Compound having melanin production inhibitory activity, synthesis thereof, and composition for preventing, treating or ameliorating hyperpigmentation disease comprising same as active ingredient

Abstract

The present invention relates to a compound having melanin production inhibitory activity and a composition for preventing, treating or ameliorating a hyperpigmentation disease, the composition comprising same as an active ingredient. The compound or a salt thereof, according to the present invention, was confirmed to have low cytotoxicity while exhibiting a melanin production inhibitory effect. Therefore, a composition comprising the compound or a salt thereof as an active ingredient, according to the present invention, not only can be used for preventing, ameliorating or treating a hyperpigmentation disease, but is also expected to have various applications in the field of skin beauty, such as skin whitening through the amelioration of hyperpigmentation.

Description

Compound having melanin production inhibitory activity and its synthesis, and composition for preventing, treating, or improving hyperpigmentation disease comprising the compound as an active ingredient

[0001] The present invention relates to a compound having melanin production inhibitory activity, its synthesis, and a composition for preventing, treating, or improving hyperpigmentation diseases comprising the compound as an active ingredient.

[0002] This application claims priority to Korean Patent Application No. 10-2024-0057949, filed April 30, 2024, the entire disclosure of which is incorporated herein by reference.

[0003]

[0004] Human skin color is influenced by environmental and physiological conditions, such as solar UV rays, fatigue, and stress, but it is fundamentally determined by the composition and distribution of various chromophores within the skin, such as melanin, hemoglobin, and carotenoids. Melanin is a dark-brown polymer pigment synthesized by melanocytes. The enzyme tyrosinase converts tyrosine to DOPA, which then undergoes a series of oxidation processes to synthesize melanin. Melanosomes containing melanin migrate to adjacent keratinocytes and distribute melanin throughout the epidermis. Human skin color is controlled by the composition and distribution of melanin. The greater the amount of melanin, the darker the skin.

[0005] Melanogenesis is the biosynthesis of melanin pigment in melanocytes, a process regulated by the intracellular and extracellular environment. Melanin production is triggered by tyrosinase, which oxidizes tyrosine to dopaquinone, which is then converted into pheomelanin, a pale yellow / red compound, and eumelanin, a light brown to black pigment. In the skin, melanin contributes to pigmentation and protects the skin from UV rays and other skin conditions. However, abnormal accumulation of melanin can lead to hyperpigmentation, including melasma and freckles. Pigmentation, or hyperpigmentation, is a condition in which melanin increases in the skin, fingernails, and mucous membranes surrounding the oral or nasal passages, giving the skin a darker color. It can be caused by a variety of factors, including genetic disorders, medications, inflammation, trauma, UV exposure, and hyperpigmented skin conditions like freckles. These skin pigmentation disorders are considered socially significant because they can cause psychological stress and lower quality of life.

[0006] Conventional treatments for skin pigmentation disorders include chemical peels, laser surgery, medications, and cosmetic procedures. However, these methods often involve side effects and high costs. Tyrosinase inhibitors, such as kojic acid and arbutin, are currently used as medications, but they present safety concerns, including skin irritation. Hydroquinone, in particular, is commonly used alone or in combination with other medications to treat skin pigmentation disorders, but it is known to cause side effects such as allergies and cancer.

[0007] Therefore, there is a need for the development of a substance that can effectively prevent, improve, and treat hyperpigmentation diseases by inhibiting melanin production without causing side effects to the human body.

[0008]

[0009] The present inventors conducted research to discover a substance that can effectively suppress skin hyperpigmentation without causing side effects in the human body, and as a result, confirmed that a derivative of the TRL 0 compound exhibits a melanin production suppression effect without cytotoxicity, and completed the present invention based on this.

[0010] Accordingly, the present invention provides a compound or a salt thereof having melanin production inhibitory activity.

[0011] Another object of the present invention is to provide a composition or topical application preparation for preventing, treating, or improving hyperpigmentation disease, comprising a compound according to the present invention or a salt thereof as an active ingredient.

[0012]

[0013] However, the technical problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by a person having ordinary skill in the technical field to which the present invention belongs from the description below.

[0014]

[0015] To achieve the above purpose, the present invention provides a compound represented by the following chemical formula 1 or a salt thereof.

[0016] [Chemical Formula 1]

[0017]

[0018] In the above chemical formula 1,

[0019] X is , , , or And,

[0020] Y is , , , or And,

[0021] R1 is hydrogen (H) or a halogen element,

[0022] R2 and R4 are each independently hydrogen (H) or a C1-C6 alkyl group,

[0023] R3 is hydrogen (H), a halogen element, or a substituted or unsubstituted C1-C6 alkoxy group,

[0024] A1 to A9 are each independently a substituted or unsubstituted carbon (C), a substituted or unsubstituted nitrogen (N), oxygen (O), sulfur (S), or C=O,

[0025] n is 2 or 3,

[0026] The above 'substituted or unsubstituted' means substituted or unsubstituted with one or more selected from the group consisting of a halogen element, a C1-C6 alkyl group, and a C1-C6 alkylcarbonyl group.

[0027] As one embodiment of the present invention, the X is , , or It may include, but is not limited to.

[0028] As another embodiment of the present invention, the Y is , , or It may include, but is not limited to.

[0029] In another embodiment of the present invention, A1 is substituted or unsubstituted carbon (C), substituted or unsubstituted nitrogen (N), oxygen (O), or sulfur (S),

[0030] The above A2 to A9 may each independently be a substituted or unsubstituted carbon (C), a substituted or unsubstituted nitrogen (N), oxygen (O), or C=O, but are not limited thereto.

[0031] In another embodiment of the present invention, A1 is a substituted or unsubstituted carbon (C),

[0032] The above A2, A4, A5, A6 and A8 are each independently a substituted or unsubstituted nitrogen (N),

[0033] The above A3, A7 and A9 may each independently be C=O, but are not limited thereto.

[0034] As another embodiment of the present invention, the X is And,

[0035] The above Y is or And,

[0036] The above R1 is hydrogen (H) or a halogen element,

[0037] The above R2 and R4 are each independently hydrogen (H) or a C1-C6 alkyl group,

[0038] The above A1 is carbon (C),

[0039] A2, A above 4, A5, A6 and A8 are each independently a substituted or unsubstituted carbon (C) or a substituted or unsubstituted nitrogen (N),

[0040] The above A3, A7 and A9 are each independently C=O,

[0041] n is 2 or 3,

[0042] The above 'substituted or unsubstituted' may mean substituted or unsubstituted with one or more selected from the group consisting of a halogen element, a C1-C6 alkyl group, and a C1-C6 alkylcarbonyl group, but is not limited thereto.

[0043] As another embodiment of the present invention, the compound may be represented by any one selected from the following chemical formulas 2 to 8, but is not limited thereto.

[0044] [Chemical Formula 2]

[0045]

[0046] In the above chemical formula 2,

[0047] R1 is hydrogen (H) or chlorine (Cl),

[0048] R2 and R4 are each independently hydrogen (H) or a methyl group (CH3),

[0049] A1 is carbon (C),

[0050] A2 and A4 are each independently a substituted or unsubstituted carbon (C), a substituted or unsubstituted nitrogen (N), or an oxygen (O),

[0051] A3 is carbon (C) or C=O,

[0052] The above 'substituted or unsubstituted' means one or more methyl groups (CH3) and acetyl groups ( ) means substituted or unsubstituted with one or more selected from the group consisting of.

[0053]

[0054] [Chemical Formula 3]

[0055]

[0056] In the above chemical formula 3,

[0057] R1 is hydrogen (H) or chlorine (Cl),

[0058] R2 is hydrogen (H) or methyl group (CH3),

[0059] A1 is carbon (C),

[0060] A5 is carbon (C) or nitrogen (N),

[0061] A6 is substituted or unsubstituted nitrogen (N) or oxygen (O),

[0062] A7 is carbon (C) or C=O,

[0063] A8 and A9 are each independently substituted or unsubstituted nitrogen (N) or C=O,

[0064] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with a methyl group (CH3).

[0065]

[0066] [Chemical Formula 4]

[0067]

[0068] In the above chemical formula 4,

[0069] Y is or And,

[0070] R1 is hydrogen (H) or chlorine (Cl),

[0071] R2 is hydrogen (H) or methyl group (CH3),

[0072] R3 is fluorine (F) or a substituted or unsubstituted methoxy group (OMe),

[0073] A1 is carbon (C) or oxygen (O),

[0074] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0075]

[0076] [Chemical Formula 5]

[0077]

[0078] In the above chemical formula 5,

[0079] R2 is hydrogen (H) or methyl group (CH3),

[0080] R3 is a substituted or unsubstituted methoxy group (OMe),

[0081] A1 is carbon (C),

[0082] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0083]

[0084] [Chemical Formula 6]

[0085]

[0086] In the above chemical formula 6,

[0087] R2 is hydrogen (H) or methyl group (CH3),

[0088] R3 is a substituted or unsubstituted methoxy group (OMe),

[0089] A1 is sulfur (S),

[0090] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0091]

[0092] [Chemical Formula 7]

[0093]

[0094] In the above chemical formula 7,

[0095] R1 is hydrogen (H) or chlorine (Cl),

[0096] R2 is hydrogen (H) or methyl group (CH3),

[0097] R3 is a substituted or unsubstituted methoxy group (OMe),

[0098] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0099]

[0100] [Chemical Formula 8]

[0101]

[0102] In the above chemical formula 8,

[0103] R2 is hydrogen (H) or methyl group (CH3),

[0104] R3 is a substituted or unsubstituted methoxy group (OMe),

[0105] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0106] As another embodiment of the present invention, the compound represented by the above chemical formula 1 may be one or more selected from the group consisting of, but is not limited thereto.

[0107] (1)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide;

[0108] (2) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide;

[0109] (3) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide;

[0110] (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0111] (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide;

[0112] (6)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0113] (7)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-Nmethylbenzenesulfonamide;

[0114] (8) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide;

[0115] (9) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide;

[0116] (10)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0117] (11)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0118] (12)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide;

[0119] (13)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-N-methylbenzenesulfonamide;

[0120] (14)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide;

[0121] (15)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylquinoline-8-sulfonamide;

[0122] (16)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0123] (17)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0124] (18)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide;

[0125] (19)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-5-sulfonamide;

[0126] (20)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide;

[0127] (21)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0128] (22)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide;

[0129] (23)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethyl-2-oxoindoline-5-sulfonamide;

[0130] (24)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide;

[0131] (25)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide;

[0132] (26)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethylindoline-6-sulfonamide;

[0133] (27)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide;

[0134] (28)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide;

[0135] (29)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide;

[0136] (30)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,4-dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide;

[0137] (31)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethyl-2-oxoindoline-5-sulfonamide;

[0138] (32)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0139] (33)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide;

[0140] (34)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylquinoline-8-sulfonamide;

[0141] (35)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide;

[0142] (36)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethyl-2-oxoindoline-5-sulfonamide;

[0143] (37)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide;

[0144] (38)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide;

[0145] (39)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide;

[0146] (40)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide;

[0147] (41)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide;

[0148] (42)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide;

[0149] (43)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide;

[0150] (44)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide;

[0151] (45)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide;

[0152] (46)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide;

[0153] (47)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide;

[0154] (48)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,4-dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide;

[0155] (49)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0156] (50)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0157] (51)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide;

[0158] (52)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide;

[0159] (53)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide;

[0160] (54)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide;

[0161] (55)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0162] (56)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0163] (57)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-5-sulfonamide;

[0164] (58)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethyl-2-oxoindoline-5-sulfonamide;

[0165] (59)N-(3-(10H-phenothiazin-10-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide;

[0166] (60)N-(3-(10H-phenothiazin-10-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide;

[0167] (61)N-(2-(9H-carbazol-9-yl)ethyl)-4-(trifluoromethoxy)benzenesulfonamide;

[0168] (62)N-(2-(9H-carbazol-9-yl)ethyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide;

[0169] (63)N-(3-(9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide;

[0170] (64)N-(3-(9H-carbazol-9-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide;

[0171] (65)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide;

[0172] (66)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide;

[0173] (67)N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide;

[0174] (68)N-methyl-N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide;

[0175] (69)N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide; and

[0176] (70)N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide.

[0177] In addition, the present invention provides a compound represented by the following chemical formula 1 or a salt thereof.

[0178] [Chemical Formula 1]

[0179]

[0180] In the above chemical formula 1,

[0181] X is , , or And,

[0182] Y is , , or And,

[0183] R1 is hydrogen (H) or a halogen element,

[0184] R2 and R4 are each independently hydrogen (H) or a methyl group,

[0185] R3 is a fluorine (F) or trifluoromethoxy group (OCF3),

[0186] A1 is carbon (C), oxygen (O), or sulfur (S),

[0187] A2 is carbon (C) or substituted nitrogen (N),

[0188] A3 is carbon (C) or C=O,

[0189] A4 is substituted or unsubstituted carbon (C), substituted nitrogen (N), or oxygen (O),

[0190] A5 is nitrogen (N),

[0191] A6 and A8 are each independently substituted nitrogen (N),

[0192] A7 and A9 are each independently C=O,

[0193] n is 3,

[0194] The above 'substituted or unsubstituted' means one or more methyl groups (CH3), and acetyl groups ( ) means substituted or unsubstituted with one or more selected from the group consisting of.

[0195] As one embodiment of the present invention, the compound represented by the above chemical formula 1 may be one or more selected from the group consisting of, but is not limited thereto.

[0196] (1) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide;

[0197] (2) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide;

[0198] (3)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0199] (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0200] (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-Nmethylbenzenesulfonamide;

[0201] (6) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide;

[0202] (7)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0203] (8)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0204] (9)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-N-methylbenzenesulfonamide;

[0205] (10)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide;

[0206] (11)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide;

[0207] (12)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide;

[0208] (13)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide;

[0209] (14)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide;

[0210] (15)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide;

[0211] (16)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide;

[0212] (17)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide;

[0213] (18)N-(3-(10H-phenothiazin-10-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide;

[0214] (19)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide; and

[0215] (20)N-methyl-N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide.

[0216] In addition, the present invention provides a compound represented by the following chemical formula 1 or a salt thereof.

[0217] [Chemical Formula 1]

[0218]

[0219] In the above chemical formula 1,

[0220] X is And,

[0221] Y is or And,

[0222] R1 is hydrogen (H) or a halogen element,

[0223] R2 is hydrogen (H) or a methyl group,

[0224] R4 is hydrogen (H),

[0225] A1 is carbon (C),

[0226] A2, A4, A6, and A8 are each independently substituted nitrogen (N),

[0227] A3, A7 and A9 are each independently C=O,

[0228] A5 is nitrogen (N),

[0229] n is 3,

[0230] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with a methyl group.

[0231] As one embodiment of the present invention, the compound represented by the chemical formula 1 may be one or more selected from the group consisting of, but is not limited thereto.

[0232] (1)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0233] (2)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0234] (3)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide;

[0235] (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide;

[0236] (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; and

[0237] (6)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide.

[0238] In addition, the present invention provides a pharmaceutical composition for preventing or treating hyperpigmentation disease, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0239] In addition, the present invention provides a cosmetic composition for skin whitening, comprising the compound or a cosmetically acceptable salt thereof as an active ingredient.

[0240] In addition, the present invention provides a food composition for preventing or improving hyperpigmentation disease, comprising the compound or a food-related acceptable salt thereof as an active ingredient.

[0241] In addition, the present invention provides a pharmaceutical composition for preventing or improving hyperpigmentation disease, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0242] In one embodiment of the present invention, the hyperpigmentation disease may be at least one selected from the group consisting of, but is not limited to, freckles, liver spots, lentigines, moles, coffee-colored spots, nevus of Ota, blue nevus, hyperpigmented spots, hyperpigmentation after drug use, gravidic chloasma, post-inflammatory hyperpigmentation due to wound or dermatitis, age-related pigmentation, dyspigmentation, and solar lentigines.

[0243] In another embodiment of the present invention, the compound may inhibit melanin production, but is not limited thereto.

[0244] As another embodiment of the present invention, the composition may be for systemic application or topical application, but is not limited thereto.

[0245] As another embodiment of the present invention, the cosmetic composition may be one or more formulations selected from the group consisting of serum, toner, paste, patch, gel, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, cream, massage cream, nourishing cream, mist, moisture cream, hand cream, hand lotion, foundation, essence, nourishing essence, pack, soap, oil, foundation, makeup base, wax, spray, cleansing foam, cleansing lotion, cleansing cream, cleansing oil, cleansing balm, body lotion, and body cleanser, but is not limited thereto.

[0246] In addition, the present invention provides a method for preventing, treating, or improving hyperpigmentation disease, comprising administering a therapeutically effective amount of the compound or a salt thereof; or a composition containing the compound as an active ingredient, to a subject in need thereof.

[0247] In addition, the present invention provides a use of the compound or a salt thereof; or a composition containing the compound as an active ingredient, for preventing, treating, or improving hyperpigmentation disease.

[0248] In addition, the present invention provides a use of the compound or a salt thereof; or a composition comprising the compound or a salt thereof as an active ingredient; for the manufacture of a preparation for preventing, treating, or improving hyperpigmentation disease.

[0249]

[0250] The compound or salt thereof according to the present invention was confirmed to exhibit a melanin production inhibitory effect while exhibiting low cytotoxicity. Therefore, a composition comprising the compound or salt thereof according to the present invention as an active ingredient is expected to be useful not only for the prevention, improvement, or treatment of hyperpigmentation disorders, but also for various applications in the field of skin care, such as skin whitening through improvement of hyperpigmentation disorders.

[0251]

[0252] Figures 1a to 1d are drawings showing cell viability after treating a mouse melanocyte cell line with TRL 0 and its derivatives TRL 1 to TRL 69 at different concentrations according to one embodiment of the present invention.

[0253] Figures 2a to 2d are drawings showing cell viability after treating human primary melanocyte cell lines with TRL 0 and its derivatives TRL 1 to TRL 69 at various concentrations according to one embodiment of the present invention.

[0254] Figures 3a to 3d are drawings showing the results of measuring melanin content compared to the basal control group after treating a mouse melanocyte cell line with TRL 0 and its derivatives TRL 1 to TRL 69 at various concentrations according to one embodiment of the present invention.

[0255] Figures 4a to 4d are drawings showing the results of measuring melanin content by comparing the FSK treatment group with the mouse melanocyte cell line treated with TRL 0 and its derivatives TRL 1 to TRL 69 at different concentrations according to one embodiment of the present invention.

[0256] FIGS. 5a to 5d are drawings showing the results of measuring melanin content compared to the basal control group after treating human primary melanocyte cell lines with TRL 0 and its derivatives TRL 1 to TRL 69 at various concentrations according to one embodiment of the present invention.

[0257] FIGS. 6A and 6B are drawings showing cell viability after treating mouse melanoma cell lines with TRL 1, 2, 3, 5, 6, 8, 9, 10, 12, 16, 23, 40, 41, 42, 43, 51, 53, 59, 65, and 67 at different concentrations according to one embodiment of the present invention.

[0258]

[0259] In one experimental example of the present invention, cell viability was confirmed after treating Mel-Ab, a mouse melanocyte cell line, and NHM, a human primary melanocyte cell line, with TRL 0 and its derivatives. As a result, it was confirmed that Mel-Ab maintained more than 78%, and in the case of NHM cells, it was confirmed that cell viability was maintained more than 50% even when treated at a concentration of 10 μM, except for TRL 4, 11, 57, 58, 60, 62, 64, and 66 (see Experimental Example 1).

[0260] In another experimental example of the present invention, the melanin production inhibitory effect was confirmed after treating Mel-Ab, a mouse melanocyte cell line, and NHM, human primary melanocytes, with TRL 0 and its derivatives. As a result, in Mel-Ab, it was confirmed that the TRL 5, 6, 10, 12, 43, 51, 53, 59, 65, and 67 treatment groups showed a high melanin production inhibitory effect compared to the basal control group or FSK treatment group. In addition, in NHM, it was confirmed that the TRL 1, 2, 3, 5, 8, 9, 12, 16, 23, 40, 41, and 42 treatment groups showed a high melanin production inhibitory effect compared to the basal control group (see Experimental Example 2).

[0261] In another experimental example of the present invention, 20 derivatives (TRL 1, 2, 3, 5, 6, 8, 9, 10, 12, 16, 23, 40, 41, 42, 43, 51, 53, 59, 65, and 67) that showed excellent melanin production inhibitory effects in Mel-Ab or NHM cells were selected, and the melanin production inhibitory effects were confirmed in mouse melanoma cells B16F10. As a result, it was confirmed that TRL 5, 9, 10, 40, 41, and 53 showed similar or improved melanin production inhibitory effects, particularly compared to TRL 0 (see Experimental Example 3).

[0262] In another experimental example of the present invention, 20 derivatives (TRL 1, 2, 3, 5, 6, 8, 9, 10, 12, 16, 23, 40, 41, 42, 43, 51, 53, 59, 65, and 67) that showed excellent melanin production inhibitory effects in Mel-Ab or NHM cells were selected and their cytotoxicity against B16F10 cells, a mouse melanoma cell line, was confirmed to be non-cytotoxic by MTT analysis (see Experimental Example 4).

[0263]

[0264] Hereinafter, the present invention will be described in detail.

[0265]

[0266] The present invention provides a compound represented by the following chemical formula 1 or a salt thereof.

[0267] [Chemical Formula 1]

[0268]

[0269] In the above chemical formula 1,

[0270] X is , , , or And,

[0271] Y is , , , or And,

[0272] R1 is hydrogen (H) or a halogen element,

[0273] R2 and R4 are each independently hydrogen (H) or a C1-C6 alkyl group,

[0274] R3 is hydrogen (H), a halogen element, or a substituted or unsubstituted C1-C6 alkoxy group,

[0275] A1 to A9 are each independently a substituted or unsubstituted carbon (C), a substituted or unsubstituted nitrogen (N), oxygen (O), sulfur (S), or C=O,

[0276] n is 2 or 3,

[0277] The above 'substituted or unsubstituted' means substituted or unsubstituted with one or more selected from the group consisting of a halogen element, a C1-C6 alkyl group, and a C1-C6 alkylcarbonyl group.

[0278]

[0279] In the present invention, “C1-C6 alkyl group” means a monovalent alkyl group having 1 to 6 carbon atoms. This term includes functional groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, tert-butyl, n-hexyl, etc. The alkyl and other substituents containing alkyl moieties described in the present invention include both straight-chain and branched forms.

[0280] In the present invention, the “halogen element” may include fluorine (F), chlorine (Cl), bromine (Br), and iodine (I), and according to one embodiment of the present invention, may be fluorine or chlorine, but is not limited thereto.

[0281] In the present invention, “substitution” includes single substitution, double substitution, triple substitution, quadruple substitution, etc.

[0282] In the present invention, “C1-C6 alkoxy group” means an alkyl ether group -OR group, where R means “C1-C6 alkyl”. The alkoxy group may include, for example, methoxy (OMe), ethoxy (OEt), n-propoxy (On-Pr), isopropoxy (Oi-Pr), n-butoxy (On-Bu), iso-butoxy (Oi-Bu), sec-butoxy (Osec-Bu), tert-butoxy (Otert-Bu), n-pentoxy (On-Pen), etc., and according to one embodiment of the present invention, it may be methoxy, but is not limited thereto. A substituted C1-C6 alkoxy group means a C1-C6 alkyl group of -O-(C1-C6 alkyl) in which at least one hydrogen atom is substituted with another substituent, and the substituent is not limited, but includes a halogen element, etc. According to one embodiment of the present invention, the substituted C1-C6 alkoxy group may be, but is not limited to, fluorinated alkoxy (OCF3).

[0283] In the present invention, “C1-C6 alkylcarbonyl group” means a carbonyl group (-C=O-) to which a C1-C6 alkyl group is bonded, and according to one embodiment of the present invention, the C1-C6 alkyl group may be a methyl group (CH3), but is not limited thereto.

[0284]

[0285] In some embodiments of the present invention, X is , , or may be. According to one embodiment of the present invention, the X is It may include, but is not limited to.

[0286]

[0287] In some embodiments of the present invention, Y is , , or may be. According to one embodiment of the present invention, the Y is or It may include, but is not limited to.

[0288]

[0289] In some embodiments of the present invention, A1 may be substituted or unsubstituted carbon (C), substituted or unsubstituted nitrogen (N), oxygen (O), or sulfur (S). According to one embodiment of the present invention, A1 may be substituted or unsubstituted carbon (C). According to one embodiment of the present invention, A1 may be unsubstituted carbon (C), but is not limited thereto.

[0290]

[0291] In some embodiments of the present invention, A2 to A9 may each independently be substituted or unsubstituted carbon (C), substituted or unsubstituted nitrogen (N), oxygen (O), or C=O. According to one embodiment of the present invention, A2, A4, A5, A6, and A8 may each independently be substituted or unsubstituted carbon (C) or substituted or unsubstituted nitrogen (N), and A3, A7, and A9 may each independently be C=O. According to one embodiment of the present invention, A2, A4, A5, A6, and A8 may each independently be substituted or unsubstituted nitrogen (N), and A3, A7, and A9 may each independently be C=O, but are not limited thereto.

[0292]

[0293] In some embodiments of the present invention, X is , , or , and the above A1 may be substituted or unsubstituted carbon (C), substituted or unsubstituted nitrogen (N), oxygen (O), or sulfur (S), but is not limited thereto.

[0294]

[0295] In some embodiments of the present invention, X is , and the above A1 may be a substituted or unsubstituted carbon (C), but is not limited thereto.

[0296]

[0297] In some embodiments of the present invention, R3 may be, but is not limited to, hydrogen (H); a halogen element; or a C1-C6 alkoxy group unsubstituted or substituted with a halogen element or a C1-C6 alkyl group.

[0298]

[0299] In the present invention, the compound may be represented by any one selected from the following chemical formulas 2 to 8, but is not limited thereto.

[0300] [Chemical Formula 2]

[0301]

[0302] In the above chemical formula 2,

[0303] R1 is hydrogen (H) or chlorine (Cl),

[0304] R2 and R4 are each independently hydrogen (H) or a methyl group (CH3),

[0305] A1 is carbon (C),

[0306] A2 and A4 are each independently a substituted or unsubstituted carbon (C), a substituted or unsubstituted nitrogen (N), or an oxygen (O),

[0307] A3 is carbon (C) or C=O,

[0308] The above 'substituted or unsubstituted' means one or more methyl groups (CH3) and acetyl groups ( ) means substituted or unsubstituted with one or more selected from the group consisting of.

[0309]

[0310] [Chemical Formula 3]

[0311]

[0312] In the above chemical formula 3,

[0313] R1 is hydrogen (H) or chlorine (Cl),

[0314] R2 is hydrogen (H) or methyl group (CH3),

[0315] A1 is carbon (C),

[0316] A5 is carbon (C) or nitrogen (N),

[0317] A6 is substituted or unsubstituted nitrogen (N) or oxygen (O),

[0318] A7 is carbon (C) or C=O,

[0319] A8 and A9 are each independently substituted or unsubstituted nitrogen (N) or C=O,

[0320] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with a methyl group (CH3).

[0321]

[0322] [Chemical Formula 4]

[0323]

[0324] In the above chemical formula 4,

[0325] Y is or And,

[0326] R1 is hydrogen (H) or chlorine (Cl),

[0327] R2 is hydrogen (H) or methyl group (CH3),

[0328] R3 is fluorine (F) or a substituted or unsubstituted methoxy group (OMe),

[0329] A1 is carbon (C) or oxygen (O),

[0330] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0331]

[0332] [Chemical Formula 5]

[0333]

[0334] In the above chemical formula 5,

[0335] R2 is hydrogen (H) or methyl group (CH3),

[0336] R3 is a substituted or unsubstituted methoxy group (OMe),

[0337] A1 is carbon (C),

[0338] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0339]

[0340] [Chemical Formula 6]

[0341]

[0342] In the above chemical formula 6,

[0343] R2 is hydrogen (H) or methyl group (CH3),

[0344] R3 is a substituted or unsubstituted methoxy group (OMe),

[0345] A1 is sulfur (S),

[0346] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0347]

[0348] [Chemical Formula 7]

[0349]

[0350] In the above chemical formula 7,

[0351] R1 is hydrogen (H) or chlorine (Cl),

[0352] R2 is hydrogen (H) or methyl group (CH3),

[0353] R3 is a substituted or unsubstituted methoxy group (OMe),

[0354] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0355]

[0356] [Chemical Formula 8]

[0357]

[0358] In the above chemical formula 8,

[0359] R2 is hydrogen (H) or methyl group (CH3),

[0360] R3 is a substituted or unsubstituted methoxy group (OMe),

[0361] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

[0362]

[0363] In the present invention, the compound represented by the chemical formula 1 may be one or more selected from the group consisting of the following, but is not limited thereto.

[0364] (1)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL 0);

[0365] (2) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide (TRL 1);

[0366] (3) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide (TRL 2);

[0367] (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL 3);

[0368] (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide (TRL 4);

[0369] (6)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide) (TRL 5);

[0370] (7)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-Nmethylbenzenesulfonamide (TRL 6);

[0371] (8) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide (TRL 7);

[0372] (9) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide (TRL 8);

[0373] (10)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL 9);

[0374] (11)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide) (TRL 10);

[0375] (12)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide (TRL 11);

[0376] (13)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-N-methylbenzenesulfonamide (TRL 12);

[0377] (14)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide (N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide) (TRL 13);

[0378] (15)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylquinoline-8-sulfonamide (TRL 14);

[0379] (16)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 15);

[0380] (17)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 16);

[0381] (18)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide) (TRL 17);

[0382] (19)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-5-sulfonamide (TRL 18);

[0383] (20)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide) (TRL 19);

[0384] (21)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 20);

[0385] (22)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide) (TRL 21);

[0386] (23)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethyl-2-oxoindoline-5-sulfonamide (TRL 22);

[0387] (24)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide (TRL 23);

[0388] (25)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide) (TRL 24);

[0389] (26)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethylindoline-6-sulfonamide (TRL 25);

[0390] (27)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide) (TRL 26);

[0391] (28)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (TRL 27);

[0392] (29)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide (TRL 28);

[0393] (30)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,4-dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide) (TRL 29);

[0394] (31)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethyl-2-oxoindoline-5-sulfonamide (TRL 30);

[0395] (32)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 31);

[0396] (33)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide (TRL 32);

[0397] (34)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylquinoline-8-sulfonamide (TRL 33);

[0398] (35)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (TRL 34);

[0399] (36)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethyl-2-oxoindoline-5-sulfonamide (TRL 35);

[0400] (37)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide) (TRL 36);

[0401] (38)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide (N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide) (TRL 37);

[0402] (39)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide (TRL 38);

[0403] (40)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide) (TRL 39);

[0404] (41)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide) (TRL 40);

[0405] (42)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide) (TRL 41);

[0406] (43)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide (TRL 42);

[0407] (44)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide) (TRL 43);

[0408] (45)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (TRL 44);

[0409] (46)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (TRL 45);

[0410] (47)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide) (TRL 46);

[0411] (48)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,4-dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide) (TRL 47);

[0412] (49)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 48);

[0413] (50)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 49);

[0414] (51)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide (TRL 50);

[0415] (52)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide (TRL 51);

[0416] (53)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide (TRL 52);

[0417] (54)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide) (TRL 53);

[0418] (55)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 54);

[0419] (56)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 55);

[0420] (57)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-5-sulfonamide (TRL 56);

[0421] (58)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethyl-2-oxoindoline-5-sulfonamide (TRL 57);

[0422] (59)N-(3-(10H-phenothiazin-10-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL 58);

[0423] (60)N-(3-(10H-phenothiazin-10-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL 59);

[0424] (61)N-(2-(9H-carbazol-9-yl)ethyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL 60);

[0425] (62)N-(2-(9H-carbazol-9-yl)ethyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL 61);

[0426] (63)N-(3-(9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL 62);

[0427] (64)N-(3-(9H-carbazol-9-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL 63);

[0428] (65)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide) (TRL 64);

[0429] (66)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide) (TRL 65);

[0430] (67)N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL 66);

[0431] (68)N-methyl-N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL 67);

[0432] (69)N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL 68); and

[0433] (70)N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL 69).

[0434]

[0435] In the present invention, TRL 0 means a compound having the structure of compound 1 below.

[0436] [Compound 1]

[0437]

[0438] In the present invention, a derivative of TRL 0 represented by the compound 1 was synthesized, and preferred embodiments of the TRL 0 derivative represented by the chemical formula 1 are as shown in Table 1 below.

[0439]

[0440]

[0441]

[0442]

[0443]

[0444]

[0445]

[0446]

[0447]

[0448]

[0449]

[0450] In addition, the present invention provides a compound represented by the following chemical formula 1 or a salt thereof.

[0451] [Chemical Formula 1]

[0452]

[0453] In the above chemical formula 1,

[0454] X is , , or And,

[0455] Y is , , or And,

[0456] R1 is hydrogen (H) or a halogen element,

[0457] R2 and R4 are each independently hydrogen (H) or a methyl group,

[0458] R3 is a fluorine (F) or trifluoromethoxy group (OCF3),

[0459] A1 is carbon (C), oxygen (O), or sulfur (S),

[0460] A2 is carbon (C) or substituted nitrogen (N),

[0461] A3 is carbon (C) or C=O,

[0462] A4 is substituted or unsubstituted carbon (C), substituted nitrogen (N), or oxygen (O),

[0463] A5 is nitrogen (N),

[0464] A6 and A8 are each independently substituted nitrogen (N),

[0465] A7 and A9 are each independently C=O,

[0466] n is 3,

[0467] The above 'substituted or unsubstituted' means one or more methyl groups (CH3), and acetyl groups ( ) means substituted or unsubstituted with one or more selected from the group consisting of.

[0468] In the present invention, substituted carbon or substituted nitrogen means that one or more methyl groups or acetyl groups are bonded to a carbon or nitrogen atom.

[0469] In the present invention, the compound represented by the chemical formula 1 may be one or more selected from the group consisting of the following, but is not limited thereto.

[0470] (1) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide (TRL 1);

[0471] (2) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide (TRL 2);

[0472] (3)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL 3);

[0473] (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide) (TRL 5);

[0474] (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-Nmethylbenzenesulfonamide (TRL 6);

[0475] (6) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide (TRL 8);

[0476] (7)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL 9);

[0477] (8)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide) (TRL 10);

[0478] (9)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-N-methylbenzenesulfonamide (TRL 12);

[0479] (10)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL 16);

[0480] (11)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide (N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide) (TRL 23);

[0481] (12)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide) (TRL 40);

[0482] (13)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide) (TRL 41);

[0483] (14)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide (TRL 42);

[0484] (15)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide) (TRL 43);

[0485] (16)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide (N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide) (TRL 51);

[0486] (17)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide) (TRL 53);

[0487] (18)N-(3-(10H-phenothiazin-10-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL 59);

[0488] (19)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide) (TRL 65); and

[0489] (20)N-methyl-N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL 67).

[0490]

[0491] In addition, the present invention provides a compound represented by the following chemical formula 1 or a salt thereof.

[0492] [Chemical Formula 1]

[0493]

[0494] In the above chemical formula 1,

[0495] X is And,

[0496] Y is or And,

[0497] R1 is hydrogen (H) or a halogen element,

[0498] R2 is hydrogen (H) or a methyl group,

[0499] R4 is hydrogen (H),

[0500] A1 is carbon (C),

[0501] A2, A4, A6, and A8 are each independently substituted nitrogen (N),

[0502] A3, A7 and A9 are each independently C=O,

[0503] A5 is nitrogen (N),

[0504] n is 3,

[0505] The above ‘substituted or unsubstituted’ means substituted or unsubstituted with a methyl group.

[0506] In the present invention, the substituted nitrogen means a methyl group bonded to a nitrogen atom.

[0507] In the present invention, the compound represented by the chemical formula 1 may be one or more selected from the group consisting of the following, but is not limited thereto.

[0508] (1)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL 5);

[0509] (2)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL 9);

[0510] (3)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide) (TRL 10);

[0511] (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide (TRL 40);

[0512] (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide (N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide) (TRL 41); and

[0513] (6)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide (TRL 53).

[0514]

[0515] The present invention also provides a composition comprising the compound or a salt thereof as an active ingredient. The compound or salt of the present invention can be formulated into a pharmaceutical composition, cosmetic composition, or food composition together with a pharmaceutically, cosmetically, or food-wise acceptable carrier, diluent, or excipient. The composition of the present invention also provides a composition comprising the compound or a salt thereof and one or more carriers, diluents, or excipients. The composition of the present invention can be used to inhibit melanin production. The composition of the present invention can be used to prevent, improve, or treat hyperpigmentation or for skin whitening.

[0516] In addition, the present invention provides a pharmaceutical composition for preventing or treating hyperpigmentation disease, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0517] In the present invention, “pharmaceutically acceptable salt” includes a salt derived from a pharmaceutically acceptable inorganic acid, organic acid, or base.

[0518] Examples of suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid, benzoic acid, malonic acid, gluconic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess aqueous acid solution and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone, or acetonitrile. Alternatively, they can be prepared by heating equimolar amounts of the compound and the acid or alcohol in water, followed by evaporation of the mixture to dryness, or by suction filtration of the precipitated salt.

[0519] Salts derived from suitable bases may include, but are not limited to, alkali metals such as sodium and potassium, alkaline earth metals such as magnesium, and ammonium. Alkali metal or alkaline earth metal salts can be obtained, for example, by dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering out the undissolved compound salt, and then evaporating and drying the filtrate. In this case, it is pharmaceutically suitable to prepare sodium, potassium, or calcium salts as the metal salt, and the corresponding silver salts can also be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0520] In the present invention, “hyperpigmentation disease” means any disease or condition of the skin caused by discoloration of the skin or proliferation of abnormally pigmented cells, and includes excessive or unwanted pigmentation. Factors such as aging, environmental stress, and UV exposure can be potential causes of skin pigmentation diseases. Hyperpigmentation of the present invention may be due to an increase in one or more different types of melanin synthesized in the skin and / or hair follicles and deposited in the hair or skin compared to the patient’s baseline pigmentation, and specific examples may include, but are not limited to, one or more selected from the group consisting of melasma, freckles, lentigines, liver spots, moles, coffee-colored spots, nevus of Ota, blue nevus, hyperpigmented spots, hyperpigmentation after drug use, gravidarum, post-inflammatory hyperpigmentation due to injury or dermatitis, senile pigmentation, dyspigmentation, and solar lentigines.

[0521] In the present invention, "melanin" refers to the black or brown pigment present in animal tissues such as skin and eyes. Melanin, in particular, is a key factor in determining human skin color. Melanin-expressing genes vary by race, and the amount and distribution of melanocytes are controlled accordingly, thereby determining skin color. While melanin protects the skin by blocking ultraviolet rays, excessive melanin production can cause various skin pigmentation conditions, such as freckles, age spots, and blemishes, and is further associated with the risk of skin cancer.

[0522]

[0523] In the present invention, the compound or its salt can inhibit melanin production, but is not limited thereto.

[0524] In the present invention, a compound or a salt thereof at a specific concentration that reduces the melanin amount to less than 100 based on the melanin amount of 100 in the control group can be used as a composition for preventing, treating, or improving hyperpigmentation diseases, including at least one selected from the group consisting of freckles, lentigines, liver spots, moles, coffee-colored spots, nevus of Ota, blue nevus, hyperpigmentation spots, hyperpigmentation after drug use, gravidic chloasma, post-inflammatory hyperpigmentation due to wounds or dermatitis, senile pigmentation, dyspigmentation, and solar lentigines. According to one experimental example of the present invention, among the derivatives of TRL 0, TRL 1, 2, 3, 5, 6, 8, 9, 10, 12, 16, 23, 40, 41, 42, 43, 51, 53, 59, 65, and 67 exhibited excellent melanin production inhibitory effects without exhibiting cytotoxicity, and in particular, TRL 5, 9, 10, 40, 41, and 53 exhibited similar or improved melanin production inhibitory effects compared to TRL 0, and thus were confirmed to be usable for the prevention, treatment, or improvement of hyperpigmentation diseases.

[0525] In the present invention, the pharmaceutical composition may be a systemic or local application pharmaceutical composition, but is not limited thereto.

[0526] The pharmaceutical composition according to the present invention may further comprise suitable carriers, excipients, and diluents commonly used in the manufacture of pharmaceutical compositions. The excipients may be, for example, one or more selected from the group consisting of diluents, binders, disintegrants, lubricants, adsorbents, moisturizers, film-coating materials, and controlled-release additives.

[0527] The pharmaceutical composition according to the present invention may be formulated and used in the form of external preparations such as powders, granules, sustained-release granules, enteric-coated granules, liquids, eye drops, ellipsoids, emulsions, suspensions, alcohols, troches, aromatic waters, limonades, tablets, sustained-release tablets, enteric-coated tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, irrigation solutions, ointments, lotions, pastes, sprays, inhalants, patches, sterile injection solutions, or aerosols, according to a conventional method, and the external preparations may have formulations such as creams, gels, patches, sprays, ointments, ointments, lotions, liniments, pastes, or cataplasmas.

[0528] Carriers, excipients and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

[0529] When formulating, it is usually prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants.

[0530] The additives of the tablets, powders, granules, capsules, pills, and troches according to the present invention include excipients such as corn starch, potato starch, wheat starch, lactose, sucrose, glucose, fructose, D-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, calcium hydrogen phosphate, calcium sulfate, sodium chloride, sodium bicarbonate, purified lanolin, microcrystalline cellulose, dextrin, sodium alginate, methylcellulose, sodium carboxymethylcellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropyl methylcellulose (HPMC) 1928, HPMC 2208, HPMC 2906, HPMC 2910, propylene glycol, casein, calcium lactate, and Primogel; Gelatin, gum arabic, ethanol, agar powder, cellulose acetate phthalate, carboxymethylcellulose, calcium carboxymethylcellulose, glucose, purified water, sodium caseinate, glycerin, stearic acid, sodium carboxymethylcellulose, sodium methylcellulose, methylcellulose, microcrystalline cellulose, dextrin, hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, refined shellac, starch starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinyl pyrrolidone, and binders such as hydroxypropyl methylcellulose, corn starch, agar powder, methylcellulose, bentonite, hydroxypropyl starch, sodium carboxymethylcellulose, sodium alginate, Disintegrants such as carboxymethylcellulose calcium, calcium citrate, sodium lauryl sulfate, anhydrous silicic acid, 1-hydroxypropyl cellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, baking soda, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, amylopectin, pectin, sodium polyphosphate, ethylcellulose, sucrose, magnesium aluminum silicate, di-sorbitol solution, and light anhydrous silicic acid;Lubricants such as calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopodium dentata, kaolin, petrolatum, sodium stearate, cacao butter, sodium salicylate, magnesium salicylate, polyethylene glycol (PEG) 4000, PEG 6000, liquid paraffin, hydrogenated soybean oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, macrogol, synthetic aluminum silicate, anhydrous silicic acid, higher fatty acids, higher alcohols, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, starch, sodium chloride, sodium acetate, sodium oleate, dl-leucine, and light anhydrous silicic acid can be used.;

[0531] As additives of the liquid formulation according to the present invention, water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, monostearate sucrose, polyoxyethylene sorbitol fatty acid esters (twin esters), polyoxyethylene monoalkyl ethers, lanolin ethers, lanolin esters, acetic acid, hydrochloric acid, ammonia water, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethylcellulose, sodium carboxymethylcellulose, etc. can be used.

[0532] The syrup according to the present invention may include a solution of white sugar, other sugars, or sweeteners, and may also include a fragrance, a coloring agent, a preservative, a stabilizer, a suspending agent, an emulsifier, a viscosity modifier, and the like, as needed.

[0533] Purified water may be used in the emulsion according to the present invention, and emulsifiers, preservatives, stabilizers, fragrances, etc. may be used as needed.

[0534] The suspension according to the present invention may include suspending agents such as acacia, tragacanth, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose (HPMC), HPMC 1828, HPMC 2906, and HPMC 2910, and surfactants, preservatives, stabilizers, colorants, and fragrances may be used as needed.

[0535] The injection according to the present invention includes a solvent such as distilled water for injection, 0.9% sodium chloride injection, Ringer's injection, dextrose injection, dextrose + sodium chloride injection, PEG, lactated Ringer's injection, ethanol, propylene glycol, non-volatile oils - sesame oil, cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristate, and benzene benzoate; a solubilizing agent such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, tween, nitrile acid amide, hexamine, and dimethylacetamide; a buffer such as weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, albumin, peptone, and gums; It may include isotonic agents such as sodium chloride; stabilizers such as sodium bisulfite (NaHSO3), carbon dioxide gas, sodium metabisulfite (Na2S2O5), sodium sulfite (Na2SO3), nitrogen gas (N2), and ethylenediaminetetraacetic acid; oxidizing agents such as sodium bisulfite 0.1%, sodium formaldehyde sulfoxylate, thiourea, disodium ethylenediaminetetraacetic acid, and acetone sodium bisulfite; analgesics such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; and suspending agents such as sodium cis-methylenediamine, sodium alginate, Tween 80, and aluminum monostearate.

[0536] The suppository according to the present invention comprises cocoa butter, lanolin, withepsol, polyethylene glycol, glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture of stearic acid and oleic acid, Subanal, cottonseed oil, peanut oil, palm oil, cocoa butter + cholesterol, lecithin, ranet wax, glycerol monostearate, Tween or Span, Imhausen, monolene (propylene glycol monostearate), glycerin, Adeps solidus, Buytyrum Tego-G, Cebes Pharma 16, hexalide base 95, Cotomar, Hydroxocote SP, S-70-XXA, S-70-XX75 (S-70-XX95), Mechanisms such as Hydrokote 25, Hydrokote 711, Idropostal, Massa estrarium (A, AS, B, C, D, E, I, T), Massa-MF, Masupol, Masupol-15, Neosupostal-N, Paramound-B, Suposiro (OSI, OSIX, A, B, C, D, H, L), Suppository type IV (AB, B, A, BC, BBG, E, BGF, C, D, 299), Supostal (N, Es), Wecovi (W, R, S, M, Fs), Tezester triglyceride basis (TG-95, MA, 57) can be used.

[0537] Solid dosage forms for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid dosage forms are prepared by mixing the extract with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

[0538] Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups. 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. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

[0539] The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment. The effective dosage level can be determined based on factors including the type and severity of the patient's disease, drug activity, drug sensitivity, administration time, administration route and excretion rate, treatment period, concurrently used drugs, and other factors well known in the medical field.

[0540] The pharmaceutical composition according to the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents. It can be administered sequentially or simultaneously with conventional therapeutic agents, or in single or multiple doses. Taking all of the above factors into account, it is important to administer an amount that achieves maximum efficacy with minimal side effects. This amount can be readily determined by those skilled in the art to which the present invention pertains.

[0541] The pharmaceutical composition of the present invention can be administered to a subject via various routes. All modes of administration are conceivable, including oral ingestion, subcutaneous injection, intraperitoneal administration, intravenous injection, intramuscular injection, intrathecal injection, sublingual administration, buccal mucosal administration, rectal insertion, vaginal insertion, ocular administration, otic administration, nasal administration, inhalation, oral or nasal spraying, dermal administration, and transdermal administration.

[0542] The pharmaceutical composition of the present invention is determined according to the type of drug as an active ingredient along with various related factors such as the disease to be treated, route of administration, age, sex, weight, and severity of the disease of the patient.

[0543] In the present invention, “subject” means a subject requiring treatment for a disease, and more specifically, means a mammal such as a human or non-human primate, mouse, rat, dog, cat, horse, and cow.

[0544] In the present invention, "administration" means providing a given composition of the present invention to a subject by any suitable method. Therefore, in the present invention, "administration" includes not only injection or ingestion into a subject, but also application.

[0545] In the present invention, “prevention” means any action that suppresses or delays the onset of a target disease, “treatment” means any action that improves or beneficially changes a target disease and its metabolic abnormality symptoms by administering a pharmaceutical composition according to the present invention, and “improvement” means any action that reduces a parameter related to a target disease, for example, the severity of a symptom, by administering a composition according to the present invention.

[0546] In the present invention, the compound according to the present invention or its salt may be included in the entire composition at a concentration of 0.05 to 25 μM, 0.1 to 10 μM, 1 to 10 μM, or 10 to 25 μM, but is not limited thereto. The concentration may be a concentration that appears in an individual upon administration of the composition, but is not limited thereto.

[0547]

[0548] In addition, the present invention provides a cosmetic composition for preventing or improving hyperpigmentation disease, comprising the compound or a cosmetically acceptable salt thereof as an active ingredient.

[0549] In addition, the present invention provides a cosmetic composition for skin whitening, comprising the compound or a cosmetically acceptable salt thereof as an active ingredient.

[0550] In the present invention, the term "cosmetically acceptable salt" includes a salt derived from a cosmetically acceptable inorganic acid, organic acid, or base. Specific examples include the salts described above, and further include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate), and p-toluenesulfonate (tosylate) salts.

[0551] The formulation of the cosmetic composition according to the present invention may be a serum, toner, paste, patch, gel, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, cream, massage cream, nourishing cream, mist, moisture cream, hand cream, hand lotion, foundation, essence, nourishing essence, pack, soap, oil, foundation, makeup base, wax, spray, cleansing foam, cleansing lotion, cleansing cream, cleansing oil, cleansing balm, body lotion, or body cleanser formulation.

[0552] The cosmetic composition of the present invention may further include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymeric peptides, polymeric polysaccharides, and sphingolipids.

[0553] Any water-soluble vitamin that can be mixed into cosmetics may be used, but examples thereof include vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinamide, folic acid, vitamin C, vitamin H, etc. Their salts (thiamine hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbate-2-phosphate, magnesium ascorbate-2-phosphate, etc.) are also included in the water-soluble vitamins that can be used in the present invention. Water-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification from microbial culture, enzymatic method, or chemical synthesis method.

[0554] Any vitamin that can be incorporated into cosmetics may be used as a functional vitamin, but examples thereof include vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), and their derivatives (ascorbic acid palmitate, ascorbic acid stearate, ascorbic acid dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol nicotinate, vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenyl ethyl ether, etc.). Functional vitamins can be obtained by conventional methods such as microbial transformation, purification from microbial culture, enzymatic or chemical synthesis, etc.

[0555] Any polymer peptide that can be incorporated into cosmetics may be used, but examples include collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, and keratin. Polymer peptides can be purified and obtained by conventional methods such as purification from microbial cultures, enzymatic methods, or chemical synthesis methods, or can be purified and used from natural products such as the dermis of pigs or cows, or silkworm fibers.

[0556] Any polymeric polysaccharide that can be incorporated into cosmetics may be used, but examples include hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate, or its salts (sodium salt, etc.). For example, chondroitin sulfate or its salts can usually be purified from mammals or fish and used.

[0557] Any sphingolipid that can be incorporated into cosmetics may be used, but examples include ceramide, phytosphingosine, and sphingoglycolipids. Sphingolipids can be purified by conventional methods from mammals, fish, shellfish, yeast, or plants, or obtained by chemical synthesis.

[0558] In addition to the above essential ingredients, the cosmetic composition of the present invention may contain other ingredients commonly incorporated into cosmetics as needed.

[0559] In addition, other compounding ingredients that may be added include oil components, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohol, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, etc.

[0560] Examples of maintenance ingredients include ester-based oils, hydrocarbon-based oils, silicone-based oils, fluorine-based oils, animal oils, and plant oils.

[0561] As ester-based fats and oils, tri-2-ethylhexanoate glyceryl, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, diisopropyl adipate, isoalkyl neopentanoate, tri(caprylic, capric) glyceryl, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, tetra-2-ethylhexanoate pentaellistolate, cetyl caprylate, decyl laurate, Hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, di(caprylic, capric acid) propylene glycol, propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, Glyceryl triundecyl acid, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerol oleate ester, polyglycerol isostearate ester, triisocetyl citrate, triisoalkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malate, hydroxystearic acid 2-Ethylhexyl, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate,Examples include esters such as cholesterol stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoylhydroxystearate, stearyl 12-stearoylhydroxystearate, and isostearyl 12-stearoylhydroxystearate.

[0562] Examples of hydrocarbon-based fats include squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, and vaseline.

[0563] Examples of silicone-based oils include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methyl stearoxysiloxane copolymer, alkyl-modified silicone oil, and amino-modified silicone oil.

[0564] Examples of fluorine-based oils include perfluoropolyether.

[0565] Examples of animal or plant fats include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, sunflower oil, soybean oil, corn oil, rapeseed oil, almond oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil, cottonseed oil, coconut oil, kukui nut oil, wheat germ oil, rice germ oil, shea butter, colostrum oil, marc deimia nut oil, meadowsweet oil, egg yolk oil, beef tallow, horse oil, mink oil, orange rapeseed oil, jojoba oil, candelilla wax, carnauba wax, liquid lanolin, and hydrogenated castor oil.

[0566] Examples of moisturizers include water-soluble low-molecular-weight moisturizers, fat-soluble molecular-weight moisturizers, water-soluble polymers, and fat-soluble polymers.

[0567] Examples of water-soluble low-molecular-weight moisturizers include serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (polymerization degree n=2 or higher), polypropylene glycol (polymerization degree n=2 or higher), polyglycerin B (polymerization degree n=2 or higher), lactic acid, and lactate salts.

[0568] Examples of fat-soluble low-molecular-weight moisturizers include cholesterol and cholesterol esters.

[0569] Examples of water-soluble polymers include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, water-soluble chitin, chitosan, and dextrin.

[0570] Examples of lipid-soluble polymers include polyvinylpyrrolidone-eicosene copolymer, polyvinylpyrrolidone-hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and polymer silicone.

[0571] Examples of emollients include long-chain acylglutamic acid cholesteryl ester, hydroxystearate cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, and lanolin fatty acid cholesteryl ester.

[0572] Examples of surfactants include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.

[0573] Nonionic surfactants include self-emulsifying monostearate glycerin, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POEㆍPOP (polyoxyethyleneㆍpolyoxypropylene) copolymer, POEㆍPOP alkyl ether, polyether-modified silicone, lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, etc.

[0574] Examples of anionic surfactants include fatty acid soaps, alpha-acyl sulfonates, alkyl sulfonates, alkyl allyl sulfonates, alkyl naphthalene sulfonates, alkyl sulfates, POE alkyl ether sulfates, alkyl amide sulfates, alkyl phosphates, POE alkyl phosphates, alkyl amide phosphates, alkyloyl alkyl taurine salts, N-acyl amino acids, POE alkyl ether carboxylates, alkyl sulfosuccinates, sodium alkyl sulfoacetate, acylated hydrolyzed collagen peptide salts, and perfluoroalkyl phosphate esters.

[0575] Examples of cationic surfactants include alkyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, cetostearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzylammonium chloride, behenyl trimethyl ammonium bromide, benzalkonium chloride, diethyl amino ethyl amide stearate, dimethyl amino propyl amide stearate, and quaternary ammonium salts of lanolin derivatives.

[0576] Examples of amphoteric surfactants include carboxybetaine type, amidebetaine type, sulfobetaine type, hydroxysulfobetaine type, amidesulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, and amideamine type.

[0577] Organic and inorganic pigments include inorganic pigments such as silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium-coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, aluminum oxide, calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine, chromium oxide, chromium hydroxide, calamine, and complexes thereof; Examples thereof include organic pigments such as polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene-styrene copolymer, silk powder, cellulose, CI pigment yellow, CI pigment orange, and composite pigments of inorganic pigments and organic pigments.

[0578] Examples of organic powders include metal soaps such as calcium stearate; alkyl phosphate metal salts such as sodium zinc cetylphosphate, zinc laurylate, and calcium laurylate; acylamino acid polyvalent metal salts such as calcium N-lauroyl-beta-alanine, zinc N-lauroyl-beta-alanine, and calcium N-lauroylglycine; amide sulfonic acid polyvalent metal salts such as calcium N-lauroyl-taurine and calcium N-palmitoyl-taurine; N-acyl basic amino acids such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoyl lysine, N-alpha-paritoyl olnitine, N-alpha-lauroyl arginine, and N-alpha-hydrogenated beef tallow fatty acid acylarginine; N-acyl polypeptides such as N-lauroyl glycyl glycine; Alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid; polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzene-styrene copolymer, and ethylene tetrafluoride.

[0579] UV absorbers include para-aminobenzoic acid, para-aminobenzoic acid ethyl, para-aminobenzoic acid amyl, para-aminobenzoic acid octyl, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, benzyl cinnamic acid, 2-ethoxyethyl para-methoxycinnamic acid, octyl para-methoxycinnamic acid, mono-2-ethylhexaneglyceryl dipara-methoxycinnamic acid, isopropyl para-methoxycinnamic acid, diisopropyl-diisopropyl cinnamic acid ester mixture, urocanic acid, ethyl urocanic acid, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenone disulfonate, dihydroxybenzophenone, tetrahydroxybenzophenone, Examples include 4-tert-butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine, and 2-(2-hydroxy-5-methylphenyl)benzotriazole.

[0580] Examples of disinfectants include hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zincpyrithione, benzalkonium chloride, photosensitive agent No. 301, sodium mononitroguaiacol, and undecylenic acid.

[0581] Antioxidants include butylated hydroxyanisole, propyl gallate, and ellisorbic acid. pH adjusters include citric acid, sodium citrate, malic acid, sodium malate, formaldehyde, sodium formalate, succinic acid, sodium succinate, sodium hydroxide, and sodium hydrogen phosphate. Alcohols include higher alcohols such as cetyl alcohol.

[0582] In addition, the mixing components that may be added are not limited to these, and any of the above components may be mixed within a range that does not impair the purpose and effect of the present invention, but may be mixed at a weight percentage of 0.01-5% or a weight percentage of 0.01-3% with respect to the total weight.

[0583] When the formulation of the present invention is a lotion, paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.

[0584] When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether may be additionally included.

[0585] In the case where the formulation of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

[0586] When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth may be used as carrier components.

[0587] When the formulation of the present invention is a surfactant-containing cleansing agent, a fatty alcohol sulfate, a fatty alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyl taurate, a sarcosinate, a fatty acid amide ether sulfate, an alkyl amidobetaine, a fatty alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a linolenic derivative, or an ethoxylated glycerol fatty acid ester may be used as a carrier component.

[0588] The present invention also provides a skin care method for preventing or improving skin pigmentation, comprising a step of applying a cosmetic composition according to the present invention to the skin of an individual in need thereof. In the present invention, "application" includes all means capable of applying the cosmetic composition to the skin, such as administration, injection, or coating.

[0589]

[0590] In addition, the present invention provides a systemic or topical preparation for preventing, treating, or improving hyperpigmentation disease, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0591] In the present invention, the topical application preparation may be in the form of a cream, gel, lotion, powder, powder spray, oil, roll-on formulation, ointment, foam, spray, stick or tincture, but is not limited thereto.

[0592]

[0593] In addition, the present invention provides a food composition for preventing or improving hyperpigmentation disease, comprising the compound or a food-related acceptable salt thereof as an active ingredient.

[0594] In addition, the present invention provides a food composition for skin whitening, comprising the compound or a food-wise acceptable salt thereof as an active ingredient.

[0595] In the present invention, the food composition may be a health functional food composition, but is not limited thereto.

[0596] In the present invention, “food-wise acceptable salt” includes a salt derived from a food-wise acceptable organic acid, inorganic acid, or base.

[0597] When the compound of the present invention or its food-related acceptable salt is used as a food additive, the compound or its food-related acceptable salt can be added as is or used together with other foods or food ingredients, and can be used appropriately according to a conventional method. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when manufacturing a food or beverage, the compound of the present invention or its food-related acceptable salt can be added in an amount of 15 wt% or less, or 10 wt% or less, based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount can be below the above range, and since there is no problem in terms of safety, the active ingredient can also be used in an amount above the above range.

[0598] There are no specific restrictions on the types of the above foods. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and all health functional foods in the conventional sense are included.

[0599] The health beverage composition according to the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients, like conventional beverages. The natural carbohydrates mentioned above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame can be used. The proportion of the natural carbohydrate is generally about 0.01-0.20 g, or about 0.04-0.10 g, per 100 mL of the composition of the present invention.

[0600] In addition to the above, the composition of the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients may be used independently or in combination. The proportion of these additives is not particularly critical, but is typically selected within the range of 0.01 to 0.20 parts by weight per 100 parts by weight of the composition of the present invention.

[0601] In the present invention, “health functional food” is the same term as food for special health use (FoSHU), and means a food with high medical or therapeutic effects that is processed to efficiently exhibit a bioregulatory function in addition to providing nutrition. The food can be manufactured in various forms such as tablets, capsules, powders, granules, liquids, and pills to obtain a useful effect in preventing or improving obesity.

[0602] The health functional food of the present invention can be manufactured using methods commonly used in the art, and can be manufactured by adding raw materials and ingredients commonly used in the art. Furthermore, unlike conventional drugs, it has the advantage of being food-based, eliminating the side effects that can occur with long-term use of drugs, and can be highly portable.

[0603] The above health functional food has the advantage of having even better effects when consumed in the form of inner beauty food. The inner beauty is a food referred to as an "edible cosmetic or beauty food", and refers to a food that changes the skin constitution to a healthy one by allowing various skin-friendly ingredients to be absorbed into the body. Just as one selects cosmetics that suit one's skin type, one can select and consume inner beauty food that suits one's skin condition and lifestyle. For example, when a cosmetic containing the above cosmetic composition is combined with an inner beauty food containing the compound of the present invention or a salt thereof, the effect is significantly enhanced compared to using only cosmetics or drugs, and can have the advantage of having a more effective skin pigmentation prevention or improvement effect as well as a whitening effect.

[0604]

[0605] In addition, the present invention provides a kit for preventing, treating, or improving hyperpigmentation disease, comprising a pharmaceutical composition, cosmetic composition, topical application preparation, or food composition according to the present invention.

[0606] The “kit” according to the present invention may include tools and / or reagents known in the art necessary to achieve the purpose of the present invention, i.e., prevention, improvement, or treatment of hyperpigmentation diseases; skin whitening; or skin beautification, etc. For example, the kit according to the present invention may further include instructions describing a skin beautification method for preventing or improving melanin abnormalities, or may further include devices necessary for administering, applying, or absorbing the composition according to the present invention, such as syringes, cotton, cotton swabs, sheets, etc.

[0607]

[0608] In addition, the present invention provides a pharmaceutical composition for preventing or improving hyperpigmentation disease, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0609] In addition, the present invention provides a skin whitening quasi-drug composition comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0610] The term "quasi-drug" used in the present invention refers to products that have a milder effect than pharmaceutical products among products used for the purpose of diagnosing, treating, improving, alleviating, managing or preventing diseases of humans or animals. For example, according to the Pharmaceutical Affairs Act, quasi-drugs are products other than those used for pharmaceutical purposes, and include products used for treating or preventing diseases of humans or animals, products that have a mild effect on the human body or do not act directly, etc.

[0611]

[0612] When the compound of the present invention or a pharmaceutically acceptable salt thereof is used as an over-the-counter drug additive, it may be added as is or used in combination with other over-the-counter drugs or over-the-counter drug ingredients, and may be used appropriately according to conventional methods. The mixing ratio with other ingredients used together may be appropriately determined depending on the intended use (e.g., preventive, improvement, or therapeutic treatment).

[0613] Examples of the pharmaceutical composition of the present invention include, but are not limited to, scalp and hair care compositions such as masks, ointments, creams, lotions, essences, sprays, shampoos, and rinses, body cleansers, foams, and soaps.

[0614]

[0615] In addition, the present invention provides a method for preventing, treating, or improving hyperpigmentation disease, comprising administering a therapeutically effective amount of the compound or a salt thereof; or a composition containing the compound as an active ingredient, to a subject in need thereof.

[0616] In addition, the present invention provides a use of the compound or a salt thereof; or a composition containing the compound as an active ingredient, for preventing, treating, or improving hyperpigmentation disease.

[0617] In addition, the present invention provides a use of the compound or a salt thereof; or a composition comprising the compound or a salt thereof as an active ingredient; for the manufacture of a preparation for preventing, treating, or improving hyperpigmentation disease.

[0618]

[0619] In the present invention, when the term "comprising" is used, it means that other components can be included rather than excluding other components unless specifically stated otherwise. As used throughout the present invention, the terms "step of doing" or "step of" do not mean "step for."

[0620]

[0621] Hereinafter, preferred examples and experimental examples are presented to aid in understanding the present invention. However, the following examples and experimental examples are provided solely to facilitate a better understanding of the present invention, and the scope of the present invention is not limited by the following examples and experimental examples.

[0622]

[0623] [Experimental Method]

[0624] 1. Cell culture

[0625] Mel-Ab cells, a mouse melanocyte cell line, were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 10% FBS, 1% penicillin / streptomycin, 100 nM TPA (Tissue type plasminogen activator), and 1 nM CT (Cefixime Tellurite). For the experiment, 7 × 10 cells were seeded in a 100 mm dish. 5 After seeding the dog cells, they were cultured for 6 days at 37°C and 5% CO2, and the existing medium was replaced with new medium every 48 to 72 hours during the culture period.

[0626] Mouse melanoma cells B16F10 were cultured under the same conditions as Mel-Ab in DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0627] Normal human melanocytes (NHM) were cultured in Medium 254 (Gibco) supplemented with Human Melanocyte Growth Supplement (Gibco). Cultures were performed at 37°C and 5% CO2, with the medium replaced every 2–3 days. Experiments were performed when cell confluency reached 70% or greater.

[0628]

[0629] 2. Absorbance-based melanin content measurement

[0630] Mel-Ab, which was pretreated or not with 10 μM FSK (Forskolin) for 1 hour, and NHM were treated with 0.1, 1, or 10 μM TRL 0 or its derivative compounds, and cultured for 72 hours. Before measuring the melanin content, the cells were observed under a microscope (Olympus, Tokyo, Japan) to confirm the cell status. The cell culture medium was removed, and the cells were washed with PBS. The cells were dissolved in 550 μl of 1 N NaOH and heated at 100 °C for 30 minutes. After cooling briefly at room temperature, the cells were centrifuged at 13,000 rpm for 5 minutes. The absorbance of the supernatant was measured at 405 nm using a microplate reader. The intracellular melanin content was expressed as a percentage of the control group (CTRL, basal) or the FSK-treated group (FSK) that was not treated with FSK.

[0631]

[0632] 3. Fluorescence-based melanin content measurement

[0633] B16F10 cells were pretreated with TRL 0 or derivatives at concentrations of 0.47, 0.94, 1.88, 3.75, 7.50, 15.00, or 30.00 μM for 1 h, and then treated with FSK to obtain concentrations of TRL 0 and its derivatives of 0.39, 0.78, 1.56, 3.12, 6.25, 12.50, or 25.00 μM and 5 μM, respectively. After culturing for 72 h, the cultures were extracted, treated with H2O2 to a final concentration of 15%, and melanin was oxidized for 3 h. The oxidized melanin was then measured by fluorescence (excitation / emission: 475 / 525). At this time, a quantitative standard curve was derived using the oxidized melanin whose concentration was confirmed, and the amount of melanin released into the medium was measured based on this curve. Then, the amount of melanin according to the treatment concentration of TLR 0 and its derivatives was calculated, and the IC50 value was calculated based on this to derive the melanin production inhibition ability.

[0634]

[0635] 4. Cytotoxicity analysis

[0636] Mel-Ab cells and B16F10 cells were cultured at 1.2×10 5 Cells were seeded in 6-well cell culture plates at 1 × 10 cells / well. After 24 hours, the medium was replaced with DMEM containing 10% FBS and 1% AA (antibiotic antimycotic), and the drug was treated 1 hour later. Mel-Ab cells and B16F10 cells were seeded at 3 × 10 5 Cells were seeded in 6-well cell culture plates at 1 / well. After washing with 1× PBS, the medium was replaced with DMEM medium containing 10% FBS and 1% AA without CT (Cefixime Tellurite) and TPA (Tissue-type plasminogen activator), and the drugs were treated after 1 hour.

[0637] NHM cells were 6.0×10 5Cells were seeded in 6-well cell culture plates at 10 cells / well. After 24 hours, the medium was replaced with Media 254 containing Human Melanocyte Growth Supplement (HMGS) and 1% AA, and the drug was treated 1 hour later, and cultured for 72 hours after drug treatment.

[0638] Cell viability was measured using the MTT assay. After 72 hours of drug treatment, the medium was removed, washed with PBS, and then MTT solution dissolved in PBS was added to the medium at a concentration of 2.5 mg / mL. The cells were incubated at 37°C in a 5% CO2 atmosphere for 2 hours. The resulting formazan crystals were dissolved in DMSO, and the absorbance was measured at 565 nm using a microplate reader (Molecular Devices, Sunnyvale, CA, USA). Cell viability was expressed as a percentage of the untreated control group.

[0639]

[0640] [Example]

[0641] Example 1. Synthesis procedure of compounds

[0642] 1-1. General Procedure A for Acylation

[0643] To a stirred solution of a tricyclic amine (1.0 equiv.) dissolved in toluene (0.5 M) was added chloroacetyl chloride (1.0 equiv.) and heated to 100 °C for 1 or 24 h. The reaction mixture was then cooled to room temperature and concentrated in vacuo to remove most of the solvent. The residue was suspended in a minimal amount of ethyl acetate, treated with hexane, and the formed precipitate was collected by filtration.

[0644]

[0645] 1-2. General procedure B for nucleophilic substitution with nitrile

[0646] To a stirred solution of acetyl chloride residue (1.0 equiv.) dissolved in DMF or CH2Cl2 (0.4 M) was added sodium cyanide or tetrabutylammonium cyanide (1.2 equiv.) at 0 °C. The mixture was stirred at room temperature for 24 h, the solution was diluted with EtOAc, and the organic layer was washed three times with H2O. The organic phase was then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was filtered through a minimal amount of ethyl acetate and precipitated by the addition of hexane.

[0647]

[0648] 1-3. General procedure for reduction C

[0649] To a stirred solution of a nitrile compound (1.0 equiv.) dissolved in THF (0.3 M) was added BH3-THF (1 M solution in THF, 4.0 equiv.) at 0 °C. The reaction mixture was then heated to 70 °C for 5 h and then cooled to room temperature. The solution was slowly treated, dropwise added with 1 M aqueous HCl, stirred for an additional 0.5 h, and then heated to 70 °C for 1 h. The reaction mixture was cooled to room temperature, treated with aqueous 4 M NaOH until the pH became > 8, and the mixture was extracted with CH2Cl2. The combined organic phases were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by column chromatography.

[0650]

[0651] 1-4. General procedure D for nucleophilic aromatic substitution

[0652] To a stirred solution of amine (1.0 equiv.) dissolved in DMF (0.4 M) were added Et3N (4.0 equiv.) and aryl sulfonyl chloride (1.1 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 3 h, diluted with EtOAc, and the organic phase was washed three times with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by column chromatography.

[0653]

[0654] 1-5. General Procedure E for N-Methylation

[0655] To a stirred solution of sulfonamide (1.0 equiv.) dissolved in DMF (0.2 M) were added K2CO3 (6.0 equiv.) and MeI (1.5 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 24 h, diluted with EtOAc, and the organic phase was washed three times with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by column chromatography.

[0656]

[0657] 1-6. General Procedure F for Reductive Amination

[0658] To a mixture of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine or 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv.) and a suspension of sodium methanolate (5.0 equiv.) in MeOH (0.05 M) was added a suspension of formaldehyde (1.4 equiv.) in MeOH. The reaction mixture was stirred at room temperature for 1 h, after which NaBH4 (1.0 equiv.) was added. After 1 h, the mixture was quenched with 1 M KOH and extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was then purified by column chromatography.

[0659]

[0660] Example 2. Synthesis reaction scheme of the compound

[0661] [Reaction Formula 1]

[0662]

[0663] 2-1. 2-chloro-1-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethan-1-one

[0664] [Compound 1-1]

[0665]

[0666] Following the reaction of 10,11-dihydro-5H-dibenzo[b,f]azepine (1.0 equiv., 100 mg, 0.512 mmol) and chloroacetyl chloride (1.0 equiv., 41 μl, 0.512 mmol) via general procedure A of Example 1-1, 128 mg (92%) of the product was obtained as a yellow oil via recrystallization;

[0667] 1H NMR (CDCl3, 400 MHz) δ- 7.17 (m, 8H), 4.20 - 3.91 (m, 2H), 3.43 (m, 2H), 2.90 - 2.78 (m, 2H).

[0668]

[0669] 2-2. 2-chloro-1-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethan-1-one

[0670] [Compound 1-2]

[0671]

[0672] Following the reaction of 3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepine (1.0 equiv., 2.0 g, 1.02 mmol) and chloroacetyl chloride (1.0 equiv., 0.70 ml, 1.02 mmol) via general procedure A of Example 1-1, 2.38 g (76%) of the product was obtained as a pale pink solid via recrystallization;

[0673] 1 H NMR (CDCl3, 400 MHz) δ- 7.03 (m, 7H), 4.15 - 3.92 (m, 2H), 3.49 - 3.25 (m, 2H), 2.83 (m, 2H).

[0674] MS (ESI + )m / zcalcd for C 16 H 14 Cl2NO [M + H] + 306.04; found 306.02.

[0675]

[0676] 2-3. 2-chloro-1-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)ethan-1-one

[0677] [Compounds 1-3]

[0678]

[0679] Following the reaction of 2,3,4,5-tetrahydro-1H-benzo[b]azepine (1.0 equiv., 500 mg, 3.40 mmol) and chloroacetyl chloride (1.0 equiv., 0.33 ml, 4.08 mmol) via general procedure A of Example 1-1, 607 mg (80%) of the product was obtained as an ivory solid via recrystallization (hexane only);

[0680] 1 H NMR (CDCl3, 400 MHz) δ- 7.22 (m, 3H), 7.19 - 7.15 (m, 1H), 4.69 (m, 1H), 3.93 (d,J= 12.8 Hz, 1H), 3.80 (d,J= 12.8 Hz, 1H), 2.83 (m, 1H), 2.76 - 2.60 (m, 2H), 2.04 - 1.90 (m, 2H), 1.86 - 1.73 (m, 1H), 1.46 - 1.31 (m, 1H).

[0681] MS (ESI + )m / zcalcd for C 12 H 15 ClNO [M + H] + 224.08; found 223.96

[0682]

[0683] 2-4. 2-chloro-1-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)ethan-1-one

[0684] [Compounds 1-4]

[0685]

[0686] Following the reaction of 5,11-dihydrodibenzo[b,e][1,4]oxazepine (1.0 equiv., 500 mg, 2.54 mmol) and chloroacetyl chloride (1.2 equiv., 244 μl, 3.04 mmol) using the general procedure A of Example 1-1, 597 mg (86%) of the product was obtained as an ivory solid by purification using MPLC (EtOAc / n-hexane = 1:2);

[0687] 1 H NMR (CDCl3, 400 MHz) δ- 7.42 (m, 4H), 7.19 (d,J= 24.3 Hz, 2H), 6.94 - 6.86 (m, 2H), 5.71 (d,J= 12.5 Hz, 1H), 4.88 (d,J= 12.6 Hz, 1H), 4.25 (s, 1H), 4.03 (d,J=23.9 Hz, 1H).

[0688] MS (ESI + )m / zcalcd for C 15 H 13 ClNO2[M + H] + 274.06; found 274.02.

[0689]

[0690] 2-5. 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-3-oxopropanenitrile

[0691] [Compounds 1-5]

[0692]

[0693] Following the reaction of 2-chloro-1-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethan-1-one (1.0 equiv., 122 mg, 0.403 mmol) and sodium cyanide (1.0 equiv., 19.8 mg, 0.403 mmol) using the general procedure B of Example 1-2, 88 mg (83%) of the product was obtained as an ivory solid through recrystallization;

[0694] 1 H NMR (CDCl3, 400 MHz) δ- 7.28 (m, 5H), 7.26 - 7.14 (m, 3H), 3.55 - 3.29 (m, 4H), 2.92 - 2.81 (m, 2H).

[0695] MS (ESI + )m / zcalcd for C 17 H 15 N2O [M + H] + 262.11; found 263.06.

[0696]

[0697] 2-6. 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-3-oxopropanenitrile

[0698] [Compound 1-6]

[0699]

[0700] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-3-oxopropanenitrile (1.0 equiv., 2.67 g, 8.72 mmol) and sodium cyanide (1.2 equiv., 513 mg, 10.5 mmol) via general procedure B of Example 1-2, 1.8 g (70%) of the product was obtained as an ivory-colored solid through recrystallization;

[0701] 1H NMR (CDCl3, 400 MHz) δ 7.40 - 7.09 (m, 7H), 3.56 - 3.27 (m, 4H), 2.92 - 2.79 (m, 2H).

[0702]

[0703] 2-7. 3-oxo-3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propanenitrile

[0704] [Compound 1-7]

[0705]

[0706] Following the reaction of 2-chloro-1-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)ethan-1-one (1.0 equiv., 600 mg, 2.68 mmol) and tetrabutylammonium cyanide (1.0 equiv., 720 mg, 2.68 mmol) using the general procedure B of Example 1-2, 517 mg (86%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[0707] 1 H NMR (CDCl3, 400 MHz) δ 7.31 - 7.24 (m, 3H), 7.17 - 7.11 (m, 1H), 4.67 (m, 1H), 3.35 (d,J= 18.0 Hz, 1H), 3.13 (d,J= 17.9 Hz, 1H), 2.85 - 2.65 (m, 3H), 2.09 - 1.90 (m, 2H), 1.83 (m, 1H), 1.40 (m, 1H).

[0708] MS (ESI + )m / zcalcd for C 13 H 15 N2O [M + H] + 215.11; found 214.51.

[0709]

[0710] 2-8. 3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)-3-oxopropanenitrile

[0711] [Compound 1-8]

[0712]

[0713] Following the reaction of 2-chloro-1-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)ethan-1-one (1.0 equiv., 423 mg, 1.55 mmol) and tetrabutylammonium cyanide (1.0 equiv., 415 mg, 1.55 mmol) using the general procedure B of Example 1-2, 314 mg (75%) of the product was obtained as a white solid by purification using MPLC (EtOAc / n-hexane = 1:2);

[0714] 1 H NMR (CDCl3, 400 MHz) δ7.53 - 7.16 (m, 6H), 6.91 (dd,J= 36.8, 8.1 Hz, 2H), 5.65 (dd,J= 30.2, 12.8 Hz, 1H), 4.92 (d,J= 12.8 Hz, 1H), 3.79 - 3.55 (m, 1H), 3.55 - 3.20 (m, 1H).

[0715] MS (ESI + )m / zcalcd for C 16 H 13 N2O2[M + H] + 265.09; found 265.08.

[0716]

[0717] 2-9. 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine

[0718] [Compound 1-9]

[0719]

[0720] Reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-3-oxopropanenitrile (1.0 equiv., 86 mg, 0.326 mmol) and BH3-THF (1 M solution in THF, 4.0 equiv., 1.30 ml, 17.74 mmol) via general procedure C of Example 1-3 was followed by MPLC purification on amino silica gel (DCM / MeOH = 1:10) to give 35 mg (43%) of the product as a colorless oil;

[0721] 1 H NMR (CD3OD, 400 MHz) δ- 7.04 (m, 6H), 6.90 - 6.86 (m, 2H), 3.74 (t, J = 6.7 Hz, 2H), 3.10 (s, 4H), 2.62 (t, J = 7.2 Hz, 2H), 1.68 (p, J = 6.9 Hz, 2H).

[0722] MS (ESI + )m / zcalcd for C 17 H 21 N2[M + H] + 253.16; found 253.16 .

[0723]

[0724] 2-10. 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine

[0725] [Compounds 1-10]

[0726]

[0727] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-3-oxopropanenitrile (1.0 equiv., 400 mg, 1.35 mmol) and BH3-THF (1 M solution in THF, 4.0 equiv., 5.39 ml, 5.39 mmol) via general procedure C of Example 1-3, 186 mg (48%) of the product was obtained as a pale yellow gum by purification by MPLC on amino silica gel (DCM / MeOH = 1:20);

[0728] 1 H NMR (CD3OD, 400 MHz) δ- 6.29 (m, 4H), 6.22 (d,J= 8.1 Hz, 1H), 6.18 - 6.12 (m, 1H), 6.05 (dd,J= 8.1, 2.1 Hz, 1H), 2.96 (t,J= 6.7 Hz, 2H), 2.30 (p,J= 5.8, 4.8 Hz, 4H), 1.88 - 1.83 (m, 2H), 0.91 (p,J= 6.9 Hz, 2H).

[0729] MS (ESI + )m / zcalcd for C 17 H 20 ClN2[M + H] + 287.12; found 287.13.

[0730]

[0731] 2-11. 3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propan-1-amine

[0732] [Compound 1-11]

[0733]

[0734] Reaction of 3-oxo-3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propanenitrile (1.0 equiv., 500 mg, 2.33 mmol) and BH3-THF (1 M solution in THF, 4.0 equiv., 9.3 ml, 9.33 mmol) via general procedure C of Example 1-3 above gave 92 mg (19%) of the product as a pale colorless oil, which was purified by MPLC on amino silica gel (DCM / MeOH = 2:1);

[0735] 1 H NMR (CD3OD, 400 MHz) δ- 7.04 (m, 2H), 6.96 (d,J= 7.9 Hz, 1H), 6.82 (td,J= 7.4, 1.2 Hz, 1H), 3.20 (t,J= 6.6 Hz, 2H), 2.91 - 2.86 (m, 2H), 2.76 (m, 4H), 1.73 (m, 4H), 1.61 - 1.54 (m, 2H).

[0736] MS (ESI + )m / zcalcd for C 13 H 21 N2[M + H] + 205.16; found 205.08.

[0737]

[0738] 2-12. 3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propan-1-amine

[0739] [Compound 1-12]

[0740]

[0741] Reaction of 3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)-3-oxopropanenitrile (1.0 equiv., 307 mg, 1.16 mmol) and BH3-THF (1 M solution in THF, 4.0 equiv., 4.6 ml, 4.65 mmol) via general procedure C of Example 1-3 above gave 92 mg (30%) of the product as a pale colorless oil, which was purified by MPLC on amino silica gel (DCM / MeOH = 1:10);

[0742] 1 H NMR (CD3OD, 400 MHz) δ- 7.25 (m, 2H), 7.18 (d,J= 7.9 Hz, 1H), 7.09 - 7.01 (m, 2H), 6.83 - 6.68 (m, 3H), 5.28 (s, 2H), 3.81 (t,J= 6.7 Hz, 2H), 2.68 (t,J= 7.2 Hz, 2H), 1.79 (p,J= 6.9 Hz, 2H).

[0743] MS (ESI + )m / zcalcd for C 16 H 19 N2O [M + H] + 255.14; found 255.12.

[0744]

[0745] [Reaction Formula 2]

[0746]

[0747] 2-13. 2-(3-(2-chloro-9H-carbazol-9-yl)propyl)isoindoline-1,3-dione

[0748] [Compound 1-13]

[0749]

[0750] To a stirred solution of 2-chloro-9H-carbazole (1.0 equiv., 30 mg, 0.149 mmol) dissolved in DMF was added NaH (2.0 equiv., 11.9 mg, 0.298 mmol) at 0 °C. Then, 2-(3-bromopropyl)isoindoline-1,3-dione (1.2 equiv., 47.9 mg, 0.1749 mmol) was added, and the reaction mixture was stirred at 50 °C for 3 h. After the mixture was diluted with EtOAc, the organic phase was washed three times with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by MPLC (EtOAc / hexane = 1:5) to give 24 mg (42%) of the product as an ivory solid;

[0751] 1 H NMR (CDCl3, 400 MHz) δ(d,J= 7.8 Hz, 1H), 7.95 (d,J= 8.3 Hz, 1H), 7.86 - 7.81 (m, 2H), 7.74 - 7.70 (m, 2H), 7.47 - 7.43 (m, 1H), 7.38 - 7.35 (m, 2H), 7.25 - 7.21 (m, 1H), 7.17 (dd,J= 8.3, 1.8 Hz, 1H), 4.33 (t,J= 7.5 Hz, 2H), 3.80 (t,J= 7.2 Hz, 2H), 2.26 (p,J= 7.4 Hz, 2H).

[0752]

[0753] 2-14. 3-(2-chloro-9H-carbazol-9-yl)propan-1-amine

[0754] [Compound 1-14]

[0755]

[0756] To a stirred solution of 2-(3-(2-chloro-9H-carbazol-9-yl)propyl)isoindoline-1,3-dione (1.0 equiv., 23 mg, 0.059 mmol) in EtOH (0.5 M) was added hydrazine hydrate (1.1 equiv., 5.01 mg, 0.065 mmol) and heated to 90 °C. The reaction mixture was cooled to room temperature, diluted with EtOAc, and the organic phase was washed three times with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by MPLC (EtOAc / hexane = 1:5) to give 24 mg (42%) of the product as an ivory solid;

[0757] 1 H NMR (CD3OD, 400 MHz) δ(dd,J= 16.3, 8.0 Hz, 2H), 7.55 (d,J= 1.8 Hz, 1H), 7.50 (d,J= 8.2 Hz, 1H), 7.44 (t,J= 7.6 Hz, 1H), 7.20 (t,J= 7.4 Hz, 1H), 7.14 (dd,J= 8.2, 1.8 Hz, 1H), 4.36 (t,J= 7.1 Hz, 2H), 2.64 (t,J= 7.3 Hz, 2H), 1.96 (p,J= 7.2 Hz, 2H).

[0758]

[0759] [Reaction Formula 3]

[0760]

[0761]

[0762] 2-15. 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine

[0763] [Compound 1-15]

[0764]

[0765] Montmorillonite K10 (1.0 equiv., 16.9 mg, 0.60 mmol) was added to a stirred solution of paraformaldehyde in MeOH (0.2 M). The reaction mixture was then stirred in a microwave tube at room temperature for 15 min, and 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine was added. The reaction mixture was then stirred in a microwave at 80 °C for 30 min. After the product was cooled to room temperature, a mixture of montmorillonite K10 and sodium borohydride (1.5 equiv., 3.39 mg, 0.060 mmol) was added to the reaction mixture. The mixture was stirred overnight, diluted with MeOH, filtered, and dried. Then, the residue was purified by MPLC on aminosilica gel (EtoAc / hexane = 1:1) to obtain 4.4 mg (4.4%) of the product as a colorless oil;

[0766] 1 H NMR (CDCl3, 400 MHz) δ- 7.05 (m, 6H), 6.94 - 6.86 (m, 2H), 3.77 (t,J= 7.0 Hz, 2H), 3.16 (s, 3H), 2.30 (t,J= 7.3 Hz, 2H), 2.15 (s, 4H), 1.72 (p,J= 7.1 Hz, 2H).

[0767] MS (ESI + )m / zcalcd for C 18 H 23 N2[M + H] + 267.18; found 267.28.

[0768]

[0769] 2-16. 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine

[0770] [Compound 1-16]

[0771]

[0772] 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 50 mg, 0.174 mmol) was added to a suspension of sodium methanolate (5.0 equiv., 174 μl, 0.872 mmol) in methanol (0.05 M). The reaction solution was then added to a suspension of formaldehyde (1.4 equiv., 7.33 mg, 0.244 mmol) in methanol. The reaction mixture was stirred at room temperature for 1 h, after which sodium tetrahydroborate (1.0 equiv., 6.60 mg, 0.174 mmol) was added, the solvent was evaporated, and the mixture was treated with 1 M KOH. The product was extracted with CH2Cl2, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by MPLC (EtOAc / hexane = 1:2) to obtain 21 mg (39%) of the product as a colorless oil;

[0773] 1 H NMR (CDCl3, 400 MHz) δ- 7.03 (m, 4H), 7.00 - 6.94 (m, 2H), 6.86 (dd,J= 8.1, 2.1 Hz, 1H), 3.77 (t,J= 6.8 Hz, 2H), 3.15 - 3.08 (m, 4H), 2.66 (t,J= 7.1 Hz, 2H), 2.39 (s, 3H), 1.81 (p,J= 6.9 Hz, 2H).

[0774] MS (ESI + )m / zcalcd for C 18 H 22 ClN2[M + H] + 301.14; found 301.11.

[0775]

[0776] Example 3. Synthesis of different types of compounds

[0777] 3-1. 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide (TRL-001)

[0778] [Compound 2-1]

[0779]

[0780] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 101.2 mg, 0.401 mmol), triethylamine (4.0 equiv., 224 μl, 1.604 mmol), and 1-acetylindoline-5-sulfonyl chloride (1.1 equiv., 115 mg, 1.604 mmol) via general procedure D of Example 1-4, 103 mg (52%) of the product was obtained as a white solid via recrystallization (DCM / n-hexane = 1:30);

[0781] 1 H NMR (CDCl3, 400 MHz) δ(d,J= 8.6 Hz, 1H), 7.58 (dd,J= 8.5, 1.9 Hz, 1H), 7.54 (s, 1H), 7.12 - 7.05 (m, 4H), 6.98 (d,J= 8.0 Hz, 2H), 6.91 (t,J= 7.3 Hz, 2H), 4.50 (t,J= 6.2 Hz, 1H), 4.11 (t,J= 8.6 Hz, 2H), 3.70 (t,J= 6.3 Hz, 2H), 3.16 (t,J= 8.6 Hz, 2H), 3.06 (s, 4H), 2.97 (q,J= 6.5 Hz, 2H), 2.26 (s, 3H), 1.72 (p,J= 6.5 Hz, 2H).

[0782] MS (ESI + )m / zcalcd for C 27 H 30 N3O3S [M + H]+ 476.19; found 476.16 .

[0783]

[0784] 3-2. 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide (TRL-002)

[0785] [Compound 2-2]

[0786]

[0787] Following the reaction of 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide (1.0 equiv., 35 mg, 0.074 mmol), potassium carbonate (6.0 equiv., 61 mg, 0.442 mmol), and iodomethane (1.5 equiv., 6.87 μl, 0.110 mmol) through general procedure E of Example 1-5, 19.3 mg (52%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 2:1);

[0788] 1 H NMR (400 MHz, CDCl3) δ(d,J= 8.5 Hz, 1H), 7.53 (dd,J= 8.5, 1.9 Hz, 1H), 7.50 (s, 1H), 7.15 - 7.05 (m, 6H), 6.92 (td,J= 7.3, 1.3 Hz, 2H), 4.12 (t,J= 8.6 Hz, 2H), 3.78 (t,J= 6.7 Hz, 2H), 3.22 (t,J= 8.5 Hz, 2H), 3.14 (s, 4H), 3.03 (t,J= 7.0 Hz, 2H), 2.60 (s, 3H), 2.26 (s, 3H), 1.78 (p,J= 6.9 Hz, 2H).

[0789] MS (ESI +)m / zcalcd for C 28 H 32 N3O3S [M + H] + 490.21; found 490.10.

[0790]

[0791] 3-3.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL-003)

[0792] [Compound 2-3]

[0793]

[0794] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 65.1 mg, 0.260 mmol), triethylamine (4.0 equiv., 145 μl, 1.041 mmol), and 1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonyl chloride (1.1 equiv., 74.7 mg, 0.286 mmol) via general procedure D of Example 1-4, 50 mg (40%) of the product was obtained as a white solid via recrystallization (EtOAc / n-hexane = 1:30);

[0795] 1 H NMR (400 MHz, DMSO-d6) δ- 7.39 (m, 3H), 7.21 (d,J= 8.2 Hz, 1H), 7.07 - 6.95 (m, 6H), 6.84 (td,J= 7.3, 1.3 Hz, 2H), 3.58 (t,J= 6.5 Hz, 2H), 3.37 (s, 3H), 3.28 (s, 3H), 2.88 (s, 4H), 2.76 (q,J= 5.9 Hz, 2H), 1.49 (p,J= 6.7 Hz, 2H).

[0796] MS (ESI + )m / zcalcd for C 26 H 29 N4O3S [M + H] + 477.19; found 477.18.

[0797]

[0798] 3-4.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL-005)

[0799] [Compound 2-4]

[0800]

[0801] Following the general procedure E of Example 1-5, reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (1.0 equiv., 30 mg, 0.063 mmol), potassium carbonate (6.0 equiv., 52.2 mg, 0.378 mmol), and iodomethane (1.5 equiv., 5.88 μl, 0.094 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:1) to give 16 mg (52%) of the product as a white gum;

[0802] 1H NMR (400 MHz, CDCl3) δ(dd,J= 8.3, 1.7 Hz, 1H), 7.34 (d,J= 1.7 Hz, 1H), 7.14 - 7.04 (m, 6H), 6.98 (d,J= 8.3 Hz, 1H), 6.92 (td,J= 7.3, 1.4 Hz, 2H), 3.78 (t,J= 6.7 Hz, 2H), 3.46 (s, 3H), 3.44 (s, 3H), 3.12 (s, 4H), 3.06 (t,J= 7.0 Hz, 2H), 2.64 (s, 3H), 1.78 (p,J= 6.8 Hz, 2H).

[0803] MS (ESI + )m / zcalcd for C 27 H 31 N4O3S [M + H] + 491.20; found 491.20.

[0804]

[0805] 3-5.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide (TRL-004)

[0806] [Compound 2-5]

[0807]

[0808] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 67 mg, 0.260 mmol), triethylamine (4.0 equiv., 148 μl, 1.062 mmol), and 4-fluorobenzenesulfonyl chloride (1.1 equiv., 51.7 mg, 0.265 mmol) through general procedure D of Example 1-4, 72.9 mg (67%) of the product was obtained as a white gum by purification by MPLC (EtOAc / n-hexane = 1:4);

[0809] 1 H NMR (400 MHz, CDCl3) δ- 7.68 (m, 2H), 7.13 - 7.05 (m, 6H), 7.00 - 6.91 (m, 4H), 4.57 (t,J= 6.2 Hz, 1H), 3.71 (t,J= 6.2 Hz, 2H), 3.06 (s, 4H), 3.00 (q,J= 6.6 Hz, 2H), 1.72 (p,J= 6.5 Hz, 2H).

[0810] MS (ESI + )m / zcalcd for C 23 H 24 FN2O2S [M + H] + 411.15; found 411.14.

[0811]

[0812] 3-6.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-Nmethylbenzenesulfonamide (TRL-006)

[0813] [Compound 2-6]

[0814]

[0815] Following the general procedure E of Example 1-5, the reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide (1.0 equiv., 30 mg, 0.073 mmol), potassium carbonate (6.0 equiv., 60.6 mg, 0.438 mmol), and iodomethane (1.5 equiv., 6.82 μl, 0.110 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:10) to give 22.5 mg (73%) of the product as a white gum;

[0816] 1H NMR (400 MHz, CDCl3) δ- 7.65 (m, 2H), 7.13 (m, 6H), 7.05 (d,J= 7.8 Hz, 2H), 6.94 (td,J= 7.3, 1.3 Hz, 2H), 3.78 (t,J= 6.6 Hz, 2H), 3.15 (s, 4H), 3.08 (t,J= 7.1 Hz, 2H), 2.62 (s, 3H), 1.77 (p,J= 6.8 Hz, 2H).

[0817] MS (ESI + )m / zcalcd for C 24 H 26 FN2O2S [M + H] + 425.16; found 425.17.

[0818]

[0819] 3-7.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide (TRL-013)

[0820] [Compound 2-7]

[0821]

[0822] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 67 mg, 0.260 mmol), triethylamine (4.0 equiv., 100 μl, 0.716 mmol), and quinoline-8-sulfonyl chloride (1.1 equiv., 44.9 mg, 0.197 mmol) using the general procedure D of Example 1-4, 48.8 mg (59%) of the product was obtained as an ivory solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[0823] 1H NMR (400 MHz, CDCl3) δ(dd,J= 4.3, 1.7 Hz, 1H), 8.39 (dd,J= 7.3, 1.5 Hz, 1H), 8.22 (dd,J= 8.3, 1.8 Hz, 1H), 8.04 (dd,J= 8.3, 1.5 Hz, 1H), 7.68 - 7.60 (m, 1H), 7.40 (dd,J= 8.3, 4.3 Hz, 1H), 7.11 - 7.01 (m, 2H), 6.96 (dd,J= 7.5, 1.8 Hz, 2H), 6.93 - 6.85 (m, 4H), 6.38 (t,J= 6.4 Hz, 1H), 3.64 (t,J= 6.4 Hz, 2H), 2.89 (q,J= 6.5 Hz, 2H), 2.73 (s, 4H), 1.71 (p,J= 6.4 Hz, 2H).

[0824] MS (ESI + )m / zcalcd for C 26 H 26 N3O2S [M + H] + 444.17; found 444.23.

[0825]

[0826] 3-8.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylquinoline-8-sulfonamide (TRL-014)

[0827] [화합물 2-8]

[0828]

[0829] Following the general procedure E of Example 1-5, reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide (1.0 equiv., 12.3 mg, 0.028 mmol), potassium carbonate (6.0 equiv., 23 mg, 0.166 mmol), and iodomethane (1.5 equiv., 2.59 μl, 0.042 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:1) to obtain 11.6 mg (89%) of the product as a white gum;

[0830] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 4.3, 1.8 Hz, 1H), 8.43 (dd,J= 7.4, 1.5 Hz, 1H), 8.21 (dd,J= 8.3, 1.8 Hz, 1H), 7.99 (dd,J= 8.2, 1.5 Hz, 1H), 7.58 (t,J= 7.8 Hz, 1H), 7.49 (dd,J= 8.3, 4.2 Hz, 1H), 7.12 - 7.04 (m, 4H), 6.99 (d,J= 7.7 Hz, 2H), 6.90 (td,J= 7.4, 1.2 Hz, 2H), 3.74 (t,J= 6.9 Hz, 2H), 3.41 (t,J= 7.0 Hz, 2H), 3.10 (s, 4H), 2.89 (s, 3H), 1.79 (p,J= 7.0 Hz, 2H).

[0831] MS (ESI + )m / zcalcd for C 27 H 28 N3O2S [M + H] + 458.18; found 458.22.

[0832]

[0833] 3-9.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL-015)

[0834] [Compound 2-9]

[0835]

[0836] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 67 mg, 0.260 mmol), triethylamine (4.0 equiv., 100 μl, 0.716 mmol), and 2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride (1.1 equiv., 41.6 mg, 0.178 mmol) through general procedure D of Example 1-4, 17.6 mg (24%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 2:1);

[0837] 1 H NMR (400 MHz, CD3OD) δ(dd,J= 8.1, 1.7 Hz, 1H), 7.51 (d,J= 1.7 Hz, 1H), 7.07 - 6.95 (m, 7H), 6.86 (td,J= 7.4, 1.3 Hz, 2H), 3.63 (t,J= 6.3 Hz, 2H), 2.98 (s, 4H), 2.91 (t,J= 6.9 Hz, 2H), 1.62 (p,J= 6.6 Hz, 2H).

[0838] MS (ESI + )m / zcalcd for C 24 H 24 N3O4S [M + H] + 450.14; found 450.18.

[0839]

[0840] 3-10.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL-031)

[0841] [Compound 2-10]

[0842]

[0843] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine (1.0 equiv., 30 mg, 0.113 mmol), triethylamine (2.0 equiv., 0.31 μl, 0.225 mmol), and 2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride (1.2 equiv., 31.6 mg, 0.135 mmol) through general procedure E of Example 1-5, 10.1 mg (19%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[0844] 1 H NMR (CDCl3) δ(s, 1H), 7.54 (m, 2H), 7.15 - 7.09 (m, 5H), 7.04 (d,J= 7.5 Hz, 2H), 6.93 (td,J= 7.3, 1.3 Hz, 2H), 3.77 (t,J= 6.6 Hz, 2H), 3.14 (s, 4H), 3.09 (t,J= 7.1 Hz, 2H), 2.65 (s, 3H), 1.78 (p,J= 6.8 Hz, 2H).

[0845] MS (ESI + )m / zcalcd for C 25 H 26 N3O4S [M + H] + 464.16; found 464.40.

[0846]

[0847] 3-11.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL-016)

[0848] [Compound 2-11]

[0849]

[0850] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 32.8 mg, 0.130 mmol), triethylamine (4.0 equiv., 72.5 μl, 0.520 mmol), and 3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride (1.3 equiv., 41.8 mg, 0.169 mmol) through general procedure D of Example 1-4, 25.2 mg (41%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 2:1);

[0851] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.7 Hz, 1H), 7.56 (d,J= 1.6 Hz, 1H), 7.12 - 7.05 (m, 4H), 6.97 - 6.89 (m, 5H), 4.47 (t,J= 6.3 Hz, 1H), 3.68 (t,J= 6.2 Hz, 2H), 3.44 (s, 3H), 3.06 (s, 4H), 3.02 (q,J= 6.6 Hz, 2H), 1.71 (p,J= 6.4 Hz, 2H).

[0852] MS (ESI + )m / zcalcd for C 25 H 26 N3O4S [M + H] + 464.16; found 464.35.

[0853]

[0854] 3-12.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL-020)

[0855] [Compound 2-12]

[0856]

[0857] Following the general procedure E of Example 1-5, reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (1.0 equiv., 10.3 mg, 0.022 mmol), potassium carbonate (6.0 equiv., 18 mg, 0.133 mmol) and iodomethane (1.5 equiv., 2.08 μl, 0.033 mmol) was performed to obtain 9.8 mg (89%) of the product as a white solid, followed by purification by MPLC (EtOAc / n-hexane = 1:1);

[0858] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.7 Hz, 1H), 7.53 (d,J= 1.6 Hz, 1H), 7.17 - 7.04 (m, 6H), 7.00 - 6.92 (m, 3H), 3.78 (t,J= 6.7 Hz, 2H), 3.45 (s, 3H), 3.15 (s, 4H), 3.07 (t,J= 7.0 Hz, 2H), 2.65 (s, 3H), 1.78 (p,J= 6.8 Hz, 2H).

[0859]

[0860] MS (ESI + )m / zcalcd for C 26 H 28 N3O4S [M + H] + 478.17; found 478.28.

[0861]

[0862] 3-13.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide (TRL-017)

[0863] [Compound 2-13]

[0864]

[0865] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 46.7 mg, 0.185 mmol), triethylamine (4.0 equiv., 103 μl, 0.740 mmol), and 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonyl chloride (1.1 equiv., 58.8 mg, 0.204 mmol) through general procedure D of Example 1-4, 28.1 mg (29%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 2:1);

[0866] 1 H NMR (400 MHz, CDCl3) δ(d,J= 2.2 Hz, 1H), 7.99 (dd,J= 8.8, 2.3 Hz, 1H), 7.15 (d,J= 8.8 Hz, 1H), 7.10 - 6.98 (m, 6H), 6.90 (t,J= 7.4 Hz, 2H), 4.74 (s, 1H), 3.67 (t,J= 6.1 Hz, 2H), 3.61 (s, 3H), 3.50 (s, 3H), 3.05 (m, 6H), 1.72 (p,J= 6.3 Hz, 2H).

[0867] MS (ESI+ )m / zcalcd for C 27 H 29 N4O4S [M + H] + 505.18; found 505.35.

[0868]

[0869] 3-14.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide (TRL-019)

[0870] [Compound 2-14]

[0871]

[0872] Following the general procedure E of Example 1-5, the reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide (1.0 equiv., 11.9 mg, 0.024 mmol), potassium carbonate (6.0 equiv., 19.7 mg, 0.141 mmol) and iodomethane (1.5 equiv., 2.20 μl, 0.035 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 2:1) to give 8.8 mg (70%) of the product as a white gum;

[0873] 1H NMR (400 MHz, CDCl3) δ(d,J= 2.2 Hz, 1H), 7.91 (dd,J= 8.8, 2.2 Hz, 1H), 7.19 (d,J= 8.8 Hz, 1H), 7.14 - 7.06 (m, 4H), 7.03 (dd,J= 8.1, 1.3 Hz, 2H), 6.92 (td,J= 7.4, 1.3 Hz, 2H), 3.74 (t,J= 6.6 Hz, 2H), 3.63 (s, 3H), 3.50 (s, 3H), 3.12 (m, 6H), 2.69 (s, 3H), 1.76 (p,J= 6.8 Hz, 2H).

[0874] MS (ESI + )m / zcalcd for C 28 H 31 N4O4S [M + H] + 519.20; found 519.33.

[0875]

[0876] 3-15.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-5-sulfonamide (TRL-018)

[0877] [화합물 2-15]

[0878]

[0879] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 42.6 mg, 0.169 mmol), triethylamine (4.0 equiv., 94 μl, 0.675 mmol), and 1-methyl-2-oxoindoline-5-sulfonyl chloride (1.5 equiv., 62.2 mg, 0.253 mmol) through general procedure D of Example 1-4, 10.1 mg (13%) of the product was obtained as a yellow gum by purification by MPLC (EtOAc / n-hexane = 1:1);

[0880] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.8 Hz, 1H), 7.58 (s, 1H), 7.08 (tt,J= 11.3, 8.2 Hz, 6H), 6.94 (t,J= 7.0 Hz, 2H), 6.79 (d,J= 8.3 Hz, 1H), 4.49 (s, 1H), 3.71 (t,J= 6.3 Hz, 2H), 3.47 (s, 2H), 3.24 (s, 3H), 3.05 (s, 4H), 3.00 (m, 2H), 1.75 - 1.69 (m, 2H).

[0881] MS (ESI + )m / zcalcd for C 26 H 28 N3O3S [M + H] + 461.18; found 462.33.

[0882]

[0883] 3-16.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethyl-2-oxoindoline-5-sulfonamide (TRL-030)

[0884] [Compound 2-16]

[0885]

[0886] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine (1.0 equiv., 20 mg, 0.075 mmol), triethylamine (2.5 equiv., 26 μl, 0.188 mmol) and 1-methyl-2-oxoindoline-5-sulfonyl chloride (1.1 equiv., 20.3 mg, 0.083 mmol) through general procedure E of Example 1-5, 16.3 mg (46%) of the product was obtained as a yellow oil by purification by MPLC (EtOAc / n-hexane = 1:1);

[0887] 1 H NMR (CDCl3) δ(dd,J= 8.2, 1.8 Hz, 1H), 7.55 (s, 1H), 7.15 - 7.04 (m, 6H), 6.93 (td,J= 7.3, 1.3 Hz, 2H), 6.83 (d,J= 8.3 Hz, 1H), 3.78 (t,J= 6.6 Hz, 2H), 3.53 (s, 2H), 3.24 (s, 3H), 3.14 (s, 4H), 3.07 (t,J= 7.0 Hz, 2H), 2.62 (s, 3H), 1.78 (q,J= 6.8 Hz, 2H).

[0888] MS (ESI + )m / zcalcd for C 27 H 30 N3O3S [M + H] + 475.19; found 476.36.

[0889]

[0890] 3-17.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (TRL-021)

[0891] [Compound 2-17]

[0892]

[0893] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 68.7 mg, 0.272 mmol), triethylamine (4.0 equiv., 152 μl, 1.089 mmol), and 1,3,3-trimethyl-2-oxoindoline-5-sulfonyl chloride (1.0 equiv., 74.5 mg, 0.272 mmol) through general procedure D of Example 1-4, 61.7 mg (45%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[0894] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.9 Hz, 1H), 7.61 (d,J= 1.9 Hz, 1H), 7.13 - 7.05 (m, 4H), 6.99 (d,J= 7.7 Hz, 2H), 6.92 (td,J= 7.4, 1.3 Hz, 2H), 6.82 (d,J= 8.2 Hz, 1H), 4.38 (t,J= 6.3 Hz, 1H), 3.73 (t,J= 6.4 Hz, 2H), 3.25 (s, 3H), 3.06 (s, 4H), 3.00 (q,J= 6.6) Hz, 2H), 1.74 (p,J= 6.6 Hz, 2H), 1.37 (s, 6H).

[0895] MS (ESI + )m / zcalcd for C 28 H 32 N3O3S [M + H] + 490.21; found 490.32.

[0896]

[0897] 3-18.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethyl-2-oxoindoline-5-sulfonamide (TRL-022)

[0898] [Compound 2-18]

[0899]

[0900] Following the general procedure E of Example 1-5, reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (1.0 equiv., 14 mg, 0.029 mmol), potassium carbonate (6.0 equiv., 23.7 mg, 0.172 mmol) and iodomethane (1.5 equiv., 2.67 μl, 0.043 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:1) to give 14 mg (97%) of the product as a colorless oil;

[0901] 1 H NMR (CDCl3) δ(dd,J= 8.2, 1.8 Hz, 1H), 7.55 (d,J= 1.8 Hz, 1H), 7.16 - 7.04 (m, 6H), 6.93 (td,J= 7.3, 1.4 Hz, 2H), 6.87 (d,J= 8.2 Hz, 1H), 3.80 (t,J= 6.8 Hz, 2H), 3.25 (s, 3H), 3.14 (s, 4H), 3.05 (t,J= 7.0 Hz, 2H), 2.61 (s, 3H), 1.79 (p,J= 6.8 Hz, 2H), 1.38 (s, 6H).

[0902] MS (ESI + )m / zcalcd for C 29 H 34 N3O3S [M + H] + 504.22; found 504.25.

[0903]

[0904] 3-19.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide (TRL-023)

[0905] [Compound 2-19]

[0906]

[0907] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 44.5 mg, 0.176 mmol), triethylamine (2.5 equiv., 61.4 μl, 0.441 mmol), and 1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonyl chloride (1.3 equiv., 66 mg, 0.229 mmol) through general procedure D of Example 1-4, 52.2 mg (57%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[0908] 1 H NMR (400 MHz, CDCl3) δ(s, 2H), 7.13 - 7.05 (m, 4H), 7.00 (d,J= 8.0 Hz, 2H), 6.92 (t,J= 7.3 Hz, 2H), 4.38 (t,J= 6.3 Hz, 1H), 3.73 (t,J= 6.4 Hz, 2H), 3.53 (s, 3H), 3.06 (s, 4H), 2.98 (q,J= 6.6 Hz, 2H), 2.59 (s, 3H), 1.76 (p,J= 6.6 Hz, 2H), 1.34 (s, 6H).

[0909] MS (ESI + )m / zcalcd for C 29 H 34 N3O3S [M + H] + 504.22.; found 504.39.

[0910]

[0911] 3-20.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide (TRL-024)

[0912] [Compound 2-20]

[0913]

[0914] Following the general procedure E of Example 1-5, reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide (1.0 equiv., 6.2 mg, 0.012 mmol), potassium carbonate (4.0 equiv., 6.81 mg, 0.049 mmol) and iodomethane (1.5 equiv., 1.15 μl, 0.018 mmol) was performed to obtain 5.4 mg (84%) of the product as a white solid, which was purified by MPLC (EtOAc / n-hexane = 1:1);

[0915] 1 H NMR (CDCl3) δ- 7.37 (m, 2H), 7.15 - 7.06 (m, 6H), 6.92 (td,J= 7.2, 1.4 Hz, 2H), 3.81 (t,J= 6.8 Hz, 2H), 3.53 (s, 3H), 3.13 (s, 4H), 3.03 (t,J= 6.9 Hz, 2H), 2.62 (s, 3H), 2.60 (s, 3H), 1.80 (p,J= 6.9 Hz, 2H), 1.35 (s, 6H).

[0916] MS (ESI + )m / zcalcd for C 30 H 36N3O3S [M + H] + 518.24; found 518.40.

[0917]

[0918] 3-21.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (TRL-026)

[0919] [Compound 2-21]

[0920]

[0921] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 49.6 mg, 0.197 mmol), triethylamine (4.0 equiv., 110 μl, 0.786 mmol), and 3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonyl chloride (1.2 equiv., 58.4 mg, 0.236 mmol) through general procedure D of Example 1-4, 27.8 mg (30%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[0922] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.7 Hz, 1H), 7.56 (d,J= 1.7 Hz, 1H), 7.11 - 7.05 (m, 4H), 6.99 (d,J= 7.9 Hz, 2H), 6.95 - 6.88 (m, 3H), 4.56 (s, 1H), 3.69 (t,J= 6.2 Hz, 2H), 3.44 (s, 3H), 3.07 (s, 4H), 3.02 (q,J= 6.3 Hz, 2H), 1.71 (p,J= 6.4 Hz, 2H).

[0923] MS (ESI + )m / zcalcd for C 25 H 26 N3O4S [M + H] + 464.16.; found 464.32.

[0924]

[0925] 3-22.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (TRL-027)

[0926] [Compound 2-22]

[0927]

[0928] Following the general procedure E of Example 1-5, the reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (1.0 equiv., 10.4 mg, 0.022 mmol), potassium carbonate (4.0 equiv., 12.4 mg, 0.090 mmol) and iodomethane (1.5 equiv., 2.10 μl, 0.034 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:1) to give 11.1 mg (99%) of the product as a white formic solid;

[0929] 1H NMR (CDCl3) δ(dd,J= 8.2, 1.7 Hz, 1H), 7.52 (d,J= 1.6 Hz, 1H), 7.16 - 7.07 (m, 4H), 7.04 (d,J= 7.5 Hz, 2H), 6.97 (d,J= 8.2 Hz, 1H), 6.93 (td,J= 7.3, 1.3 Hz, 2H), 3.76 (t,J= 6.6 Hz, 2H), 3.44 (s, 3H), 3.14 (s, 4H), 3.07 (t,J= 7.1 Hz, 2H), 2.65 (s, 3H), 1.77 (p,J= 6.8 Hz, 2H).

[0930] MS (ESI + )m / zcalcd for C 26 H 28 N3O4S [M + H] + 478.17; found 478.33.

[0931]

[0932] 3-23.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide (TRL-028)

[0933] [화합물 2-23]

[0934]

[0935] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 20.6 mg, 0.082 mmol), triethylamine (2.0 equiv., 22.8 μl, 0.163 mmol), and 4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonyl chloride (1.1 equiv., 23.5 mg, 0.090 mmol) through general procedure D of Example 1-4, 18.3 mg (46%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[0936] 1 H NMR (400 MHz, CDCl3) δ- 7.34 (m, 2H), 7.14 - 7.02 (m, 6H), 6.98 (d,J= 8.3 Hz, 1H), 6.94 (t,J= 7.3 Hz, 2H), 4.70 (s, 2H), 4.54 (d,J= 24.0 Hz, 1H), 3.74 (t,J= 6.3 Hz, 2H), 3.31 (s, 3H), 3.05 (s, 4H), 3.00 (t,J= 6.6 Hz, 2H), 1.75 (p,J= 6.5 Hz, 2H).

[0937] MS (ESI + )m / zcalcd for C 26 H 28 N3O4S [M + H] + 478.17.; found 478.36.

[0938]

[0939] 3-24.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,4-dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide (TRL-029)

[0940] [Compound 2-24]

[0941]

[0942] Following the general procedure E of Example 1-5, N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide (1.0 equiv., 3.5 mg, 7.33 μmol), potassium carbonate (2.0 equiv., 2.03 mg, 0.015 mmol) and iodomethane (1.5 equiv., 0.68 μl, 11.0 μmol) was reacted with 2.1 mg (56%) of the product as a yellow solid, followed by purification by MPLC (EtOAc / n-hexane = 1:2);

[0943] 1 H NMR (CDCl3) δ- 7.30 (m, 2H), 7.15 - 7.04 (m, 6H), 7.04 - 7.00 (m, 1H), 6.93 (td,J= 7.3, 1.3 Hz, 2H), 4.70 (s, 2H), 3.79 (t,J= 6.7 Hz, 2H), 3.36 (s, 3H), 3.13 (s, 4H), 3.08 (t,J= 7.0 Hz, 2H), 2.64 (s, 3H), 1.79 (p,J= 6.8 Hz, 2H).

[0944] MS (ESI + )m / zcalcd for C 27 H 30 N3O4S [M + H] + 492.19; found 492.52.

[0945]

[0946] 3-25.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide (TRL-037)

[0947] [Compound 2-25]

[0948]

[0949] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 22 mg, 0.087 mmol), triethylamine (2.5 equiv., 30.4 μl, 0.218 mmol), and 1-methylindoline-6-sulfonyl chloride (1.2 equiv., 24.2 mg, 0.105 mmol) through general procedure D of Example 1-4, 21.5 mg (54%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[0950] 1 H NMR (400 MHz, CDCl3) δ- 7.05 (m, 6H), 7.00 (d,J= 7.8 Hz, 2H), 6.92 (td,J= 7.3, 1.2 Hz, 2H), 6.77 (s, 1H), 4.35 (t,J= 6.3 Hz, 1H), 3.73 (t,J= 6.5 Hz, 2H), 3.42 (t,J= 8.3 Hz, 2H), 3.06 (s, 4H), 3.02 - 2.95 (m, 4H), 2.76 (s, 3H), 1.73 (q,J= 6.6 Hz, 2H).

[0951] MS (ESI + )m / zcalcd for C 26 H 30 N3O2S [M + H] + 448.20.; found 448.33.

[0952]

[0953] 3-26.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide (TRL-038)

[0954] [Compound 2-26]

[0955]

[0956] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine (1.0 equiv., 20 mg, 0.075 mmol), triethylamine (2.5 equiv., 26.2 μl, 0.188 mmol) and 1-methylindoline-6-sulfonyl chloride (1.1 equiv., 19.1 mg, 0.083 mmol) through general procedure E of Example 1-5, 11.2 mg (84%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[0957] 1 H NMR (CDCl3) δ- 7.06 (m, 7H), 6.98 (dd,J= 7.5, 1.6 Hz, 1H), 6.92 (td,J= 7.2, 1.4 Hz, 2H), 6.72 (d,J= 1.5 Hz, 1H), 3.80 (t,J= 6.9 Hz, 2H), 3.41 (t,J= 8.3 Hz, 2H), 3.14 (s, 4H), 3.07 - 2.97 (m, 4H), 2.78 (s, 3H), 2.62 (s, 3H), 1.79 (p,J= 6.9 Hz, 2H).

[0958] MS (ESI + )m / zcalcd for C 27 H 32 N3O2S [M + H] + 462.21; found 462.35.

[0959]

[0960] 3-27.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrid[2,3-d]pyrimidine-6-sulfonamide (TRL-041)

[0961] [Compound 2-27]

[0962]

[0963] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 18 mg, 0.071 mmol), triethylamine (4.0 equiv., 39.8 μl, 0.285 mmol), and 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonyl chloride (1.2 equiv., 24.8 mg, 0.086 mmol) through the general procedure D of Example 1-4, 5.6 mg (15%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:5);

[0964] 1 H NMR (400 MHz, CDCl3) δ(d,J= 2.4 Hz, 1H), 8.73 (d,J= 2.4 Hz, 1H), 7.03 (m, 6H), 6.87 (t,J= 7.4 Hz, 2H), 4.69 (s, 1H), 3.72 (s, 3H), 3.66 (t,J= 6.1 Hz, 2H), 3.50 (s, 3H), 3.12 - 3.02 (m, 6H), 2.04 - 1.98 (m, 2H).

[0965] MS (ESI + )m / zcalcd for C 26 H 28 N5O4S [M + H] + 506.18; found 506.26.

[0966]

[0967] 3-28.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrid[2,3-d]pyrimidine-6-sulfonamide (TRL-040)

[0968] [Compound 2-28]

[0969]

[0970] Following the reaction of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine (1.0 equiv., 20 mg, 0.075 mmol), triethylamine (4.0 equiv., 41.9 μl, 0.300 mmol) and 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonyl chloride (1.2 equiv., 30.4 mg, 0.090 mmol) through the general procedure E of Example 1-5, 36.3 mg (93%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[0971] 1 H NMR (CDCl3) δ(d,J= 2.4 Hz, 1H), 8.71 (d,J= 2.4 Hz, 1H), 7.12 - 7.02 (m, 6H), 6.91 (td,J= 7.3, 1.3 Hz, 2H), 3.77 - 3.73 (m, 5H), 3.50 (s, 3H), 3.13 - 3.10 (m, 6H), 2.74 (s, 3H), 1.81 (p,J= 6.7 Hz, 2H).

[0972] MS (ESI + )m / zcalcd for C 27 H 30 N5O4S [M + H] + 520.19; found 520.32.

[0973]

[0974] 3-29.N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethylindoline-6-sulfonamide (TRL-025)

[0975] [Compound 2-29]

[0976]

[0977] Following the general procedure E of Example 1-5, reaction of N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-6-sulfonamide (1.0 equiv., 15.5 mg, 0.034 mmol), potassium carbonate (6.0 equiv., 15.5 mg, 0.0.34 mmol) and iodomethane (1.5 equiv., 3.14 μl, 0.050 mmol) was performed to obtain 3.3 mg (19%) of the product as a white solid, which was purified by MPLC (EtOAc / n-hexane = 2:1);

[0978] 1 H NMR (CDCl3) δ7.64 (dd,J= 8.2, 1.8 Hz, 1H), 7.55 (d,J= 1.8 Hz, 1H), 7.15 - 7.06 (m, 6H), 6.93 (td,J= 7.3, 1.4 Hz, 2H), 6.87 (d,J= 8.2 Hz, 1H), 3.80 (t,J= 6.7 Hz, 2H), 3.25 (s, 3H), 3.14 (s, 4H), 3.05 (t,J= 6.9 Hz, 2H), 2.61 (s, 3H), 1.79 (p,J= 6.9 Hz, 2H), 1.38 (s, 6H).

[0979] MS (ESI +)m / zcalcd for C 29 H 34 N3O3S [M + H] + 504.22; found 504.42.

[0980]

[0981] 3-30. 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide (TRL-007)

[0982] [Compound 2-30]

[0983]

[0984] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 52.9 mg, 0.184 mmol), triethylamine (4.0 equiv., 0.103 ml, 0.738 mmol), and 1-acetylindoline-5-sulfonyl chloride (1.1 equiv., 52.7 mg, 0.203 mmol) via general procedure D of Example 1-4, 71.9 mg (76%) of the product was obtained as an ivory solid via recrystallization (DCM / n-hexane = 1:20);

[0985] 1H NMR (400 MHz, CDCl3) δ(d,J= 8.5 Hz, 1H), 7.59 (dd,J= 8.5, 2.0 Hz, 1H), 7.54 (s, 1H), 7.15 - 7.07 (m, 2H), 6.99 - 6.91 (m, 4H), 6.85 (dd,J= 8.1, 2.1 Hz, 1H), 4.49 (s, 1H), 4.11 (t,J= 8.6 Hz, 2H), 3.65 (t,J= 6.3 Hz, 2H), 3.17 (t,J= 8.6 Hz, 2H), 3.03 (s, 4H), 2.97 (q,J= 6.5 Hz, 2H), 2.26 (s, 3H), 1.71 (p,J= 6.5 Hz, 2H).

[0986] MS (ESI + )m / zcalcd for C 27 H 29 ClN3O3S [M + H] + 509.15; found 510.16.

[0987]

[0988] 3-31. 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide (TRL-008)

[0989] [화합물 2-31]

[0990]

[0991] Following the general procedure E of Example 1-5, reaction of 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide (1.0 equiv., 18.5 mg, 0.036 mmol), potassium carbonate (6.0 equiv., 30.1 mg, 0.218 mmol), and iodomethane (1.5 equiv., 3.39 μl, 0.054 mmol) was performed to obtain 15.7 mg (56%) of the product as a yellow solid by recrystallization (DCM / n-hexane = 1:20);

[0992] 1 H NMR (CDCl3) δ(d,J= 8.5 Hz, 1H), 7.54 (d,J= 8.7 Hz, 1H), 7.50 (s, 1H), 7.17 - 7.10 (m, 2H), 7.06 (d,J= 8.0 Hz, 1H), 7.02 - 6.96 (m, 3H), 6.87 (dd,J= 8.1, 2.1 Hz, 1H), 4.13 (t,J= 8.5 Hz, 2H), 3.74 (t,J= 6.6 Hz, 2H), 3.23 (t,J= 8.6 Hz, 2H), 3.15 - 3.10 (m, 4H), 3.03 (t,J=6.9 Hz, 2H), 2.62 (s, 3H), 2.26 (s, 3H), 1.77 (p,J= 6.8 Hz, 2H).

[0993] MS (ESI + )m / zcalcd for C 28 H 31 ClN3O3S [M + H] + 524.17; found 524.19.

[0994]

[0995] 3-32.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL-009)

[0996] [Compound 2-32]

[0997]

[0998] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 42.1 mg, 0.147 mmol), triethylamine (4.0 equiv., 0.082 ml, 0.587 mmol), and 1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonyl chloride (1.1 equiv., 42.1 mg, 0.161 mmol) via general procedure D of Example 1-4, 52.1 mg (70%) of the product was obtained as a white gum via recrystallization (EtOAc / n-hexane = 2:1);

[0999] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.7 Hz, 1H), 7.39 (d,J= 1.6 Hz, 1H), 7.13 - 7.03 (m, 2H), 6.98 - 6.87 (m, 5H), 6.84 (dd,J= 8.1, 2.1 Hz, 1H), 4.55 (t,J= 6.2 Hz, 1H), 3.63 (t,J= 6.3 Hz, 2H), 3.46 (s, 3H), 3.40 (s, 3H), 3.02 - 2.93 (m, 6H), 1.69 (p,J= 6.5 Hz, 2H).

[1000] MS (ESI + )m / zcalcd for C 26 H 28 ClN4O3S [M + H] + 511.15; found 511.16.

[1001]

[1002] 3-33.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (TRL-010)

[1003] [Compound 2-33]

[1004]

[1005] Following the general procedure E of Example 1-5, the reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (1.0 equiv., 12.9 mg, 0.025 mmol), potassium carbonate (6.0 equiv., 20.9 mg, 0.151 mmol), and iodomethane (1.5 equiv., 2.36 μl, 0.038 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:1) to give 10.9 mg (80%) of the product as a white gum;

[1006] 1H NMR (CDCl3) δ(dd,J= 8.2, 1.7 Hz, 1H), 7.34 (d,J= 1.7 Hz, 1H), 7.18 - 7.08 (m, 2H), 7.05 (d,J= 7.4 Hz, 1H), 7.02 - 6.94 (m, 4H), 6.87 (dd,J= 8.2, 2.1 Hz, 1H), 3.74 (t,J= 6.7 Hz, 2H), 3.46 (s, 3H), 3.44 (s, 3H), 3.14 - 3.05 (m, 6H), 2.66 (s, 3H), 1.77 (q,J= 6.8 Hz, 2H).

[1007] MS (ESI + )m / zcalcd for C 27 H 30 ClN4O3S [M + H] + 525.16; found 525.18.

[1008]

[1009] 3-34.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide (TRL-011)

[1010] [Compound 2-34]

[1011]

[1012] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 47 mg, 0.164 mmol), triethylamine (4.0 equiv., 0.091 ml, 0.656 mmol), and 4-fluorobenzenesulfonyl chloride (1.1 equiv., 35.1 mg, 0.180 mmol) via general procedure D of Example 1-4, 56.8 mg (78%) of the product was obtained as a white solid via recrystallization (EtOAc / n-hexane = 1:1);

[1013] 1 H NMR (400 MHz, CDCl3) δ- 7.71 (m, 2H), 7.16 - 7.04 (m, 4H), 7.01 - 6.93 (m, 4H), 6.88 (dd,J= 8.1, 2.1 Hz, 1H), 4.79 (t,J= 6.2 Hz, 1H), 3.66 (t,J= 6.3 Hz, 2H), 3.02 (s, 4H), 3.00 - 2.94 (m, 2H), 1.69 (p,J= 6.6 Hz, 2H).

[1014] MS (ESI + )m / zcalcd for C 23 H 23 ClFN2O2S [M + H] + 445.11; found 445.14.

[1015]

[1016] 3-35.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-N-methylbenzenesulfonamide (TRL-012)

[1017] [Compound 2-35]

[1018]

[1019] Following the general procedure E of Example 1-5, the reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide (1.0 equiv., 8.3 mg, 0.019 mmol), potassium carbonate (6.0 equiv., 15.5 mg, 0.112 mmol), and iodomethane (1.5 equiv., 1.74 μl, 0.028 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:5) to give 7.5 mg (87%) of the product as a colorless oil;

[1020] 1 H NMR (CDCl3) δ- 7.64 (m, 2H), 7.18 - 7.10 (m, 4H), 7.05 (d,J= 7.7 Hz, 1H), 7.03 - 6.97 (m, 3H), 6.89 (dd,J= 8.2, 2.1 Hz, 1H), 3.74 (t,J= 6.6 Hz, 2H), 3.16 - 3.05 (m, 6H), 2.64 (s, 3H), 1.76 (p,J= 6.8 Hz, 2H).

[1021] MS (ESI + )m / zcalcd for C 24 H 25 ClFN2O2S [M + H] + 458.12; found 459.16.

[1022]

[1023] 3-36.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide (TRL-032)

[1024] [Compound 2-36]

[1025]

[1026] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 35.5 mg, 0.124 mmol), triethylamine (2.5 equiv., 43.1 μl, 0.309 mmol), and quinoline-8-sulfonyl chloride (1.1 equiv., 31 mg, 0.136 mmol) using the general procedure D of Example 1-4, 33.1 mg (55%) of the product was obtained as a yellow solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[1027] 1H NMR (400 MHz, CDCl3) δ(dd,J= 4.3, 1.8 Hz, 1H), 8.38 (dd,J= 7.2, 1.5 Hz, 1H), 8.22 (dd,J= 8.4, 1.7 Hz, 1H), 8.02 (dd,J= 8.2, 1.5 Hz, 1H), 7.63 (dd,J= 8.2, 7.3 Hz, 1H), 7.45 (dd,J= 8.3, 4.3 Hz, 1H), 7.07 (td,J= 7.6, 1.8 Hz, 1H), 7.00 (dd,J= 7.5, 1.8 Hz, 1H), 6.93 (dd,J= 7.4, 1.2 Hz, 1H), 6.91 - 6.78 (m, 4H), 6.43 (s, 1H), 3.54 (t,J= 6.4 Hz, 2H), 2.93 (t,J= 6.4 Hz, 2H), 2.80 - 2.74 (m, 4H), 1.68 (p,J= 6.4 Hz, 2H).

[1028] MS (ESI + )m / zcalcd for C 26 H 25 ClN3O2S [M + H] + 478.13; found 478.39.

[1029]

[1030] 3-37.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylquinoline-8-sulfonamide (TRL-033)

[1031] [화합물 2-37]

[1032]

[1033] Following the general procedure E of Example 1-5, reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide (1.0 equiv., 13.6 mg, 0.028 mmol), potassium carbonate (4.0 equiv., 15.7 mg, 0.114 mmol), and iodomethane (1.5 equiv., 2.66 μl, 0.043 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:3) to give 14.1 mg (99%) of the product as a white solid;

[1034] 1 H NMR (CDCl3) δ(dd,J= 4.2, 1.8 Hz, 1H), 8.43 (dd,J= 7.4, 1.5 Hz, 1H), 8.20 (dd,J= 8.3, 1.8 Hz, 1H), 7.98 (dd,J= 8.2, 1.4 Hz, 1H), 7.56 (dd,J= 8.2, 7.4 Hz, 1H), 7.49 (dd,J= 8.3, 4.2 Hz, 1H), 7.14 - 7.06 (m, 2H), 7.00 - 6.92 (m, 3H), 6.89 (d,J= 2.1 Hz, 1H), 6.85 (dd,J=8.1, 2.1 Hz, 1H), 3.65 (t,J= 6.8 Hz, 2H), 3.41 (t,J= 6.9 Hz, 2H), 3.13 - 3.02 (m, 4H), 2.93 (s, 3H), 1.74 (q,J= 6.9 Hz, 2H).

[1035] MS (ESI + )m / zcalcd for C 27 H 27 ClN3O2S [M + H] + 492.14; found 492.28.

[1036]

[1037] 3-38.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (TRL-034)

[1038] [Compound 2-38]

[1039]

[1040] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 24.4 mg, 0.085 mmol), triethylamine (2.5 equiv., 29.6 μl, 0.213 mmol), and 1,3,3-trimethyl-2-oxoindoline-5-sulfonyl chloride (1.2 equiv., 27.9 mg, 0.102 mmol) through general procedure D of Example 1-4, 24.7 mg (55%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[1041] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.9 Hz, 1H), 7.62 (d,J= 1.8 Hz, 1H), 7.16 - 7.07 (m, 2H), 7.01 - 6.93 (m, 4H), 6.88 (dd,J= 8.1, 2.1 Hz, 1H), 6.82 (d,J= 8.2 Hz, 1H), 4.39 (s, 1H), 3.68 (t,J= 6.4 Hz, 2H), 3.25 (s, 3H), 3.06 - 2.99 (m, 6H), 1.73 (p,J= 6.6 Hz, 2H), 1.37 (s, 6H).

[1042] MS (ESI + )m / zcalcd for C 28 H 31 ClN3O3S [M + H] +524.17; found 524.33.

[1043]

[1044] 3-39.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethyl-2-oxoindoline-5-sulfonamide (TRL-035)

[1045] [Compound 2-39]

[1046]

[1047] Following the general procedure E of Example 1-5, reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (1.0 equiv., 10.2 mg, 0.019 mmol), potassium carbonate (4.0 equiv., 10.8 mg, 0.078 mmol), and iodomethane (1.2 equiv., 1.45 μl, 0.023 mmol) was performed to obtain 8.8 mg (83%) of the product as a white solid, which was purified by MPLC (EtOAc / n-hexane = 1:2);

[1048] 1 H NMR (CDCl3) δ(dd,J= 8.2, 1.9 Hz, 1H), 7.55 (d,J= 1.8 Hz, 1H), 7.19 - 7.09 (m, 2H), 7.07 (dd,J= 8.1, 1.3 Hz, 1H), 7.04 - 6.95 (m, 3H), 6.91 - 6.84 (m, 2H), 3.76 (t,J= 6.7 Hz, 2H), 3.25 (s, 3H), 3.16 - 3.01 (m, 6H), 2.64 (s, 3H), 1.77 (p,J= 6.8 Hz, 2H), 1.38 (s, 6H).

[1049] MS (ESI + )m / zcalcd for C29 H 33 ClN3O3S [M + H] + 538.19; found 538.25.

[1050]

[1051] 3-40.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide (TRL-036)

[1052] [Compound 2-40]

[1053]

[1054] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 22.2 mg, 0.077 mmol), triethylamine (2.5 equiv., 27 μl, 0.194 mmol), and 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonyl chloride (1.1 equiv., 24.6 mg, 0.085 mmol) through general procedure D of Example 1-4, 19.9 mg (47%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[1055] 1H NMR (400 MHz, CDCl3) δ(d,J= 2.2 Hz, 1H), 7.98 (dd,J= 8.8, 2.3 Hz, 1H), 7.16 (d,J= 8.8 Hz, 1H), 7.11 - 7.03 (m, 2H), 6.96 - 6.91 (m, 2H), 6.90 (d,J= 7.9 Hz, 1H), 6.85 - 6.77 (m, 2H), 4.78 (t,J= 6.2 Hz, 1H), 3.62 (s, 3H), 3.58 (t,J= 6.2 Hz, 2H), 3.50 (s, 3H), 3.09 - 2.99 (m, 6H), 1.68 (q,J= 6.4 Hz, 2H).

[1056] MS (ESI + )m / zcalcd for C 27 H 28 ClN4O4S [M + H] + 539.14; found 539.46.

[1057]

[1058] 3-41.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide (TRL-039)

[1059] [화합물 2-41]

[1060]

[1061] Following the general procedure E of Example 1-5, reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (1.0 equiv., 10.8 mg, 0.020 mmol), potassium carbonate (4.0 equiv., 11.1 mg, 0.080 mmol), and iodomethane (1.2 equiv., 1.50 μl, 0.024 mmol) was performed to obtain 9.9 mg (88%) of the product as a white solid, which was purified by MPLC (EtOAc / n-hexane = 1:1);

[1062] 1 H NMR (CDCl3) δ(d,J= 2.2 Hz, 1H), 7.86 (dd,J= 8.8, 2.3 Hz, 1H), 7.20 (d,J= 8.8 Hz, 1H), 7.17 - 7.09 (m, 2H), 7.03 (d,J= 7.9 Hz, 1H), 7.00 - 6.95 (m, 3H), 6.86 (dd,J= 8.1, 2.1 Hz, 1H), 3.70 (t,J= 6.5 Hz, 2H), 3.63 (s, 3H), 3.50 (s, 3H), 3.16 - 3.08 (m, 6H), 2.71 (s, 3H), 1.74 (p,J= 6.7 Hz, 2H).

[1063] MS (ESI + )m / zcalcd for C 28 H 30 ClN4O4S [M + H] + 553.16; found 553.29.

[1064]

[1065] 3-42.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide (TRL-042)

[1066] [Compound 2-42]

[1067]

[1068] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 26.3 mg, 0.092 mmol), triethylamine (2.5 equiv., 32 μl, 0.229 mmol), and 1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonyl chloride (1.2 equiv., 31.7 mg, 0.110 mmol) through general procedure D of Example 1-4, 28.2 mg (56%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:3);

[1069] 1 H NMR (400 MHz, CDCl3) δ(s, 2H), 7.16 - 7.08 (m, 2H), 7.01 (d,J= 7.8 Hz, 1H), 7.00 - 6.93 (m, 3H), 6.87 (dd,J= 8.1, 2.1 Hz, 1H), 3.70 (t,J= 6.5 Hz, 2H), 3.53 (s, 3H), 3.07 - 3.02 (m, 4H), 2.98 (t,J= 6.7 Hz, 2H), 2.59 (s, 3H), 1.75 (p,J= 6.6 Hz, 3H), 1.34 (s, 6H).

[1070] MS (ESI + )m / zcalcd for C 29 H 33 ClN3O3S [M + H] +538.19; found 538.33.

[1071]

[1072] 3-43.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide (TRL-043)

[1073] [Compound 2-43]

[1074]

[1075] Following the general procedure E of Example 1-5, reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (1.0 equiv., 13.6 mg, 0.025 mmol), potassium carbonate (4.0 equiv., 14 mg, 0.101 mmol), and iodomethane (1.2 equiv., 1.89 μl, 0.030 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:2) to give 11 mg (77%) of the product as a colorless oil;

[1076] 1 H NMR (CDCl3) δ(d,J= 2.5 Hz, 2H), 7.18 - 7.03 (m, 4H), 7.02 - 6.94 (m, 2H), 6.87 (dd,J= 8.1, 2.1 Hz, 1H), 3.78 (t,J= 6.8 Hz, 2H), 3.52 (s, 3H), 3.15 - 3.08 (m, 4H), 3.03 (t,J= 6.8 Hz, 2H), 2.62 (s, 6H), 1.80 (p,J= 6.8 Hz, 2H), 1.35 (s, 6H).

[1077] MS (ESI + )m / zcalcd for C 30 H 35ClN3O3S [M + H] + 552.20; found 552.00.

[1078]

[1079] 3-44.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (TRL-044)

[1080] [Compound 2-44]

[1081]

[1082] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 26.3 mg, 0.092 mmol), triethylamine (2.5 equiv., 35 μl, 0.248 mmol), and 3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonyl chloride (1.2 equiv., 29.5 mg, 0.119 mmol) through general procedure D of Example 1-4, 26.7 mg (52%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[1083] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.7 Hz, 1H), 7.58 (d,J= 1.7 Hz, 1H), 7.15 - 7.05 (m, 2H), 7.00 - 6.94 (m, 3H), 6.92 (d,J= 8.2 Hz, 1H), 6.89 - 6.82 (m, 2H), 4.55 (s, 1H), 3.62 (t,J= 6.2 Hz, 2H), 3.44 (s, 3H), 3.08 - 3.01 (m, 6H), 1.69 (p,J= 6.5 Hz, 2H).

[1084] MS (ESI + )m / zcalcd for C 25 H 25 ClN3O4S [M + H] + 498.12; found 498.20.

[1085]

[1086] 3-45.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide (TRL-045)

[1087] [Compound 2-45]

[1088]

[1089] Following the general procedure E of Example 1-5, the reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide (1.0 equiv., 9.4 mg, 0.019 mmol), potassium carbonate (4.0 equiv., 10.4 mg, 0.076 mmol), and iodomethane (1.2 equiv., 1.41 μl, 0.023 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:1) to obtain 7.5 mg (76%) of the product as a pale yellow solid;

[1090] 1H NMR (CDCl3) δ(dd,J= 8.1, 1.4 Hz, 1H), 7.53 (s, 1H), 7.18 - 7.10 (m, 2H), 7.04 (d,J= 7.9 Hz, 1H), 7.02 - 6.96 (m, 4H), 6.90 - 6.85 (m, 1H), 3.72 (t,J= 6.5 Hz, 2H), 3.45 (s, 3H), 3.15 - 3.07 (m, 6H), 2.68 (s, 3H), 1.77 - 1.72 (m, 2H).

[1091] MS (ESI + )m / zcalcd for C 26 H 27 ClN3O4S [M + H] + 512.13; found 512.45.

[1092]

[1093] 3-46.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide (TRL-046)

[1094] [화합물 2-46]

[1095]

[1096] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 22.5 mg, 0.078 mmol), triethylamine (2.5 equiv., 27.3 μl, 0.196 mmol), and 4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonyl chloride (1.2 equiv., 24.6 mg, 0.094 mmol) through general procedure D of Example 1-4, 20.6 mg (49%) of the product was obtained as a pale yellow solid by purification by MPLC (EtOAc / n-hexane = 1:3);

[1097] 1 H NMR (400 MHz, CDCl3) δ- 7.34 (m, 2H), 7.14 - 7.07 (m, 2H), 7.01 - 6.94 (m, 5H), 6.87 (dd,J= 8.1, 2.1 Hz, 1H), 4.70 (s, 2H), 4.63 (s, 1H), 3.68 (t,J= 6.3 Hz, 2H), 3.31 (s, 3H), 3.02 - 2.98 (m, 6H), 1.73 (p,J= 6.5 Hz, 2H).

[1098] MS (ESI + )m / zcalcd for C 26 H 27 ClN3O4S [M + H] + 512.13; found 512.15.

[1099]

[1100] 3-47.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,4-dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide (TRL-047)

[1101] [Compound 2-47]

[1102]

[1103] Following the general procedure E of Example 1-5, reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide (1.0 equiv., 10.5 mg, 0.021 mmol), potassium carbonate (4.0 equiv., 11.3 mg, 0.082 mmol), and iodomethane (1.2 equiv., 1.53 μl, 0.025 mmol) was performed to obtain 9.9 mg (90%) of the product as a white solid, which was purified by MPLC (EtOAc / n-hexane = 1:2);

[1104] 1 H NMR (CDCl3) δ- 7.30 (m, 2H), 7.18 - 7.10 (m, 2H), 7.07 (d,J= 7.9 Hz, 1H), 7.04 - 6.96 (m, 4H), 6.88 (dd,J= 8.1, 2.1 Hz, 1H), 4.70 (s, 2H), 3.76 (t,J= 6.7 Hz, 2H), 3.36 (s, 3H), 3.13 - 3.05 (m, 6H), 2.67 (s, 3H), 1.79 (p,J= 6.8 Hz, 2H).

[1105] MS (ESI + )m / zcalcd for C 27 H 29 ClN3O4S [M + H] + 526.15; found 526.30.

[1106]

[1107] 3-48.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL-048)

[1108] [Compound 2-48]

[1109]

[1110] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 19.9 mg, 0.069 mmol), triethylamine (2.5 equiv., 24.2 μl, 0.173 mmol), and 3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride (1.2 equiv., 20.6 mg, 0.083 mmol) through general procedure D of Example 1-4, 20.1 mg (55%) of the product was obtained as a pale brown solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[1111] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.7 Hz, 1H), 7.57 (d,J= 1.6 Hz, 1H), 7.14 - 7.07 (m, 2H), 7.00 - 6.94 (m, 3H), 6.92 (d,J= 8.2 Hz, 1H), 6.89 - 6.83 (m, 2H), 4.56 (t,J= 6.1 Hz, 1H), 3.62 (t,J= 6.2 Hz, 2H), 3.44 (s, 3H), 3.06 - 3.01 (m, 6H), 1.69 (q,J= 6.4 Hz, 2H).

[1112] MS (ESI + )m / zcalcd for C 25 H 25 ClN3O4S [M + H] + 498.12; found 498.17.

[1113]

[1114] 3-49.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL-049)

[1115] [Compound 2-49]

[1116]

[1117] Following the general procedure E of Example 1-5, reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (1.0 equiv., 8.8 mg, 0.018 mmol), potassium carbonate (4.0 equiv., 9.77 mg, 0.071 mmol), and iodomethane (1.2 equiv., 1.32 μl, 0.021 mmol) was performed to obtain 9 mg (96%) of the product as an ivory solid, which was purified by MPLC (EtOAc / n-hexane = 1:2);

[1118] 1 H NMR (400 MHz, CDCl3) δ- 7.51 (m, 2H), 7.17 - 7.11 (m, 2H), 7.05 (d,J= 8.0 Hz, 1H), 7.02 - 6.96 (m, 4H), 6.88 (dd,J= 8.1, 2.1 Hz, 1H), 3.72 (t,J= 6.6 Hz, 2H), 3.45 (s, 3H), 3.15 - 3.06 (m, 6H), 2.68 (s, 3H), 1.75 (p,J= 6.8 Hz, 2H).

[1119] MS (ESI +)m / zcalcd for C 26 H 27 ClN3O4S [M + H] + 512.13; found 512.22.

[1120]

[1121] 3-50.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide (TRL-050)

[1122] [Compound 2-50]

[1123]

[1124] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 20.1 mg, 0.070 mmol), triethylamine (2.5 equiv., 24.4 μl, 0.175 mmol), and 1-methylindoline-6-sulfonyl chloride (1.2 equiv., 19.5 mg, 0.084 mmol) using general procedure D of Example 1-4, 14.8 mg (42%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:5);

[1125] 1 H NMR (400 MHz, CDCl3) δ(s, 1H), 7.36 - 7.27 (m, 3H), 7.20 - 7.14 (m, 4H), 7.06 (dd,J= 8.1, 2.1 Hz, 1H), 7.02 (s, 1H), 4.63 (t,J= 6.4 Hz, 1H), 3.88 (t,J= 6.5 Hz, 2H), 3.63 (t,J= 8.3 Hz, 2H), 3.24 - 3.14 (m, 8H), 2.97 (s, 3H), 1.93 (q,J= 6.6 Hz, 2H).

[1126] MS (ESI+ )m / zcalcd for C 26 H 29 ClN3O2S [M + H] + 481.16 ; found 482.27.

[1127]

[1128] 3-51.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide (TRL-051)

[1129] [Compound 2-51]

[1130]

[1131] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine (1.0 equiv., 6.5 mg, 0.022 mmol), triethylamine (4.0 equiv., 12.1 μl, 0.086 mmol), and 1-methylindoline-6-sulfonyl chloride (1.2 equiv., 6.01 mg, 0.026 mmol) through general procedure E of Example 1-5, 4.4 mg (41%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[1132] 1 H NMR (400 MHz, CDCl3) δ7.17 - 7.04 (m, 4H), 7.04 - 6.94 (m, 4H), 6.87 (dd,J= 8.1, 2.1 Hz, 1H), 6.78 (s, 1H), 3.76 (t,J= 6.8 Hz, 2H), 3.44 (t,J= 8.1 Hz, 2H), 3.15 - 3.00 (m, 8H), 2.81 (s, 3H), 2.64 (s, 3H), 1.78 (p,J= 6.9 Hz, 2H).

[1133] MS (ESI + )m / zcalcd for C 27 H 31 ClN3O2S [M + H] + 496.17 ; found 496.17.

[1134]

[1135] 3-52.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrid[2,3-d]pyrimidine-6-sulfonamide (TRL-052)

[1136] [Compound 2-52]

[1137]

[1138] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 32.1 mg, 0.112 mmol), triethylamine (2.5 equiv., 39 μl, 0.280 mmol), and 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonyl chloride (1.2 equiv., 38.9 mg, 0.134 mmol) through the general procedure D of Example 1-4, 14.6 mg (23%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:2);

[1139] 1H NMR (400 MHz, CDCl3) δ(d,J= 2.4 Hz, 1H), 8.74 (d,J= 2.4 Hz, 1H), 7.10 - 7.01 (m, 2H), 6.94 - 6.88 (m, 3H), 6.86 (d,J= 2.1 Hz, 1H), 6.79 (dd,J= 8.1, 2.0 Hz, 1H), 4.85 (t,J= 5.4 Hz, 1H), 3.73 (s, 3H), 3.60 (t,J= 6.1 Hz, 2H), 3.50 (s, 3H), 3.09 (q,J= 6.2 Hz, 2H), 3.02 (s, 4H), 1.74 (p,J= 6.3 Hz, 2H).

[1140] MS (ESI + )m / zcalcd for C 26 H 27 ClN5O4S [M + H] + 540.14 ; found 540.13.

[1141]

[1142] 3-53.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide (TRL-053)

[1143] [화합물 2-53]

[1144]

[1145] Following the general procedure E of Example 1-5, the reaction of N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide (1.0 equiv., 10.7 mg, 0.020 mmol), potassium carbonate (4.0 equiv., 10.9 mg, 0.079 mmol), and iodomethane (1.2 equiv., 1.48 μl, 0.024 mmol) was performed to obtain 9.5 mg (83%) of the product as a white solid, which was purified by MPLC (EtOAc / n-hexane = 1:2);

[1146] 1 H NMR (400 MHz, CDCl3) δ(d,J= 2.4 Hz, 1H), 8.71 (d,J= 2.4 Hz, 1H), 7.16 - 7.08 (m, 2H), 7.02 (d,J= 7.6 Hz, 1H), 6.99 - 6.93 (m, 3H), 6.85 (dd,J= 8.1, 2.0 Hz, 1H), 3.74 (s, 3H), 3.71 (t,J= 6.5 Hz, 2H), 3.50 (s, 3H), 3.16 - 3.04 (m, 6H), 2.76 (s, 3H), 1.80 (p,J= 6.7 Hz, 2H).

[1147] MS (ESI + )m / zcalcd for C 27 H 29 ClN5O4S [M + H] + 554.16; found 554.09.

[1148]

[1149] 3-54.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL-054)

[1150] [Compound 2-54]

[1151]

[1152] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 25.1 mg, 0.088 mmol), triethylamine (2.5 equiv., 30.5 μl, 0.219 mmol), and 2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride (1.2 equiv., 24.5 mg, 0.105 mmol) through general procedure D of Example 1-4, 13.4 mg (31%) of the product was obtained as a pale yellow solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[1153] 1 H NMR (400 MHz, CDCl3) δ(s, 1H), 7.62 - 7.59 (m, 2H), 7.14 - 7.04 (m, 3H), 6.97 (dd,J= 7.9, 5.0 Hz, 3H), 6.91 (d,J= 2.0 Hz, 1H), 6.86 (dd,J= 8.1, 2.0 Hz, 1H), 4.76 (s, 1H), 3.65 (t,J= 6.2 Hz, 2H), 3.04 - 3.03 (m, 6H), 1.72 (q,J= 6.5 Hz, 2H).

[1154] MS (ESI + )m / zcalcd for C 24 H 23 ClN3O4S [M + H] +484.10 ; found 484.09.

[1155]

[1156] 3-55.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (TRL-055)

[1157] [Compound 2-55]

[1158]

[1159] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine (1.0 equiv., 6.1 mg, 0.020 mmol), triethylamine (4.0 equiv., 11.3 μl, 0.081 mmol), and 2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride (1.2 equiv., 5.68 mg, 0.024 mmol) through general procedure E of Example 1-5, 5.3 mg (52%) of the product was obtained as an ivory solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[1160] 1 H NMR (400 MHz, CDCl3) δ(s, 1H), 7.54 - 7.52 (m, 2H), 7.17 - 6.96 (m, 7H), 6.91 - 6.85 (m, 1H), 3.72 (t,J= 6.5 Hz, 2H), 3.17 - 3.04 (m, 6H), 2.68 (s, 3H), 1.80 - 1.72 (m, 2H).

[1161] MS (ESI + )m / zcalcd for C 25 H 25 ClN3O4S [M + H] +498.12; found 498.04.

[1162]

[1163] 3-56.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-5-sulfonamide (TRL-056)

[1164] [Compound 2-56]

[1165]

[1166] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine (1.0 equiv., 20.8 mg, 0.073 mmol), triethylamine (2.5 equiv., 25.3 μl, 0.181 mmol), and 1-methyl-2-oxoindoline-5-sulfonyl chloride (1.2 equiv., 21.4 mg, 0.087 mmol) using general procedure D of Example 1-4, 13.4 mg (37%) of the product was obtained as a pale orange solid by purification by MPLC (EtOAc / n-hexane = 1:1);

[1167] 1 H NMR (400 MHz, CDCl3) δ(dd,J= 8.2, 1.8 Hz, 1H), 7.60 (d,J= 1.8 Hz, 1H), 7.15 - 7.05 (m, 2H), 7.01 - 6.92 (m, 3H), 6.92 (d,J= 2.1 Hz, 1H), 6.86 (dd,J= 8.1, 2.1 Hz, 1H), 6.79 (d,J= 8.3 Hz, 1H), 4.55 (s, 1H), 3.65 (t,J= 6.3 Hz, 2H), 3.48 (s, 2H), 3.24 (s, 3H), 3.06 - 2.99 (m, 6H), 1.71 (q,J= 6.5 Hz, 2H).

[1168] MS (ESI + )m / zcalcd for C 26 H 27 ClN3O3S [M + H] + 495.14 ; found 496.17.

[1169]

[1170] 3-57.N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethyl-2-oxoindoline-5-sulfonamide (TRL-057)

[1171] [Compound 2-57]

[1172]

[1173] Following the reaction of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine (1.0 equiv., 6.7 mg, 0.022 mmol), triethylamine (4.0 equiv., 12.4 μl, 0.089 mmol), and 1-methyl-2-oxoindoline-5-sulfonyl chloride (1.2 equiv., 6.57 mg, 0.027 mmol) through general procedure E of Example 1-5, 1.8 mg (15%) of the product was obtained as a colorless oil by purification by MPLC (EtOAc / n-hexane = 1:1);

[1174] 1H NMR (400 MHz, CDCl3) δ(d,J= 8.1 Hz, 1H), 7.56 (s, 1H), 7.19 - 7.09 (m, 2H), 7.05 (d,J= 8.0 Hz, 1H), 7.03 - 6.95 (m, 3H), 6.88 (dd,J= 8.1, 1.9 Hz, 1H), 6.83 (d,J= 8.1 Hz, 1H), 3.74 (t,J= 6.5 Hz, 2H), 3.54 (s, 2H), 3.25 (s, 3H), 3.18 - 3.04 (m, 6H), 2.65 (s, 3H), 1.80 - 1.73 (m, 2H).

[1175] MS (ESI + )m / zcalcd for C 27 H 29 ClN3O3S [M + H] + 510.15; found 510.09.

[1176]

[1177] 3-58.N-(3-(10H-phenothiazin-10-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL-058)

[1178] [Compound 2-58]

[1179]

[1180] Following the reaction of 3-(10H-phenothiazin-10-yl)propan-1-amine (1.0 equiv., 30 mg, 0.117 mmol), triethylamine (2.5 equiv., 40.8 μl, 0.293 mmol), and (4-(trifluoromethoxy)benzenesulfonyl chloride (1.2 equiv., 36.6 mg, 0.140 mmol) through general procedure D of Example 1-4, 44 mg (77%) of the product was obtained as a colorless oil by purification by MPLC (EtOAc / n-hexane = 1:5);

[1181] 1 H NMR (400 MHz, MeOD) δ- 7.77 (m, 2H), 7.39 - 7.29 (m, 2H), 7.19 - 7.13 (m, 2H), 7.11 (dd,J= 7.9, 1.5 Hz, 2H), 6.95 - 6.91 (m, 4H), 3.94 (t,J= 6.5 Hz, 2H), 3.00 (t,J= 6.9 Hz, 2H), 1.90 (p,J= 6.7 Hz, 2H).

[1182] MS (ESI + )m / zcalcd for C 22 H 20 F3N2O3S2[M + H] + 481.08 ; found 481.01

[1183]

[1184] 3-59.N-(3-(10H-phenothiazin-10-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL-059)

[1185] [Compound 2-59]

[1186]

[1187] Following the general procedure E of Example 1-5, reaction of N-(3-(10H-phenothiazin-10-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (1.0 equiv., 12.8 mg, 0.027 mmol), potassium carbonate (4.0 equiv., 14.7 mg, 0.107 mmol), and iodomethane (1.2 equiv., 1.99 μl, 0.032 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:3) to give 11.2 mg (85%) of the product as a colorless oil;

[1188] 1H NMR (400 MHz, CDCl3) δ- 7.74 (m, 2H), 7.30 (d,J= 8.1 Hz, 2H), 7.20 - 7.14 (m, 4H), 6.94 (td,J= 7.5, 1.2 Hz, 2H), 6.90 (d,J= 7.9 Hz, 2H), 4.00 (t,J= 6.6 Hz, 2H), 3.13 (t,J= 6.8 Hz, 2H), 2.67 (s, 3H), 2.06 (p,J= 6.7 Hz, 2H).

[1189] MS (ESI + )m / zcalcd for C 23 H 22 F3N2O3S2[M + H] + 495.09; found 495.00.

[1190]

[1191] 3-60.N-(2-(9H-carbazol-9-yl)ethyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL-060)

[1192] [Compound 2-60]

[1193]

[1194] Following the reaction of 2-(9H-carbazol-9-yl)ethan-1-amine (1.0 equiv., 30 mg, 0.143 mmol), triethylamine (2.5 equiv., 49.7 μl, 0.357 mmol), and 4-(trifluoromethoxy)benzenesulfonyl chloride (1.2 equiv., 44.6 mg, 0.171 mmol) through general procedure D of Example 1-4, 33.6 mg (53%) of the product was obtained as a colorless oil by purification by MPLC (EtOAc / n-hexane = 1:3);

[1195] 1H NMR (400 MHz, CDCl3) δ(d,J= 7.8 Hz, 2H), 7.64 - 7.57 (m, 2H), 7.46 - 7.42 (m, 2H), 7.35 (d,J= 8.2 Hz, 2H), 7.26 - 7.20 (m, 2H), 7.10 (d,J= 8.2 Hz, 2H), 4.61 (t,J= 6.5 Hz, 1H), 4.49 (t,J= 6.0 Hz, 2H), 3.49 (q,J= 6.1 Hz, 2H).

[1196] MS (ESI + )m / zcalcd for C 21 H 18 F3N2O3S [M + H] + 435.09; found 434.88.

[1197]

[1198] 3-61.N-(2-(9H-carbazol-9-yl)ethyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL-061)

[1199] [Compound 2-61]

[1200]

[1201] Following the general procedure E of Example 1-5, reaction of N-(2-(9H-carbazol-9-yl)ethyl)-4-(trifluoromethoxy)benzenesulfonamide (1.0 equiv., 9.5 mg, 0.022 mmol), potassium carbonate (4.0 equiv., 12.1 mg, 0.087 mmol), and iodomethane (1.2 equiv., 1.64 μl, 0.026 mmol) was performed to obtain 6.3 mg (64%) of the product as a white solid, which was purified by MPLC (EtOAc / n-hexane = 1:3);

[1202] 1H NMR (400 MHz, CDCl3) δ(dt,J= 7.9, 1.0 Hz, 2H), 7.74 - 7.69 (m, 2H), 7.52 - 7.41 (m, 4H), 7.27 - 7.21 (m, 4H), 4.59 (t,J= 6.7 Hz, 2H), 3.46 (t,J= 6.7 Hz, 2H), 2.69 (s, 3H).

[1203] MS (ESI + )m / zcalcd for C 22 H 20 F3N2O3S [M + H] + 449.11; found 449.05.

[1204]

[1205] 3-62.N-(3-(9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL-062)

[1206] [Compound 2-62]

[1207]

[1208] Following the reaction of 3-(9H-carbazol-9-yl)propan-1-amine (1.0 equiv., 30 mg, 0.134 mmol), triethylamine (2.0 equiv., 37.3 μl, 0.267 mmol), and 4-(trifluoromethoxy)benzenesulfonyl chloride (1.2 equiv., 41.8 mg, 0.160 mmol) through general procedure D of Example 1-4, 56.2 mg (93%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:3);

[1209] 1H NMR (400 MHz, CDCl3) δ(d,J= 7.7 Hz, 2H), 7.79 - 7.69 (m, 2H), 7.50 - 7.43 (m, 2H), 7.36 (d,J= 8.1 Hz, 2H), 7.26 (t,J= 7.5 Hz, 4H), 4.52 (t,J= 6.2 Hz, 1H), 4.40 (t,J= 6.7 Hz, 2H), 2.93 (q,J= 6.6 Hz, 2H), 2.12 (q,J= 6.7 Hz, 2H).

[1210] MS (ESI + )m / zcalcd for C 22 H 20 F3N2O3S [M + H] + 449.11 ; found 449.03

[1211]

[1212] 3-63.N-(3-(9H-carbazol-9-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL-063)

[1213] [Compound 2-63]

[1214]

[1215] Following the general procedure E of Example 1-5, reaction of N-(3-(9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (1.0 equiv., 18.9 mg, 0.042 mmol), potassium carbonate (4.0 equiv., 23.3 mg, 0.169 mmol), and iodomethane (1.2 equiv., 3.16 μl, 0.051 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:2) to give 18 mg (92%) of the product as a colorless oil;

[1216] 1H NMR (400 MHz, CDCl3) δ(d,J= 7.8 Hz, 2H), 7.81 - 7.71 (m, 2H), 7.48 (t,J= 7.5 Hz, 2H), 7.40 (d,J= 8.2 Hz, 2H), 7.30 (d,J= 8.4 Hz, 2H), 7.27 - 7.23 (m, 2H), 4.44 (t,J= 7.3 Hz, 2H), 3.11 (t,J= 7.0 Hz, 2H), 2.72 (s, 3H), 2.11 (p,J= 7.1 Hz, 2H).

[1217] MS (ESI + )m / zcalcd for C 23 H 22 F3N2O3S [M + H] + 463.12; found 463.30.

[1218]

[1219] 3-64.N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL-064)

[1220] [Compound 2-64]

[1221]

[1222] Following the reaction of 3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propan-1-amine (1.0 equiv., 30 mg, 0.118 mmol), triethylamine (2.0 equiv., 32.9 μl, 0.236 mmol), and 4-(trifluoromethoxy)benzenesulfonyl chloride (1.2 equiv., 36.9 mg, 0.142 mmol) through general procedure D of Example 1-4, 41.6 mg (73%) of the product was obtained as a colorless oil by purification by MPLC (EtOAc / n-hexane = 1:2);

[1223] 1H NMR (400 MHz, CDCl3) δ- 7.72 (m, 2H), 7.32 - 7.26 (m, 1H), 7.25 - 7.20 (m, 3H), 7.03 (t,J= 7.4 Hz, 2H), 6.95 - 6.90 (m, 1H), 6.89 - 6.82 (m, 3H), 5.22 (s, 2H), 4.88 (t,J= 6.2 Hz, 1H), 3.76 (t,J= 6.2 Hz, 2H), 3.04 (q,J= 6.4 Hz, 2H), 1.81 (p,J= 6.4 Hz, 2H).

[1224] MS (ESI + )m / zcalcd for C 23 H 22 F3N2O4S [M + H] + 479.12 ; found 479.02.

[1225]

[1226] 3-65.N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL-065)

[1227] [Compound 2-65]

[1228]

[1229] Following the general procedure E of Example 1-5, reaction of N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (1.0 equiv., 7.9 mg, 0.017 mmol), potassium carbonate (4.0 equiv., 9.13 mg, 0.066 mmol), and iodomethane (1.2 equiv., 1.24 μl, 0.020 mmol) was performed to obtain 6.3 mg (77%) of the product as a colorless oil, which was purified by MPLC (EtOAc / n-hexane = 1:2);

[1230] 1 H NMR (400 MHz, CDCl3) δ- 7.69 (m, 2H), 7.36 - 7.26 (m, 4H), 7.12 - 7.03 (m, 2H), 7.00 - 6.94 (m, 1H), 6.86 - 6.78 (m, 3H), 5.31 (s, 2H), 3.80 (t,J= 6.6 Hz, 2H), 3.11 (t,J= 6.9 Hz, 2H), 2.66 (s, 3H), 1.86 (p,J= 6.8 Hz, 2H).

[1231] MS (ESI + )m / zcalcd for C 24 H 24 F3N2O4S [M + H] + 493.13; found 493.30.

[1232]

[1233] 3-66.N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL-066)

[1234] [Compound 2-66]

[1235]

[1236] Following the reaction of 3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propan-1-amine (1.0 equiv., 17 mg, 0.083 mmol), triethylamine (2.0 equiv., 23.2 μl, 0.166 mmol), and 4-(trifluoromethoxy)benzenesulfonyl chloride (1.2 equiv., 26 mg, 0.10 mmol) through general procedure D of Example 1-4, 30 mg (82%) of the product was obtained as a colorless oil by purification by MPLC (EtOAc / n-hexane = 1:1);

[1237] 1 H NMR (400 MHz, CDCl3) δ- 7.57 (m, 2H), 7.20 - 7.09 (m, 4H), 6.98 (td,J= 7.4, 1.2 Hz, 1H), 6.83 (dd,J= 8.0, 1.1 Hz, 1H), 6.30 (t,J= 5.1 Hz, 1H), 3.16 - 3.06 (m, 4H), 2.87 - 2.80 (m, 4H), 1.78 (p,J= 5.9 Hz, 2H), 1.70 (p,J= 5.9 Hz, 2H), 1.63 - 1.59 (m, 2H).

[1238] MS (ESI + )m / zcalcd for C 20 H 24 F3N2O3S [M + H] + 428.14; found 429.06

[1239]

[1240] 3-67.N-methyl-N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL-067)

[1241] [화합물 2-67]

[1242]

[1243] Following the general procedure E of Example 1-5, the reaction of N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (1.0 equiv., 18 mg, 0.042 mmol), potassium carbonate (4.0 equiv., 23.2 mg, 0.168 mmol), and iodomethane (1.2 equiv., 3.15 μl, 0.050 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:2) to give 16.7 mg (87%) of the product as a colorless oil;

[1244] 1 H NMR (400 MHz, CDCl3) δ- 7.70 (m, 2H), 7.30 (d,J= 8.2 Hz, 2H), 7.18 - 7.04 (m, 2H), 6.89 (t,J= 7.3 Hz, 2H), 3.20 - 3.13 (m, 4H), 2.93 - 2.85 (m, 2H), 2.80 - 2.74 (m, 2H), 2.73 (s, 3H) 1.83 - 1.75 (m, 2H), 1.75 - 1.69 (m, 2H), 1.65 - 1.55 (m, 2H).

[1245] MS (ESI + )m / zcalcd for C 21 H 26 F3N2O3S [M + H] + 443.15; found 443.04.

[1246]

[1247] 3-68.N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (TRL-068)

[1248] [Compound 2-68]

[1249]

[1250] Following the reaction of 3-(2-chloro-9H-carbazol-9-yl)propan-1-amine (1.0 equiv., 29 mg, 0.112 mmol), triethylamine (2.0 equiv., 31.2 μl, 0.224 mmol), and 4-(trifluoromethoxy)benzenesulfonyl chloride (1.2 equiv., 35.1 mg, 0.134 mmol) through general procedure D of Example 1-4, 28.3 mg (52%) of the product was obtained as a white solid by purification by MPLC (EtOAc / n-hexane = 1:3);

[1251] 1 H NMR (400 MHz, CDCl3) δ(d,J= 7.8 Hz, 1H), 7.97 (d,J= 8.3 Hz, 1H), 7.82 - 7.75 (m, 2H), 7.48 - 7.44 (m, 1H), 7.38 - 7.31 (m, 2H), 7.29 - 7.23 (m, 3H), 7.20 (dd,J= 8.3, 1.8 Hz, 1H), 4.60 (t,J= 6.2 Hz, 1H), 4.33 (t,J= 6.8 Hz, 2H), 2.95 (q,J= 6.6 Hz, 2H), 2.08 (p,J= 6.8 Hz, 2H).

[1252]

[1253] MS (ESI + )m / zcalcd for C 22 H 19 ClF3N2O3S [M + H] + 483.07; found 483.05

[1254]

[1255] 3-69.N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (TRL-069)

[1256] [Compound 2-69]

[1257]

[1258] Following the general procedure E of Example 1-5, the reaction of N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide (1.0 equiv., 14.1 mg, 0.029 mmol), potassium carbonate (4.0 equiv., 16.1 mg, 0.117 mmol), and iodomethane (1.2 equiv., 2.19 μl, 0.035 mmol) was performed, followed by purification by MPLC (EtOAc / n-hexane = 1:2) to give 10.5 mg (72%) of the product as a colorless oil;

[1259] 1 H NMR (400 MHz, CDCl3) δ(d,J= 7.7 Hz, 1H), 7.99 (d,J= 8.3 Hz, 1H), 7.82 - 7.71 (m, 2H), 7.52 - 7.46 (m, 1H), 7.40 (d,J= 8.2 Hz, 1H), 7.37 (d,J= 1.8 Hz, 1H), 7.33 (d,J= 8.2 Hz, 2H), 7.29 - 7.24 (m, 1H), 7.21 (dd,J= 8.3, 1.8 Hz, 1H), 4.39 (t,J= 7.3 Hz, 2H), 3.11 (t,J=6.9 Hz, 2H), 2.74 (s, 3H), 2.10 (p,J= 7.1 Hz, 2H).

[1260] MS (ESI + )m / zcalcd for C 23 H 21 F3N2O3S [M + H] + 497.08; found 497.05.

[1261]

[1262] [Experimental Example]

[1263] Experimental Example 1. Confirmation of Mel-Ab and NHM cytotoxicity of the compound.

[1264] 1-1. Confirmation of cytotoxicity in Mel-Ab cells

[1265] The cytotoxicity of TRL 0 and its derivatives TRL 1 to TRL 69 against Mel-Ab cells, a mouse melanocyte cell line, was confirmed through MTT assay.

[1266] As a result, as shown in Figures 1a to 1d and Table 2 below, the cell viability was high when Mel-Ab cells were treated with TRL 0 and its derivatives, and it was confirmed that the cell viability was maintained at a high level of 78% or higher even when treated at a concentration of 10 μM.

[1267]

[1268] 1-2. Confirmation of cytotoxicity in NHM cells

[1269] The cytotoxicity of TRL 0 and its derivatives TRL 1 to TRL 69 against human primary melanocyte NHM was determined by MTT assay.

[1270] As a result, as shown in FIGS. 2a to 2d and Table 3 below, when NHM cells were treated with 0.1 μM and 1 μM of TRL 0 and its derivatives, the cell viability was found to be high at 85% or higher, and it was confirmed that cell viability was maintained at 50% or higher even when treated with a concentration of 10 μM, except for TRL 4, 11, 57, 58, 60, 62, 64, and 66.

[1271]

[1272] Experimental Example 2. Confirmation of the compound's melanin production-regulating effect in Mel-Ab and NHM cells.

[1273] 2-1. Confirmation of the inhibitory effect on melanin production in Mel-Ab cells

[1274] The melanin production-regulating effects of TRL 0 and its derivatives TRL 1 to 69 were confirmed in Mel-Ab cells, a mouse melanocyte cell line, and are shown in Figures 3a to 4d, Table 4, and Table 5.

[1275] In Figures 3a to 3d, CTRL represents the basal control group, and 1 μM and 10 μM represent the groups treated with 1 μM and 10 μM of TRL 0 or its derivative, respectively.

[1276] In Figures 4a to 4d, CTRL means 10 μM FSK treatment group, 1 μM means 10 μM FSK+1 μM TRL 0 or its derivative treatment group, and 10 μM means 10 μM FSK+10 μM TRL 0 or its derivative treatment group.

[1277]

[1278]

[1279] As a result of confirming the melanin production inhibitory effect of TRL 0 or its derivatives TRL 1 to 69 compared to the basal control group (Figs. 3a to 3d and Table 4) or FSK treatment group (Figs. 4a to 4d and Table 5), it was confirmed that the TRL 5, 6, 10, 12, 43, 51, 53, 59, 65, and 67 treatment groups showed high melanin production inhibitory effects.

[1280]

[1281] 2-2. Confirmation of the inhibitory effect on melanin production in NHM cells

[1282] The melanogenesis-regulating effects of TRL 0 and its derivatives TRL 1 to 69 in human primary melanocyte NHM were confirmed and are shown in Figures 5a to 5d and Table 6.

[1283] In Figures 5a to 5d, CTRL represents the basal control group, 0.1 μM, 1 μM, and 10 μM represent the TRL 0 or its derivative treatment groups at 0.1 μM, 1 μM, and 10 μM, respectively.

[1284]

[1285] As shown in FIGS. 5a to 5d and Table 6 above, the melanin production regulating effect of TRL 0 or its derivatives TRL 1 to 69 was confirmed compared to the basal control group, and it was confirmed that the TRL 1, 2, 3, 5, 8, 9, 12, 16, 23, 40, 41, and 42 treatment groups showed a high melanin production inhibitory effect.

[1286]

[1287] Experimental Example 3. Confirmation of the compound's inhibitory effect on melanin production in B16F10 cells.

[1288] In the above Experimental Example 2, 20 derivatives (TRL 1, 2, 3, 5, 6, 8, 9, 10, 12, 16, 23, 40, 41, 42, 43, 51, 53, 59, 65, and 67) that showed excellent melanin production inhibition effects in Mel-Ab or NHM cells were selected, and the IC50 was confirmed in mouse melanoma cells B16F10 using the fluorescence-based melanin content measurement method of the above Experimental Method 3, and the melanin production inhibition rate was shown.

[1289] As a result, as shown in Table 7 below, it was confirmed that TRL 5, 9, 10, 40, 41, and 53 in particular exhibited a similar or improved melanin production inhibition effect compared to TRL 0.

[1290] CandidatesRepeatsIC50 (uM)Inhibition Rate (%)AverageSDAverageSDT01043.81.544%14%T01314.32.933%10%T023NDNDNDNDT033NDNDNDNDT05314. 93.370%8%T06418.58.442%10%T08410.93.856%22%T09412.30.280%8%T1034.40.481%2%T12310.72.15 3%3%T163NDNDNDNDT2349.32.365%13%T4082.20.372%8%T41410.77.889%7%T4238.50.441%6%T4347.50 .951%6%T5148.25.154%19%T5362.30.570%8%T59311.21.728%1%T65316.63.075%23%T6739.01.629%2%

[1291]

[1292] Experimental Example 4. Confirmation of the cytotoxicity of the compound in B16F10 cells.

[1293] The cytotoxicity of 20 derivatives (TRL 1, 2, 3, 5, 6, 8, 9, 10, 12, 16, 23, 40, 41, 42, 43, 51, 53, 59, 65, and 67) selected through the above Experimental Example 2 against B16F10 cells, a mouse melanoma cell line, was confirmed through MTT analysis.

[1294] As a result, it was confirmed that all 20 selected derivatives did not exhibit cytotoxicity, as shown in Figures 6a to 6b and Table 8.

[1295]

[1296] The foregoing description of the present invention is provided for illustrative purposes only. Those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

[1297]

[1298] The compound or salt thereof according to the present invention can be used not only for the prevention, improvement, or treatment of hyperpigmentation diseases, but is also expected to be utilized in various fields of skin beauty, such as skin whitening through improvement of hyperpigmentation diseases, and thus has industrial applicability.

Claims

1. A compound represented by the following chemical formula 1 or a salt thereof: [Chemical Formula 1] In the above chemical formula 1, X is , , , or And, Y is , , , or And, R1 is hydrogen (H) or a halogen element, R2 and R4 are each independently hydrogen (H) or a C1-C6 alkyl group, R3 is hydrogen (H), a halogen element, or a substituted or unsubstituted C1-C6 alkoxy group, A1 to A9 are each independently a substituted or unsubstituted carbon (C), a substituted or unsubstituted nitrogen (N), oxygen (O), sulfur (S), or C=O, n is 2 or 3, The above 'substituted or unsubstituted' means substituted or unsubstituted with one or more selected from the group consisting of a halogen element, a C1-C6 alkyl group, and a C1-C6 alkylcarbonyl group.

2. In paragraph 1, The above X is , , or A compound or a salt thereof, characterized by being.

3. In paragraph 1, The above Y is , , or A compound or a salt thereof, characterized by being.

4. In paragraph 1, The above A1 is substituted or unsubstituted carbon (C), substituted or unsubstituted nitrogen (N), oxygen (O), or sulfur (S), A compound or a salt thereof, characterized in that each of the above A2 to A9 is independently a substituted or unsubstituted carbon (C), a substituted or unsubstituted nitrogen (N), oxygen (O), or C=O.

5. In paragraph 1, The above A1 is a substituted or unsubstituted carbon (C), The above A2, A4, A5, A6 and A8 are each independently a substituted or unsubstituted nitrogen (N), A compound or a salt thereof, characterized in that the above A3, A7 and A9 are each independently C=O.

6. In paragraph 1, The above X is And, The above Y is or And, The above R1 is hydrogen (H) or a halogen element, The above R2 and R4 are each independently hydrogen (H) or a C1-C6 alkyl group, The above A1 is carbon (C), A2, A above 4, A5, A6 and A8 are each independently a substituted or unsubstituted carbon (C) or a substituted or unsubstituted nitrogen (N), The above A3, A7 and A9 are each independently C=O, n is 2 or 3, A compound or a salt thereof, characterized in that the above 'substituted or unsubstituted' means substituted or unsubstituted with one or more selected from the group consisting of a halogen element, a C1-C6 alkyl group, and a C1-C6 alkylcarbonyl group.

7. In paragraph 1, The compound is characterized by being represented by any one selected from the following chemical formulas 2 to 8, or a salt thereof: [Chemical Formula 2] In the above chemical formula 2, R1 is hydrogen (H) or chlorine (Cl), R2 and R4 are each independently hydrogen (H) or a methyl group (CH3), A1 is carbon (C), A2 and A4 are each independently a substituted or unsubstituted carbon (C), a substituted or unsubstituted nitrogen (N), or an oxygen (O), A3 is carbon (C) or C=O, The above 'substituted or unsubstituted' means one or more methyl groups (CH3) and acetyl groups ( ) means substituted or unsubstituted with one or more selected from the group consisting of. [Chemical Formula 3] In the above chemical formula 3, R1 is hydrogen (H) or chlorine (Cl), R2 is hydrogen (H) or methyl group (CH3), A1 is carbon (C), A5 is carbon (C) or nitrogen (N), A6 is substituted or unsubstituted nitrogen (N) or oxygen (O), A7 is carbon (C) or C=O, A8 and A9 are each independently substituted or unsubstituted nitrogen (N) or C=O, The above ‘substituted or unsubstituted’ means substituted or unsubstituted with a methyl group (CH3). [Chemical Formula 4] In the above chemical formula 4, Y is or And, R1 is hydrogen (H) or chlorine (Cl), R2 is hydrogen (H) or methyl group (CH3), R3 is fluorine (F) or a substituted or unsubstituted methoxy group (OMe), A1 is carbon (C) or oxygen (O), The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F). [Chemical Formula 5] In the above chemical formula 5, R2 is hydrogen (H) or methyl group (CH3), R3 is a substituted or unsubstituted methoxy group (OMe), A1 is carbon (C), The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F). [Chemical Formula 6] In the above chemical formula 6, R2 is hydrogen (H) or methyl group (CH3), R3 is a substituted or unsubstituted methoxy group (OMe), A1 is sulfur (S), The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F). [Chemical Formula 7] In the above chemical formula 7, R1 is hydrogen (H) or chlorine (Cl), R2 is hydrogen (H) or methyl group (CH3), R3 is a substituted or unsubstituted methoxy group (OMe), The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F). [Chemical Formula 8] In the above chemical formula 8, R2 is hydrogen (H) or methyl group (CH3), R3 is a substituted or unsubstituted methoxy group (OMe), The above ‘substituted or unsubstituted’ means substituted or unsubstituted with one or more fluorine (F).

8. In paragraph 1, A compound represented by the above chemical formula 1, characterized in that it is at least one selected from the group consisting of: (1)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide; (2) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide; (3) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide; (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide; (6)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (7)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-Nmethylbenzenesulfonamide; (8) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide; (9) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide; (10)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (11)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (12)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluorobenzenesulfonamide; (13)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-N-methylbenzenesulfonamide; (14)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide; (15)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylquinoline-8-sulfonamide; (16)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (17)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (18)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide; (19)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-5-sulfonamide; (20)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide; (21)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (22)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide; (23)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethyl-2-oxoindoline-5-sulfonamide; (24)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide; (25)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide; (26)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethylindoline-6-sulfonamide; (27)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide; (28)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide; (29)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide; (30)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,4-dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide; (31)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethyl-2-oxoindoline-5-sulfonamide; (32)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (33)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)quinoline-8-sulfonamide; (34)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylquinoline-8-sulfonamide; (35)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3-trimethyl-2-oxoindoline-5-sulfonamide; (36)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3-tetramethyl-2-oxoindoline-5-sulfonamide; (37)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide; (38)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide; (39)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide; (40)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide; (41)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; (42)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; (43)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide; (44)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide; (45)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide; (46)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-5-sulfonamide; (47)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide; (48)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,4-dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-sulfonamide; (49)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (50)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,3-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (51)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methylindoline-6-sulfonamide; (52)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide; (53)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; (54)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; (55)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (56)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (57)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1-methyl-2-oxoindoline-5-sulfonamide; (58)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethyl-2-oxoindoline-5-sulfonamide; (59)N-(3-(10H-phenothiazin-10-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide; (60)N-(3-(10H-phenothiazin-10-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide; (61)N-(2-(9H-carbazol-9-yl)ethyl)-4-(trifluoromethoxy)benzenesulfonamide; (62)N-(2-(9H-carbazol-9-yl)ethyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide; (63)N-(3-(9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide; (64)N-(3-(9H-carbazol-9-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide (65)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide; (66)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide; (67)N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide; (68)N-methyl-N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide; (69)N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide; and (70)N-(3-(2-chloro-9H-carbazol-9-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide.

9. A compound represented by the following chemical formula 1 or a salt thereof: [Chemical Formula 1] In the above chemical formula 1, X is , , or And, Y is , , or And, R1 is hydrogen (H) or a halogen element, R2 and R4 are each independently hydrogen (H) or a methyl group, R3 is a fluorine (F) or trifluoromethoxy group (OCF3), A1 is carbon (C), oxygen (O), or sulfur (S), A2 is carbon (C) or substituted nitrogen (N), A3 is carbon (C) or C=O, A4 is substituted or unsubstituted carbon (C), substituted nitrogen (N), or oxygen (O), A5 is nitrogen (N), A6 and A8 are each independently substituted nitrogen (N), A7 and A9 are each independently C=O, n is 3, The above 'substituted or unsubstituted' means one or more methyl groups (CH3), and acetyl groups ( ) means substituted or unsubstituted with one or more selected from the group consisting of.

10. In paragraph 9, A compound represented by the above chemical formula 1, characterized in that it is at least one selected from the group consisting of: (1) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)indoline-5-sulfonamide; (2) 1-acetyl-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide; (3)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-Nmethylbenzenesulfonamide; (6) 1-acetyl-N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N-methylindoline-5-sulfonamide; (7)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (8)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (9)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-fluoro-N-methylbenzenesulfonamide; (10)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamide; (11)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide; (12)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; (13)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; (14)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3,3,7-tetramethyl-2-oxoindoline-5-sulfonamide; (15)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3,3,7-pentamethyl-2-oxoindoline-5-sulfonamide; (16)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1-dimethylindoline-6-sulfonamide; (17)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; (18)N-(3-(10H-phenothiazin-10-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide; (19)N-(3-(dibenzo[b,e][1,4]oxazepin-5(11H)-yl)propyl)-N-methyl-4-(trifluoromethoxy)benzenesulfonamide; and (20)N-methyl-N-(3-(2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide.

11. A compound represented by the following chemical formula 1 or a salt thereof: [Chemical Formula 1] In the above chemical formula 1, X is And, Y is or And, R1 is hydrogen (H) or a halogen element, R2 is hydrogen (H) or a methyl group, R4 is hydrogen (H), A1 is carbon (C), A2, A4, A6, and A8 are each independently substituted nitrogen (N), A3, A7 and A9 are each independently C=O, A5 is nitrogen (N), n is 3, The above ‘substituted or unsubstituted’ means substituted or unsubstituted with a methyl group.

12. In paragraph 11, A compound represented by the above chemical formula 1, characterized in that it is at least one selected from the group consisting of: (1)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (2)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (3)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide; (4)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; (5)N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide; and (6)N-(3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-N,1,3-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-sulfonamide.

13. A pharmaceutical composition for preventing or treating hyperpigmentation disease, comprising a compound of any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof as an active ingredient.

14. In paragraph 13, A pharmaceutical composition characterized in that the hyperpigmentation disease is at least one selected from the group consisting of freckles, liver spots, lentigines, moles, coffee-colored spots, nevus of Ota, blue nevus, hyperpigmented spots, hyperpigmentation after drug use, gravidic chloasma, post-inflammatory hyperpigmentation due to wounds or dermatitis, senile pigmentation, dyspigmentation, and solar lentigines.

15. In paragraph 13, A pharmaceutical composition characterized in that the compound inhibits melanin production.

16. In paragraph 13, A pharmaceutical composition, characterized in that the composition is for systemic application or topical application.

17. A cosmetic composition for skin whitening, comprising a compound of any one of claims 1 to 12 or a cosmetically acceptable salt thereof as an active ingredient.

18. In paragraph 17, The cosmetic composition is characterized in that the cosmetic composition is at least one formulation selected from the group consisting of serum, toner, paste, patch, gel, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, cream, massage cream, nourishing cream, mist, moisture cream, hand cream, hand lotion, foundation, essence, nourishing essence, pack, soap, oil, foundation, makeup base, wax, spray, cleansing foam, cleansing lotion, cleansing cream, cleansing oil, cleansing balm, body lotion, and body cleanser.

19. A food composition for preventing or improving hyperpigmentation disease, comprising a compound of any one of claims 1 to 12 or a food-related acceptable salt thereof as an active ingredient.

20. A pharmaceutical composition for preventing or improving hyperpigmentation disease, comprising a compound of any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof as an active ingredient.

21. A method for preventing or treating hyperpigmentation disease, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a compound of any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof as an active ingredient.

22. Use of a composition comprising a compound of any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or treatment of hyperpigmentation disease.

23. Use of a compound of any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof for the manufacture of a preparation for preventing or treating hyperpigmentation diseases.

Images