Piperazine-substituted benzothiophenes for the treatment of psychiatric disorders

Abstract

This application relates to novel compounds that are prodrugs of brexpiprazole. Upon administration to a subject, the novel compounds of the present invention undergo chemical conversion in vivo by one or more metabolic processes to release the pharmacologically active agent. Brexpiprazole, marketed as Rexulti®, is an atypical antipsychotic indicated as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults and pediatric patients 13 years of age and older.

Description

[Technical Field]

[0001] This application relates to novel compounds that are prodrugs of brexpiprazole. Upon administration to a subject, the novel compounds of the present invention undergo chemical conversion in vivo by one or more metabolic processes to release the pharmacologically active agent. Brexpiprazole, marketed as Rexulti®, is an atypical antipsychotic indicated as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults and pediatric patients 13 years of age and older. [Background technology]

[0002] Brexpiprazole (7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one) or its salts has a dopamine D2 receptor partial agonist effect and a serotonin 5-HT 2A Brexpiprazole or a salt thereof has serotonin receptor antagonist activity and adrenergic α1 receptor antagonist activity. In addition to these activities, brexpiprazole or a salt thereof also has serotonin uptake inhibitory activity or serotonin reuptake inhibitory activity, and is known to have the potential to treat a wide range of nervous system diseases (Patent Document 1 and Patent Document 2).

[0003] One approach to drug design in the pharmaceutical field is to chemically convert or modify one or more functional groups of a known drug molecule to improve its pharmacological or pharmacokinetic properties, for example, to enhance its efficacy or slow its metabolism in vivo. Such chemical conversions or modifications include the formation of conjugates between multiple active ingredient molecules and a carrier moiety (Patent Document 3). There is a need for novel compounds that can be converted to brexpiprazole in vivo, exhibit improved pharmacological or pharmacokinetic properties, have fewer side effects, and are more tolerable and safe. [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 Summary of the Invention [Problem to be solved by the invention]

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

[0006] The present invention describes compounds or pharmaceutically acceptable salts thereof that have antipsychotic activity. The compounds of the present invention or pharmaceutically acceptable salts thereof are therefore useful in medicine, for example in the treatment and / or prophylaxis of humans with related antipsychotic diseases and conditions.

[0007] In one embodiment, the present invention provides a compound of formula (I): [ka] [In the formula, a is 2 or 3; R 1 is an optionally substituted straight or branched chain C 1-20 Alkylene; optionally substituted C 2-10 Alkenylene; optionally substituted divalent C 3-8 Cycloalkyl; optionally substituted divalent heterocyclic group; optionally substituted divalent C 6-10 Aryl; -NH (optionally substituted straight or branched chain C 1-20 alkylene); or optionally substituted divalent C 3-8is cycloalkenyl; R 2 -C(O)-, -OC(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 linear or branched C 1-20 is alkylene; R a is hydrogen or an optionally substituted straight or branched chain C 1-20 is alkyl; If a is 2, R 3 is bivalent; If a is 3, R 3 is trivalent; R 2 and R 3 are covalently linked; However, R 1 is a linear alkylene, and R 2 is -CH2- or a direct bond, R 3 is not a straight chain alkylene] or a pharmaceutically acceptable salt thereof. [Effects 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 multiple brexpiprazole molecules are covalently bonded to each other via a chemical linker. When administered to a subject, the compound of formula (I) or a pharmaceutically acceptable salt thereof may be chemically converted to the pharmacologically active substance brexpiprazole under physiological conditions, such as one or more metabolic processes, and release brexpiprazole in vivo.

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

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

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

[0012] In another aspect, the present invention provides a compound of formula (II): [ka] [In the formula, b is 2 or 3; R 4 is an optionally substituted straight or branched chain C 1-20 Alkylene; optionally substituted C 2-10 Alkenylene; optionally substituted divalent C 3-8 Cycloalkyl; optionally substituted divalent heterocyclic group; optionally substituted divalent C 6-10 Aryl; -NH (optionally substituted straight or branched chain C 1-20 alkylene); or optionally substituted divalent C 3-8 is cycloalkenyl; R 5-C(O)-, -OC(O)-, -C(O)-NR b -CH2-, -O-, -CH2-, -NR b -C(O)- or a direct bond; R 6 is an optionally substituted non-aromatic divalent or trivalent heterocyclic group, an optionally substituted aromatic divalent or trivalent heterocyclic group, or an optionally substituted linear or branched C 1-20 is alkylene; R b is hydrogen or an optionally substituted straight or branched chain C 1-20 is alkyl; If b is 2, R 6 is bivalent; If b is 3, R 6 is trivalent; R 5 and R 6 are covalently linked] or a pharmaceutically acceptable salt thereof.

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

[0014] In one aspect, the present invention provides a method for producing a pharmaceutical composition comprising: a is 2 or 3; R 1 optionally substituted straight or branched chain C 2-16alkylene, wherein one or more methylene groups can be replaced with a functional group selected from -O- or -NH-, or one or more methylene groups can be replaced with a spirocyclopentane or a divalent piperidine, or one or more methylene groups can 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 optionally substituted divalent or trivalent piperazine, optionally substituted divalent or trivalent 2,5-diazabicyclo[2.2.2]octane, optionally substituted divalent or trivalent 2,5-diazabicyclo[2.2.1]heptane, optionally substituted divalent or trivalent octahydropyrrolo[3,4-c]pyrrole, optionally substituted divalent or trivalent pyrazine, optionally substituted divalent or trivalent 3,9-diazaspiro[5.5]undecane, optionally substituted divalent or trivalent 1,4,7-triazonane, optionally substituted divalent or trivalent 2,6-diazaspiro[3.3]heptane, optionally substituted divalent or trivalent 1,3,5-triazine, optionally substituted divalent or trivalent 1,3-thiazole, or optionally substituted linear or branched C 2-6 is alkylene; If a is 2, R 3 is bivalent; If a is 3, R 3 is trivalent; R 2 and R 3 is covalently linked to

[0015] In one aspect, the present invention provides a method for producing a pharmaceutical composition comprising: a is 2; R1 optionally substituted straight or branched chain C 2-16 alkylene, in which one or more methylene groups can be replaced by oxygen or an amino group, or one or more methylene groups can be replaced by spirocyclopentane or a divalent piperidine, or one or more methylene groups can 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 optionally substituted divalent piperazine, optionally substituted divalent 2,5-diazabicyclo[2.2.2]octane, optionally substituted divalent 2,5-diazabicyclo[2.2.1]heptane, optionally substituted divalent octahydropyrrolo[3,4-c]pyrrole, optionally substituted divalent pyrazine, optionally substituted divalent 3,9-diazaspiro[5,5]undecane, optionally substituted divalent 2,6-diazaspiro[3.3]heptane, optionally substituted divalent 1,3-thiazole, or optionally substituted straight or branched chain C 2-6 A compound of formula (I) is provided, wherein:

[0016] In one aspect, the present invention provides a method for producing a pharmaceutical composition comprising: a is 3; R 1 optionally substituted straight or branched chain C 2-6 alkylene, where one or more methylene groups can be replaced by a divalent piperidine; R 2 is —C(O)—, —O—, or a direct bond; R 3is an optionally substituted trivalent 1,4,7-triazonane or an optionally substituted trivalent 1,3,5-triazine.

[0017] In one aspect, the present invention provides a method for producing a pharmaceutical composition comprising: 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 is -(CH2)4-, [ka] The present invention provides a compound of formula (I),

[0018] In one aspect, the present invention provides a method for producing a pharmaceutical composition comprising: a is 3; R 1 is -(CH2)2-, -(CH2)5-, or [ka] and; R 2 is —C(O)—, —O—, or a direct bond; R 3 but [ka] The present invention provides a compound of formula (I),

[0019] In one aspect, the present invention provides a method for producing a pharmaceutical composition comprising: a is 2; R 1 optionally substituted straight or branched chain C 1-20 is alkylene; R 2 is -C(O)-; R 3 is an optionally substituted divalent piperazine.

[0020] In another aspect, the present invention provides a method for producing a pharmaceutical composition comprising: a is 2; R 1 optionally substituted straight or branched chain C 1-20 is alkylene; R 2 is -C(O)-; R 3 but [ka] The present invention provides a compound of formula (I),

[0021] The term "alkyl," as used herein, means a saturated hydrocarbon moiety having straight or branched chain moieties or combinations thereof, containing 1 to 20 carbon atoms. One or more methylene (-CH-) groups of an alkyl group may be substituted with oxygen, sulfur, sulfoxide, amino, carbonyl, carboxyl, sulfonyl, sulfate, sulfonate, amide, sulfonamide, divalent C 3-8 The alkyl groups may 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. The monovalent alkyl groups may be independently substituted with a halogen atom ...onate groups, nitro groups, amide groups, or sulfonamide groups. The monovalent alkyl groups may be independently substituted with a halogen atom, hydroxyl groups, cycloalkyl groups, amino groups, heterocyclic groups, aryl groups, carboxylic acid groups, phosphonic acid groups, sulfonate groups, nitro groups, amide groups, or sulfonamide groups. The monovalent alkyl groups may be independently substituted with a halogen atom, hydroxyl groups, cycloalkyl groups, amino groups, heterocyclic groups, aryl groups, carboxylic acid groups, phosphonic acid groups, sulfonate groups, nitro groups, amide groups, or sulfonamide groups. The monovalent alkyl groups may be independently substituted with a halogen atom, hydroxyl groups, cycloalkyl groups, amino groups, heterocyclic groups, aryl groups, carboxylic acid groups, phosphonic acid groups, nitro groups, amide groups, or sulfonamide groups. The monovalent alkyl groups may be independently substituted with a halogen atom, hydroxyl groups, cycloalkyl groups, amino groups, heterocyclic groups, aryl groups, carboxylic acid groups, phosphonic acid groups, nitro groups, amide groups, or sulfonamide groups. The monovalent alkyl groups may be independently substituted with a halogen atom, hydroxyl groups, cycloalkyl groups, hydroxyl groups, cycloalkyl groups, hydroxyl groups, cycloalkyl groups, hydroxyl groups, cyclo n H 2n+1 or may be referred to by its abbreviated common name.

[0022] As used herein, the term "alkylene" means a saturated divalent hydrocarbon moiety having straight or branched chain moieties, or combinations thereof, and containing 1 to 20 carbon atoms. One or more methylene (-CH-) groups of an alkylene group may be substituted with oxygen, sulfur, sulfoxide, amino, carbonyl, carboxyl, sulfonyl, sulfate, sulfonate, amide, sulfonamide, or a divalent C 3-8 The alkylene groups may 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. The alkylene groups may 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. The alkylene groups may be independently substituted with halogen atoms, hydroxyl groups, cycloalkyl groups, amino groups, heterocyclic groups, aryl groups, carboxylic acid groups, phosphonic acid groups, sulfonate groups, nitro groups, amide groups, or sulfonamide groups. The alkylene groups may be independently substituted with halogen atoms, hydroxyl groups, cycloalkyl groups, divalent heterocyclic groups, or divalent aryl ... divalent heterocyclic groups, or divalent aryl groups. The alkylene groups may be independently substituted with halogen atoms, hydroxyl groups, cycloalkyl groups, divalent heterocyclic groups, divalent aryl groups, carboxylic acid groups, phosphonic acid groups, sulfonate groups, nitro groups, amide groups, or sulfonamide groups. The alkylene groups may be independently substituted with halogen atoms, hydroxyl groups, cycloalkyl groups, divalent heterocyclic groups, divalent aryl groups, divalent heterocyclic groups, divalent aryl groups, divalent heterocyclic groups, divalent aryl groups, divalent heterocyclic groups, divalent aryl groups, di n H 2n - can be shown by

[0023] As used herein, the term "halogen" refers to a chlorine atom, a bromine atom, a fluorine atom, or an iodine atom.

[0024] As used herein, the term "alkenyl" refers to a hydrocarbon group having 2 to 10 carbon atoms derived from a saturated alkyl and having at least one double bond. One or more methylene (-CH-) groups of the alkenyl may be substituted with oxygen, sulfur, sulfoxide, amino, carbonyl, carboxyl, sulfonyl, sulfate, sulfonate, amide, sulfonamide, or a divalent C 3-8 It may be replaced by a cycloalkyl, a divalent heterocyclic group, or a divalent aryl group. 2-10 Alkenyl can be in the E or Z configuration. Alkenyl groups can be substituted with alkyl or halogen atoms as defined above.

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

[0026] As used herein, the term "heterocycle" refers to a 3- to 12-membered ring that contains, in a carbocyclic ring structure, at least one heteroatom selected from oxygen, amino, sulfur, or a combination of at least two thereof, and can be aromatic or non-aromatic, saturated or unsaturated. The heterocycle can be interrupted by C=O, and the S and N heteroatoms can be oxidized. The heterocycle can be monocyclic or polycyclic, trivalent, divalent, monovalent, or spiro. The heterocycle moiety can be 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, ketone group, alkylamino group, amino group, aryl group, C 3-8 The heterocyclic groups may be substituted with cycloalkyl groups or hydroxyl groups. Examples of heterocycles include 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 may be independently substituted with halogen atoms or hydroxyl groups.

[0027] As used herein, the term "aryl" refers to an organic moiety derived from an aromatic hydrocarbon consisting of a ring containing 6 to 10 carbon atoms by the removal of one hydrogen atom. Aryl is substituted with halogen atoms, sulfonyl C 1-6 Alkyl groups, sulfoxide C 1-6 Alkyl group, sulfonamide group, carboxyl (carboxcyclic acid group), C1-6 Alkyl carboxylate (ester) group, amide group, nitro group, cyano group, -OC 1-6 Alkyl group, -SC 1-6 Alkyl group, -C 1-6 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, ketone group, aldehyde, alkylamino group, amino group, aryl group, C 3-8 It may be substituted with a cycloalkyl group or a hydroxyl group. The aryl may be monocyclic or polycyclic. The aryl moiety may be divalent or monovalent.

[0028] As used herein, the term "cycloalkyl" refers to a monovalent or divalent saturated carbocyclic group of 3 to 8 carbon atoms. Cycloalkyl groups can be spiro, monocyclic, or polycyclic. Cycloalkyl groups can independently contain halogen atoms, sulfonyl groups, sulfoxide groups, sulfonyl C groups, and the like. 1-8 Alkyl groups, sulfoxide C 1-8 Alkyl group, sulfonamide group, nitro group, cyano group, -OC 1-8 Alkyl group, -SC 1-8 Alkyl group, -C 1-8 Alkyl group, -C 2-6 Alkenyl group, -C 2-6 Alkynyl group, ketone group, alkylamino group, amino group, aryl group, C 3-8 It may be substituted with a cycloalkyl group or a hydroxyl group.

[0029] As used herein, the term "cycloalkenyl" refers to a monovalent or divalent group of 3 to 8 carbon atoms derived from a saturated cycloalkyl having at least one double bond. Cycloalkenyl groups can be monocyclic or polycyclic. Cycloalkenyl groups can independently contain halogen atoms, sulfonyl groups, sulfoxide groups, sulfonyl C groups, and the like. 1-8 Alkyl groups, sulfoxide C 1-8 Alkyl group, sulfonamide group, nitro group, cyano group, -OC 1-8 Alkyl group, -SC 1-8 Alkyl group, -C 1-8 Alkyl group, -C 2-6 Alkenyl group, -C2-6 Alkynyl 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] As used herein, the term "hydroxyl" refers to a group of the formula "-OH."

[0031] As used herein, the term "carbonyl" refers to a group of the formula "-C(O)-".

[0032] As used herein, the term "ketone" refers to a -(CO)R x (where R x represents an organic compound having a carbonyl group attached to a carbon atom such as alkyl, aryl, cycloalkyl, cycloalkenyl, or heterocycle, as defined above.

[0033] As used herein, the term "amine" or "amino" refers to a group of the formula "-NR x R y ” (where R x and R y are the same or independently H, a group which may be alkyl, aryl, cycloalkyl, cycloalkenyl, or a heterocycle as defined above.

[0034] As used herein, the term "carboxyl" refers to a group of the formula "-C(O)O-".

[0035] As used herein, the term "sulfonyl" refers to a group of the formula "-SO2-".

[0036] As used herein, the term "sulfate" refers to a group of the formula "-OS(O)2-O-".

[0037] As used herein, the term "sulfonate" refers to a group of the formula "-S(O)2-O-".

[0038] As used herein, the term "carboxylic acid" refers to a group of the formula "-C(O)OH".

[0039] As used herein, the term "nitro" refers to a group of the formula "-NO2".

[0040] As used herein, the term "cyano" refers to a group of the formula "-CN".

[0041] As used herein, the term "amide" refers to a group of the formula "-C(O)NR x R y " group (where R x and R y may be the same or independently H, alkyl, aryl, cycloalkyl, cycloalkenyl, or heterocycle as defined above.

[0042] As used herein, the term "sulfonamide" refers to a compound of the formula "-S(O)NR x R y " group (where R x and R y may be the same or independently H, alkyl, aryl, cycloalkyl, cycloalkenyl, or heterocycle as defined above.

[0043] As used herein, the term "azide" refers to a group of the formula "-N=N + It indicates the group "=N-" or "-N3".

[0044] As used herein, the term "sulfoxide" refers to a group of the formula "-S(O)-".

[0045] As used herein, the term "phosphonic acid" refers to a group of formula "-P(O)(OH)2".

[0046] As used herein, the term "phosphate" refers to a group of formula "-OP(O)(OH)2".

[0047] As used herein, the term "sulfonic acid" refers to a group of the formula "-S(O)2OH".

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

[0049] As used herein, the formula "O" represents an oxygen atom.

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

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

[0052] As used herein, the term "1,3,5-triazole" refers to a compound having the structure: [ka] Shows.

[0053] As used herein, the term "azetidine" refers to the structure: [ka] Shows.

[0054] As used herein, the term "piperidine" refers to the structure: [ka] Shows.

[0055] As used herein, the term "piperazine" refers to the structure: [ka] Shows.

[0056] As used herein, the term "2,5-diazabicyclo[2.2.2]octane" refers to a compound having the structure: [ka] Shows.

[0057] As used herein, the term "2,5-diazabicyclo[2.2.1]heptane" refers to a compound having the structure: [ka] Shows.

[0058] As used herein, the term "octahydropyrrolo[3,4-c]pyrrole" refers to a compound having the structure: [ka] Shows.

[0059] As used herein, the term "pyrazine" refers to the structure: [ka] Shows.

[0060] As used herein, the term "3,9-diazaspiro[5,5]undecane" refers to a compound having the structure: [ka] Shows.

[0061] As used herein, the term "1,4,7-triazonane" refers to a compound having the structure: [ka] Shows.

[0062] As used herein, the term "2,6-diazaspiro[3.3]heptane" refers to a compound of the formula: [ka] represents the group:

[0063] As used herein, the term "1,3,5-triazine" refers to a compound of the formula: [ka] represents the group:

[0064] As used herein, the term "1,3-thiazole" refers to a compound of the formula: [ka] represents the group:

[0065] As used herein, the term "(2S)-2-ethylpiperazine" refers to a compound of the formula: [ka] represents the group:

[0066] As used herein, the term "1,4-diazidobutane" refers to a compound of the formula: [ka] represents the group:

[0067] As used herein, the term "pyrazine-2,5-dicarbonyl dichloride" refers to a compound of the formula: [ka] represents the group:

[0068] The above names, formulas, and structures are used interchangeably herein and may refer to the same items. In formulas (I, IA, IB, II, IIA, and IIB) described throughout the specification, it should be apparent to one of ordinary skill in the art that the "R" groups and their values ​​are subject to allowed valence and substitutions that result in stable compounds of these formulas.

[0069] In another aspect, the present invention provides -R 1 -, -R 2 -, R 3 and the value of "a" is as shown in Table 1. [Table 1] TIFF2026508301000030.tif239160 TIFF2026508301000031.tif250160 TIFF2026508301000032.tif234160 TIFF2026508301000033.tif237160 TIFF2026508301000034.tif239160 TIFF2026508301000035.tif237160 TIFF2026508301000036.tif39160

[0070] In yet another aspect, the present invention also provides a compound of formula (X): [ka] [In the formula, R 7 , R 8 , R 9 , and R 10 Typical and exemplary values ​​of are shown in Table 2] The present invention provides a compound represented by the formula: [Table 2] TIFF2026508301000039.tif171165

[0071] Some compounds of formula (I) and formula (II) and intermediates thereof have at least one asymmetric center in their structure, which may exist in the R or S configuration, and the R and S designations are used in accordance with the rules set out in Pure Appli. Chem. (1976), 45, 11-13.

[0072] As used herein, the term "pharmaceutically acceptable salt" refers to a salt or complex that retains the desired biological activity of the compound identified above. The "pharmaceutically acceptable salt" of the present invention includes therapeutically active base or acid salt forms that the compounds of formula (I) and formula (II) can form.

[0073] The acid addition salt forms of the compounds of formula (I) and formula (II), in which the free form is generated 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 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 formula (I) and formula (II) which are produced in acid form can be obtained by treating the acid with a suitable base, for example, an inorganic base such as sodium hydroxide, magnesium hydroxide, potassium hydroxide, calcium hydroxide, ammonia, etc.; or an organic base such as L-arginine, ethanolamine, betaine, benzathine, morpholine, etc. (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 salts thereof may be in the form of solvates, which are included within the scope of the present invention. Examples of such solvates include hydrates, alcoholates, etc.

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

[0077] The compounds provided herein can be synthesized according to the procedures described herein. The synthetic methods herein are merely exemplary, and the compounds disclosed herein may also be synthesized by alternative routes using alternative synthetic strategies recognized by those of skill in the art. At this stage, one of skill in the art may prepare many additional compounds within the scope of the present invention by using a variety of general chemical reactions. Details of some specific chemical transformations are provided in the Examples. One of skill in the art would typically be able to modify and / or adapt the following schemes to synthesize any compound of the present invention encompassed by Formula (I), Formula (IA), or Formula (IB), respectively. In general, compounds of Formula (I), Formula (IA), or Formula (IB), respectively, can be synthesized according to the following schemes. Any variables ("R" groups) used in the following schemes are those 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 conventional techniques. Starting materials may also be synthesized according to the 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: Reactions for compounds of formula (IA) [ka] where R 1 , R 2 , and R 3 is as defined herein. Compounds of general formula (IA) can be prepared from intermediates of formula (IX) and formula (IY) through the coupling reaction shown in Scheme 1.

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

[0080] Examples of reactive groups "Y" in formula (IY) involved in the coupling reaction can be azide, amine, acyl chloride, alkyl halide, or halogenated cyclic moiety. An intermediate in which "Y" is azide is Int78, an intermediate listed in Table 7. Other intermediates included in formula (IY) include 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, 1-[5-(aminomethyl)pyrazin-2-yl]methan ... The intermediates included in formula (IY) are methyl({5-[(methylamino)methyl]pyrazin-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. Some intermediates within formula (IY) are commercially available.

[0081] The reaction in Scheme 1 can 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 Huisgen cycloaddition reaction, according to methods described in the literature or known to those skilled in the art. The amount of amide coupling reagent used can generally correspond to at least an equimolar amount, preferably 1.5 times the molar amount, relative to the compound of formula (IX).

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

[0083] The ratio of the compounds of formula (IX) and formula (IY) used in Scheme 1 is generally at least 1.5 times by mol, preferably about 1.5 to 3 times by mol, relative to the former. The 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] When the group "X" is a terminal alkyne, as described in intermediate Int77, compounds of general formula (IA) can be prepared by a copper-catalyzed Huisgen cycloaddition reaction. The group "Y" is an azide in the intermediate of formula (IY) involved in this reaction. Example 58 and the examples listed in Table 11 were synthesized by this reaction.

[0085] Some 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 intermediates described in Tables 4, 5, and 6. Int26 is described by formula (IPG). Some intermediates of formula (ILG) are Int01 and the intermediates described in Table 3.

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

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

[0088] Some intermediates of formula (IY), where Y is azide, can be prepared by an amide coupling reaction, where the starting material is an alkylcarboxylic acid. Amide coupling reagents, such as HATU or TBTU, and organic bases, such as TEA or DIPEA, are described in the literature or can be used according to methods known to those skilled in the art.

[0089] Compounds of formula (IB) can be prepared according to the general reaction depicted in Scheme 4. Scheme 4: Reactions for compounds of formula (IB) [ka] Reactants of formula (IBY) are generally commercially available or can be prepared by literature described reactions familiar to those skilled in the art.

[0090] It should be understood that the general synthetic procedures and specific examples provided herein are illustrative only and are not to be construed as limiting the scope of the disclosure in any way.

[0091] Detailed Description of the Invention It is to be understood that both the following general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. As used herein, the singular forms "a," "an," and "the" include the plural unless specifically stated otherwise.

[0092] It will be readily apparent to those skilled in the art that some compounds of the present invention may contain one or more asymmetric centers, and that the compounds may exist in enantiomeric and diastereomeric forms. Unless otherwise specified, the scope of the present invention includes all enantiomeric, diastereomeric, and racemic mixtures. Some 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 isotopically enriched compounds. Any of the compounds and intermediates of the present invention may contain one or more isotopically enriched elements, or may contain hydrogen. 1 Deuterium instead of H (or H) 2 H (or D) or 12 Instead of C 13 The natural ratio may be different, such as by using a C-rich material. Similar substitutions can be used for N, O, and S. Examples of isotopes 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 I, etc. The use of isotopes may be useful not only for therapeutic aspects of the invention, but also for analytical aspects. For example, the use of deuterium may alter the metabolism (rate) of the compounds of the invention, thereby increasing their in vivo half-life. These compounds can be prepared according to the preparation methods described using isotopically enriched reagents.

[0094] In some embodiments, the compounds of Formula (I) and Formula (II) or pharmaceutically acceptable salts thereof may have an average particle size in the range of 0.05 to 10 μm, e.g., 0.1 to 10 μm, e.g., 0.1 to 5 μm, e.g., 0.1 to 3.4 μm, e.g., 0.2 to 1.9 μm, e.g., 0.2 to 0.4 μm, as measured by laser diffraction, e.g., using a laser diffraction particle size analyzer. An appropriate average particle size may be advantageous for providing a desired absorption rate and / or acceptable irritation at the injection site. As used herein, the term "average particle size" refers to the volume-average diameter measured by laser light scattering (LLS). The particle size distribution is measured by LLS, and the corresponding average particle size is calculated from the particle size distribution.

[0095] Medical uses The compounds of Formula (I) and Formula (II) or pharmaceutically acceptable salts thereof may be converted to brexpiprazole in the systemic circulation upon administration to a subject. The multivalent brexpiprazole molecule may be bioconverted in vivo, such as in plasma, to an intermediate such as N-hydroxymethylbrexpiprazole, which may then be hydrolyzed to brexpiprazole by enzyme-mediated hydrolysis. Brexpiprazole is used for the treatment of 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 attack; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorder; conversion disorder; pain disorder; hypochondriasis; factitious disorder; dissociative disorder; sexual dysfunction; sexual desire disorder; sexual arousal disorder; erectile dysfunction; anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia; iatrogenic anhedonia The compounds are useful for treating and / or preventing antipsychotic-related central nervous system disorders such as: anhedonia due to psychogenic or psychiatric 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, refractory, or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorders; attention deficit hyperactivity disorder (ADHD); conduct disorder; Down's syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder. Thus, the compounds of formula (I) and formula (II) may also be useful for treating and / or preventing central nervous system disorders.

[0096] As used herein, the terms "prophylaxis," "prevention," or "preventing" refer to prior presentation, and as such may involve the prevention of symptoms of a disease or disorder in a subject, or the prevention of the recurrence of symptoms of a disease or disorder in an affected subject, but are not limited to the complete prevention of the disease. As used herein, the terms "treatment" or "treating" include the control, alleviation, relief, or modulation of a disease state or its symptoms. A subject will typically be in need of treatment or prevention according to the present invention. A subject is typically a mammal. A subject is suitably a human.

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

[0098] The pharmaceutical preparations herein may be selected from various forms depending on the purpose of treatment. The 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 preparations may be administered orally, intravenously, intramuscularly, intradermally, subcutaneously, intraperitoneally, or rectally as needed. Examples of pharmaceutical preparations include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, and injections (liquids, suspensions, etc.). Tablets include coated tablets such as sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, bilayer tablets, and multilayer tablets.

[0099] The compound of formula (I) or formula (II) or its pharmaceutically acceptable salt may be combined with a pharmaceutically acceptable carrier to be formulated into any form of pharmaceutical preparation.Examples of the carrier include substances that are commonly used as ingredients for pharmaceutical preparations, such as excipients such as lactose; binders such as polyvinylpyrrolidone; disintegrants such as starch; absorption aids such as sodium lauryl sulfate; moisturizers such as glycerin and starch; adsorbents such as colloidal silicic acid; lubricants such as magnesium stearate and polyethylene glycol; diluents; fillers; extenders; and surfactants.

[0100] Specific examples of pharmaceutically acceptable carriers used for formulation into tablets include excipients such as lactose; binders such as polyvinylpyrrolidone; disintegrating agents such as starch; absorption aids such as sodium lauryl sulfate; moisturizing agents such as glycerin and starch; adsorbents such as colloidal silicic acid; and lubricants such as magnesium stearate and polyethylene glycol.

[0101] Specific examples of pharmaceutically acceptable carriers used for formulating into pills include excipients such as glucose; binders such as gum arabic powder; and disintegrants such as laminaran.

[0102] Pharmaceutically acceptable diluents used for formulation into solutions, emulsions, or suspensions include, for example, water. Any conventional solubilizers and / or buffers, as well as coloring agents, preservatives, fragrances, flavoring agents, and sweeteners, may also be included in the formulation, and other drugs may also be included as needed.

[0103] A specific example of a pharmaceutically acceptable carrier used in formulation into suppositories is cocoa butter.

[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 the preparation of an injection. In some embodiments, the injection is preferably sterilized and is preferably isotonic with blood. The injection may be formulated with a conventional diluent, such as water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid ester. The injection may also contain a stabilizer, such as a polymeric stabilizer, for example, poloxamer 188, 338; PEG 200, 1000, 4000; PPG 4000, and a surfactant, for example, PS20, 80; sodium deoxycholate, sodium cholate, or sodium dodecyl sulfate. The isotonic injection may contain a sufficient amount of sodium chloride and a soothing agent, such as glucose, amino acids, and glycerin, and may also contain other ingredients, such as coloring agents, preservatives, flavoring agents, and sweeteners. Preferably, the injection is an intramuscular injection or a subcutaneous injection.

[0105] The amount of a compound of formula (I) or (II) or a pharmaceutically acceptable salt thereof contained in a pharmaceutical formulation (also referred to herein as an "effective amount") may be any amount commonly used in the art, but is not limited thereto, and preferably includes any amount of 1% to 70% of the pharmaceutical formulation. The administered dose of a compound of formula (I) or (II) or a pharmaceutically acceptable salt thereof may be any dose selected depending on the route of administration, the age and sex of the patient, 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 all at once 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 of care agent useful for one of the above-mentioned diseases, also referred to herein as a combination drug. When the compound of Formula (I) or Formula (II) or a pharmaceutically acceptable salt thereof is used in combination with a combination drug, the compound of Formula (I) or Formula (II) or a pharmaceutically acceptable salt thereof and the combination drug may be administered simultaneously or together, separately or sequentially at about the same time, or separately or sequentially at different times with appropriate intervals. The compound of Formula (I) or Formula (II) or a pharmaceutically acceptable salt thereof and the combination drug may be formulated in separate preparations, or mixed or formulated in a single preparation.

[0107] Implementation Term 1: Formula (I): [ka] [In the formula, a is 2 or 3; R 1 is an optionally substituted straight or branched chain C 1-20 Alkylene; optionally substituted C 2-10 Alkenylene; optionally substituted divalent C 3-8 Cycloalkyl; optionally substituted divalent heterocyclic group; optionally substituted divalent C 6-10 Aryl; -NH (optionally substituted straight or branched chain C 1-20 alkylene); or optionally substituted divalent C 3-8 is cycloalkenyl; R 2 -C(O)-, -OC(O)-, -C(O)-NR a -CH2-, -O-, -CH2-, -NR a -C(O)- or a direct bond; R 3is an optionally substituted non-aromatic divalent or trivalent heterocyclic group, an optionally substituted aromatic divalent or trivalent heterocyclic group, or an optionally substituted linear or branched C 1-20 is alkylene; R a is hydrogen or an optionally substituted straight or branched chain C 1-20 is alkyl; If a is 2, R 3 is bivalent; If a is 3, R 3 is trivalent; R 2 and R 3 are covalently linked; However, R 1 is a linear alkylene, and R 2 is -CH2- or a direct bond, R 3 is not a straight chain alkylene] or a pharmaceutically acceptable salt thereof.

[0108] Term 2: a is 2 or 3; R 1 optionally substituted straight or branched chain C 2-16 alkylene, wherein one or more methylene groups can be replaced with a functional group selected from -O- or -NH-, or one or more methylene groups can be replaced with a spirocyclopentane or a divalent piperidine, or one or more methylene groups can 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 3optionally substituted divalent or trivalent piperazine, optionally substituted divalent or trivalent 2,5-diazabicyclo[2.2.2]octane, optionally substituted divalent or trivalent 2,5-diazabicyclo[2.2.1]heptane, optionally substituted divalent or trivalent octahydropyrrolo[3,4-c]pyrrole, optionally substituted divalent or trivalent pyrazine, optionally substituted divalent or trivalent 3,9-diazaspiro[5.5]undecane, optionally substituted divalent or trivalent 1,4,7-triazonane, optionally substituted divalent or trivalent 2,6-diazaspiro[3.3]heptane, optionally substituted divalent or trivalent 1,3,5-triazine, optionally substituted divalent or trivalent 1,3-thiazole, or optionally substituted linear or branched C 2-6 is alkylene; If a is 2, R 3 is bivalent; If a is 3, R 3 Item 2. The compound according to item 1, or a pharmaceutically acceptable salt thereof, wherein is trivalent.

[0109] Term 3: a is 2; R 1 optionally substituted straight or branched chain C 2-16 alkylene, in which one or more methylene groups can be replaced by oxygen or an amino group, or one or more methylene groups can be replaced by spirocyclopentane or a 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(CH3)-CH2-, -C(O)-NH-CH2-, -CH2-, -NH-C(O)-, or a direct bond; R 3optionally substituted divalent piperazine, optionally substituted divalent 2,5-diazabicyclo[2.2.2]octane, optionally substituted divalent 2,5-diazabicyclo[2.2.1]heptane, optionally substituted divalent octahydropyrrolo[3,4-c]pyrrole, optionally substituted divalent pyrazine, optionally substituted divalent 3,9-diazaspiro[5,5]undecane, optionally substituted divalent 2,6-diazaspiro[3.3]heptane, optionally substituted divalent 1,3-thiazole, or optionally substituted straight or branched chain C 2-6 Item 3. The compound according to item 1 or 2, wherein R is alkylene, or a pharmaceutically acceptable salt thereof.

[0110] Term 4: a is 3; R 1 optionally substituted straight or branched chain C 2-6 alkylene, where one or more methylene groups can be replaced by a divalent piperidine; R 2 is —C(O)—, —O—, or a direct bond; R 3 Item 3. The compound according to Item 1 or 2, wherein is an optionally substituted trivalent 1,4,7-triazonane or an optionally substituted trivalent 1,3,5-triazine, or a pharmaceutically acceptable salt thereof.

[0111] Term 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-, [ka] and; R 2is -C(O)-, -OC(O)-, -C(O)-N(CH3)-CH2-, -C(O)-NH-CH2-, -CH2-, -NH-C(O)-, or a direct bond; R 3 is -(CH2)4-, [ka] Item 4. The compound according to any one of Items 1 to 3, or a pharmaceutically acceptable salt thereof, wherein:

[0112] Term 6: a is 3; R 1 is -(CH2)2-, -(CH2)5-, or [ka] and; R 2 is —C(O)—, —O—, or a direct bond; R 3 but [ka] Item 3. The compound according to Item 1 or 2, or a pharmaceutically acceptable salt thereof, wherein:

[0113] Item 7: The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}piperazin-1-yl)-6-oxohexanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-[(2R,5S)-4-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-dimethylpiperazin-1-yl]-8-oxooctanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(5-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(6-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(9-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanamido}methyl)pyrazin-2-yl]methyl}carbamoyl)heptanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-N-methyl-8-oxooctanamido}methyl)pyrazin-2-yl]methyl}(methyl)carbamoyl)heptanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}piperazin-1-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[(2S,5R)-4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-2,5-dimethylpiperazin-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-[(3ar,6ar)-5-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[4,7-bis({4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl})-1,4,7-triazonan-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-(4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}piperazin-1-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-[(2R,5S)-4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}-2,5-dimethylpiperazin-1-yl]-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-(5-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-9-({[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-N-methyl-10-oxodecanamido}methyl)pyrazin-2-yl]methyl}(methyl)carbamoyl)nonanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}piperazin-1-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-[(2S,5R)-4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-2,5-dimethylpiperazin-1-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(6-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-[(3ar,6ar)-5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-N-methyl-6-oxohexanamido}methyl)pyrazin-2-yl]methyl}(methyl)carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanamido}methyl)pyrazin-2-yl]methyl}carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(2E)-4-{4-[(2E)-4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobut-2-enoyl]piperazin-1-yl}-4-oxobut-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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-{4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-[(2S,5R)-2,5-dimethyl-4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1s,4s)-4-{4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1s,4s)-4-[(2S,5R)-2,5-dimethyl-4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 1-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)piperazine-1-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[(3ar,6ar)-5-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-3-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-5-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3,3-dimethyl-5-oxopentanoyl}piperazin-1-yl)-3,3-dimethyl-5-oxopentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-2-{2-[4-(2-{2-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-2-oxoethoxy}acetyl)piperazin-1-yl]-2-oxoethoxy}acetate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-N-(8-{4-[8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)octanoyl]piperazin-1-yl}-8-oxooctyl)carbamate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-N-[(2S)-1-{4-[(2S)-2-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]piperazin-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-4-carbonyl)piperazine-1-carbonyl]piperidine-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)methyl]pyrazin-2-yl}methyl)piperidin-4-yl]propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazol-2-yl]formamido}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)pyrazin-2-yl]formamido}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-{[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecyl}carbamoyl)pyrazin-2-yl]formamide}decanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}piperazin-1-yl)hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-{4-[({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}oxy)carbonyl]piperazine-1-carbonyloxy}hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-[(4-{[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexyl]methyl}piperazin-1-yl)methyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazin-2-yl]oxy}hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-{1-[4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(5-{4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]piperazin-1-yl}-5-oxopentyl)-1H-1,2,3-triazol-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(1-{5-[(2S,5R)-4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]-2,5-dimethylpiperazin-1-yl]-5-oxopentyl}-1H-1,2,3-triazol-4-yl)butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(5-{5-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]-2,5-diazabicyclo[2.2.2]octan-2-yl}-5-oxopentyl)-1H-1,2,3-triazol-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(6-{4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)hexanoyl]piperazin-1-yl}-6-oxohexyl)-1H-1,2,3-triazol-4-yl]butanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(1-{6-[(2S,5R)-4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)hexanoyl]-2,5-dimethylpiperazin-1-yl]-6-oxohexyl}-1H-1,2,3-triazol-4-yl)butanoate Item 1. The compound according to item 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

[0114] Item 8: The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[4,7-bis({4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl})-1,4,7-triazonan-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-4-yl}propanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazin-2-yl]oxy}hexanoate Item 7. The compound according to item 6, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

[0115] Term 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] Item 2. The compound according to Item 1, or a pharmaceutically acceptable salt thereof, wherein:

[0116] Item 10: The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}piperazin-1-yl)-6-oxohexanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-[(2R,5S)-4-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-dimethylpiperazin-1-yl]-8-oxooctanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(5-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}piperazin-1-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[(2S,5R)-4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-2,5-dimethylpiperazin-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-(4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}piperazin-1-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-[(2R,5S)-4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}-2,5-dimethylpiperazin-1-yl]-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-(5-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}piperazin-1-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-[(2S,5R)-4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-2,5-dimethylpiperazin-1-yl]-6-oxohexanoate; (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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-N-(8-{4-[8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)octanoyl]piperazin-1-yl}-8-oxooctyl)carbamate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}piperazin-1-yl)hexanoate Item 10. The compound according to item 9, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

[0117] Term 11: a is 2; R 1 but [ka] and; R 2 is -C(O)-, -CH2-, or a direct bond; R 3 is -(CH2)4-, [ka] Item 2. The compound according to Item 1, or a pharmaceutically acceptable salt thereof, wherein:

[0118] Item 12: The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-{4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-[(2S,5R)-2,5-dimethyl-4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1s,4s)-4-{4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1s,4s)-4-[(2S,5R)-2,5-dimethyl-4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 1-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)piperazine-1-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[(3ar,6ar)-5-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-3-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-5-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3,3-dimethyl-5-oxopentanoyl}piperazin-1-yl)-3,3-dimethyl-5-oxopentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-2-{2-[4-(2-{2-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-2-oxoethoxy}acetyl)piperazin-1-yl]-2-oxoethoxy}acetate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-N-[(2S)-1-{4-[(2S)-2-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]piperazin-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-4-carbonyl)piperazine-1-carbonyl]piperidine-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)methyl]pyrazin-2-yl}methyl)piperidin-4-yl]propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-[(4-{[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexyl]methyl}piperazin-1-yl)methyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-{1-[4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(5-{4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]piperazin-1-yl}-5-oxopentyl)-1H-1,2,3-triazol-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(1-{5-[(2S,5R)-4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]-2,5-dimethylpiperazin-1-yl]-5-oxopentyl}-1H-1,2,3-triazol-4-yl)butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(5-{5-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]-2,5-diazabicyclo[2.2.2]octan-2-yl}-5-oxopentyl)-1H-1,2,3-triazol-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(6-{4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)hexanoyl]piperazin-1-yl}-6-oxohexyl)-1H-1,2,3-triazol-4-yl]butanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(1-{6-[(2S,5R)-4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)hexanoyl]-2,5-dimethylpiperazin-1-yl]-6-oxohexyl}-1H-1,2,3-triazol-4-yl)butanoate Item 12. The compound according to item 11, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

[0119] Term 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] Item 2. The compound according to Item 1, or a pharmaceutically acceptable salt thereof, wherein:

[0120] Item 14: The compound is the following compound: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(6-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(9-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-[(3ar,6ar)-5-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(6-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-[(3ar,6ar)-5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-N-methyl-6-oxohexanamido}methyl)pyrazin-2-yl]methyl}(methyl)carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanamido}methyl)pyrazin-2-yl]methyl}carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazol-2-yl]formamido}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)pyrazin-2-yl]formamido}pentanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-{[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecyl}carbamoyl)pyrazin-2-yl]formamido}decanoate Item 14. The compound according to item 13, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

[0121] Item 15: The compound or pharmaceutically acceptable salt thereof according to any one of Items 1 to 14, including any of the Example compounds described herein, having an average particle size measured by laser diffraction in the range of 0.05 to 10 μm.

[0122] Item 16: A pharmaceutical composition comprising the compound according to any one of items 1 to 15 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0123] Item 17: A drug for treating and / or preventing a central nervous system disorder, comprising the compound according to any one of items 1 to 15 or a pharmaceutically acceptable salt thereof.

[0124] Item 18: Central nervous system disorders include 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 disorders; 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; sexual desire 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; anhedonia due to psychogenic or psychiatric 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, refractory or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down's syndrome; impulsive symptoms associated with dementia (e.g. agitation associated with Alzheimer's disease); and borderline personality disorder.

[0125] Item 19: Use of the compound according to any one of Items 1 to 15 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating and / or preventing a central nervous system disorder.

[0126] Item 20: Central nervous system disorders include 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 disorders; 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; sexual desire 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; anhedonia due to psychogenic or psychiatric 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, refractory or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down's syndrome; impulsive symptoms associated with dementia (e.g. agitation associated with Alzheimer's disease); and borderline personality disorder.

[0127] Item 21: A method for treating and / or preventing a central nervous system disorder, which comprises administering the compound according to any one of items 1 to 15 or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0128] Item 22: Central nervous system disorders include 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 disorders; 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; sexual desire 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; anhedonia due to psychogenic or psychiatric 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, refractory or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down's syndrome; impulsive symptoms associated with dementia (e.g. agitation associated with Alzheimer's disease); and borderline personality disorder.

[0129] Item 23: The compound according to any one of items 1 to 15 or a pharmaceutically acceptable salt thereof for use in the treatment and / or prevention of a central nervous system disorder.

[0130] Item 24: Central nervous system disorders include 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 disorder; pain disorders; hypochondriasis; factitious disorder; dissociative disorders; sexual dysfunction; sexual desire disorders; sexual arousal disorders; erectile dysfunction; anorexia nervosa; bulimia nervosa; sleep disorders; adjustment disorders; alcohol abuse; alcoholism; drug addiction; stimulant addiction; narcotic addiction; anhedonia; 24. The compound according to clause 23, wherein the compound is selected from the group consisting of iatrogenic anhedonia; anhedonia due to psychogenic or psychiatric 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, refractory or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down's syndrome; impulsive symptoms associated with dementia (e.g. agitation associated with Alzheimer's disease); and borderline personality disorder.

[0131] Item 25: A method for producing a compound according to any one of items 1 to 15 or a pharmaceutically acceptable salt thereof as described herein.

[0132] Item 26: An intermediate compound in a method for producing the compound according to any one of 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 is -(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)] or a salt thereof.

[0134] The following examples are illustrative only and are not intended to, and should not be construed as, limiting the present invention in any way. Those skilled in the art will appreciate that variations and modifications of the following examples can be made without departing from the spirit or scope of the present invention. As will be apparent to those skilled in the art, individual isomers can be obtained by separation of the mixture by conventional methods. For example, in the case of diastereomeric isomers, chromatographic separation may be used. [Example]

[0135] General Experimental Details and Methods Analysis method Equipment, materials and methods used in the analysis 1H-NMR spectra were measured on a 400 Agilent INOVA, 500 Agilent VNMRS, 600 Agilent INOVA spectrometer, or a Bruker Avance III 400 spectrometer operating at 400, 500, or 600 MHz (proton frequency). Chemical shifts are reported as 6 values ​​in ppm using the residual solvent peak as the internal standard. Coupling constants (J values) are given in Hertz (Hz) and multiplicities are 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 doublet, quin = quintuplet, td = triple doublet, tt = triple triplet, qd = quadruple doublet).

[0136] LC / UV / MS analysis method LC / MS retention times are estimated subject to an experimental error of +0.5 minutes. LCMS may be recorded under the following conditions: diode array DAD chromatographic traces, mass chromatograms and mass spectra may be measured on a UPLC / PDA / MS Acquity™ system connected to a Micromass ZQ™ or Waters SQD single quadrupole mass spectrometer operated in positive and / or negative electrospray electron spurt ionization mode, and / or on a Fractionlynx system used in analytical mode connected to a ZQ™ single quadrupole operated in positive and / or negative electron spurt ionization mode. The quality control methods used were operated 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 was milliQ water + 0.1% HCOOH, and mobile phase solvent B was MeCN + 0.1% HCOOH. Flow rate was 1 mL / min. Gradient: 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 was 210-350 nm, and ES+ / ES- range was 100-1900 AMU. Method 2, high pH conditions: Column: Kinetex EVO C18 2.1 x 50 mm 1.7 μm, column temperature 40 °C; mobile phase solvent A was 10 mM aqueous NH4HCO3 adjusted to pH = 10 with ammonia, and mobile phase solvent B was MeCN. Flow rate was 1 mL / min. Gradient: 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 was 210-350 nm, and ES+ / ES- range was 100-1200 AMU. Method 3, low pH conditions: Column: Acquity Peptide BEH C18 2.1 x 50 mm 1.7 μm, column temperature 40°C; mobile phase solvent A was milliQ water + 0.05% TFA, and mobile phase solvent B was MeCN + 0.05% TFA. Flow rate was 0.7 mL / min. Gradient: 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 was 210-350 nm, and ES+ / ES- range was 100-1900 AMU. Method 4, low pH conditions: Column: Acquity Peptide BEH C18 2.1 x 50 mm 1.7 μm, column temperature 40°C; mobile phase solvent A was milliQ water + 0.05% TFA, and mobile phase solvent B was MeCN + 0.05% TFA. Flow rate was 0.7 mL / min. Gradient: 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 was 210-350 nm, and ES+ / ES- range was 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, a mass spectrometer (MS: ZQ2000) and a DAD detector 220. The mobile phase used was a gradient of MeCN + HCOOH in HO, 50% to 70% in 10 min (flow rate = 40.00 mL / min).

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

[0139] All reagents whose synthesis is not described in the experimental section are commercially available, are known compounds, or may be prepared 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 = atmosphere Boc = tert-butyloxycarbonyl BocO = di-tert-butyl dicarbonate cHex = cyclohexane CuI = copper(I) iodide DCM = dichloromethane DIAD = diisopropyl azodicarboxylate DIPEA = N,N-diisopropylethylamine DMAP = 4-(dimethylamino)pyridine DMF = dimethylformamide DMSO = dimethyl sulfoxide EtOAc = 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-benzotriazol-1-yl-oxy)(dimethylamino)methylidene]dimethylazanium; hexafluoro-lambda 5-phosphanide HCl = hydrochloric acid H2O = Water IPA = Propan-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 on 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] Intermediate production 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 HO (44 mL) was added NaHCO (5.4 g) and TBA-HSO (5.5 g). The mixture was cooled to 0 °C, and a solution of chloromethyl chlorosulfonate (1.6 mL) in 8 mL of DCM was added dropwise. The reaction was then stirred at room temperature for 3 h. The mixture was diluted with DCM and washed with HO. The organic layer was dried over NaSO, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0% to 10% EtOAc / cHex) to give Int01 (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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 8-tert-butyl octanedioate [ka] Under a N2 atmosphere, NaH (60% in mineral oil, 0.14 g) was added to 1,4-dioxane (30 mL), followed by 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinolin-2-one (1.4 g), and the reaction was stirred at room temperature for 15 min. A solution of Int01 (1.35 g) in 1,4-dioxane (7 mL) was then added dropwise. The reaction mixture was stirred at 60 °C (external temperature) for 2.5 h. The reaction was cooled to room temperature, diluted with EtOAc, and quenched with saturated NH4Cl solution. The resulting mixture was extracted with EtOAc (2 x). The combined organic layers were dried through a phase separator, and the solvent was concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 10% to 100% EtOAc / cHex) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoic acid hydrochloride [ka] To a solution of Int02 (2.9 g) in DCM (91 mL) was added TFA (5.25 mL) dropwise at room temperature. The mixture was stirred at room temperature for 48 h. The solvent was evaporated, and the residual TFA was partially azeotroped with toluene. 1,4-dioxane (10 mL) and HCl 4N / 1,4-dioxane (15 mL) were then added, and the mixture was evaporated under high vacuum to give a yellow oil. This was taken up in DCM and washed twice with saturated NaHCO3 solution. The organic phase was filtered through a phase separator and acidified (pH = 3-4) with 1.8 mL of aqueous HCl (1 M). The organic phase was washed with H2O (twice), dried over Na2SO4, filtered, and concentrated under vacuum to give Int03 (2.0 g). LC-MS (ESI): m / z (M+1): 620.0, Rt= 0.68 min. (Method 1).

[0144] Int04: Methyl({5-[(methylamino)methyl]pyrazin-2-yl}methyl)amine [ka] A 2M THF solution of methanamine (8 mL) was diluted with additional THF (10 mL) and cooled to 0°C. 2,5-bis(bromomethyl)pyrazine (0.28 g) in THF (3 mL) was added dropwise at 0°C. The reaction mixture was sealed in a vial and stirred at room temperature for 5 hours. The solvent was then removed under high vacuum, and the residue was purified on an SCX column (eluent = MeOH, then 2M ammonia / MeOH) to give 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)pyrazin-2-yl]methanamine dihydrochloride [ka] Step A: To a solution of [5-(hydroxymethyl)pyrazin-2-yl]methanol (50 mg) in dry THF (3.5 mL) were added PPh3 (206 mg) and phthalimide (105 mg) 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 give 2-({5-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]pyrazin-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: To a suspension of 2-({5-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]pyrazin-2-yl}methyl)-2,3-dihydro-1H-isoindole-1,3-dione (127 mg) in DCM (4 mL) was added hydrazine (0.04 mL) and the mixture was refluxed for 3 h. The mixture was cooled to room temperature, and TEA (0.2 mL) and BocO (0.21 g) were added, and the resulting mixture was stirred at 35 °C for 24 h. The mixture was cooled to room temperature, and the solid was filtered off. The organic layer was washed with HO, and the organic phase was filtered through a phase separator and evaporated under high vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0% to 40% EtOAc / cHex) to give tert-butyl N-{[5-({[(tert-butoxy)carbonyl]amino}methyl)pyrazin-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]pyrazin-2-yl]methyl]carbamate (48 mg) in 1,4-dioxane (2 mL) was added HCl 4M / 1,4-dioxane (0.57 mL), and the reaction mixture was stirred at room temperature overnight. Then, additional HCl 4M / 1,4-dioxane (0.2 mL) was added, and the mixture was stirred at room temperature for an additional 6 hours. The mixture was evaporated under high vacuum to give 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) was added TFA (0.6 mL) dropwise at 0° C. After stirring at room temperature for 3 h, the mixture was evaporated under high vacuum to give 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 in Int08 to give Int09 (0.197 g). 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] The starting materials used in the synthesis of each compound and their characterization are listed in Table 3. [Table 3] TIFF2026508301000064.tif238166 TIFF2026508301000065.tif241166 TIFF2026508301000066.tif232166 TIFF2026508301000067.tif219166

[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] The starting materials used in the synthesis of each compound and their characterization are listed in Table 4. [Table 4] TIFF2026508301000069.tif251166 TIFF2026508301000070.tif240166 TIFF2026508301000071.tif217166 TIFF2026508301000072.tif252166 TIFF2026508301000073.tif252166 TIFF2026508301000074.tif248166 TIFF2026508301000075.tif29166

[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] The starting materials used in the synthesis of each compound and their characterization are listed in Table 5. [Table 5] TIFF2026508301000077.tif252166 TIFF2026508301000078.tif222166 TIFF2026508301000079.tif248166 TIFF2026508301000080.tif251166 TIFF2026508301000081.tif97166

[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 min to give a clear solution, and then heated to 100 °C and N,N-dimethylformamide di-tert-butyl acetal (11.1 mL) was added dropwise over 5 min. The mixture was refluxed for 5 h, cooled to room temperature, and the solvent was removed in vacuo. The crude product was purified by silica gel cartridge chromatography (eluent = 20% to 50% EtOAc / cHex) to give Int 26 (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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-tert-butyl 2,2-dimethylbutanedioate [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 give a mixture of 4-tert-butyl 1-chloromethyl 2,2-dimethylbutanedioate and 1-tert-butyl 4-chloromethyl 2,2-dimethylbutanedioate (0.45 g). Step B: The resulting mixture was reacted with 7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinolin-2-one (0.45 g) according to the procedure described for Int02. The resulting mixture was further purified by chiral semi-preparative HPLC column Chiralcel OJ-H (eluent = nHex / EtOH: 80 / 20) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 5-tert-butyl 3,3-dimethylpentanedioate [ka] Under a N2 atmosphere, NaH (60% in mineral oil, 0.154 g) was added to a suspension of 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinolin-2-one (1.67 g) in 2-MeTHF (20 mL) at room temperature. The reaction was stirred at 70 °C (external 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 (external temperature) for 3 hours. The reaction was cooled to room temperature, diluted with EtOAc, and quenched with saturated NH4Cl solution. The resulting mixture was extracted with EtOAc (twice). The combined organic layers were dried on a phase separator, and the solvent was removed under vacuum. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 10% to 100% EtOAc / cHex) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)octanoate [ka] Under a N2 atmosphere, NaH (60% in mineral oil, 24 mg) was added to DMF (2 mL) and 2-MeTHF (2 mL) at room temperature, followed by 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinolin-2-one (220 mg). The reaction was stirred at 60 °C for 5 minutes and 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. Cold saturated NH4Cl solution was added, and the mixture was extracted with DCM (twice). The combined organic layers were dried through a phase separator, and the solvent was removed under vacuum to give a solution of [7-[4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy]-2-oxoquinolin-1-yl]methyl (4-nitrophenyl)carbonate in DMF. To this was added a solution of tert-butyl 8-aminooctanoate (109 mg) in DCM (5 mL) and TEA (0.35 mL) at room temperature, and the reaction mixture was stirred at room temperature for 16 hours. The volatiles were removed under vacuum, and the resulting crude product was purified by C-18 cartridge chromatography (eluent = 0% to 100% MeCN in 0.1% TFA / HO) to give Int 47 (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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)octanoic acid trifluoroacetate [ka] To a solution of tert-butyl Int47 (98 mg) in DCM (4 mL) was added TFA (0.24 mL) dropwise at room temperature. The reaction was stirred at room temperature for 16 hours. Toluene (10 mL) was added and the volatiles were removed in vacuo to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)-3-methylbutanoate [ka] Int49 was prepared from 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinolin-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 give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)-3-methylbutanoic acid trifluoroacetate [ka] Int50 was prepared from Int49 (570 mg) according to the procedure described for Int48 to give Int50 (370 mg). 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 according to the method used for the synthesis of Int49. The starting materials used for the synthesis of each compound and their characterization are listed in Table 6. [Table 6] TIFF2026508301000090.tif215166 TIFF2026508301000091.tif81166

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

[0163] Int57: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 3-(piperidin-4-yl)propanoate [ka] Int57 was prepared from Int56 (1.28 g) following the procedure described for Int54 to give Int57 (1.24 g). 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 1-tert-butyl azetidine-1,3-dicarboxylate [ka] Int59 was prepared from 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinolin-2-one (1.6 g) and Int58 (1.4 g) according to the procedure described for Int49 to give Int59 (1.9 g). LC-MS (ESI): m / z (M+1): 647.5, Rt= 0.83 min. (Method 1).

[0165] Int60: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl azetidine-3-carboxylate [ka] Int60 was prepared from Int59 (1.9 g) according to the procedure described for Int54 to give Int60 (1.6 g). 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-dihydroquinolin-7-yl)oxy]butyl}piperazin-1-ium fluoride [ka] N-Ethyldiisopropylamine trihydrofluoride (1.5 mL) was added to a solution of Int 67 (1 g) in THF (8 mL) at 0 °C. The reaction was stirred at room temperature for 7 h. Saturated NaHCO3 solution was added and the mixture was extracted with EtOAc (2 times). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and evaporated in vacuo. The resulting crude product was triturated with ether:EtOAc 90:10 to give Int 68 (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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 6-(methanesulfonyloxy)hexanoate [ka] MsCl (0.06 mL) was added to a mixture of Int68 (250 mg), TEA (0.16 mL), and DMAP (4.8 mg) in DCM (4.3 mL) at 0 °C. The reaction was stirred at room temperature for 3 h. 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% to 10% MeOH / DCM) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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 was stirred at room temperature overnight. The reaction mixture was diluted with DCM and washed with saturated NaHCO3 solution (5 times). The organic phase was dried over a phase separator and evaporated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0% to 100% MeOH / MeCN) to give 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-dihydroquinolin-7-yl)oxy]butyl}piperazin-1-ium fluoride [ka] Int73 was prepared from Int72 (970 mg) according to the procedure described for Int68 to give Int73 (744 mg). LC-MS (ESI): m / z (M+1): 604.2, Rt= 0.75 min. (Method 1).

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

[0171] Int78: 5-azido-1-[4-(5-azidopentanoyl)piperazin-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 was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc and washed with saturated NaHCO solution (twice). The organic phase was dried on a phase separator, and the solvent was evaporated under vacuum at 37 °C. The resulting crude product was purified by C18-cartridge chromatography (eluent = 5% to 50% MeCN / HO) to give 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 according to the method used for the synthesis of Int78.

[0173] The starting materials used in the synthesis of each compound and their characterization are listed in Table 7. [Table 7] TIFF2026508301000103.tif24166

[0174] Int83 : 4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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 h. Then, additional TFA (6.1 mL, 80 mmol) was added, and the mixture was stirred at room temperature for an additional 8 h. The solvent was evaporated, and the residual TFA was partially azeotroped with toluene. The residue was concentrated in vacuo to give 4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoic acid trifluoroacetate (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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}piperazine-1-carboxylate [ka] To a solution of Int83 (710 mg, 1.05 mmol) in dry DMF (5 mL) was added TBTU (405 mg, 1.26 mmol). After 5 min, TEA (0.58 mL, 4.2 mmol) and tert-butyl piperazine-1-carboxylate (215 mg, 1.16 mmol) in DMF (10 mL) were added, and the reaction was stirred at room temperature for 3 h. HO and DCM were added to the reaction mixture, the mixed phases were separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with brine, dried over NaSO, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM to 6% MeOH / DCM) to give tert-butyl 4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}piperazine-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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-oxo-4-(piperazin-1-yl)butanoate [ka] Int85 was prepared from Int84 (150 mg, 0.156 mmol) according to the procedure described for Int03 to give (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-{4-[4-(tert-butoxy)-4-oxobutanoyl]piperazin-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 give (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-{4-[4-(tert-butoxy)-4-oxobutanoyl]piperazin-1-yl}-4-oxobutanoate trifluoroacetate (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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}piperazin-1-yl)-4-oxobutanoic acid [ka] Int87 was prepared from Int86 (70 mg, 0.089 mmol) according to the procedure described for Int03 to give 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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)piperazin-1-yl]-4-oxobutanoic acid [ka] A suspension of piperazine (1.0 g, 11.6 mmol) and oxolane-2,5-dione (2.3 g, 23.2 mmol) in toluene (15 mL) was stirred at 110 °C for 1 h. DMF (5 mL) was then added, and the suspension was stirred at 110 °C for an additional 4 h. The solvent was removed under reduced pressure. The solid residue was taken up in EtOH, filtered, and washed with EtOH. The solid residue was dried under vacuum to give 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 similarly to the method described herein.

[0181] Preparation of the final compound Example 01: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}piperazin-1-yl)-6-oxohexanoate [ka] To a solution of Int15 (0.19 g) in dry DMF (13 mL) was added TBTU (543 mg). After 5 min, TEA (0.54 mL) and piperazine (50 mg) were added, and the reaction was stirred at room temperature overnight. Additional piperazine (17 mg) and TEA (0.15 mL) were added, and the reaction was stirred at room temperature for an additional 1 h. HO and DCM were added to the reaction mixture, the mixed phases were separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with saturated brine, dried over NaSO, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM to 3% MeOH / DCM) to give 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 to synthesize Example 01.

[0183] The starting materials used in the synthesis of each compound and their characterization are listed in Table 8. [Table 8] TIFF2026508301000113.tif198166 TIFF2026508301000114.tif223166 TIFF2026508301000115.tif199166 TIFF2026508301000116.tif205166 TIFF2026508301000117.tif215166 TIFF2026508301000118.tif204166 TIFF2026508301000119.tif210166 TIFF2026508301000120.tif201166 TIFF2026508301000121.tif186166 TIFF2026508301000122.tif194166 TIFF2026508301000123.tif210166 TIFF2026508301000124.tif204166 TIFF2026508301000125.tif203166 TIFF2026508301000126.tif210166 TIFF2026508301000127.tif198166 TIFF2026508301000128.tif215166 TIFF2026508301000129.tif217166 TIFF2026508301000130.tif206166 TIFF2026508301000131.tif203166 TIFF2026508301000132.tif253166 TIFF2026508301000133.tif253166 TIFF2026508301000134.tif227166 TIFF2026508301000135.tif189166 TIFF2026508301000136.tif196166 TIFF2026508301000137.tif205166 TIFF2026508301000138.tif201166 TIFF2026508301000139.tif204166 TIFF2026508301000140.tif248166 TIFF2026508301000141.tif251166 TIFF2026508301000142.tif217166 TIFF2026508301000143.tif188166 TIFF2026508301000144.tif251166 TIFF2026508301000145.tif251166 TIFF2026508301000146.tif252166 TIFF2026508301000147.tif182166

[0184] Example 04: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.1]heptan-2-yl]-8-oxooctanoate; tris(trifluoroacetic acid) [ka] To a solution of Int03 (90 mg) and (2S)-2-ethylpiperazine dihydrochloride (12 mg) in dry DMF (13 mL) was added TBTU (543 mg). The final compound was purified by C18-cartridge chromatography (eluent = 5% to 50% MeCN in 0.1% TFA / HO) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanamido}methyl)pyrazin-2-yl]methyl}carbamoyl)heptanoate [ka] To a solution of Int03 (110 mg) and Int05 (16 mg) in dry DMF (13 mL) was added TBTU (543 mg). After 5 min, TEA (0.54 mL) and piperazine (50 mg) were added, and the reaction was stirred at room temperature overnight. Additional piperazine (17 mg) and TEA (0.15 mL) were added, and the reaction was stirred at room temperature for an additional 1 h. HO and DCM were added to the reaction mixture, the mixed phases were separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with brine, dried over NaSO, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM to 3% MeOH / DCM) to give 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-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}piperazin-1-yl)-4-oxobutanoate [ka] To a solution of Int07 (568 mg) in dry DMF (7.73 mL) was added TBTU (395 mg). After 5 min, piperazine (37 mg) and TEA (0.26 mL) were added. The mixture was stirred at room temperature for 16 h. Water and DCM were added to the reaction mixture, which was then extracted with DCM (3 times). The combined organic layers were 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 give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-4-oxobutanoate [ka] To a solution of Int07 (200 mg) and Int09 (57 mg) in dry DMF (13 mL) was added TBTU (543 mg). After 5 min, TEA (0.54 mL) and piperazine (50 mg) were added, and the reaction was stirred at room temperature overnight. Additional piperazine (17 mg) and TEA (0.15 mL) were added, and the reaction was stirred at room temperature for an additional 1 h. HO and DCM were added to the reaction mixture, the mixed phases were separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with brine, dried over NaSO, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM to 3% MeOH / DCM) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}piperazin-1-yl)-8-oxooctanoate [ka] To a solution of Int03 (890 mg) in dry DMF (13 mL) was added TBTU (543 mg). After 5 min, TEA (0.54 mL) and piperazine (50 mg) were added, and the reaction was stirred at room temperature overnight. Additional piperazine (17 mg) and TEA (0.15 mL) were added, and the reaction was stirred at room temperature for an additional 1 h. HO and DCM were added to the reaction mixture, the mixed phases were separated, and the aqueous phase was extracted with DCM (3 times). The combined organic layers were washed with brine, dried over NaSO, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = DCM to 3% MeOH / DCM) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate [ka] Pyrazine-2,5-dicarbonyl dichloride (36 mg) was added to a solution of Int 54 (200 mg) and TEA (0.24 mL) in DCM (6 mL) at 0 °C. The reaction was stirred at room temperature for 1 h. The mixture was diluted with DCM and washed with H2O and saturated brine. The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0% to 10% MeOH / DCM) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-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 was stirred at room temperature for 16 hours. The mixture was diluted with EtOAc and washed with H2O (twice) and saturated brine (twice). The organic phase was dried over Na2SO4, filtered, and evaporated in vacuo. The crude product was purified by silica gel cartridge chromatography (eluent = 0% to 10% MeOH / DCM) followed by C-18 cartridge chromatography (eluent = 5% to 50% MeCN in 0.1% HCOOH / H2O). 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 in vacuo to give 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-dihydroquinolin-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-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-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 h. The mixture was cooled to room temperature, diluted with EtOAc, and washed with HO (twice) and saturated brine (twice). The organic phase was dried over NaSO, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0% to 10% MeOH / DCM). The product was further purified by C-18 cartridge chromatography (eluent = 5% to 50% MeCN in 0.1% HCOOH / HO) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)methyl]pyrazin-2-yl}methyl)piperidin-4-yl]propanoate [ka] Example 48 was prepared from 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% to 4% MeOH / DCM) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidin-4-yl}propanoate [ka] Pyrazine-2,5-dicarbonyl dichloride (43 mg) was added to a solution of Int57 (250 mg) and TEA (0.58 mL) in DMF (8 mL) at 0 °C. The reaction was stirred at room temperature for 16 h. The reaction mixture was diluted with EtOAc and washed with H2O and saturated brine (twice). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0% to 10% MeOH / DCM) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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 to give Example 50 (8.2 mg). 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazol-2-yl]formamido}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 was stirred at room temperature for 4 hours. Toluene (20 mL) was added, and the volatiles were evaporated in vacuo. 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 10 minutes of stirring, the mixture was concentrated in vacuo to give Example 51 - Step A: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 5-aminopentanoate dihydrochloride (658 mg, quantitative yield). Step B: 1,3-Thiazole-2,5-dicarbonyl dichloride (33 mg) was added to a solution of the crude product (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 5-aminopentanoate dihydrochloride (0.20 g) in DMF (6 mL) at room temperature, followed by the addition of TEA (0.6 mL). The reaction was stirred at 100° C. for 3 hours. The reaction was cooled to room temperature, diluted with cold saturated NH4Cl solution, and extracted with DCM (2×). The combined organic layers were dried over a phase separator and concentrated in vacuo. The resulting crude product was purified by C-18 cartridge chromatography (eluent = 0% to 100% MeCN in 0.1% TFA / HO) followed by silica gel cartridge chromatography (eluent = 0% to 10% MeOH / DCM) to give 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 characterization are listed in Table 9. [Table 9] TIFF2026508301000161.tif149166

[0197] Example 54: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}piperazin-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 h. The solution was cooled to room temperature, diluted with EtOAc, and washed with H2O (twice) and saturated brine. The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0% to 10% MeOH / DCM) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-{4-[({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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 the addition of piperazine (0.9 mg). The reaction was stirred at room temperature for 6 h. The reaction mixture was diluted with DCM and washed with Na2CO3 (twice). The organic phase was filtered through a phase separator and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge chromatography (eluent = 0% to 10% MeOH / DCM) to give 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 characterization 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-dihydroquinolin-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazin-2-yl]oxy}hexanoate tetrakis(trifluoroacetic acid) salt DIPEA (0.11 mL) was added dropwise to a solution of 2,4,6-trichloro-1,3,5-triazine (16 mg) and Int68 (150 mg) in MeCN (1 mL) at 0 °C. The reaction was stirred at room temperature for 5 days. The reaction mixture was diluted with DCM (10 mL) and washed with HO (3 mL). The organic phase was dried over a phase separator and concentrated in vacuo. The resulting crude product was purified by silica gel cartridge (eluent = 0% to 7% MeOH / DCM) followed by C-18 cartridge chromatography (eluent = 5% to 95% in 0.1% TFA / HO) to give 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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}pentanoate formate [ka] DIPEA (0.04 mL) and CuI (48 mg) were dissolved in degassed DMF (1.5 mL). Int76 (357 mg) and 1,4-diazidobutane (35.0 mg) were then added at room temperature, and the reaction was stirred at 40 °C overnight. The reaction mixture was cooled to room temperature and directly purified by C18 cartridge chromatography (eluent = 3% to 40% MeCN in 0.1% HCOOH / HO) to give 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 characterization are listed in Table 11. [Table 11] TIFF2026508301000168.tif253166 TIFF2026508301000169.tif248166 TIFF2026508301000170.tif252166 TIFF2026508301000171.tif252166 TIFF2026508301000172.tif252166 TIFF2026508301000173.tif62166

[0203] Preparation of crystalline forms The instruments used in this specification are shown 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 of crystalline form A of the compound of Example 10 was prepared according to the following procedure. The compound of 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 wax to a white solid. The solvent was concentrated under vacuum. A portion of the white solid was recovered. The solid was suspended in 2-propanol (2 mL). The suspension was warmed to 50°C, and DCM (0.9 mL) was added at the same temperature. The suspension changed from a light pink wax to a white solid, then to a clear solution. Upon completion of the DCM addition, an opaque solution was observed, heating was discontinued, and the suspension was allowed to reach room temperature (in a heating mantle without stirring) over the weekend. Example 10 (48.0 mg, 0.040 mmol) was collected by filtration and washed with cold IPA. The characteristic XRPD peaks of crystalline form A of the compound of Example 10 are shown below. [Table 12] The XRPD pattern of crystalline form A is shown in Figure 1. Crystalline form A is characterized by at least 1, 2, 3, 4, 5, or 6 XRPD peaks (°2θ) selected from about 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. DSC showed one endothermic reaction at 176°C due to the melting of crystalline form A, as shown in Figure 2. Crystalline form A has a DSC thermogram characterized by an endothermic peak at about 176±3°C.

[0204] (2) The compound of Example 10 (50 mg) was suspended in DMSO (20 volumes). The suspension was heated to 75°C (heating plate temperature) and dissolved at approximately 70-71°C. The solution was cooled to 50°C, and then seed crystals of crystalline form B (approximately 4-5 mg) were added, followed by aging the suspension for approximately 10 minutes. Heating was stopped, and the suspension was cooled to room temperature and aged overnight with stirring. The next day, the solid was isolated by filtration, dewatered under vacuum, and then dried overnight in a vacuum oven at 50°C under reduced pressure. Product: 44.1 mg (88% w / w uncorrected recovery) The characteristic XRPD peaks of crystalline form B are shown below. [Table 13] The XRPD pattern of crystalline form B is shown in Figure 3. Crystalline form B is characterized by at least 1, 2, 3, 4, 5, or 6 XRPD peaks (°2θ) selected from about 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. DSC showed a slight initial change associated with desolvation, followed by a characteristic endothermic peak with an onset temperature of 159°C (enthalpy 83 J / g), as shown in Figure 4. Crystalline form B has a DSC thermogram characterized by an endothermic peak at approximately 159±3°C.

[0205] (3) Crystalline Form 1 of the compound of Example 19 was prepared according to the following procedure. The compound of Example 19 (55.4 g, 42.96 mmol) was suspended in ethanol (664.8 mL) and stirred at 47°C (external temperature) for 2 days. The suspension was then cooled to room temperature and stirred at the same temperature for an additional 2 days. The product was collected 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 crystalline form 1 are shown below. [Table 14] The XRPD pattern of crystalline form 1 is shown in Figure 5. Crystalline form 1 is characterized by at least 1, 2, 3, 4, 5, or 6 XRPD peaks (°2θ) selected from about 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 showed a weight loss of 2.7% w / w from ambient 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 FIG. DSC showed one endothermic reaction at 81°C associated with the melting of the crystals, as shown in Figure 7. Crystalline Form 1 has a DSC thermogram characterized by an endothermic peak at about 81±3°C.

[0206] Test Example 1: Stability of S9 on human skin Skin S9 from human donors (male and female) 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. Test compounds were dissolved in DMSO to obtain 10 mM stock solutions. 5 μL of a 10 mM stock solution in DMSO was diluted with 995 μL of methanol to obtain a 50 μM spiked solution. A positive control (clopidogrel) was dissolved in DMSO to obtain a 10 mM stock solution. A 50 μM spiked solution was prepared by diluting 5 μL of a 10 mM stock solution in DMSO with 995 μL of methanol. The general procedure consisted of incubating 0.5 μM (final concentration) of test compound with 2.5 mg / mL pooled skin S9 (final concentration) plus NADPH-regenerating system and UDPGA solution. A negative control was performed using pooled skin S9 without any cofactors. Five microliters of 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 incubated for 5 minutes at 37°C. The incubation reaction was initiated by adding 50 μL of prewarmed NADPH-regenerating system and 50 μL of UDPGA or 100 μL of buffer (for negative control) to the incubation mixture. Test compounds were run in duplicate with or without cofactors, and the positive control was run in one duplicate with or without cofactors. Incubations were carried out in a shaking water bath at 37°C for 1 hour. At each time point (0, 5, 15, 30, 45, and 60 minutes), 25 μL of spiked skin S9 suspension was removed and added to 25 μL of milliQ water and 150 μL of stop solution (1% formic acid in acetonitrile and 0.2 μM brexpiprazole-D8) to precipitate proteins. The sample was thoroughly mixed and centrifuged at 3000 rpm at 4°C for 10 minutes. The supernatant (100 μL) was collected and diluted with 18% acetonitrile / Milli-Q water (200 μL) before being 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 remaining percentage of the test compound was calculated using the zero time point sample as the reference (100%).The half-life was calculated from the relationship T = -0.693 / k, where k is the slope of the concentration vs. time curve. Additionally, the active parent compound (brexpiprazole) in each sample was quantified based on the MS response of brexpiprazole-D8 in the same sample. The stability results of the exemplary compounds in human skin S9 are shown in Table 15. When multiple values ​​were measured, the average half-life was calculated.

[0207] [Table 15]

[0208] Test Example 2: Human hepatocyte stability Cryopreserved hepatocytes from human donors were stored in the vapor phase of a liquid nitrogen freezer until use. After thawing, cell viability was checked using a trypan blue dye exclusion test before use. Incubations of test compounds and positive controls (testosterone and 7-hydroxycoumarin) were performed at a cell concentration of 0.5 × 10 cells in William's medium E supplemented with 200 mM glutamine and 1 M HEPES. 6 0.495 mL of cell suspension was dispensed into a 48-well plate and pre-incubated at 37°C for at least 10 minutes. Test compounds and positive controls were dissolved in DMSO to give stock solutions of 10 mM, 50 mM, and 5 mM for test compounds, testosterone, and 7-hydroxycoumarin, respectively. The stock solutions were further diluted with methanol to give final addition solutions of 50 μM, 1 mM, and 500 μM for test compounds, 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 to 0.5 × 10 6The test compound, testosterone, and 7-hydroxycoumarin were added to 0.495 mL of cell suspension at final concentrations of 0.5 μM, 10 μM, and 5 μM, respectively. Incubations were performed at 37°C with gentle shaking at 350 rpm, with two test compounds and one positive control. At each time point (0, 5, 10, 15, 20, 30, 45, 60, 90, 120, and 180 min), 30 μL of incubation mixture from each well was added to 30 μL of milliQ water and 180 μL of stop solution (1% formic acid in acetonitrile and 0.2 μM brexpiprazole-D8) to precipitate proteins. The samples were mixed thoroughly and centrifuged at 3000 rpm and 4°C for 10 min. 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. The metabolic stability was calculated from the ratio of the peak area of ​​the remaining test compound or positive control substance to the internal standard versus time. -1 The CLi was calculated by plotting the peak area of ​​the remaining test compound relative to the internal standard versus time on a log-linear plot using XLFit or Morphit Software. The half-life was calculated from the relationship T = -0.693 / k. The CLi value was calculated based on the actual volume of the culture (mL), the number of hepatocytes in the culture (10 6 The first-order elimination constant k(min -1 ) was calculated. Additionally, the active parent compound (brexpiprazole) in each sample was quantified based on the MS response of brexpiprazole-D8 in the same sample. Stability results for example compounds in human plasma and human hepatocytes are shown in Table 16. When multiple values ​​were measured, the average half-life was calculated.

[0209] [Table 16] "Yes" means that the parent compound was detected at at least one time point and that differences in parent compound production were observed between incubations of the test compounds.

[0210] Test Example 3: Short-term rat PK study The study protocol was designed to evaluate the pharmacokinetic (PK) profile of the test compound after intravenous (IV) and subcutaneous (SC) administration to rats. Male Sprague-Dawley rats purchased from Charles River were housed in cages of 3-4 rats in humidity- and temperature-controlled ventilated racks (relative humidity 45-65%, temperature 20-22°C, light on / off approximately 6:00-18:00) and allowed to acclimate for a minimum of 5 days. During the study, the animals had free access to standard rodent chow (Altromin 1324) and water. Animals were randomly assigned to groups (n=3 per group) to receive either IV or SC 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 post-dose: 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose. For SC administration, the test compound was suspended in 1% hydroxymethylpropylcellulose and 0.2% Tween 80 in water and administered at a dose of 30 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 over a period up to 120 hours post-dose: 3, 6, 10, 24, 27, 30, 34, 48, 51, 54, 58, 72, 75, 78, 82, 96, 99, 102, 106, and 120 hours post-dose. For both groups, blood was collected from the lateral tail vein and aliquoted into K3EDTA tubes. After collection, the blood was gently mixed and then immediately transferred to a microfuge tube for online protein precipitation using acetonitrile containing 1% formic acid and rolipram as an internal standard. 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 excised, collected in vials, and stored frozen at -80°C until analysis. On the day of analysis, the skin was thawed, weighed, and diluted so that it could be homogenized. Calibration standards (CS) and quality control samples (QC) were prepared on the day of administration by adding standard solutions (test compound and brexpiprazole prepared separately) to blank matrix (blood and skin homogenate) and stored under the same conditions as the test samples. The test samples, along with the CS, QC, and blank samples, were analyzed using an LC-MS / MS system. The test compound and brexpiprazole were quantified in each sample. The area under the blood concentration curve (AUC) of the test compound and brexpiprazole in blood was calculated 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 after test compound administration to the AUC after brexpiprazole administration. After SC administration, brexpiprazole in the skin was calculated as the ratio of the brexpiprazole concentration after test compound administration to the brexpiprazole concentration in skin tissue.

[0211] The results of Test Example 3 are shown in the table below. [Table 17] The IV dose of test compound was 1 mg / kg. The dose of test compound administered SC was 30 mg / kg except for Example 24, which was administered SC at 45 mg / kg.

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

[0213] Example 19 Preparation of a 17.8% aqueous suspension A vehicle 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 with sodium hydroxide. This vehicle was sterilized by filtration through a 0.22 μm polyvinylidene fluoride (PVDF) membrane. 4150 mg of the vehicle and 890 mg of Example 19 were added to two glass vials and suspended. Zirconia beads (1 mm diameter) and a stir bar were then added, and the suspension was stirred and milled at 5°C for 17 or 65 hours using a magnetic stirrer. After milling, the suspension was separated from the zirconia beads with a pipette and transferred to separate vials. The suspension was then sterilized by 25 kGy of gamma irradiation to prepare the test formulations. The average particle size of Example 19 in the test formulation was measured using SALD-3100 under conditions of ultrasonic irradiation and a refractive index of 1.70 to 0.20i, and was found to be 1.5 μm and 0.8 μm.

[0214] method The test formulation was subcutaneously administered to male rats, and the plasma concentrations of the prodrug compound and brexpiprazole were measured. Rats were purchased from Japan SLC Co., Ltd. at 7 weeks of age and used in the experiments after acclimatization. The housing environment was as follows: food and water supply: ad libitum, rats per cage: 3, temperature: 21–25°C, humidity: 50–70%, light hours: 7:00–19:00. Under isoflurane anesthesia, the formulations of Examples 10 and 19 were subcutaneously administered to the 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 each rat 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, blood samples were mixed with 2-thenoyltrifluoroacetone 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 profile, the cumulative absorption rate at each blood sampling point was calculated by the deconvolution method.

[0215] Results and Discussion When the suspensions of Examples 10 and 19 were subcutaneously administered to rats, brexpiprazole was continuously detected in the blood for 28 days after administration. These results suggest that these compounds have suitable properties as active pharmaceutical ingredients for long-acting brexpiprazole injections. The PK profiles of Examples 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 subcutaneously administered to male and female beagle dogs, and after observation for 7 or 28 days, the dogs were dissected and the injection sites were subjected to histopathological examination. Beagle dogs were purchased from Kitayama Labes Co., Ltd. at 6–8 months of age and used in the experiments after acclimation. The housing conditions were as follows: feeding: 300 g of solid food once daily, water intake: unlimited, cage size: 1, temperature: 20–26°C, humidity: 30–70%, light hours: 7:00–19:00. Dogs were anesthetized with 1 mg / kg xylazine hydrochloride and 15 mg / kg ketamine hydrochloride and subcutaneously administered 10 mg / kg of each test formulation at different sites on the lumbar back using a plastic syringe. After administration, the dogs were observed for 7 or 28 days and then euthanized by exsanguination under anesthesia with 0.08 mg / kg medetomidine hydrochloride, 0.5 mg / kg butorphanol tartrate, and 20 mg / kg thiopental sodium. Tissue samples were collected from the injection site. The collected tissues were fixed in 10% neutral buffered formalin, and hematoxylin and eosin stained specimens were prepared for histopathological examination.

[0217] Results and Discussion During the observation period, edema and induration were observed at the injection site of each test formulation. Histopathological examination revealed that the main finding at the injection site was 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. From these results, it was concluded that Examples 10 and 19 did not have limited irritation potential. [Industrial Applicability]

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

Claims

1. Formula (I): 【Chemistry 1】 [In the formula, a is 2 or 3; R 1 is an optionally substituted straight or branched chain C 1-20 Alkylene; optionally substituted C 2-10 Alkenylene; optionally substituted divalent C 3-8 Cycloalkyl; optionally substituted divalent heterocyclic group; optionally substituted divalent C 6-10 Aryl; -NH(optionally substituted straight or branched chain C 1-20 alkylene); or optionally substituted divalent C 3-8 is cycloalkenyl; R 2 -C(O)-, -OC(O)-, -C(O)-NR a -CH 2 -, -O-, -CH 2 -, -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 linear or branched C 1-20 alkylene; R a is hydrogen or an optionally substituted straight or branched chain C 1-20 is alkyl; If a is 2, R 3 is bivalent; If a is 3, R 3 is trivalent; R 2 and R 3 are covalently linked; However, R 1 is a linear alkylene, and R 2 Ga-CH 2 - or when R is a direct bond 3 is not a straight chain alkylene] or a pharmaceutically acceptable salt thereof.

2. a is 2 or 3; R 1 optionally substituted straight or branched chain C 2-16 alkylene, wherein one or more methylene groups can be replaced by a functional group selected from -O- or -NH-, 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 -, -O-, -NH-C(O)-, -CH 2 - or a direct bond; R 3 optionally substituted divalent or trivalent piperazine, optionally substituted divalent or trivalent 2,5-diazabicyclo[2.2.2]octane, optionally substituted divalent or trivalent 2,5-diazabicyclo[2.2.1]heptane, optionally substituted divalent or trivalent octahydropyrrolo[3,4-c]pyrrole, optionally substituted divalent or trivalent pyrazine, optionally substituted divalent or trivalent 3,9-diazaspiro[5.5]undecane, optionally substituted divalent or trivalent 1,4,7-triazonane, optionally substituted divalent or trivalent 2,6-diazaspiro[3.3]heptane, optionally substituted divalent or trivalent 1,3,5-triazine, optionally substituted divalent or trivalent 1,3-thiazole, or optionally substituted linear or branched C 2-6 alkylene; If a is 2, R 3 is bivalent; If a is 3, R 3 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:

3. a is 2; R 1 optionally substituted straight or branched chain C 2-16 alkylene, in which one or more methylene groups can be replaced by oxygen or an amino group, or one or more methylene groups can be replaced by spirocyclopentane or a 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 a direct bond; R 3 optionally substituted divalent piperazine, optionally substituted divalent 2,5-diazabicyclo[2.2.2]octane, optionally substituted divalent 2,5-diazabicyclo[2.2.1]heptane, optionally substituted divalent octahydropyrrolo[3,4-c]pyrrole, optionally substituted divalent pyrazine, optionally substituted divalent 3,9-diazaspiro[5,5]undecane, optionally substituted divalent 2,6-diazaspiro[3.3]heptane, optionally substituted divalent 1,3-thiazole, or optionally substituted straight or branched chain C 2-6 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, which is alkylene.

4. a is 3; R 1 optionally substituted straight or branched chain C 2-6 alkylene, where one or more methylene groups can be replaced by a divalent piperidine; R 2 is —C(O)—, —O—, or a direct bond; R 3 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: is an optionally substituted trivalent 1,4,7-triazonane or an optionally substituted trivalent 1,3,5-triazine.

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 a direct bond; R 3 Ga-(CH 2 ) 4 -, 【Transformation 3】 2. The compound of claim 1, wherein:

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】 2. The compound of claim 1, wherein:

7. The compound is: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}piperazin-1-yl)-6-oxohexanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-[(2R,5S)-4-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-dimethylpiperazin-1-yl]-8-oxooctanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(5-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(6-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(9-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanamido}methyl)pyrazin-2-yl]methyl}carbamoyl)heptanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-7-({[5-({8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-N-methyl-8-oxooctanamido}methyl)pyrazin-2-yl]methyl}(methyl)carbamoyl)heptanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}piperazin-1-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[(2S,5R)-4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-2,5-dimethylpiperazin-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-[(3ar,6ar)-5-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[4,7-bis({4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl})-1,4,7-triazonan-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-(4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}piperazin-1-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-[(2R,5S)-4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}-2,5-dimethylpiperazin-1-yl]-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-(5-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-9-({[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-N-methyl-10-oxodecanamido}methyl)pyrazin-2-yl]methyl}(methyl)carbamoyl)nonanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}piperazin-1-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-[(2S,5R)-4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-2,5-dimethylpiperazin-1-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(6-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-[(3ar,6ar)-5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-N-methyl-6-oxohexanamido}methyl)pyrazin-2-yl]methyl}(methyl)carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanamido}methyl)pyrazin-2-yl]methyl}carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(2E)-4-{4-[(2E)-4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobut-2-enoyl]piperazin-1-yl}-4-oxobut-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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-{4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-[(2S,5R)-2,5-dimethyl-4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1s,4s)-4-{4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1s,4s)-4-[(2S,5R)-2,5-dimethyl-4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 1-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclopentanecarbonyl)piperazine-1-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[(3ar,6ar)-5-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-3-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-5-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3,3-dimethyl-5-oxopentanoyl}piperazin-1-yl)-3,3-dimethyl-5-oxopentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-2-{2-[4-(2-{2-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-2-oxoethoxy}acetyl)piperazin-1-yl]-2-oxoethoxy}acetate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-N-(8-{4-[8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)octanoyl]piperazin-1-yl}-8-oxooctyl)carbamate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-N-[(2S)-1-{4-[(2S)-2-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]piperazin-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-4-carbonyl)piperazine-1-carbonyl]piperidine-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)methyl]pyrazin-2-yl}methyl)piperidin-4-yl]propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazol-2-yl]formamido}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)pyrazin-2-yl]formamido}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-{[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecyl}carbamoyl)pyrazin-2-yl]formamide}decanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}piperazin-1-yl)hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-{4-[({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}oxy)carbonyl]piperazine-1-carbonyloxy}hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-[(4-{[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexyl]methyl}piperazin-1-yl)methyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazin-2-yl]oxy}hexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-{1-[4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(5-{4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]piperazin-1-yl}-5-oxopentyl)-1H-1,2,3-triazol-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(1-{5-[(2S,5R)-4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]-2,5-dimethylpiperazin-1-yl]-5-oxopentyl}-1H-1,2,3-triazol-4-yl)butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(5-{5-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]-2,5-diazabicyclo[2.2.2]octan-2-yl}-5-oxopentyl)-1H-1,2,3-triazol-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(6-{4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)hexanoyl]piperazin-1-yl}-6-oxohexyl)-1H-1,2,3-triazol-4-yl]butanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(1-{6-[(2S,5R)-4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)hexanoyl]-2,5-dimethylpiperazin-1-yl]-6-oxohexyl}-1H-1,2,3-triazol-4-yl)butanoate 2. The compound of claim 1, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

8. The compound is: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[4,7-bis({4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl})-1,4,7-triazonan-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-4-yl}propanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-{[4,6-bis({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}oxy)-1,3,5-triazin-2-yl]oxy}hexanoate 7. The compound of claim 6, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

9. a is 2; R 1 Ga-(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 - and; R 2 -C(O)-, -CH 2 - or a direct bond; R 3 but 【Transformation 6】 2. The compound of claim 1, wherein:

10. The compound is: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}piperazin-1-yl)-6-oxohexanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-[(2R,5S)-4-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-dimethylpiperazin-1-yl]-8-oxooctanoate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(5-{8-[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-[(1S,4S)-5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}piperazin-1-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[(2S,5R)-4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-2,5-dimethylpiperazin-1-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-(4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}piperazin-1-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-[(2R,5S)-4-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}-2,5-dimethylpiperazin-1-yl]-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-(5-{10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecanoyl}-2,5-diazabicyclo[2.2.2]octan-2-yl)-10-oxodecanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(4-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}piperazin-1-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-[(2S,5R)-4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-2,5-dimethylpiperazin-1-yl]-6-oxohexanoate; (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)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-N-(8-{4-[8-({[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)octanoyl]piperazin-1-yl}-8-oxooctyl)carbamate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(4-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexyl}piperazin-1-yl)hexanoate 10. The compound of claim 9, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

11. a is 2; R 1 but 【Transformation 7】 and R 2 -C(O)-, -CH 2 - or a direct bond; R 3 Ga-(CH 2 ) 4 -, 【Transformation 8】 2. The compound of claim 1, wherein:

12. The compound is: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-{4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-[(2S,5R)-2,5-dimethyl-4-[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1s,4s)-4-{4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl}cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1s,4s)-4-[(2S,5R)-2,5-dimethyl-4-[(1s,4s)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexanecarbonyl]piperazine-1-carbonyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 1-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclopentanecarbonyl) piperazine-1-carbonyl]cyclopentane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[(3ar,6ar)-5-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-3-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl 4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-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-dihydroquinolin-1-yl)methyl-5-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3,3-dimethyl-5-oxopentanoyl}piperazin-1-yl)-3,3-dimethyl-5-oxopentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-2-{2-[4-(2-{2-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-2-oxoethoxy}acetyl)piperazin-1-yl]-2-oxoethoxy}acetate; (7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-N-[(2S)-1-{4-[(2S)-2-({[(7-{5-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]piperazin-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[4-(1-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-4-carbonyl)piperazine-1-carbonyl]piperidine-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidine-4-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[4-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)-1,3,5-triazin-2-yl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-[1-({5-[(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidin-1-yl)methyl]pyrazin-2-yl}methyl)piperidin-4-yl]propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-3-{1-[5-(4-{3-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-3-oxopropyl}piperidine-1-carbonyl)pyrazine-2-carbonyl]piperidin-4-yl}propanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-1-[5-(3-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}azetidine-1-carbonyl)pyrazine-2-carbonyl]azetidine-3-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-(1r,4r)-4-[(4-{[(1r,4r)-4-{[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]carbonyl}cyclohexyl]methyl}piperazin-1-yl)methyl]cyclohexane-1-carboxylate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{1-[4-(4-{5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-{1-[4-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)butyl]-1H-1,2,3-triazol-4-yl}butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(5-{4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]piperazin-1-yl}-5-oxopentyl)-1H-1,2,3-triazol-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(1-{5-[(2S,5R)-4-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]-2,5-dimethylpiperazin-1-yl]-5-oxopentyl}-1H-1,2,3-triazol-4-yl)butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(5-{5-[5-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)pentanoyl]-2,5-diazabicyclo[2.2.2]octan-2-yl}-5-oxopentyl)-1H-1,2,3-triazol-4-yl]butanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-[1-(6-{4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)hexanoyl]piperazin-1-yl}-6-oxohexyl)-1H-1,2,3-triazol-4-yl]butanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(1-{6-[(2S,5R)-4-[6-(4-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutyl}-1H-1,2,3-triazol-1-yl)hexanoyl]-2,5-dimethylpiperazin-1-yl]-6-oxohexyl}-1H-1,2,3-triazol-4-yl)butanoate 12. The compound of claim 11, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

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】 2. The compound of claim 1, wherein:

14. The compound is: (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(5-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(6-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-8-(9-{8-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-8-oxooctanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-8-oxooctanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-4-(9-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-3,9-diazaspiro[5.5]undecan-3-yl)-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl 4-[(3ar,6ar)-5-{4-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-4-oxobutanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl]-4-oxobutanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(6-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-2,6-diazaspiro[3.3]heptan-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-[(3ar,6ar)-5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl]-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-6-(5-{6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanoyl}-octahydropyrrolo[3,4-c]pyrrol-2-yl)-6-oxohexanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-N-methyl-6-oxohexanamido}methyl)pyrazin-2-yl]methyl}(methyl)carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-({[5-({6-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-6-oxohexanamido}methyl)pyrazin-2-yl]methyl}carbamoyl)pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)-1,3-thiazol-2-yl]formamido}pentanoate; (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-5-{[5-({5-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-5-oxopentyl}carbamoyl)pyrazin-2-yl]formamido}pentanoate; and (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methyl-10-{[5-({10-[(7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-2-oxo-1,2-dihydroquinolin-1-yl)methoxy]-10-oxodecyl}carbamoyl)pyrazin-2-yl]formamido}decanoate 14. The compound of claim 13, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

15. 2. The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein the average particle size measured by laser diffraction is in the range of 0.05 to 10 μm.

16. A pharmaceutical composition comprising the compound of any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

17. A drug for treating and / or preventing central nervous system disorders, comprising the compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof.

18. Central nervous system disorders include 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 attack; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorder; conversion disorder; pain disorder; hypochondriasis; factitious disorder; dissociative disorder; sexual dysfunction; Sexual desire disorder; sexual arousal disorder; erectile dysfunction; 18. The drug of claim 17, wherein the drug is 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, refractory or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorders; attention deficit hyperactivity disorder; conduct disorder; Down's syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

19. Use of a compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating and / or preventing central nervous system disorders.

20. Central nervous system disorders include 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 attack; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorder; conversion disorder; pain disorder; hypochondriasis; factitious disorder; dissociative disorder; sexual dysfunction; Sexual desire disorder; sexual arousal disorder; erectile dysfunction; 20. The use of claim 19, wherein the condition is 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, refractory or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorders; attention deficit hyperactivity disorder; conduct disorder; Down's 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 to a subject in need thereof a compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof.

22. Central nervous system disorders include 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 attack; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorder; conversion disorder; pain disorder; hypochondriasis; factitious disorder; dissociative disorder; sexual dysfunction; Sexual desire disorder; sexual arousal disorder; erectile dysfunction; 22. The method of claim 21, wherein the disorder is 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, refractory or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorders; attention deficit hyperactivity disorder; conduct disorder; Down's syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

23. 16. A compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof for use in the treatment and / or prevention of central nervous system disorders.

24. Central nervous system disorders include 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 attack; panic disorder; agoraphobia; social phobia; obsessive-compulsive disorder; post-traumatic stress disorder; generalized anxiety disorder; acute stress disorder; hysteria; somatoform disorder; conversion disorder; pain disorder; hypochondriasis; factitious disorder; dissociative disorder; sexual dysfunction; Sexual desire disorder; sexual arousal disorder; erectile dysfunction; 24. The compound of claim 23, 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, refractory or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autistic disorder (autism); Tourette's syndrome; tic disorders; attention deficit hyperactivity disorder; conduct disorder; Down's syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder.

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