8 H).

[0202] Examples 59, 60, 61, 62, 63, and 64 were prepared according to the procedure described for Example 58. The reactants used in the synthesis of each compound and their characteristics are listed in Table 11. [Table 11] TIFF2026047308000167.tif251165 TIFF2026047308000168.tif252170 TIFF2026047308000169.tif250164 TIFF2026047308000170.tif249164 TIFF2026047308000171.tif248164 TIFF2026047308000172.tif60170

[0203] Preparation of various crystal forms The equipment used in this specification is listed below. XRPD: Empyrean, Malvern Panalytical DSC: DSC Q2000 V24.11 Build 124, TA Instruments TGA: TGA Q5000 V3.17 Build 265, TA Instruments (1) A reference crystal form A of the compound of Example 10 was prepared according to the following procedure. The compound from Example 10 (48.0 mg, 0.040 mmol) was suspended in 2-propanol (2 mL). The suspension was heated to 50°C, and DCM was added at the same temperature. The suspension changed from a pale pink waxy substance to a white solid. The solvent was concentrated under vacuum. A portion of the white solid was recovered. The solid was suspended in 2 mL of 2-propanol. The suspension was heated to 50°C, and 0.9 mL of DCM was added at the same temperature. The suspension changed from a pale pink waxy substance to a white solid, and then to a clear solution. An opaque solution was observed at the end of the DCM addition, so heating was stopped, and the suspension was allowed to cool to room temperature over the weekend (in a heated mantle without stirring). The compound from Example 10 (48.0 mg, 0.040 mmol) was recovered by filtration and washed with cold IPA. The characteristic XRPD peaks of crystalline form A of the compound in Example 10 are shown below. [Table 12] The XRPD pattern for crystal form A is shown in Figure 1. Crystal form A is characterized by at least 1, 2, 3, 4, 5, or 6 XRPD peaks (°2θ) selected from approximately 5.4±0.2, 9.7±0.2, 11.8±0.2, 12.1±0.2, 12.6±0.2, 13.7±0.2, 14.3±0.2, 15.0±0.2, 16.2±0.2, 16.7±0.2, 20.5±0.2, 21.2±0.2, 21.7±0.2, 23.7±0.2, and 27.6±0.2. As shown in Figure 2, the DSC exhibited an endothermic reaction at 176°C due to the melting of crystal form A. Crystal form A has a DSC thermogram characterized by an endothermic peak at approximately 176±3°C.

[0204] (2) The compound from Example 10 (50 mg) was suspended in DMSO (20 times volume). The suspension was heated to 75°C (temperature of the heating plate), and dissolved at approximately 70-71°C. The solution was cooled to 50°C, then seed crystals of crystalline form B (approximately 4-5 mg) were added, and the suspension was allowed to mature for approximately 10 minutes. Heating was stopped, the suspension was cooled to room temperature, and it was allowed to mature overnight under stirring. The next day, the solid was isolated by filtration, deliquidated under vacuum, and then dried overnight in a vacuum oven under reduced pressure at 50°C. Product: 44.1 mg (88% w / w uncorrected recovery) The characteristic XRPD peaks of crystal form B are shown below. [Table 13] The XRPD pattern for crystal form B is shown in Figure 3. Crystal form B is characterized by at least 1, 2, 3, 4, 5, or 6 XRPD peaks (°2θ) selected from approximately 7.5±0.2, 8.8±0.2, 10.1±0.2, 11.1±0.2, 11.5±0.2, 11.9±0.2, 12.5±0.2, 15.5±0.2, 15.7±0.2, 16.4±0.2, 17.4±0.2, 18.4±0.2, 19.9±0.2, 21.0±0.2, and 22.0±0.2. As shown in Figure 4, the DSC exhibited a small change immediately after the start of desolvation, followed by a characteristic endothermic peak at the onset temperature of 159°C (enthalpy 83 J / g). Crystal form B has a DSC thermogram characterized by an endothermic peak at approximately 159±3°C.

[0205] (3) Crystalline form 1 of the compound in Example 19 was prepared according to the following procedure. The compound from Example 19 (55.4 g, 42.96 mmol) was suspended in ethanol (664.8 mL), stirred at 47°C (ambient temperature) for 2 days, then the suspension was cooled to room temperature and stirred for another 2 days at the same temperature. The product was recovered by filtration and dried at room temperature for 2 days. Product: 45.3 g, 35.13 mmol (81.7% yield), white solid. The characteristic XRPD peaks of crystal form 1 are shown below. [Table 14] The XRPD pattern for crystal form 1 is shown in Figure 5. Crystal form 1 is characterized by at least 1, 2, 3, 4, 5, or 6 XRPD peaks (°2θ) selected from approximately 7.6±0.2, 8.3±0.2, 12.4±0.2, 12.7±0.2, 13.9±0.2, 15.4±0.2, 15.8±0.2, 19.6±0.2, 20.3±0.2, and 22.9±0.2. The TGA profile shows a weight loss of 2.7% w / w from room temperature to 150°C, and the weight loss data is consistent with the theoretical amount required for the dihydrate (i.e., 2.7% w / w), as shown in Figure 6. As shown in Figure 7, the DSC exhibited an endothermic reaction at 81°C as the crystal melted. Crystal form 1 has a DSC thermogram characterized by an endothermic peak at approximately 81±3°C.

[0206] Test Example 1: Human Skin S9 Stability Human donor (male and female) skin S9 was stored at -80°C until use. On the day of the experiment, skin S9 was rapidly thawed in a 37°C water bath and diluted with 50 mM potassium phosphate buffer pH 7.4 to a protein concentration of 3.165 mg / mL. The test compound was dissolved in DMSO to obtain a 10 mM stock solution. 5 μL of the 10 mM stock solution in DMSO was diluted with 995 μL of methanol to obtain a 50 μM additive solution. The positive control (clopidogrel) was dissolved in DMSO to obtain a 10 mM stock solution. The 50 μM additive solution was prepared by diluting 5 μL of the 10 mM stock solution in DMSO with 995 μL of methanol. The general procedure consisted of incubating a 0.5 μM (final concentration) test compound with 2.5 mg / ml pooled skin S9 (final concentration) + NADPH regeneration system and UDPGA solution. The negative control was performed using pooled skin S9 without all cofactors. 5 μL of the test compound or positive control solution was added to 395 μL of 3.165 mg / ml skin S9 solution in a 96-well plate (incubation plate), and the reaction was incubated at 37°C for 5 minutes. The incubation reaction was initiated by adding 50 μL of preheated NADPH regeneration system and 50 μL of UDPGA or 100 μL of buffer (for negative control) to the incubation mixture. Two samples were tested with the test compound, regardless of the presence of cofactors, and one sample was tested with the positive control, regardless of the presence of cofactors. Incubation was performed in a 37°C shaking water bath for 1 hour. At each time point (0, 5, 15, 30, 45, 60 minutes), 25 μL of spiked skin S9 suspension was collected and added to 25 μL of milliQ water and 150 μL of reaction stop solution (1% formic acid-containing acetonitrile and brexpiprazole-D8 0.2 μM) to precipitate the protein. The samples were thoroughly mixed and centrifuged at 3000 rpm at 4°C for 10 minutes. The supernatant was collected (100 μL), diluted with 18% acetonitrile / Milli-Q water (200 μL), and injected into an LC MS / MS system. The peak area ratio of the test compound to the internal standard was monitored as a representative value of the compound concentration. At each time point, the residual percentage of the test compound was calculated relative to the sample at time zero (100%).The half-life was calculated using the relationship T1 / 2 = -0.693 / k (where k is the slope of the logarithmic concentration-time curve). Furthermore, the active parent compound (brexpiprazole) in each sample was quantified based on the MS response of brexpiprazole-D8 in the same sample. Table 15 shows the stability results of the example compounds in human skin S9. When multiple values ​​were measured, the average half-life was calculated.

[0207] [Table 15]

[0208] Test Example 2: Human Hepatocyte Stability Liver cells cryopreserved from human donors were stored in the gas phase of a liquid nitrogen freezer until use. After thawing, cell viability was checked using a trypan blue dye exclusion test before use. Incubation of test compounds and positive controls (testosterone and 7-hydroxycoumarin) was performed in William medium E supplemented with 200 mM glutamine and 1 M HEPES, at a cell concentration of 0.5 × 10⁶. 6 The procedure was performed using cells / mL. 0.495 mL of cell suspension was dispensed into 48-well plates and pre-incubated at 37°C for at least 10 minutes. The test compound and positive control were dissolved in DMSO to obtain 10 mM, 50 mM, and 5 mM stock solutions for the test compound, testosterone, and 7-hydroxycoumarin, respectively. The stock solutions were further diluted with methanol to obtain 50 μM, 1 mM, and 500 μM final additive solutions for the test compound, testosterone, and 7-hydroxycoumarin, respectively. All solutions were prepared immediately before the assay. 5 μL of 50 μM test compound, 1000 μM testosterone, and 500 μM 7-hydroxycoumarin were added in 0.5 × 10⁶ solutions. 6In addition to 0.495 mL of cell suspension, the final concentrations of the test compounds were set to 0.5 μM, testosterone to 10 μM, and 7-hydroxycoumarin to 5 μM. Incubation was performed at 37°C with gentle shaking at 350 rpm for two samples of the test compounds and one sample of the positive control. At each time point (0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180 minutes), 30 μL of the incubation mixture from each well was added to 30 μL of milliQ water and 180 μL of reaction stop solution (1% formic acid-containing acetonitrile and 0.2 μM brexpiprazole-D8) to precipitate the proteins. The samples were thoroughly mixed and centrifuged at 3000 rpm at 4°C for 10 minutes. The supernatant was collected (100 μL), diluted with 18% acetonitrile / Milli-Q water (200 μL), and then injected into an LC MS / MS system. The peak area ratio of the test compound to the internal standard was monitored as a representative value of the compound concentration. Metabolic stability was calculated from the time ratio of the peak area of ​​the remaining test compound or positive control substance relative to the internal standard. The primary elimination constant k(min) was calculated. -1 The CLi value was determined by plotting the ratio of the peak area to the internal standard substance of the remaining test compound against time from a log-linear plot using XLFit or Morphit Software. The half-life was calculated from the relationship T1 / 2 = -0.693 / k. The CLi value was obtained using the actual volume of culture (mL) and the number of hepatocytes in culture (10 6 Using the number of cells per gram of liver of various animals, and the scaling coefficient for the number of cells per gram, the first-order disappearance constant k(min -1 ) was calculated from. Furthermore, the active parent compound (brexpiprazole) in each sample was quantified based on the MS response of brexpiprazole-D8 in the same sample. Table 16 shows the stability results of example compounds in human plasma and human hepatocytes. When multiple values ​​were measured, the average half-life was calculated.

[0209] [Table 16] "Yes" means that the parent compound was detected at least one time point. The amount of parent compound produced varied depending on the compound.

[0210] Test Example 3: Short-term rat PK test The study protocol was designed to evaluate the pharmacokinetic (PK) profiles of the test compound after intravenous (IV) and subcutaneous (SC) administration to rats. Male Sprague Dawley rats purchased from Charles River Laboratories were placed in cages in groups of 3-4 in humidity and temperature-controlled ventilated racks (relative humidity 45-65%, temperature 20-22°C, lighting time approximately 6:00-18:00) and acclimated for a minimum of 5 days. During the experiment, the animals had free access to standard rodent feed (Altromin 1324) and water. Animals were randomly assigned to receive either IV or SC (n=3 in each group) administration of the test compound. For IV administration, the test compound was dissolved in 5% N-methylpyrrolidone and 10% Solutol HS15 in 50 mM acetate buffer (pH 5.5) and administered at a dose of 1 mg / kg. Blood samples were collected at nine time points up to 24 hours after administration: 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours post-administration. For SC administration, the test compound was suspended in 1% hydroxymethylpropylcellulose and 0.2% Tween 80 in water and administered at a dose of 45 mg / kg, except for Example 24, which was administered at a dose of 45 mg / kg. Blood samples were collected at up to 20 time points during the period up to 120 hours after administration: 3, 6, 10, 24, 27, 30, 34, 48, 51, 54, 58, 72, 75, 78, 82, 96, 99, 102, 106, and 120 hours post-administration. In both groups, blood was collected from the lateral tail vein and dispensed into K3EDTA tubes. After collection, the samples were gently mixed, and a portion was immediately transferred to a microtube for online protein precipitation using acetonitrile containing 1% formic acid and rolipram as an internal standard. The samples were then stored at -80°C until analysis. After SC administration, skin samples were also collected from the injection site at the final time point, approximately 2 cm from the injection site. 2Hairless skin samples were cut out, collected in vials, and frozen at -80°C until analysis. On the day of analysis, the skin was thawed, weighed, and diluted for homogenization. Calibration standard solutions (CS) and quality control samples (QC) were prepared on the day of administration by adding standard solutions (test compound and brexpiprazole prepared separately) to a blank matrix (blood and skin homogenate) and stored under the same conditions as the test samples. The test samples were analyzed together with the CS, QC, and blank samples using an LC-MS / MS system. The test compound and brexpiprazole were quantified in each sample. The results for the test compound and brexpiprazole in the blood were calculated by calculating the area under the blood concentration curve (AUC) using non-compartmental analysis with Phoenix WinNonlin 6.3. The blood conversion rate to brexpiprazole after IV administration was calculated as the ratio of the AUC of brexpiprazole at the time of test compound administration to the value at the time of brexpiprazole administration. Brexpiprazole in the skin after SC administration was calculated as the ratio of the brexpiprazole concentration to the test compound concentration in the skin tissue.

[0211] The results of Test Example 3 are shown in the table below. [Table 17] The IV dose of the test compound was 1 mg / kg. The dose of the test compound administered via SC (sponge cell) in all cases except Example 24 was 30 mg / kg. Example 24 was administered via SC at a dose of 45 mg / kg.

[0212] Example 4: Long-term rat PK study Example 10 Preparation of a 16.3% aqueous suspension A medium containing 1% sodium carboxymethylcellulose, 3.4% D(-)-mannitol, and 0.14% sodium dihydrogen phosphate monohydrate was prepared, with the pH adjusted to 6 using sodium hydroxide. This medium was filtered and sterilized through a 0.22 μm polyethersulfone (PES) membrane. 3348 mg of the medium and 652 mg of Example 10 were added to two glass vials and suspended. Zirconia beads (1.5 mm in diameter) and a stirring bar were then added, and the suspension was pulverized by stirring with a magnetic stirrer for several minutes or 3 hours. The average particle size of Example 10 after pulverization was measured using a laser diffraction particle size distribution analyzer SALD-3100 (Shimadzu Corporation) under ultrasonic irradiation and refractive index conditions of 2.00~0.20i, and was found to be 3.4 μm and 1.9 μm. The suspension was separated from the zirconia beads using a pipette, placed in separate vials, sterilized by irradiation with 25 kGy of gamma rays, and used as the test formulation.

[0213] Example 19 Preparation of a 17.8% aqueous suspension A medium containing 2% D-α-tocopherol polyethylene glycol succinate, 3.4% D(-)-mannitol, and 0.14% sodium dihydrogen phosphate monohydrate was prepared, with the pH adjusted to 6 using sodium hydroxide. This medium was filtered and sterilized through a 0.22 μm polyvinylidene fluoride (PVDF) membrane. 4150 mg of the medium and 890 mg of Example 19 were added to two glass vials and suspended. Zirconia beads (1 mm in diameter) and a stirring bar were then added, and the suspension was stirred with a magnetic stirrer at 5°C for 17 or 65 hours to pulverize it. After pulverization, the suspension was separated from the zirconia beads using a pipette, transferred to separate vials, and sterilized by irradiation with 25 kGy of gamma rays to prepare the test formulations. The average particle size of Example 19 in the test formulation was measured using SALD-3100 under ultrasonic irradiation and refractive index conditions of 1.70 to 0.20i, and was found to be 1.5 μm and 0.8 μm.

[0214] method The test formulation was administered subcutaneously to male rats, and the plasma concentrations of the prodrug compound and brexpiprazole were measured. Rats were purchased from Nippon SLC Co., Ltd. at 7 weeks of age and used in experiments after acclimatization. The rearing environment was as follows: Feeding and watering: unlimited, Number of rats per cage: 3, Temperature: 21-25°C, Humidity: 50-70%, Lighting time: 7:00-19:00. Under isoflurane anesthesia, the formulations of Example 10 and 19 were administered subcutaneously to rats using a plastic syringe at doses of 34 mg / kg and 37 mg / kg (equivalent to 25 mg / kg of brexpiprazole), respectively. Approximately 0.5 mL of blood was collected from the jugular vein of the rats using a heparinized syringe 2 hours after administration, and 1, 3, 6, 9, 14, 21, and 28 days after administration. To prevent hydrolysis of the prodrug compound, the blood samples were mixed with 2-tenoyltrifluoroacetone to a final concentration of 10 mM and rapidly cooled. Plasma was centrifuged, and the concentrations of the prodrug compound and brexpiprazole were measured by LC-MS / MS. Based on the obtained brexpiprazole plasma concentration-time profiles, the cumulative absorption rate at each blood sampling site was calculated using the deconvolution method.

[0215] Results and Discussion When the suspensions of Example 10 or 19 were administered subcutaneously to rats, brexpiprazole was continuously detected in the blood for 28 days after administration. These results suggest that these compounds possess suitable properties as active pharmaceutical ingredients for a long-acting brexpiprazole injection. The PK profiles of Example 10 and 19 are shown in Figures 8 and 9, respectively.

[0216] Test Example 5: Irritation Test in Dogs The aqueous suspensions of Examples 10 and 19, prepared in Test Example 4, were used as test formulations. Each test formulation was administered subcutaneously to male and female beagle dogs, and after observation for 7 or 28 days, dissection was performed and histopathological examination of the injection site was conducted. Beagle dogs were purchased from Kitayama Labes Co., Ltd. at 6-8 months of age and used in the experiment after acclimatization. The breeding environment was as follows: Feeding: 300 g of solid feed once a day, Water intake: Unlimited, Number of dogs per cage: 1, Temperature: 20-26°C, Humidity: 30-70%, Lighting time: 7:00-19:00. Dogs anesthetized with xylazine hydrochloride 1 mg / kg and ketamine hydrochloride 15 mg / kg were subcutaneously administered each test formulation at a dose of 10 mg / kg per formulation to different sites on the lumbar region using a plastic syringe. After administration, the dogs were observed for 7 or 28 days, then euthanized by bleeding under anesthesia with 0.08 mg / kg medetomidine hydrochloride, 0.5 mg / kg butorphanol tartrate, and 20 mg / kg thiopental sodium, and injection site tissue was collected. The collected tissues were fixed in 10% neutral buffered formalin, and specimens stained with hematoxylin and eosin were prepared for histopathological examination.

[0217] Results and Discussion During the observation period, edema and induration were observed at the injection sites of each test formulation. Histopathological examination revealed that the main findings at the injection sites were granulomatous inflammation characterized by infiltration of macrophages and foreign body giant cells. This histological change was considered to be a physiological response to the foreign body and not an indication of irritation. Based on these results, it was concluded that Examples 10 and 19 were not irritating. [Industrial applicability]

[0218] Compounds of formula (I) and formula (II) or pharmaceutically acceptable salts thereof may have antipsychotic activity and may be useful as pharmaceuticals for the treatment and / or prevention of, for example, subjects having related antipsychotic diseases and conditions.

Claims

1. Equation (I): 【Chemistry 1】 [In the formula, a is either 2 or 3; R 1 C may be a linear or branched chain that is substituted as appropriate. 1-20 Alkylene; may be substituted as appropriate. 2-10 Alkenylene; divalent carbon may be substituted as appropriate. 3-8 Cycloalkyl group; optionally substituted divalent heterocyclic group; optionally substituted divalent C 6-10 Aryl; -NH(linear or branched chain C, which may be substituted as appropriate) 1-20 Alkylene); or divalent C, which may be substituted as appropriate. 3-8 It is a cycloalkenyl; R 2 is -C(O)-, -O-C(O)-, -C(O)-NR a -CH 2 -, -O-, -CH 2 -, -NR a -C(O)-, or a direct bond; R 3 This may be a non-aromatic divalent or trivalent heterocyclic group, an aromatic divalent or trivalent heterocyclic group, or a linear or branched chain C, which may be substituted as appropriate. 1-20 It is alkylene; R a C is a straight or branched chain that may be substituted with hydrogen as appropriate. 1-20 It is alkyl; If a is 2, then R 3 It is divalent; If a is 3, R 3 It is trivalent; R 2 and R 3 They are joined by a covalent bond; However, R 1 It is a linear alkylene, and R 2 ga-CH 2 -or if it is a direct bond, R 3 [It is not a linear alkylene] A pharmaceutical product containing the compound indicated by or a pharmaceutically acceptable salt thereof.

2. a is 2 or 3; R 1 Linear or branched chain C may be appropriately substituted. 2-16 The alkylene, where one or more methylene groups may be replaced with functional groups selected from -O- or -NH-, or one or more methylene groups may be replaced with spirocyclopentane or divalent piperidine, or one or more methylene groups may be replaced with a divalent 1,3,5-triazole ring group; ethylene; optionally substituted divalent cyclohexyl; optionally substituted divalent azetidine; or optionally substituted divalent piperidine; R 2 is -C(O)-, -OC(O)-, -C(O)-N(CH 3 )-CH 2 -, -C(O)-NH-CH 2 -, -O-, -NH-C(O)-, -CH 2 -, or direct connection; R 3 Divalent or trivalent piperazines, divalent or trivalent 2,5-diazabicyclo[2.2.2]octane, divalent or trivalent 2,5-diazabicyclo[2.2.1]heptane, divalent or trivalent octahydropyrrolo[3,4-c]pyrrole, divalent or trivalent pyrazine, divalent or trivalent 3,9-diazaspiro[5,5]undecane, divalent or trivalent 1,4,7-triazonane, divalent or trivalent 2,6-diazaspiro[3.3]heptane, divalent or trivalent 1,3,5-triazine, divalent or trivalent 1,3-thiazole, or linear or branched chain C 2-6 It is alkylene; If a is 2, then R 3 It is divalent; If a is 3, R 3 The pharmaceutical product according to claim 1, wherein the compound is trivalent.

3. a is 2; R 1 Linear or branched chain C may be appropriately substituted. 2-16 It is an alkylene, where one or more methylene groups can be replaced by oxygen or amino groups, or one or more methylene groups can be replaced by spirocyclopentane or divalent piperidine, or one or more methylene groups can be replaced by a divalent 1,3,5-triazole ring group; ethylene; optionally substituted divalent cyclohexyl; optionally substituted divalent azetidine; or optionally substituted divalent piperidine; R 2 is -C(O)-, -OC(O)-, -C(O)-N(CH 3 )-CH 2 -, -C(O)-NH-CH 2 -, -CH 2 -, -NH-C(O)-, or direct bond; R 3 Divalent piperazines, divalent 2,5-diazabicyclo[2.2.2]octane, divalent 2,5-diazabicyclo[2.2.1]heptane, divalent octahydropyrrolo[3,4-c]pyrrole, divalent pyrazines, divalent 3,9-diazaspiro[5,5]undecane, divalent 2,6-diazaspiro[3.3]heptane, divalent 1,3-thiazole, or linear or branched C33s, which may be substituted as appropriate. 2-6 The pharmaceutical product according to claim 1, which is alkylene.

4. a is 3; R 1 Linear or branched chain C may be appropriately substituted. 2-6 It is an alkylene, where one or more methylene groups can be replaced by divalent piperidine; R 2 is -C(O)-, -O-, or a direct bond; R 3 The pharmaceutical product according to claim 1, wherein the compound is a trivalent 1,4,7-triazonane or a trivalent 1,3,5-triazine, which may be appropriately substituted.

5. a is 2; R 1 が-CH=CH-、-(CH 2 ) 2 -、-(CH 2 ) 4 -、-(CH 2 ) 5 -、-(CH 2 ) 6 -、-(CH 2 ) 7 -、-(CH 2 ) 8 -、-(CH 2 ) 9 -、-(CH 2 ) 12 -、-(CH 2 ) 16 - -NH-(CH 2 ) 7 - 【Chemistry 2】 And; R 2 is -C(O)-, -OC(O)-, -C(O)-N(CH 3 )-CH 2 -, -C(O)-NH-CH 2 -, -CH 2 -, -NH-C(O)-, or direct bond; R 3 ga-(CH 2 ) 4 -, 【Transformation 3】 The pharmaceutical product according to claim 1.

6. a is 3; R 1 ga-(CH 2 ) 2 -,-(CH 2 ) 5 -, or 【Chemistry 4】 And; R 2 is -C(O)-, -O-, or a direct bond; R 3 but 【Transformation 5】 The pharmaceutical product according to claim 1.

7. The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}piperazine-1-yl)-6-oxohexanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-[(2R,5S)-4-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-dimethylpiperazine-1-yl]-8-oxooctanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(5-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.1]heptan-2-yl]-8-oxooctanoate; Tris(trifluoroacetic acid); (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(6-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(9-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanaamide}methyl)pyrazine-2-yl]methyl}carbamoyl)heptanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-N-methyl-8-oxooctanaamide}methyl)pyrazine-2-yl]methyl}(methyl)carbamoyl)heptanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazine-1-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[(2S,5R)-4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-2,5-dimethylpiperazine-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-[(3ar,6ar)-5-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[4,7-bis({4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl})-1,4,7-triazonan-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-(4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}piperazine-1-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-[(2R,5S)-4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}-2,5-dimethylpiperazine-1-yl]-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-(5-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-9-({[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-N-methyl-10-oxodecanamide}methyl)pyrazine-2-yl]methyl}(methyl)carbamoyl)nonanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}piperazine-1-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-[(2S,5R)-4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-2,5-dimethylpiperazine-1-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(6-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-[(3ar,6ar)-5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-N-methyl-6-oxohexanamide}methyl)pyrazine-2-yl]methyl}(methyl)carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanamide}methyl)pyrazine-2-yl]methyl}carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(2E)-4-{4-[(2E)-4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobuta-2-enoyl]piperazine-1-yl}-4-oxobuta-2-enoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-14-(4-{14-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-14-oxotetradecanoyl}piperazine-1-yl)-14-oxotetradecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-14-[(2S,5R)-4-{14-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-14-oxotetradecanoyl}-2,5-dimethylpiperazine-1-yl]-14-oxotetradecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-18-(4-{18-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-18-oxooctadecanoyl}piperazine-1-yl)-18-oxooctadecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-18-[(2S,5R)-4-{18-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-18-octadecanoyl}-2,5-dimethylpiperazine-1-yl]-18-oxooctadecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-{4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-[(2S,5R)-2,5-dimethyl-4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1s,4s)-4-{4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1s,4s)-4-[(2S,5R)-2,5-dimethyl-4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 1-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)piperazine-1-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[(3ar,6ar)-5-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)-octahydropyrrolo[3,4-c]pyrrole-2-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2,2-dimethyl-3-oxopropanoyl}piperazin-1-yl)-2,2-dimethyl-3-oxopropanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2,2-dimethyl-4-oxobutanoyl}piperazin-1-yl)-3,3-dimethyl-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3,3-dimethyl-4-oxobutanoyl}piperazin-1-yl)-2,2-dimethyl-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3,3-dimethyl-5-oxopentanoyl}piperazin-1-yl)-3,3-dimethyl-5-oxopentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-2-{2-[4-(2-{2-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2-oxoethoxy}acetyl)piperazine-1-yl]-2-oxoethoxy}acetate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-N-(8-{4-[8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)octanoyl]piperazine-1-yl}-8-oxooctyl)carbamate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-N-[(2S)-1-{4-[(2S)-2-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]piperazine-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-4-carbonyl)piperazine-1-carbonyl]piperidine-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4,6-bis(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)methyl]pyrazine-2-yl}methyl)piperidine-4-yl]propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazole-2-yl]formamide}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)pyrazine-2-yl]formamide}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-{[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecyl}carbamoyl)pyrazine-2-yl]formamide}decanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}piperazine-1-yl)hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-{4-[({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}oxy)carbonyl]piperazine-1-carbonyloxy}hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-[(4-{[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexyl]methyl}piperazine-1-yl)methyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazine-2-yl]oxy}hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-{1-[4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(5-{4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]piperazine-1-yl}-5-oxopentyl)-1H-1,2,3-triazole-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(1-{5-[(2S,5R)-4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]-2,5-dimethylpiperazine-1-yl]-5-oxopentyl}-1H-1,2,3-triazole-4-yl)butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(5-{5-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]-2,5-diazabicyclo[2.2.2]octan-2-yl}-5-oxopentyl)-1H-1,2,3-triazole-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(6-{4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)hexanoyl]piperazine-1-yl}-6-oxohexyl)-1H-1,2,3-triazole-4-yl]butanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(1-{6-[(2S,5R)-4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)hexanoyl]-2,5-dimethylpiperazine-1-yl]-6-oxohexyl}-1H-1,2,3-triazole-4-yl)butanoate A pharmaceutical product according to claim 1, selected from the group consisting of the following.

8. The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[4,7-bis({4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl})-1,4,7-triazonan-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4,6-bis(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazine-2-yl]oxy}hexanoate A pharmaceutical product according to claim 1, selected from the group consisting of the following.

9. a is 2; R 1 is -(CH 2 ) 2 -, -(CH 2 ) 4 -, -(CH 2 ) 5 -, -(CH 2 ) 6 -, -(CH 2 ) 7 -, -(CH 2 ) 8 -, -(CH 2 ) 9 -, -(CH 2 ) 12 -, or -(CH 2 ) 16 -; R 2 -C(O)-, -CH 2 -, or direct connection; R 3 but 【Transformation 6】 The pharmaceutical product according to claim 1.

10. The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}piperazine-1-yl)-6-oxohexanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-[(2R,5S)-4-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-dimethylpiperazine-1-yl]-8-oxooctanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(5-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.1]heptan-2-yl]-8-oxooctanoate; Tris(trifluoroacetic acid); (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}piperazine-1-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[(2S,5R)-4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-2,5-dimethylpiperazine-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-(4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}piperazine-1-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-[(2R,5S)-4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}-2,5-dimethylpiperazine-1-yl]-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-(5-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}piperazine-1-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-[(2S,5R)-4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-2,5-dimethylpiperazine-1-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-14-(4-{14-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-14-oxotetradecanoyl}piperazine-1-yl)-14-oxotetradecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-14-[(2S,5R)-4-{14-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-14-oxotetradecanoyl}-2,5-dimethylpiperazine-1-yl]-14-oxotetradecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-18-(4-{18-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-18-oxooctadecanoyl}piperazine-1-yl)-18-oxooctadecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-18-[(2S,5R)-4-{18-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-18-octadecanoyl}-2,5-dimethylpiperazine-1-yl]-18-oxooctadecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-N-(8-{4-[8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)octanoyl]piperazine-1-yl}-8-oxooctyl)carbamate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexyl}piperazine-1-yl)hexanoate A pharmaceutical product according to claim 9, selected from the group consisting of the following.

11. a is 2; R 1 but 【Transformation 7】 And; R 2 -C(O)-, -CH 2 -, or direct connection; R 3 ga-(CH 2 ) 4 -, 【Transformation 8】 The pharmaceutical product according to claim 1.

12. The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-{4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-[(2S,5R)-2,5-dimethyl-4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1s,4s)-4-{4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1s,4s)-4-[(2S,5R)-2,5-dimethyl-4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 1-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)piperazine-1-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[(3ar,6ar)-5-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)-octahydropyrrolo[3,4-c]pyrrole-2-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2,2-dimethyl-3-oxopropanoyl}piperazin-1-yl)-2,2-dimethyl-3-oxopropanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2,2-dimethyl-4-oxobutanoyl}piperazin-1-yl)-3,3-dimethyl-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3,3-dimethyl-4-oxobutanoyl}piperazin-1-yl)-2,2-dimethyl-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3,3-dimethyl-5-oxopentanoyl}piperazin-1-yl)-3,3-dimethyl-5-oxopentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-2-{2-[4-(2-{2-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-2-oxoethoxy}acetyl)piperazine-1-yl]-2-oxoethoxy}acetate; (7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-N-[(2S)-1-{4-[(2S)-2-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]piperazine-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-4-carbonyl)piperazine-1-carbonyl]piperidine-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)-1,3,5-triazine-2-yl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-yl)methyl]pyrazine-2-yl}methyl)piperidine-4-yl]propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-(1r,4r)-4-[(4-{[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]carbonyl}cyclohexyl]methyl}piperazine-1-yl)methyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-{1-[4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)butyl]-1H-1,2,3-triazole-4-yl}butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(5-{4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]piperazine-1-yl}-5-oxopentyl)-1H-1,2,3-triazole-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(1-{5-[(2S,5R)-4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]-2,5-dimethylpiperazine-1-yl]-5-oxopentyl}-1H-1,2,3-triazole-4-yl)butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(5-{5-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)pentanoyl]-2,5-diazabicyclo[2.2.2]octan-2-yl}-5-oxopentyl)-1H-1,2,3-triazole-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-[1-(6-{4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)hexanoyl]piperazine-1-yl}-6-oxohexyl)-1H-1,2,3-triazole-4-yl]butanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(1-{6-[(2S,5R)-4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazole-1-yl)hexanoyl]-2,5-dimethylpiperazine-1-yl]-6-oxohexyl}-1H-1,2,3-triazole-4-yl)butanoate A pharmaceutical product according to claim 11, selected from the group consisting of the following.

13. a is 2; R 1 ga-(CH 2 ) 2 -,-(CH 2 ) 4 -,-(CH 2 ) 6 -, or -(CH 2 ) 9 -and; R 2 -C(O)-, -C(O)-N(CH 3 )-CH 2 -, -C(O)-NH-CH 2 -, or -NH-C(O)-; R 3 but 【Chemistry 9】 The pharmaceutical product according to claim 1.

14. The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(6-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-8-(9-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-8-oxooctanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecane-3-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl 4-[(3ar,6ar)-5-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-4-oxobutanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(6-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-[(3ar,6ar)-5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-6-(5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrole-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-N-methyl-6-oxohexanamide}methyl)pyrazine-2-yl]methyl}(methyl)carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-6-oxohexanamide}methyl)pyrazine-2-yl]methyl}carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazole-2-yl]formamide}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-5-oxopentyl}carbamoyl)pyrazine-2-yl]formamide}pentanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methyl-10-{[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazine-1-yl]butoxy}-2-oxo-1,2-dihydroquinoline-1-yl)methoxy]-10-oxodecyl}carbamoyl)pyrazine-2-yl]formamide}decanoate A pharmaceutical product according to claim 13, selected from the group consisting of the following.

15. The pharmaceutical product according to claim 1, wherein the compound has an average particle size in the range of 0.05 to 10 μm as measured by laser diffraction.

16. A pharmaceutical composition comprising a pharmaceutically and pharmaceutically acceptable carrier as described in any one of claims 1 to 15.

17. A pharmaceutical product according to any one of claims 1 to 15, for treating and / or preventing central nervous system disorders.

18. Central nervous system disorders including schizophrenia; treatment-resistant, intractable, or chronic schizophrenia; affective disorders; psychotic disorders; mood disorders; bipolar disorder type I; bipolar disorder type II; depression; endogenous depression; major depressive disorder (MDD); melancholic and treatment-resistant depression; dysthymia; cyclothymic disorder; panic attacks; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorders; conversion disorders; pain disorders; hypochondriasis; factitious disorders; dissociative disorders; sexual dysfunction; Sexual desire disorder; sexual arousal disorder; erectile dysfunction; A pharmacopoeia according to claim 17, selected from the group consisting of anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia; iatrogenic anhedonia; anhedonia due to psychogenic or mental causes; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment due to Alzheimer's disease; Parkinson's disease and related neurodegenerative diseases; cognitive impairment in schizophrenia; cognitive impairment due to treatment-resistant, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autism disorder; Tourette syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

19. Use of a pharmaceutical product according to any one of claims 1 to 15 in the manufacture of a pharmaceutical product for treating and / or preventing central nervous system disorders.

20. Central nervous system disorders including schizophrenia; treatment-resistant, intractable, or chronic schizophrenia; affective disorders; psychotic disorders; mood disorders; bipolar disorder type I; bipolar disorder type II; depression; endogenous depression; major depressive disorder (MDD); melancholic and treatment-resistant depression; dysthymia; cyclothymic disorder; panic attacks; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorders; conversion disorders; pain disorders; hypochondriasis; factitious disorders; dissociative disorders; sexual dysfunction; Sexual desire disorder; sexual arousal disorder; erectile dysfunction; Use according to claim 19, selected from the group consisting of anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia; iatrogenic anhedonia; anhedonia due to psychogenic or psychological causes; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment due to Alzheimer's disease; Parkinson's disease and related neurodegenerative diseases; cognitive impairment in schizophrenia; cognitive impairment due to treatment-resistant, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autism disorder; Tourette syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

21. A method for treating and / or preventing a central nervous system disorder, comprising administering a pharmaceutical product according to any one of claims 1 to 15 to a subject in need thereof.

22. Central nervous system disorders including schizophrenia; treatment-resistant, intractable, or chronic schizophrenia; affective disorders; psychotic disorders; mood disorders; bipolar disorder type I; bipolar disorder type II; depression; endogenous depression; major depressive disorder (MDD); melancholic and treatment-resistant depression; dysthymia; cyclothymic disorder; panic attacks; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorders; conversion disorders; pain disorders; hypochondriasis; factitious disorders; dissociative disorders; sexual dysfunction; Sexual desire disorder; sexual arousal disorder; erectile dysfunction; The method according to claim 21, selected from the group consisting of anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia; iatrogenic anhedonia; psychogenic or mental anhedonia; anhedonia associated with depression; anhedonia associated with schizophrenia; delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases; cognitive impairment due to Alzheimer's disease; Parkinson's disease and related neurodegenerative diseases; cognitive impairment in schizophrenia; cognitive impairment due to treatment-resistant, intractable or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autism disorder; Tourette syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

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