Novel lysyl-trna synthetase 1 inhibitor and use thereof

Abstract

The present invention relates to a novel compound as a lysyl-tRNA synthetase 1 (KARS1) inhibitor, and a use thereof, and, more specifically, to a novel compound as a lysyl-tRNA synthetase 1 inhibitor, and a use thereof for preventing or treating immune cell migration-related diseases and cancer metastasis.

Description

Novel lysyl-tRNA synthetase 1 inhibitors and uses thereof

[0001] This application claims priority to Republic of Korea Patent Application No. 10-2024-0098181, filed on July 24, 2024, the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a novel lysyl-tRNA synthetase 1 (KARS1) inhibitor and its use, and more specifically, to a novel compound as a lysyl-tRNA synthetase 1 inhibitor and its use in preventing or treating diseases related to immune cell movement and cancer metastasis.

[0003]

[0004] In various tissues within the body, each cell migrates in different ways depending on its genetic characteristics and environment. It has been reported that even the same factor interacts differently with each cell, making it more difficult to elucidate signaling processes and mechanisms. For example, AQP1 (water channel aquaporin-1) is known to promote cell migration in epithelial cells and is particularly known to promote cancer metastasis. However, despite expressing AQP1 in macrophages, it is known in the art to inhibit their migration. Because each cell has various methods and characteristics for migration, existing drugs designed to prevent specific cell migration have shown considerable limitations and insufficient efficacy. Therefore, there is a pressing need to explore new strategies to control the cell migratory switch and treat migration-related diseases.

[0005]

[0006] Meanwhile, when inflammatory immune cells are activated, increased immune cell mobility is generally observed, and specifically, in the following diseases, such immune cell migration and infiltration are reported to be closely related to the pathology of the disease.

[0007]

[0008] For example, cardiovascular disease (CVD) refers to diseases that occur in the heart and major arteries, and includes atherosclerosis and coronary artery disease. Atherosclerosis is an inflammatory disease caused by cholesterol, and is caused by atheroma, which is composed of cholesterol deposited in the inner lining of the artery and immune cells that migrate from the blood into the artery. Previously, it was known that CCL2 (CC-Chemokine ligand 2, MCP-1), which induces monocyte migration and thus triggers an inflammatory response, plays a key role in the occurrence and development of such cardiovascular diseases. Therefore, a new method for treating such cardiovascular diseases by inhibiting the action of CCL2 and the resulting monocyte migration has been proposed. Furthermore, hypertension is also related to the pathology in which various immune cells that secrete inflammatory cytokines excessively migrate into the blood vessels, thickening the blood vessel walls and causing a loss of vascular elasticity.

[0009]

[0010] Meanwhile, in diseases associated with fibrosis, a persistent (chronic) inflammatory response activates a wound-healing program, which leads to fibrosis. Following tissue damage, inflammatory immune cells, such as monocytes / macrophages, neutrophils, eosinophils, and mast cells, rapidly infiltrate the damaged area and become activated. They secrete various cytokines, which in turn activate surrounding fibroblasts, epithelial cells, and smooth muscle cells into myoblasts. These myoblasts produce and secrete large amounts of extracellular matrix proteins, ultimately leading to the accumulation of these proteins in tissues, leaving scars and inducing fibrosis or hypertrophy. This pathological mechanism is one of the fundamental causes of scarring in skin tissues caused by wounds, burns, and pressure ulcers, as well as sclerosing fibrosis in tissues such as the liver, kidneys, blood vessels, and lungs. Fibrosis is also a major pathological feature in chronic autoimmune diseases such as scleroderma, rheumatoid arthritis, Crohn's disease, ulcerative colitis, myelofibrosis, and systemic lupus erythematosus. Furthermore, the activation of inflammatory immune cells is known to contribute to the pathological phenomena of atopic diseases, asthma, COPD, psoriasis, keloids, and proliferative retinopathy.

[0011]

[0012] While monocytes and macrophages contribute to wound healing, they also secrete reactive oxygen and nitrogen, which can have detrimental effects on surrounding cells. Consequently, failure to rapidly remove monocytes and macrophages can lead to further tissue damage and fibrosis. Therefore, limiting monocytes and macrophages, which are the first to respond in the early stages of disease, is considered a therapeutic strategy for various chronic inflammatory and fibrotic diseases.

[0013]

[0014] When the above wound healing mechanism triggers a fibrotic response, platelet-derived growth factor (PDGF), involved in hemagglutination, is known to recruit other inflammatory immune cells to the wound site, and transforming growth factor-β1 (TGF-β1) promotes extracellular matrix synthesis from local fibroblasts. However, it has been reported that factors involved in hemagglutination can induce fibrosis even when they are deficient.

[0015]

[0016] As mentioned above, in diseases where excessive immune cell activation is a problem, target factors to block the movement (and infiltration) of immune cells have been proposed, and attempts are being made to devise therapeutic methods targeting these factors. However, each of these has its own limitations, and accordingly, it is still an important task to find out what the key mediator is in the movement of immune cells and what strategies to control it are for effective disease treatment.

[0017]

[0018] Accordingly, the present inventors, while researching to find a new therapeutic strategy for diseases related to immune cell migration (infiltration) through existing research, confirmed that the phenomenon of increased KARS1 levels in the cell membrane region of immune cells (monocytes / macrophages) is an important pathological phenomenon for diseases related to immune cell migration and infiltration, and confirmed that novel compounds represented by the general formula of Chemical Formula 1 have the effect of inhibiting immune cell migration and infiltration by inhibiting the activity of KARS1 and inhibiting the migration of cancer cells, thereby treating related diseases, and completed the present invention.

[0019]

[0020] Accordingly, an object of the present invention is to provide a compound selected from the group consisting of the following chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof:

[0021] [Chemical Formula 1]

[0022]

[0023] In the above chemical formula 1,

[0024] X is one of NH, O, S, CH=N,

[0025] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0026] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C2 alkoxy, -CF3, -CN or -NO2,

[0027] Q may be methylene or -(C=O)- or may not exist,

[0028] R5 is hydrogen or C1~C6 alkyl,

[0029] D is phenyl or heteroaryl of 5 to 6 atoms,

[0030] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2 and C1~C6 alkoxy,

[0031] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0032] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or halogen;

[0033]

[0034] [Chemical Formula 2]

[0035]

[0036] In the above chemical formula 2,

[0037] X is one of NH, O, S, CH=N

[0038] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0039] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0040] Q may be methylene or -(C=O)- or may not exist,

[0041] R5 is hydrogen or C1~C6 alkyl,

[0042] D is phenyl or heteroaryl of 5 to 6 atoms,

[0043] R6 is one or more substituents, each of which can be independently H, halogen, OH, NH2, C1~C6 alkyl, C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2, and C1~C6 alkoxy,

[0044] R7 and R8 are each independently H, NH2, C1~C6 alkoxy group, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group.

[0045] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or F, and when one of the substituents of R9 is F, all of R6 can be H;

[0046]

[0047] [Chemical Formula 3]

[0048]

[0049] In the above chemical formula 3,

[0050] X is independently N, NH, C, O, S, CH, CH2 or CH=N,

[0051] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0052] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0053] Q may be methylene or -(C=O)- or may not exist,

[0054] R5 is H, C1~C6 alkyl or -(C=O)-,

[0055] D is phenyl or heteroaryl of 5 to 6 atoms,

[0056] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2 and C1~C6 alkoxy,

[0057] R7 and R8 are each independently H, NH2, halogen, C1~C6 alkoxy group, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0058] When either one of R7 and R8 is halogen, both R6 can be H,

[0059] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0060]

[0061] [Chemical Formula 4]

[0062]

[0063] In the above chemical formula 4,

[0064] X is independently N, NH, C, O, S, CH, CH2 or CH=N.

[0065] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0066] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0067] Q may be methylene or -(C=O)- or may not exist,

[0068] R5 is H, C1~C6 alkyl or -(C=O)-,

[0069] D is phenyl or heteroaryl of 5 to 6 atoms,

[0070] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2, C1~C6 alkoxy,

[0071] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen, -(C=O)NH2 or C1~C6 alkyl group,

[0072] When at least one of R7 and R8 is halogen, both R6 can be H,

[0073] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F

[0074] am;

[0075]

[0076] [Chemical Formula 5]

[0077]

[0078] In the above chemical formula 5,

[0079] X is independently one of N, NH, C, O, S, CH, CH2 and CH=N, and at least one X of the double D ring must be N,

[0080] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0081] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0082] Q may be methylene or -(C=O)- or may not exist,

[0083] R5 can be H, C1~C6 alkyl or -(C=O)-,

[0084] R6 is one or more substituents, each independently H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy,

[0085] E is phenyl, heteroaryl of 5 to 6 atoms,

[0086] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0087] If at least one of R7 and R8 is double bond oxygen (=O), alkoxy, amine or sulfonic acid, all Xs of the D ring can be CH,

[0088] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0089]

[0090] [Chemical Formula 6]

[0091]

[0092] In the above chemical formula 6,

[0093] X is NH, O, S, CH or CH=N,

[0094] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0095] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0096] n is 1 or 2,

[0097] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group.

[0098] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or F;

[0099]

[0100] [Chemical Formula 7]

[0101]

[0102] In the above chemical formula 7,

[0103] R5 is H, C1~C6 alkyl or -(C=O)-,

[0104] X is independently N, C or CH,

[0105] R6 is one or more substituents, each independently H, =O, or a C1~C6 alkyl group,

[0106] E is phenyl, heteroaryl consisting of 5 to 10 atoms,

[0107] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group.

[0108] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0109]

[0110] [Chemical Formula 8]

[0111]

[0112]

[0113] In the above chemical formula 8,

[0114] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group,

[0115] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F.

[0116]

[0117] Another object of the present invention is to provide a pharmaceutical composition for preventing or treating a disease related to immune cell movement, comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0118]

[0119] Another object of the present invention is to provide a pharmaceutical composition for preventing or inhibiting cancer cell metastasis, comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0120]

[0121] Another object of the present invention is to provide a use of the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof for preparing a composition for treating a disease related to immune cell migration.

[0122]

[0123] Another object of the present invention is to provide a method for treating a disease related to immune cell migration, which comprises administering an effective amount of a composition comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0124]

[0125] Another object of the present invention is to provide a use of the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for preventing or inhibiting cancer metastasis.

[0126]

[0127] Another object of the present invention is to provide a method for preventing or inhibiting cancer metastasis, comprising administering to a subject in need thereof an effective amount of a composition comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof.

[0128]

[0129] In order to achieve the above-described object of the present invention, the present invention provides a compound selected from the group consisting of the following chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof:

[0130] [Chemical Formula 1]

[0131]

[0132] In the above chemical formula 1,

[0133] X is one of NH, O, S, CH=N,

[0134] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0135] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C2 alkoxy, -CF3, -CN or -NO2,

[0136] Q may be methylene or -(C=O)- or may not exist,

[0137] R5 is hydrogen or C1~C6 alkyl,

[0138] D is phenyl or heteroaryl of 5 to 6 atoms,

[0139] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2 and C1~C6 alkoxy,

[0140] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0141] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or halogen;

[0142]

[0143] [Chemical Formula 2]

[0144]

[0145] In the above chemical formula 2,

[0146] X is one of NH, O, S, CH=N

[0147] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0148] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0149] Q may be methylene or -(C=O)- or may not exist,

[0150] R5 is hydrogen or C1~C6 alkyl,

[0151] D is phenyl or heteroaryl of 5 to 6 atoms,

[0152] R6 is one or more substituents, each of which can be independently H, halogen, OH, NH2, C1~C6 alkyl, C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2, and C1~C6 alkoxy,

[0153] R7 and R8 are each independently H, NH2, C1~C6 alkoxy group, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group.

[0154] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or F, and when one of the substituents of R9 is F, all of R6 can be H;

[0155]

[0156] [Chemical Formula 3]

[0157]

[0158] In the above chemical formula 3,

[0159] X is independently N, NH, C, O, S, CH, CH2 or CH=N,

[0160] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0161] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0162] Q may be methylene or -(C=O)- or may not exist,

[0163] R5 is H, C1~C6 alkyl or -(C=O)-,

[0164] D is phenyl or heteroaryl of 5 to 6 atoms,

[0165] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2 and C1~C6 alkoxy,

[0166] R7 and R8 are each independently H, NH2, halogen, C1~C6 alkoxy group, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0167] When either one of R7 and R8 is halogen, both R6 can be H,

[0168] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0169]

[0170] [Chemical Formula 4]

[0171]

[0172] In the above chemical formula 4,

[0173] X is independently N, NH, C, O, S, CH, CH2 or CH=N.

[0174] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0175] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0176] Q may be methylene or -(C=O)- or may not exist,

[0177] R5 is H, C1~C6 alkyl or -(C=O)-,

[0178] D is phenyl or heteroaryl of 5 to 6 atoms,

[0179] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2, C1~C6 alkoxy,

[0180] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen, -(C=O)NH2 or C1~C6 alkyl group,

[0181] When at least one of R7 and R8 is halogen, both R6 can be H,

[0182] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F

[0183] am;

[0184]

[0185] [Chemical Formula 5]

[0186]

[0187] In the above chemical formula 5,

[0188] X is independently one of N, NH, C, O, S, CH, CH2 and CH=N, and at least one X of the double D ring must be N,

[0189] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0190] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0191] Q may be methylene or -(C=O)- or may not exist,

[0192] R5 can be H, C1~C6 alkyl or -(C=O)-,

[0193] R6 is one or more substituents, each independently H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy,

[0194] E is phenyl, heteroaryl of 5 to 6 atoms,

[0195] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0196] If at least one of R7 and R8 is double bond oxygen (=O), alkoxy, amine or sulfonic acid, all Xs of the D ring can be CH,

[0197] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0198]

[0199] [Chemical Formula 6]

[0200]

[0201] In the above chemical formula 6,

[0202] X is NH, O, S, CH or CH=N,

[0203] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0204] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0205] n is 1 or 2,

[0206] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group.

[0207] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or F;

[0208]

[0209] [Chemical Formula 7]

[0210]

[0211] In the above chemical formula 7,

[0212] R5 is H, C1~C6 alkyl or -(C=O)-,

[0213] X is independently N, C or CH,

[0214] R6 is one or more substituents, each independently H, =O, or a C1~C6 alkyl group,

[0215] E is phenyl, heteroaryl consisting of 5 to 10 atoms,

[0216] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group.

[0217] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0218]

[0219] [Chemical Formula 8]

[0220]

[0221] In the above chemical formula 8,

[0222] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group,

[0223] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F.

[0224]

[0225] In order to achieve another object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating a disease related to immune cell movement, comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0226]

[0227] In order to achieve another object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating a disease related to immune cell movement, comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof.

[0228]

[0229] In order to achieve another object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating a disease related to immune cell movement, which consists essentially of the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof.

[0230]

[0231] In order to achieve another object of the present invention, the present invention provides a pharmaceutical composition for preventing or inhibiting cancer cell metastasis, comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0232]

[0233] In order to achieve another object of the present invention, the present invention provides a use of the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof for preparing a composition for treating a disease related to immune cell movement.

[0234]

[0235] In order to achieve another object of the present invention, the present invention provides a method for treating a disease related to immune cell movement, which comprises administering an effective amount of a composition comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0236]

[0237] In order to achieve another object of the present invention, the present invention provides the use of the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for preventing or inhibiting cancer metastasis.

[0238]

[0239] In order to achieve another object of the present invention, the present invention provides a method for preventing or inhibiting cancer metastasis, comprising administering an effective amount of a composition comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0240]

[0241] In this specification, the term “comprising” is used with the same meaning as “including” or “characterized by,” and does not exclude additional components or method steps, etc. that are not specifically mentioned in the composition or method according to the present invention. In addition, the term “consisting of” means excluding additional elements, steps, or components, etc. that are not separately described. The term “essentially consisting of” means that, in the scope of the composition or method, it may include materials or steps, etc. that do not substantially affect the basic characteristics thereof, in addition to the materials or steps described.

[0242]

[0243] The 'treatment' of the present invention comprehensively refers to improving symptoms caused by cancer or the disease, which may include curing, substantially preventing, or improving the condition of the disease, and includes, but is not limited to, alleviating, curing, or preventing one or most of the symptoms resulting from the disease.

[0244]

[0245] In this specification, unless otherwise stated, the alkyl, alkenyl, or alkynyl substituents or alkyne alkenyl moieties of a substituent may be linear or branched (branched chain, side chain). The alkyl and alkenyl chains may also include intervening heteroatoms such as oxygen.

[0246]

[0247] In this specification, unless otherwise stated, one or more substituents may mean, but is not limited to, one, two, three, four, five or six substituents.

[0248]

[0249] Cx-Cy alkyl refers to a saturated aliphatic hydrocarbon group having xy carbon atoms, which may be linear or branched. C1-C6 alkyl contains 1 to 6 carbon atoms. “Branched” means that the group has one or more carbon branch points. For example, tert-butyl and isopropyl are both branched groups. Examples of C1-C6 alkyl groups include methyl, ethyl, propyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, and n-hexyl.

[0250]

[0251] A Cx-Cy alkylene moiety may be linear or branched and refers to a divalent hydrocarbon group having one less hydrogen atom from a Cx-Cy alkyl as defined above. Non-limiting examples of C1-C6 alkylene groups include methylene, ethylene, n-propylene, n-butylene, methylmethylene, and dimethylmethylene.

[0252]

[0253] C2-C6 alkenyl refers to a linear or branched hydrocarbon chain radical containing at least two carbon atoms and one or more double bonds. Non-limiting examples of alkenyl groups include ethenyl, propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 1-hexenyl, 2-methyl-1-propenyl, 1,2-butadienyl, 1,3-pentadienyl, 1,4-pentadienyl, and 1-hexadienyl.

[0254]

[0255] C1-C6 alkoxy refers to a group or a part of a group having an -O-Cx-Cy alkyl group, as defined above for Cx-Cy alkyl. Non-limiting examples of C1-C6 alkoxy may include methoxy, ethoxy, propoxy, isopropoxy, butoxy, pentoxy, and hexoxy.

[0256]

[0257] Halogen or halo refers to chlorine (Cl), bromine (Br), fluorine (F), or iodine (I) atoms.

[0258]

[0259] Cx-Cy cycloalkyl refers to a cyclic non-aromatic hydrocarbon group of xy carbon atoms. C3-C10 cycloalkyl refers to a hydrocarbon ring containing 3-10 carbon atoms. Non-limiting examples of C3-C10 cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentyl, cyclohexyl cycloheptyl, cyclooctyl, cyclononyl, and cyclodecyl.

[0260]

[0261] For example, an aryl group refers to any monocyclic or bicyclic hydrocarbon group containing at least one aromatic group, with ring members having 12 or fewer carbon atoms. Non-limiting examples of aryl groups include phenyl, naphthyl, tetrahydronaphthyl, and biphenyl.

[0262]

[0263] A heteroaryl group may be monocyclic or bicyclic. A bicyclic ring may be a fused aromatic ring, wherein the rings are aromatic or fused to one another, wherein one of the rings is non-aromatic. A heteroaryl group contains one, two, or three heteroatoms selected from oxygen (O), sulfur (S), and nitrogen (N). If the heteroatom is nitrogen, it may be oxidized. Non-limiting examples of heteroaryl include pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, furyl, thiophenyl, pyrrolyl, oxazolyl, thiazolyl, pyrazolyl, triazolyl, tetrazolyl, indolyl, indolizinyl, isoindolyl, indolinyl, purinyl, furazanyl, imidazolyl, indazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazinanyl, tetrazolyl, thiadiazolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, isobenzothiophenyl, benzimidazolyl, benzothiazolyl, naphthyridinyl, piperidinyl, pyrazinyl, 4H-quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, It may include quinazolinyl, imidazopyridinyl, pyrazolopyridinyl, thiazolopyridinyl, indolinyl, isoindolinyl, triazinyl, pyridazinyl, and quinoxalinyl.

[0264]

[0265] A heterocyclyl group may also be a single ring or may comprise two or more fused rings which may be saturated or partially unsaturated and which contain one, two or three heteroatoms selected from oxygen (O), sulfur (S) and nitrogen (N). Non-limiting examples of heterocyclyl include azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, diazepanyl, dihydrofuranyl (i.e., 2,3-dihydrofuranyl, 2,5-dihydrofuranyl), 4,5-dihydro-1H-maleimido, dioxolanyl, morpholinyl, oxazolidinyl, piperazinyl, tetrahydrofuranyl, thiomorpholinyl, dihydropyranyl (i.e., 3,4-dihydropyranyl, 3,6-dihydropyranyl), dioxanyl, hexahydropyrimidinyl, pyrazolinyl, pyrazolidinyl, pyridazinyl, 4H-quinolizinyl, quinuclinyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydropyrimidinyl, It may include tetrahydrothiophenyl, tetramethylene sulfoxide, thiazolidinyl, hydantoinyl, benzopyranyl, tetrahydrothiazolopyridinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, tetrahydropyrazolopyrazinyl, and tetrahydrothiazoloazepinyl.

[0266]

[0267] Pharmaceutically acceptable refers to compositions and molecular entities that are physiologically tolerable and do not generally cause allergic or similar adverse reactions, such as gastrointestinal upset or dizziness, when administered to humans or animals. For example, the term “pharmaceutically acceptable” means that the molecule or the like has been approved by a regulatory agency of a state or federal government in the United States, or is included in the United States Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly, in humans.

[0268]

[0269] General methods for preparing salts are well known to those skilled in the art. The salts may be formed by conventional means, such as by reacting the free acid or free base form of the compound with one or more equivalents of a suitable solvent, or, if the salt is insoluble, by removing the solvent or medium using standard techniques (e.g., vacuum, freeze-drying, or filtration). Salts may also be prepared by exchanging the counter ion of the compound with another counter ion in the form of a salt using an aqueous labeled ion exchange resin.

[0270]

[0271] Pharmaceutically acceptable salts, hydrates, solvates, tautomers, polymorphs, and prodrugs of the compounds described herein are also provided. The terms "pharmaceutically acceptable" or "physiologically acceptable" refer to compounds, salts, compositions, formulations, and other materials useful for preparing pharmaceutical compositions suitable for veterinary or human pharmaceutical use.

[0272]

[0273] The compounds described herein can be prepared and / or formulated as pharmaceutically acceptable salts or, where appropriate, as free bases. Pharmaceutically acceptable salts are non-toxic salts of the free base form of the compound that retain the desired pharmacological activity of the free base. These salts can be derived from inorganic or organic acids or bases. For example, compounds containing a basic nitrogen can be prepared as pharmaceutically acceptable salts by contacting the compound with an inorganic or organic acid. Non-limiting examples of pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caproate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexyne-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, methylsulfonate, Propylsulfonate, besylate, xylenesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, γ-hydroxybutyrate, glycolate, tartrate, and mandelate. A list of other suitable pharmaceutically acceptable salts can be found in literature known in the art.

[0274]

[0275] Examples of “pharmaceutically acceptable salts” of the compounds disclosed herein also include salts derived from suitable bases such as alkali metals (e.g., sodium, potassium), alkaline earth metals (e.g., magnesium), ammonium, and N(C1-C4 alkyl)4+. Also included are base addition salts such as sodium or potassium salts.

[0276]

[0277] General methods for preparing salts are well known to those skilled in the art. The salts may be formed by conventional means, such as by reacting the free acid or free base form of the compound with one or more equivalents of a suitable solvent, or, if the salt is insoluble, by removing the solvent or medium using standard techniques (e.g., vacuum, freeze-drying, or filtration). Salts may also be prepared by exchanging the counter ion of the compound with another counter ion in the form of a salt using an aqueous labeled ion exchange resin.

[0278]

[0279] Also provided are compounds described herein, or pharmaceutically acceptable salts, isomers or mixtures thereof, wherein 1 to n hydrogen atoms attached to a carbon atom may be replaced with deuterium atoms or D, wherein n is the number of hydrogen atoms in the molecule. As is known in the art, deuterium atoms are non-radioactive isotopes of hydrogen atoms. Such compounds may be useful for increasing the half-life of the compounds described herein, or pharmaceutically acceptable salts, isomers or mixtures thereof, when administered to a mammal, since such compounds may increase metabolic resistance. See, for example, literature known in the art. Such compounds are synthesized by means well known in the art, for example, using starting materials in which one or more hydrogen atoms are replaced with deuterium. In some embodiments, the compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), or (If) comprises one or more deuterium atoms.

[0280]

[0281] Examples of isotopes that can be incorporated into the disclosed compounds are also, respectively, 2 H, 3 H, 11 C, 　13 C,14 C, 13 N, 　15 N, 15 O, 17 O, 18 O, 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I and 125 I include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine. Substitution with positron-emitting isotopes such as 11C, 18F, 15O, and 13N may be useful in positron emission topography (PET) studies to investigate substrate receptor occupancy. Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art or by methods analogous to those described in the Examples presented below using appropriate isotopically labeled reagents in place of previously used unlabeled reagents.

[0282]

[0283] The compounds of the embodiments disclosed herein, or pharmaceutically acceptable salts thereof, contain one or more asymmetric centers and therefore can form enantiomers, diastereomers and other stereoisomers which can be defined in terms of absolute stereochemistry as (R)- or (S)-, or in the case of amino acids as (D)- or (L)-. The present disclosure is meant to include all such possible isomers as well as their racemates and optically pure forms. The optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques such as chromatography and fractional crystallization. Conventional techniques for the preparation / separation of individual enantiomers include chiral synthesis from appropriate optically pure precursors, or resolution of the racemate (or racemates of salts or derivatives) using, for example, chiral high pressure liquid chromatography (HPLC). When a compound described herein contains an olefinic double bond or other center of geometric asymmetry, and unless otherwise specified, the compound is intended to include both E and Z geometric isomers. Likewise, all tautomers are intended to be included. When a compound is represented by its chiral form, it is understood that embodiments include, but are not limited to, the particular diastereomeric or enantiomerically enriched form. When chirality is not specified but is present, embodiments are understood to relate to the particular diastereomeric or enantiomerically enriched form; or a racemic or scalemic mixture of such compound(s). As used herein, a “scalemic mixture” is a mixture of stereoisomers in a ratio other than 1:1.

[0284]

[0285] Stereoisomers are compounds that are non-interchangeable, having identical atoms bonded by identical bonds but different three-dimensional structures. The present disclosure contemplates various stereoisomers and mixtures thereof, including "enantiomers," which refer to two stereoisomers whose molecules are non-superimposable mirror images of each other.

[0286]

[0287] Tautomerism refers to the transfer of a proton from one atom of a molecule to another atom of the same molecule. In some embodiments, the present disclosure encompasses tautomers of the compounds.

[0288]

[0289] Solvates refer to the result of the interaction between a solvent and a compound. Solvates of salts of the compounds described herein are also provided. Hydrates of the compounds described herein are also provided.

[0290]

[0291] Hydrate refers to a compound of the present disclosure chemically bound to one or more water molecules.

[0292]

[0293] Hereinafter, the present invention will be described in detail.

[0294]

[0295] The present invention provides a compound selected from the group consisting of the following chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof:

[0296] [Chemical Formula 1]

[0297]

[0298] In the above chemical formula 1,

[0299] X is one of NH, O, S, CH=N,

[0300] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0301] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C2 alkoxy, -CF3, -CN or -NO2,

[0302] Q may be methylene or -(C=O)- or may not exist,

[0303] R5 is hydrogen or C1~C6 alkyl,

[0304] D is phenyl or heteroaryl of 5 to 6 atoms,

[0305] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2 and C1~C6 alkoxy,

[0306] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0307] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or halogen;

[0308]

[0309] [Chemical Formula 2]

[0310]

[0311] In the above chemical formula 2,

[0312] X is one of NH, O, S, CH=N

[0313] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0314] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0315] Q may be methylene or -(C=O)- or may not exist,

[0316] R5 is hydrogen or C1~C6 alkyl,

[0317] D is phenyl or heteroaryl of 5 to 6 atoms,

[0318] R6 is one or more substituents, each of which can be independently H, halogen, OH, NH2, C1~C6 alkyl, C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2, and C1~C6 alkoxy,

[0319] R7 and R8 are each independently H, NH2, C1~C6 alkoxy group, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group.

[0320] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or F, and when one of the substituents of R9 is F, all of R6 can be H;

[0321]

[0322] [Chemical Formula 3]

[0323]

[0324] In the above chemical formula 3,

[0325] X is independently N, NH, C, O, S, CH, CH2 or CH=N,

[0326] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0327] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0328] Q may be methylene or -(C=O)- or may not exist,

[0329] R5 is H, C1~C6 alkyl or -(C=O)-,

[0330] D is phenyl or heteroaryl of 5 to 6 atoms,

[0331] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2 and C1~C6 alkoxy,

[0332] R7 and R8 are each independently H, NH2, halogen, C1~C6 alkoxy group, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0333] When either one of R7 and R8 is halogen, both R6 can be H,

[0334] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0335]

[0336] [Chemical Formula 4]

[0337]

[0338] In the above chemical formula 4,

[0339] X is independently N, NH, C, O, S, CH, CH2 or CH=N.

[0340] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0341] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0342] Q may be methylene or -(C=O)- or may not exist,

[0343] R5 is H, C1~C6 alkyl or -(C=O)-,

[0344] D is phenyl or heteroaryl of 5 to 6 atoms,

[0345] R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2, C1~C6 alkoxy,

[0346] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen, -(C=O)NH2 or C1~C6 alkyl group,

[0347] When at least one of R7 and R8 is halogen, both R6 can be H,

[0348] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F

[0349] am;

[0350]

[0351] [Chemical Formula 5]

[0352]

[0353] In the above chemical formula 5,

[0354] X is independently one of N, NH, C, O, S, CH, CH2 and CH=N, and at least one X of the double D ring must be N,

[0355] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0356] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0357] Q may be methylene or -(C=O)- or may not exist,

[0358] R5 can be H, C1~C6 alkyl or -(C=O)-,

[0359] R6 is one or more substituents, each independently H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy,

[0360] E is phenyl, heteroaryl of 5 to 6 atoms,

[0361] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group,

[0362] If at least one of R7 and R8 is double bond oxygen (=O), alkoxy, amine or sulfonic acid, all Xs of the D ring can be CH,

[0363] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0364]

[0365] [Chemical Formula 6]

[0366]

[0367] In the above chemical formula 6,

[0368] X is NH, O, S, CH or CH=N,

[0369] A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S,

[0370] R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2,

[0371] n is 1 or 2,

[0372] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group.

[0373] R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or F;

[0374]

[0375] [Chemical Formula 7]

[0376]

[0377] In the above chemical formula 7,

[0378] R5 is H, C1~C6 alkyl or -(C=O)-,

[0379] X is independently N, C or CH,

[0380] R6 is one or more substituents, each independently H, =O, or a C1~C6 alkyl group,

[0381] E is phenyl, heteroaryl consisting of 5 to 10 atoms,

[0382] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group.

[0383] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F;

[0384]

[0385] [Chemical Formula 8]

[0386]

[0387] In the above chemical formula 8,

[0388] R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group,

[0389] R9 is one or more substituents, each independently H, C1~C6 alkoxy or F.

[0390]

[0391] In one aspect of the present invention, in the chemical formulas 1 to 6, A may be characterized as being benzene, pyridine, pyrimidine, pyridone or pyrrole forming a bicyclic aromatic ring together with B.

[0392]

[0393] In another aspect of the present invention, the bicyclic aromatic ring formed by A and B may be characterized by being selected from the following structures:

[0394] , , , and

[0395]

[0396] In another aspect of the present invention, the ring D in the chemical formulae 1 to 5 may be characterized as being phenyl or pyridinyl.

[0397]

[0398] 본 발명의 다른 일 양태에서, 상기 화합물은 하기 화합물로 이루어진 군에서 선택되는 것을 특징으로 할 수 있다:

[0399] (S)-1-(4-(((2-fluoro-4-methoxyphenethyl)(7-fluorobenzo[d]thiazol-2-yl)amino)methyl)phenyl)pyrrolidine-3-carboxylic acid,

[0400] 4-(3-((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)piperidin-1-yl)benzoic acid,

[0401] 3-(3-((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)pyrrolidin-1-yl)benzoic acid,

[0402] 4-(3-((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)pyrrolidin-1-yl)benzoic acid,

[0403] 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-[1,1'-biphenyl]-3-sulfonic acid,

[0404] 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-5-methoxy-[1,1'-biphenyl]-3-carboxylic acid,

[0405] 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-2-methoxy-[1,1'-biphenyl]-3-carboxylic acid,

[0406] 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-6-methoxy-[1,1'-biphenyl]-3-carboxylic acid,

[0407] 5-amino-4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-[1,1'-biphenyl]-3-carboxylic acid,

[0408] 6-amino-4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-[1,1'-biphenyl]-3-carboxylic acid,

[0409] 1-(2-fluoro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)azetidine-3-carboxylic acid,

[0410] 4-fluoro-1-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)piperidine-4-carboxylic acid,

[0411] (S)-1-(3,5-difluoro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)pyrrolidine-3-carboxylic acid,

[0412] 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-2,3,4,5-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid,

[0413] 1-(5-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)pyridin-2-yl)-1H-pyrazole-4-carboxylic acid,

[0414] 5'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-[2,2'-bipyridine]-6-carboxylic acid,

[0415] 1-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)-2-oxopiperidine-4-carboxylic acid,

[0416] 1-(3,5-difluoro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)azetidine-3-carboxylic acid,

[0417] 3-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)piperidin-1-yl)benzoic acid,

[0418] 3-(4-((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)carbamoyl)piperazin-1-yl)benzoic acid,

[0419] 4-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)piperazine-1-sulfonic acid,

[0420] (S)-1-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)-5-oxopyrrolidine-3-carboxylic acid,

[0421] 2-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)piperidin-1-yl)thiazole-5-carboxylic acid,

[0422] 1-(3-fluoro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)azetidine-3-carboxylic acid,

[0423] 1-(3-chloro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)azetidine-3-carboxylic acid,

[0424] 1-(2-fluoro-4-(((3-fluoro-4-methoxyphenethyl)(7-fluorobenzo[d]thiazol-2-yl)amino)methyl)phenyl)azetidine-3-carboxylic acid, and

[0425] 1-(2-fluoro-4-(((2-fluoro-4-methoxyphenethyl)(7-fluorobenzo[d]thiazol-2-yl)amino)methyl)phenyl)azetidine-3-carboxylic acid.

[0426]

[0427] The present invention also provides a pharmaceutical composition for preventing or treating a disease related to immune cell movement, comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[0428]

[0429] In the present invention, the term 'immune cell' refers to a cell involved in an immune response in the body, and is not particularly limited in type as long as it is known in the art as an immune cell, and in particular, is known as an immune cell existing in the human body, but includes monocytes, macrophages, neutrophils, eosinophils, basophils, dendritic cells, natural killer cells, megakaryocytes, T cells, and B cells. Preferably, it may refer to monocytes, macrophages, or neutrophils. Immune cells express KARS1.

[0430]

[0431] In the present invention, the term 'disease related to immune cell movement' is not particularly limited in its specific type as long as it is known in the art that excessive immune cell movement (or / and infiltration) is a major pathogenic mechanism, but may be selected from the group consisting of, for example, cardiovascular disease, fibrotic disease, inflammatory disease, and Alport syndrome.

[0432]

[0433] The above cardiovascular disease is not particularly limited in its specific type, but may be selected from the group consisting of, for example, hypertension (including inflammatory complications due to hypertension), pulmonary hypertension, atherosclerosis, angina pectoris, myocardial infarction, ischemic cerebrovascular disease, arteriosclerosis, and media sclerosis.

[0434]

[0435] The above fibrotic diseases are not particularly limited in their specific types, but include, for example, scleroderma, rheumatoid arthritis, neural fibrosis, Crohn's disease, ulcerative colitis, myelofibrosis, pulmonary fibrosis, hepatic fibrosis, liver cirrhosis, kidney fibrosis, glomerulosclerosis, myofibrosis, cardiac fibrosis, interstitial fibrosis, pancreatic fibrosis, splenic fibrosis, mediastinal fibrosis, vascular fibrosis, skin fibrosis, ocular fibrosis, macular degeneration, arthrofibrosis, thyroid fibrosis, endomyocardial fibrosis, peritoneal fibrosis, retroperitoneal fibrosis, progressive mass fibrosis, nephrogenic systemic fibrosis, and systemic erythematosus. It can be characterized by being selected from the group consisting of systemic lupus erythematosus, hereditary fibrosis, infectious fibrosis, irritant fibrosis, chronic autoimmune fibrosis, fibrosis due to antigen incompatibility in organ transplantation, fibrotic complications of surgery, fibrosis due to hyperlipidemia, fibrosis due to obesity, diabetic fibrosis, fibrosis due to hypertension, and occlusion due to fibrosis during stent insertion.

[0436]

[0437] In the present invention, the inflammatory disease is not particularly limited in type, but is preferably an autoimmune disease, inflammatory bowel disease, dermatitis, atopic dermatitis, eczema, psoriasis, diabetic eye disease, diabetic retinopathy, peritonitis, osteomyelitis, cellulitis, meningitis, encephalitis, pancreatitis, trauma-induced shock, bronchial asthma, rhinitis, sinusitis, otitis media, pneumonia, gastritis, enteritis, cystic fibrosis, stroke, bronchitis, bronchiolitis, hepatitis, cirrhosis, metabolic dysfunction-associated steatohepatitis, chronic kidney disease, nephritis, proteinuria, diabetic renal failure, arthritis, psoriatic arthritis, neuritis, diabetic neuropathy, multiple sclerosis, gout, spondylitis, Reiter's syndrome, polyarteritis nodosa, vasculitis, Lou Gehrig's disease, Wegener's granulomatosis, hypercytokinemia, Polymyalgia rheumatica, articular cell arteritis, calcium crystal deposition arthropathy, pseudogout, non-articular rheumatism, bursitis, tenosynovitis, epicondylitis, Charcot's joint, hemarthrosis, Henoch-Schonlein purpura, hypertrophic osteoarthropathy, multicentric reticulohistiocytoma, surcoilosis, hemochromatosis, sickle cell disease, hyperlipoproteinemia, hypogammaglobulinemia, hyperparathyroidism, acromegaly, familial Mediterranean fever, Behçet's disease, systemic lupus erythematosus, relapsing fever, psoriasis, multiple sclerosis, sepsis, septic shock, acute respiratory distress syndrome, multiple organ failure, chronic obstructive pulmonary disease, acute lung injury, and bronchopulmonary It may be characterized by being selected from the group consisting of broncho-pulmonary dysplasia.

[0438]

[0439] In the present invention, the autoimmune disease may be characterized as being selected from the group consisting of rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, psoriasis, asthma, ulcerative colitis, Behcet's disease, Crohn's disease, multiple sclerosis, dermatomyositis, collagen disease, vasculitis, arthritis, granulomatosis, organ-specific autoimmune lesions, ulcerative colitis, and graft-versus-host disease.

[0440]

[0441] The above chronic inflammatory disease refers to a state in which the above-mentioned types of inflammatory diseases have become chronic, and preferred examples thereof include, but are not limited to, asthma, atopic dermatitis, eczema, psoriasis, osteoarthritis, gout, psoriatic arthritis, cirrhosis, non-alcoholic steatohepatitis, chronic obstructive pulmonary disease, rhinitis, diabetic retinopathy, diabetic nephropathy, chronic renal failure, diabetic neuropathy, and multiple sclerosis.

[0442]

[0443] The pharmaceutical composition according to the present invention may be formulated in a suitable form, containing the compound of the present invention alone or together with one or more pharmaceutically acceptable carriers, and may additionally contain excipients or diluents. As used herein, "pharmaceutically acceptable" refers to a non-toxic composition that is physiologically acceptable and does not typically cause allergic reactions or similar reactions, such as gastrointestinal upset or dizziness, when administered to humans.

[0444]

[0445] In the present invention, the content of the composition is not particularly limited depending on the purpose or aspect of use, and may be, for example, 0.01 to 99 wt%, preferably 0.5 to 50 wt%, and more preferably 1 to 30 wt%, based on the total weight of the composition. In addition, the pharmaceutical composition according to the present invention may further include additives such as pharmaceutically acceptable carriers, excipients, or diluents in addition to the active ingredient. The pharmaceutical composition of the present invention may include 0.1 to 99.9 wt% of the compounds represented by chemical formulas 1 to 6 prepared by the method of the present invention, and may include 99.9% to 0.1 wt% of the carrier.

[0446]

[0447] Pharmaceutically acceptable carriers may further include, for example, carriers for oral administration or carriers for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc. In addition, various drug delivery substances used for oral administration of peptide formulations may be included. In addition, carriers for parenteral administration may include water, suitable oils, saline solution, aqueous glucose, and glycols, etc., and may further include stabilizers and preservatives. Suitable stabilizers include antioxidants such as sodium bisulfite, sodium sulfite, or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.

[0448]

[0449] The pharmaceutical composition of the present invention may further comprise, in addition to the above ingredients, lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, etc. Other pharmaceutically acceptable carriers and formulations may be referred to as those described in literature known in the art.

[0450]

[0451] The composition of the present invention can be administered to mammals, including humans, by any method. For example, it can be administered orally or parenterally. Specifically, the route of administration of the composition of the present invention can be, but is not limited to, injection or infusion via known routes, such as intravenous, intraperitoneal, intracerebral, subcutaneous, intramuscular, intraocular, intraarterial, intracerebrospinal, or intralesional routes, or injection or infusion using a sustained-release system as described below. For example, the compound of the present invention can be administered systemically or locally.

[0452]

[0453] The pharmaceutical composition of the present invention can be formulated as a preparation for oral administration or parenteral administration according to the administration route described above.

[0454]

[0455] In the pharmaceutical composition according to the present invention, the compound can be administered in various oral and parenteral dosage forms during clinical administration. When formulating, it can be prepared using diluents or excipients such as commonly used fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, tablets, powders, granules, capsules, troches, etc., and these solid preparations can be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, or gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, they may contain various excipients such as wetting agents, sweeteners, flavoring agents, and preservatives.

[0456]

[0457] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. The therapeutic compositions of the present invention can be prepared in the form of lyophilized cakes or aqueous solutions for storage by mixing the compound having the desired purity with any physiologically acceptable carrier, excipient, or stabilizer. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphoric acid, citric acid, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; Chelating agents, such as EDTA; sugar alcohols, such as mannitol or sorbitol; salt-forming counterions, such as sodium; and / or nonionic surfactants, such as Tween, Pluronics, or polyethylene glycol (PEG).

[0458]

[0459] For parenteral administration, preparations can be formulated into injections, creams, lotions, topical ointments, oils, moisturizers, gels, aerosols, and nasal inhalers using methods known in the art. These formulations can be found in the literature, which is a commonly known prescription manual for all pharmaceutical chemistry disciplines.

[0460]

[0461] The total effective amount of the compound of the present invention can be administered as a single dose, or can be administered by a fractionated treatment protocol in which multiple doses are administered over a long period of time. The pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the degree and / or purpose of the disease, but can typically be administered several times a day at an effective dose of 0.01 ㎍ to 10,000 mg, preferably 0.1 ㎍ to 1,000 mg, at a single administration. However, since the dosage of the pharmaceutical composition is determined by taking into consideration various factors such as the formulation method, administration route, and number of treatments, as well as the patient's age, weight, health status, sex, severity of the disease, diet, and excretion rate, a person having ordinary skill in the art will be able to determine an appropriate effective dosage of the composition of the present invention, taking these points into consideration. The pharmaceutical composition according to the present invention is not particularly limited in its formulation, administration route, and administration method as long as it exhibits the effects of the present invention.

[0462]

[0463] The present invention also provides a pharmaceutical composition for preventing or inhibiting cancer metastasis, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0464]

[0465] The cancer is not particularly limited in type as long as it is known in the art as a malignant tumor, but may be selected from the group consisting of breast cancer, colon cancer, lung cancer, small cell lung cancer, stomach cancer, liver cancer, blood cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, anal cancer, colon cancer, fallopian tube carcinoma, endometrial carcinoma, cervical cancer, vaginal cancer, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS tumor, primary CNS lymphoma, spinal cord tumor, brainstem glioma, and pituitary adenoma.

[0466]

[0467] In order to achieve another object of the present invention, the present invention provides a use of the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof for preparing a composition for treating a disease related to immune cell movement.

[0468]

[0469] In order to achieve another object of the present invention, the present invention provides a method for treating a disease related to immune cell movement, which comprises administering an effective amount of a composition comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0470]

[0471] In order to achieve another object of the present invention, the present invention provides the use of the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for preventing or inhibiting cancer metastasis.

[0472]

[0473] In order to achieve another object of the present invention, the present invention provides a method for preventing or inhibiting cancer metastasis, comprising administering an effective amount of a composition comprising the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0474]

[0475] The compound of the present invention can regulate the movement of immune cells and cancer cells by inhibiting the activity of KARS1, and thus exhibits a very remarkable effect in the prevention, improvement, and treatment of diseases related to immune cell movement and cancer metastasis.

[0476]

[0477] Figure 1 shows the results of a rat pharmacodynamic experiment of compound 11 prepared in an example of the present invention.

[0478] Figure 2 shows the results of a rat pharmacodynamic experiment of compound 18 prepared in an example of the present invention.

[0479]

[0480] Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended only to illustrate the present invention and the present invention is not limited thereto.

[0481]

[0482] Example 1: Preparation of compounds

[0483] In the present invention, the compound of chemical formula 3 was prepared according to the following synthetic method:

[0484] Synthesis method 1.

[0485]

[0486]

[0487] Synthesis method 2.

[0488]

[0489]

[0490] Synthesis method 3.

[0491]

[0492]

[0493] Synthesis method 4.

[0494]

[0495] In the above synthetic method, A, B, Q, D, E, Z and R1 to R10 are as defined above.

[0496]

[0497] Specific examples, structures and NMR analysis results of the compounds of chemical formulas 1 to 8 manufactured according to the above method are specifically shown in Tables 1 and 2 below.

[0498]

[0499] [Table 1]

[0500]

[0501]

[0502] [Table 2]

[0503]

[0504]

[0505] Example 2: Inhibition of KARS1-dependent cell migration

[0506] The effect of inhibiting monocyte / macrophage migration was evaluated through a trans-migration assay using mouse macrophage cells, Raw264.7.

[0507] It is known that KARS1 is secreted extracellularly in an inflammatory environment and induces the migration and M1 polarization of macrophages and peripheral blood monocytes.

[0508] Based on this, when KARS1 protein was directly treated externally instead of LN, the trans-cellular migration of Raw264.7 was induced, and the cell migration inhibition efficacy of the compounds, which are inhibitors of KARS1, was confirmed. In addition to the mechanism of inhibiting cell migration of Raw264.7 through inhibition of laminin-induced cell membrane migration of KARS1 and binding to 67LR, the compounds according to the present invention that specifically bind to KARS1 were confirmed to be able to inhibit cell migration by binding to extracellular KARS1, making it possible to utilize this assay as a direct analytical method to evaluate the in vitro activity of KARS1.

[0509]

[0510] An assay method to directly inhibit cell migration induced by KARS1 was established, and the compounds prepared in Example 1 were each treated at a concentration of 1 μM and analyzed (Table 3).

[0511]

[0512] [Table 3]

[0513]

[0514]

[0515] Example 3: Evaluation of pharmacodynamic (PK) characteristics

[0516] A rat iv, po pharmacodynamic analysis of compounds 11 and 18, which showed excellent effects in Example 2, was performed, and the results are shown in Tables 4, 5, Figures 1 and 2.

[0517]

[0518] [Table 4]

[0519]

[0520]

[0521] [Table 5]

[0522]

[0523]

[0524] The compound of the present invention can regulate the movement of immune cells and cancer cells by inhibiting the activity of KARS1, and thus exhibits a very remarkable effect in the prevention, improvement, and treatment of diseases related to immune cell movement and cancer metastasis, and thus has very high potential for industrial application.

Claims

1. A compound selected from the group consisting of the following chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] In the above chemical formula 1, X is one of NH, O, S, CH=N, A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C2 alkoxy, -CF3, -CN or -NO2, Q may be methylene or -(C=O)- or may not exist, R5 is hydrogen or C1~C6 alkyl, D is phenyl or heteroaryl of 5 to 6 atoms, R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2 and C1~C6 alkoxy, R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group, R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or halogen; [Chemical Formula 2] In the above chemical formula 2, X is one of NH, O, S, CH=N A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2, Q may be methylene or -(C=O)- or may not exist, R5 is hydrogen or C1~C6 alkyl, D is phenyl or heteroaryl of 5 to 6 atoms, R6 is one or more substituents, each of which can be independently H, halogen, OH, NH2, C1~C6 alkyl, C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2, and C1~C6 alkoxy, R7 and R8 are each independently H, NH2, C1~C6 alkoxy group, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group. R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or F, and when one of the substituents of R9 is F, all of R6 can be H; [Chemical Formula 3] In the above chemical formula 3, X is independently N, NH, C, O, S, CH, CH2 or CH=N, A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2, Q may be methylene or -(C=O)- or may not exist, R5 is H, C1~C6 alkyl or -(C=O)-, D is phenyl or heteroaryl of 5 to 6 atoms, R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2 and C1~C6 alkoxy, R7 and R8 are each independently H, NH2, halogen, C1~C6 alkoxy group, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group, When either one of R7 and R8 is halogen, both R6 can be H, R9 is one or more substituents, each independently H, C1~C6 alkoxy or F; [Chemical Formula 4] In the above chemical formula 4, X is independently N, NH, C, O, S, CH, CH2 or CH=N. A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2, Q may be methylene or -(C=O)- or may not exist, R5 is H, C1~C6 alkyl or -(C=O)-, D is phenyl or heteroaryl of 5 to 6 atoms, R6 is one or more substituents, each of which may independently be H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, but at least one substituent must contain one of F, Cl, OH, NH2, C1~C6 alkoxy, R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen, -(C=O)NH2 or C1~C6 alkyl group, When at least one of R7 and R8 is halogen, both R6 can be H, R9 is one or more substituents, each independently H, C1~C6 alkoxy or F am; [Chemical Formula 5] In the above chemical formula 5, X is independently one of N, NH, C, O, S, CH, CH2 and CH=N, and at least one X of the double D ring must be N, A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2, Q may be methylene or -(C=O)- or may not exist, R5 can be H, C1~C6 alkyl or -(C=O)-, R6 is one or more substituents, each independently H, halogen, OH, NH2, C1~C6 alkyl or C1~C6 alkoxy, E is phenyl, heteroaryl of 5 to 6 atoms, R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, double bond oxygen (=O), -(C=O)NH2 or C1~C6 alkyl group, If at least one of R7 and R8 is double bond oxygen (=O), alkoxy, amine or sulfonic acid, all Xs of the D ring can be CH, R9 is one or more substituents, each independently H, C1~C6 alkoxy or F; [Chemical Formula 6] In the above chemical formula 6, X is NH, O, S, CH or CH=N, A is a C5-C10 aryl forming a bicyclic aromatic ring together with B or a 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, R1, R2, R3 and R4 are each independently absent or hydrogen, halogen, C1~C6 alkyl, amine, C1~C6 alkoxy, -CF3, -CN or -NO2, n is 1 or 2, R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group. R9 is one or more substituents, each of which can independently be H, C1~C6 alkoxy or F; [Chemical Formula 7] In the above chemical formula 7, R5 is H, C1~C6 alkyl or -(C=O)-, X is independently N, C or CH, R6 is one or more substituents, each independently H, =O, or a C1~C6 alkyl group, E is phenyl, heteroaryl consisting of 5 to 10 atoms, R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group. R9 is one or more substituents, each independently H, C1~C6 alkoxy or F; [Chemical Formula 8] In the above chemical formula 8, R7 and R8 are each independently H, NH2, C1~C6 alkoxy, carboxylic acid, sulfonic acid, -(C=O)NH2 or C1~C6 alkyl group, R9 is one or more substituents, each independently H, C1~C6 alkoxy or F.

2. A compound, an isomer thereof, or a pharmaceutically acceptable salt thereof, characterized in that in the chemical formulae 1 to 6, A is benzene, pyridine, pyrimidine, pyridone, or pyrrole forming a bicyclic aromatic ring together with B.

3. In the first paragraph, a compound, an isomer thereof, or a pharmaceutically acceptable salt thereof, characterized in that the bicyclic aromatic ring formed by A and B is selected from the structures below: , , , and .

4. A compound, an isomer thereof, or a pharmaceutically acceptable salt thereof, characterized in that in the first paragraph, the ring D in the chemical formulae 1 to 5 is phenyl or pyridinyl.

5. In the first paragraph, the compound is a compound, an isomer thereof, or a pharmaceutically acceptable salt thereof, characterized in that it is selected from the group consisting of the following compounds: (S)-1-(4-(((2-fluoro-4-methoxyphenethyl)(7-fluorobenzo[d]thiazol-2-yl)amino)methyl)phenyl)pyrrolidine-3-carboxylic acid, 4-(3-((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)piperidin-1-yl)benzoic acid, 3-(3-((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)pyrrolidin-1-yl)benzoic acid, 4-(3-((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)pyrrolidin-1-yl)benzoic acid, 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-[1,1'-biphenyl]-3-sulfonic acid, 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-5-methoxy-[1,1'-biphenyl]-3-carboxylic acid, 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-2-methoxy-[1,1'-biphenyl]-3-carboxylic acid, 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-6-methoxy-[1,1'-biphenyl]-3-carboxylic acid, 5-amino-4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-[1,1'-biphenyl]-3-carboxylic acid, 6-amino-4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-[1,1'-biphenyl]-3-carboxylic acid, 1-(2-fluoro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)azetidine-3-carboxylic acid, 4-fluoro-1-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)piperidine-4-carboxylic acid, (S)-1-(3,5-difluoro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)pyrrolidine-3-carboxylic acid, 4'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-2,3,4,5-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid, 1-(5-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)pyridin-2-yl)-1H-pyrazole-4-carboxylic acid, 5'-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)-[2,2'-bipyridine]-6-carboxylic acid, 1-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)-2-oxopiperidine-4-carboxylic acid, 1-(3,5-difluoro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)azetidine-3-carboxylic acid, 3-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)piperidin-1-yl)benzoic acid, 3-(4-((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)carbamoyl)piperazin-1-yl)benzoic acid, 4-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)piperazine-1-sulfonic acid, (S)-1-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)-5-oxopyrrolidine-3-carboxylic acid, 2-(4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)piperidin-1-yl)thiazole-5-carboxylic acid, 1-(3-fluoro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)azetidine-3-carboxylic acid, 1-(3-chloro-4-(((7-fluorobenzo[d]thiazol-2-yl)(4-methoxyphenethyl)amino)methyl)phenyl)azetidine-3-carboxylic acid, 1-(2-fluoro-4-(((3-fluoro-4-methoxyphenethyl)(7-fluorobenzo[d]thiazol-2-yl)amino)methyl)phenyl)azetidine-3-carboxylic acid, and 1-(2-fluoro-4-(((2-fluoro-4-methoxyphenethyl)(7-fluorobenzo[d]thiazol-2-yl)amino)methyl)phenyl)azetidine-3-carboxylic acid.

6. A pharmaceutical composition for preventing or treating a disease related to immune cell movement, comprising a compound according to any one of claims 1 to 5, an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

7. A composition according to claim 6, wherein the disease related to immune cell movement is selected from the group consisting of cardiovascular disease, fibrotic disease, inflammatory disease, and Alport syndrome.

8. A composition according to claim 7, characterized in that the cardiovascular disease is selected from the group consisting of hypertension, pulmonary hypertension, atherosclerosis, angina pectoris, myocardial infarction, ischemic cerebrovascular disease, arteriosclerosis, and media sclerosis.

9. In paragraph 7, the fibrotic disease is scleroderma, rheumatoid arthritis, neural fibrosis, Crohn's disease, ulcerative colitis, myelofibrosis, pulmonary fibrosis, hepatic fibrosis, liver cirrhosis, kidney fibrosis, glomerulosclerosis, myofibrosis, cardiac fibrosis, interstitial fibrosis, pancreatic fibrosis, splenic fibrosis, mediastinal fibrosis, vascular fibrosis, skin fibrosis, ocular fibrosis, macular degeneration, arthrofibrosis, thyroid fibrosis, endomyocardial fibrosis, peritoneal fibrosis, retroperitoneal fibrosis, progressive mass fibrosis, nephrogenic systemic fibrosis, systemic erythematosus A composition characterized in that it is selected from the group consisting of lupus (systemic lupus erythematosus), hereditary fibrosis, infectious fibrosis, irritant fibrosis, chronic autoimmune fibrosis, fibrosis due to antigen incompatibility during organ transplantation, fibrotic complications of surgical operations, fibrosis due to hyperlipidemia, fibrosis due to obesity, diabetic fibrosis, fibrosis due to hypertension, and occlusion due to fibrosis during stent insertion.

10. In paragraph 7, the inflammatory disease is an autoimmune disease, inflammatory bowel disease, dermatitis, atopic dermatitis, eczema, psoriasis, diabetic eye disease, diabetic retinopathy, peritonitis, osteomyelitis, cellulitis, meningitis, encephalitis, pancreatitis, trauma-induced shock, bronchial asthma, rhinitis, sinusitis, otitis media, pneumonia, gastritis, enteritis, cystic fibrosis, stroke, bronchitis, bronchiolitis, hepatitis, cirrhosis, metabolic dysfunction-associated steatohepatitis, chronic kidney disease, nephritis, proteinuria, diabetic renal failure, arthritis, psoriatic arthritis, neuritis, diabetic neuropathy, multiple sclerosis, gout, spondylitis, Reiter's syndrome, polyarteritis nodosa, vasculitis, Lou Gehrig's disease, Wegener's granulomatosis, hypercytokinemia, Polymyalgia rheumatica, articular cell arteritis, calcium crystal deposition arthropathy, pseudogout, non-articular rheumatism, bursitis, tenosynovitis, epicondylitis, Charcot's joint, hemarthrosis, Henoch-Schonlein purpura, hypertrophic osteoarthropathy, multicentric reticulohistiocytoma, surcoilosis, hemochromatosis, sickle cell disease, hyperlipoproteinemia, hypogammaglobulinemia, hyperparathyroidism, acromegaly, familial Mediterranean fever, Behçet's disease, systemic lupus erythematosus, relapsing fever, psoriasis, multiple sclerosis, sepsis, septic shock, acute respiratory distress syndrome, multiple organ failure, chronic obstructive pulmonary disease, acute lung injury, and bronchopulmonary A composition characterized by being selected from the group consisting of broncho-pulmonary dysplasia.

11. A composition according to claim 10, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, psoriasis, asthma, ulcerative colitis, Behcet's disease, Crohn's disease, multiple sclerosis, dermatomyositis, collagen disease, vasculitis, arthritis, granulomatosis, organ-specific autoimmune lesions, ulcerative colitis, and graft-versus-host disease.

12. A pharmaceutical composition for preventing or inhibiting cancer metastasis, comprising as an active ingredient a compound selected from the group consisting of the above chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof.

13. Use of a compound selected from the group consisting of the above chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for treating a disease related to immune cell movement.

14. A method for treating a disease related to immune cell movement, comprising administering to a subject in need thereof an effective amount of a composition comprising a compound selected from the group consisting of the above chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof.

15. Use of a compound selected from the group consisting of the above chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for preventing or inhibiting cancer metastasis.

16. A method for preventing or inhibiting cancer metastasis, comprising administering to a subject in need thereof an effective amount of a composition comprising a compound selected from the group consisting of the chemical formulas 1 to 8, an isomer thereof, or a pharmaceutically acceptable salt thereof.

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