Aminoalcohol derivative for metabolic diseases

Abstract

A compound, of the present invention, which is an aminoalcohol derivative represented by chemical formula 1 or a pharmaceutically acceptable salt thereof, has an excellent effect of inhibiting serotonin activity, and thus a pharmaceutical composition comprising same can be effectively used for preventing or treating metabolic diseases and the like associated with serotonin activation.

Description

Aminoalcohol derivatives for metabolic diseases

[0001] The present invention relates to aminoalcohol derivatives for metabolic diseases and pharmaceutical compositions comprising them. More specifically, the present invention relates to aminoalcohol derivatives that act as serotonin 2A antagonists, and pharmaceutical compositions comprising them for the prevention or treatment of obesity, fatty liver disease, and the like.

[0002] Obesity is a condition characterized by excessive accumulation of body fat. Obesity occurs when calories consumed are less than burned, resulting in the accumulation of excess energy in the form of body fat. Causes of obesity include irregular eating habits, excessive food intake, lack of exercise, genetics, and psychological factors. In addition to shortness of breath and joint pain, obesity can also lead to cardiovascular disease, high blood pressure, sleep apnea, dyslipidemia, hyperinsulinemia, and osteoarthritis.

[0003] The goal of obesity treatment is to prevent and treat obesity-related complications. The most basic treatment for obesity involves lifestyle changes, while pharmacological treatment primarily involves appetite suppressants. However, because these appetite suppressants act on the central nervous system, they can have side effects, including mental illnesses like depression.

[0004] Appetite suppressants inhibit serotonin (5-HT), a neurotransmitter that regulates mood, sleep, and appetite in the central nervous system. Serotonin acts not only in the central nervous system but also in peripheral tissues, where it has been reported to play a crucial role in metabolic regulation. Because serotonin cannot cross the blood-brain barrier, serotonin in the central nervous system and peripheral tissues is considered to operate independently.

[0005] In addition, the synthesis of serotonin is initiated by tryptophan hydroxylase, and there are two types of tryptophan hydroxylase: tryptophan hydroxylase 1 (TPH1) and tryptophan hydroxylase 2 (TPH2). TPH1 is mainly expressed in peripheral tissues, while TPH2 is mainly expressed in neural tissues. According to a recent study, when the synthesis of serotonin in peripheral tissues is inhibited, lipogenesis in white adipocytes is reduced, and brown adipocytes are known to burn energy by generating heat (Oh C et al., Nature Communication6, 6794, 2015).

[0006] Meanwhile, fatty liver disease is a disease that occurs when excessive fat accumulates in liver cells, increasing the fat content of the liver. Fatty liver disease is broadly divided into alcoholic fatty liver disease and non-alcoholic fatty liver disease. Excessive alcohol consumption leads to the accumulation of fat in liver cells, and alcohol metabolites damage liver cells. However, non-alcoholic fatty liver disease refers to a condition in which fat accumulates in the liver despite no or minimal alcohol consumption.

[0007] Fatty liver disease encompasses a variety of liver diseases, ranging from simple fatty liver disease, which involves only fat accumulation without liver cell damage, to steatohepatitis, which causes persistent liver cell damage, and to cirrhosis, which is accompanied by symptoms such as ascites and jaundice. Fatty liver disease is characterized by the accumulation of neutral fat within hepatocytes, and the resulting triglyceride vesicles increase in size over time. These fat vesicles increase the inflammatory response, leading to hepatitis or liver fibrosis.

[0008] Treatments for fatty liver disease include weight loss through diet and exercise. Antidiabetic medications that improve insulin resistance are used for short-term treatment. However, these are short-term treatments, and long-term efficacy has not been reported to date. Furthermore, commercially available lipid-lowering and liver-protecting medications are only effective for preservation, not treatment.

[0009] A recent study found that serotonin antagonists inhibited the proliferation of damaged hepatocytes and increased the rate of apoptosis when treated with liver-damaged rats (Ruddell et al., The American Journal of Pathology, 11 (1), 52-58, 2011). In addition, treatment with serotonin receptor inhibitors ketanserin and sarpogrelate decreased the viability of liver-damaged LX-2 cells and induced apoptosis (Kim et al., Liver International, 33 (4), 535-543, 2013).

[0010] [Prior Art Literature]

[0011] (Non-patent literature 1) Oh C et al., Nature Communication 6, 6794, 2015

[0012] (Non-patent literature 2) Ruddell et al., The Amer. J. Patho., 11 (1), 52-58, 2011

[0013] (Non-patent literature 3) Kim et al., Liver International, 33 (4), 535-543, 2013

[0014] In order to treat obesity, it is important to suppress the synthesis of serotonin in the peripheral nervous system. Accordingly, the inventors of the present invention tried to find serotonin receptors associated with obesity in peripheral tissues and found that serotonin 2A (5-HT) 2A) receptor expression was confirmed to increase in an obese state. In addition, it was confirmed that knocking out the serotonin 2A receptor could reduce body weight and improve liver fibrosis.

[0015] Accordingly, the present invention seeks to provide a compound that acts as a serotonin antagonist and a pharmaceutical composition comprising the same.

[0016] Accordingly, the present invention provides a compound which is an aminoalcohol derivative represented by chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof.

[0017] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating a disease related to serotonin activation, comprising the compound according to the present invention as an active ingredient.

[0018] Another aspect of the present invention provides a method for treating a disease associated with serotonin activation, comprising administering to a subject a compound according to the present invention.

[0019] Another aspect of the present invention provides the use of a compound according to the present invention for preparing a medicament for the prevention or treatment of a disease associated with serotonin activation.

[0020] Another aspect of the present invention provides a use of the compound according to the present invention for the prevention or treatment of diseases associated with serotonin activation.

[0021] Compounds containing aminoalcohol derivatives according to the present invention can exhibit excellent antagonistic effects against serotonin, particularly serotonin 2A. Therefore, the compounds according to the present invention can be useful in the prevention or treatment of diseases associated with serotonin activation, such as obesity and fatty liver disease.

[0022] The present invention is described in detail below.

[0023] In this specification, the term “halogen” means F, Cl, Br or I unless otherwise stated.

[0024] As used herein, the term "alkyl" means a linear or branched saturated hydrocarbon residue, unless otherwise specified. For example, "C 1-10 "Alkyl" means an alkyl group having a skeleton of 1 to 10 carbons. Specifically, C 1-10 Alkyl can be methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, n-pentyl, i-pentyl, t-pentyl, sec-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc.

[0025] The term "haloalkyl" refers to an alkyl substituted with one or more halogens. Specifically, a haloalkyl may be an alkyl substituted with two or more of the same halogens or an alkyl substituted with two or more halogens.

[0026] The term "heterocycle" refers to an aromatic or non-aromatic ring having one or more heteroatoms, which may be saturated or unsaturated, and may be monocyclic or polycyclic. For example, a "4- to 10-membered heterocycle" refers to a heterocycle whose skeleton is composed of a total of 4 to 10 atoms, including heteroatoms and carbon atoms. Specifically, a 4- to 10-membered heterocycle may include azetidine, diazetidine, pyrrolidine, pyrrole, imidazolidine, imidazole, pyrazolidine, pyrazole, oxazolidine, oxazole, isoxazolidine, isoxazole, thiazolidine, thiazole, isothiazolidine, isothiazole, piperidine, pyridine, piperazine, diazine, morpholine, thiomorpholine, azepane, diazepane, and the like.

[0027] The term "heteroatom" means an atom other than carbon (C), specifically a nitrogen (N), oxygen (O), or sulfur (S) atom.

[0028] The term "substitution" refers to the replacement of a hydrogen atom within a molecular structure with a substituent, such that the resulting compound is chemically stable without exceeding the valence of the designated atom. For example, "group A is replaced with substituent B" may mean that a hydrogen atom bonded to an atom such as carbon constituting the backbone of group A is replaced with substituent B, so that group A and substituent B form a covalent bond.

[0029] The present invention provides a compound which is an aminoalcohol derivative represented by the following chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof:

[0030] [Chemical Formula 1]

[0031]

[0032] In the above formula

[0033] L 1 A 5 to 15 membered heterocycle having one or more heteroatoms including N, or and;

[0034] R 1 A 5 to 15 membered heterocycle having one or more heteroatoms, phenyl, -L 2 -phenyl, or -L 2 -R A and;

[0035] R 2 is H, C 1-10 Alkyl, or -L 2 -R A and;

[0036] R 3 Is , , , , or And,

[0037] The above heteroatom is selected from N, S and O; the heterocycle and phenyl are each R A and RB with or without one or more substituents selected from;

[0038] R A and R B are each independently H, halogen, hydroxy, oxo, methylsulfonyl, C 1-6 Alkyl, C 1-6 Alkoxy, haloC 1-6 Alkyl, haloC 1-6 Alkoxy, C 1-6 Alkoxycarbonyl, -C 1-6 Alkylene-COOH, benzyl, halobenzyl, , or , and;

[0039] L 2 is a single bond, -C(=O)-, -CH(-OH)-, or -CH2-.

[0040]

[0041] According to one embodiment, in the chemical formula 1

[0042] L 1 silver , , , , , , , , , , , or and here R A is H, C 1-6 Alkyl, haloC 1-6 Alkyl, benzyl, or halobenzyl.

[0043] According to another embodiment, R in the above formula 1 1 silver , , , , , , , , , , , , or -L 2 -R A and here R A and R B are each independently H, halogen, hydroxy, oxo, methylsulfonyl, C 1-6 Alkyl, C 1-6 Alkoxy, haloC 1-6 Alkyl, haloC 1-6 Alkoxy, C 1-6 Alkoxycarbonyl, -C 1-6 alkylene-COOH, , or , and L 2 is a single bond, -C(=O)-, -CH(-OH)-, or -CH2-.

[0044] According to another embodiment, in the chemical formula 1, R 2 is H or am.

[0045]

[0046] The amino alcohol derivative of the present invention has a substituent R of the above chemical formula 1. 3 According to this, it can be expressed more specifically by the three chemical formulas (chemical formulas 1a, 1b, 1c) described below.

[0047] According to one specific example, the aminoalcohol derivative of the present invention can be represented by the following chemical formula 1a:

[0048] [Chemical Formula 1a]

[0049]

[0050] In the above formula

[0051] is a single bond or a double bond;

[0052] L 1 silver , , , , , , , , , , , or And,

[0053] R 1 silver , , , , , , , , , , , , or -L 2 -R A and;

[0054] R 2 is H or and;

[0055] R A and R B are each independently H, halogen, hydroxy, oxo, methylsulfonyl, C 1-6 Alkyl, C 1-6 Alkoxy, haloC 1-6 Alkyl, haloC 1-6 Alkoxy, C 1-6 Alkoxycarbonyl, -C 1-6 Alkylene-COOH, benzyl, halobenzyl, , or , and;

[0056] L 2 is a single bond, -C(=O)-, -CH(-OH)-, or -CH2-.

[0057] According to another specific example, the aminoalcohol derivative of the present invention can be represented by the following chemical formula 1b:

[0058] [Chemical Formula 1b]

[0059]

[0060] In the above formula

[0061] L 1 silver , or and;

[0062] R 1 Silver halogen, or and;

[0063] R A is a halogen.

[0064]

[0065] According to another specific example, the aminoalcohol derivative of the present invention can be represented by the following chemical formula 1c:

[0066] [Chemical Formula 1c]

[0067]

[0068] In the above formula

[0069] L 1 silver or and;

[0070] R 1 Silver halogen, or and;

[0071] R A is a halogen.

[0072] The compound of the present invention comprises a pharmaceutically acceptable salt of an aminoalcohol derivative represented by the above chemical formula 1.

[0073] The pharmaceutically acceptable salt should have low toxicity to humans and should not have any negative effects on the biological activity or physicochemical properties of the parent compound. For example, the pharmaceutically acceptable salt may be an acid addition salt formed with a pharmaceutically acceptable free acid.

[0074] The above-mentioned acid may be an inorganic acid or an organic acid. In this case, the inorganic acid may be hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, hydrobromic acid, etc., and the organic acid may be acetic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, fumaric acid, maleic acid, malonic acid, phthalic acid, succinic acid, lactic acid, citric acid, gluconic acid, tartaric acid, salicylic acid, malic acid, oxalic acid, benzoic acid, embonic acid, aspartic acid, glutamic acid, etc.

[0075] The above acid addition salt can be prepared by a conventional method, for example, by dissolving the compound of formula 1 in an excess of an aqueous acid solution and precipitating the salt using a water-miscible organic solvent, for example, methanol, ethanol, acetone or acetonitrile.

[0076] In addition, the pharmaceutically acceptable salt may be an alkali metal salt (such as a sodium salt) or an alkaline earth metal salt (such as a potassium salt). The alkali metal salt or alkaline earth metal salt can be obtained, for example, by dissolving the compound of formula 1 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.

[0077] Additionally, the compounds of the present invention may have a chiral carbon center and may therefore exist in the form of R or S isomers, racemates, individual enantiomers or mixtures, individual diastereomers or mixtures, and all such stereoisomers and mixtures thereof may fall within the scope of the present invention.

[0078] Additionally, the compounds of the present invention may include prodrugs of the compound of formula 1. The prodrug may refer to a functional derivative of the compound and is readily convertible into the compound in vivo. Prodrugs may be useful in some situations because they may be more easily administered than the compound in question. For example, unlike the compound in question, these prodrugs may be available to the body by oral administration. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the compound in question. Prodrugs may also be converted into the drug in question by various mechanisms, including enzymatic processes and metabolic hydrolysis. An example of a prodrug is a compound in which the amino group of the compound in question is protected with a protecting group such as t-butyloxycarbonyl (Boc).

[0079] Additionally, the compound of the present invention may include a hydrate or solvate of the compound of the above formula 1. The hydrate or solvate may be prepared using a known method, and is preferably non-toxic and water-soluble. In particular, the hydrate or solvate may preferably be one in which 1 to 5 molecules of water or an alcoholic solvent (particularly, ethanol, etc.) are bound.

[0080]

[0081] As a specific example, specific examples of the compounds of the present invention are as follows:

[0082] 1) 1-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0083] 2) 3-((3R,4R)-1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-3,4-dimethylpiperidin-4-yl)phenol;

[0084] 3) 1-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0085] 4) (4-fluorophenyl)(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-4-yl)methanone;

[0086] 5) 1-(4-((4-fluorophenyl)(hydroxy)methyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0087] 6) 1-(4-(4-fluorobenzyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0088] 7) 1-((4-fluorobenzyl)(1-methylpiperidin-4-yl)amino)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0089] 8) 1-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0090] 9) Ethyl 2-((3S)-1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetate;

[0091] 10) Ethyl 2-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetate;

[0092] 11) t-Butyl 1'-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-[4,4'-bipiperidine]-1-carboxylate;

[0093] 12) 1-([4,4'-bipiperidin]-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol dihydrochloride;

[0094] 13) 1-(2-allylphenoxy)-3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)propan-2-ol;

[0095] 14) 1-(2-allylphenoxy)-3-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)propan-2-ol;

[0096] 15) 1'-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-N-isopropyl-[4,4'-bipiperidine]-1-carbothioamide;

[0097] 16) 3,3'-([4,4'-bipiperidine]-1,1'-diyl)bis(1-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol);

[0098] 17) 2-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetic acid;

[0099] 18) (E)-1-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxystyryl)phenoxy)propan-2-ol;

[0100] 19) (E)-1-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxystyryl)phenoxy)propan-2-ol;

[0101] 20) 4-((1-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid hydrochloride;

[0102] 21) 4-((1-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid hydrochloride;

[0103] 22) 1-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0104] 23) 4-((1-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid;

[0105] 24) 1-(5-(4-chloro-2-fluorophenyl)-2-methyl-7,8-dihydro-[1,3,4]thiadiazolo[2',3':2,3]imidazo[4,5-c]pyridin-6(5H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0106] 25) 1-(2-(3-methoxyphenethyl)phenoxy)-3-((3R,4R)-4-(3-methoxyphenyl)-3,4-dimethylpiperidin-1-yl)propan-2-ol;

[0107] 26) 2-((1S,4S)-4-(4-(3-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid;

[0108] 27) 2-((1S,4S)-4-(4-(3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid;

[0109] 28) 2-((1S,4S)-4-(4-(3-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid;

[0110] 29) 1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0111] 30) 9-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)-7-methyl-7,9-dihydro-8H-purin-8-one;

[0112] 31) 9-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)-7,9-dihydro-8H-purin-8-one;

[0113] 32) 1-((3R,4R)-3,4-dimethyl-4-(3-(2,2,2-trifluoroethoxy)phenyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0114] 33) 1-(4-(1H-Benzo[d]imidazol-1-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0115] 34) 1-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0116] 35) 1-(2,4-bis(trifluoromethyl)-5,8-dihydropyrido[3,4-d]pyrimidin-7(6H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0117] 36) 1-(2-(3-methoxyphenethyl)phenoxy)-3-(4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-yl)propan-2-ol;

[0118] 37) 1-(2-(3-methoxyphenethyl)phenoxy)-3-((S)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol;

[0119] 38) 1-(2-(3-methoxyphenethyl)phenoxy)-3-(4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)-1,4-diazepan-1-yl)propan-2-ol;

[0120] 39) 1-(4-(1H-Benzo[d]imidazol-2-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol;

[0121] 40) 1-(2-(3-methoxyphenethyl)phenoxy)-3-(1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)propan-2-ol;

[0122] 41) 1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)-1,4-diazepan-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; and

[0123] 42) 1-(2-(3-methoxyphenethyl)phenoxy)-3-(1'-(methylsulfonyl)-[4,4'-bipiperidin]-1-yl)propan-2-ol.

[0124] The present invention provides the use of a compound which is an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, as a serotonin antagonist (particularly a serotonin 2A antagonist).

[0125] In addition, the present invention provides a use of a compound which is an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, for the prevention or treatment of a disease associated with the activation of serotonin.

[0126] Here, “prevention” means any action that inhibits or delays the occurrence, spread, and recurrence of a hyperproliferative disease by administering the pharmaceutical composition, and “treatment” means any action that improves or beneficially changes the symptoms of the disease by administering the pharmaceutical composition.

[0127] The present invention also provides a use of a compound which is an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, for the manufacture of a drug for preventing or treating a disease associated with the activation of serotonin.

[0128] The present invention also provides a method for preventing or treating a disease associated with serotonin activation, comprising administering to a subject in need thereof a compound which is an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof. Here, the term "subject in need thereof" refers to all animals including humans, monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats and rabbits that have developed or may develop a disease associated with serotonin activation.

[0129] In addition, "administration" means providing a given substance to a subject in need thereof by any appropriate method, and the route of administration of the compound of the present invention can be administered through any general route as long as it can reach the target tissue.

[0130] In addition, the present invention provides a pharmaceutical composition for inhibiting serotonin activity, comprising as an active ingredient an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a prodrug thereof.

[0131] In addition, the present invention provides a pharmaceutical composition for preventing or treating a disease related to serotonin activation, comprising as an active ingredient an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a prodrug thereof.

[0132] In addition, the present invention provides a method for treating a disease associated with serotonin activation, comprising administering to a subject a compound which is an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof.

[0133] The present invention also provides a use of a compound which is an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, for preparing a drug for preventing or treating a disease associated with serotonin activation.

[0134] In addition, the present invention provides a use of a compound which is an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, for the prevention or treatment of diseases related to serotonin activation.

[0135] In the present invention, the treatment method and use may be applied in the same manner as those applied to pharmaceutical compositions.

[0136] The serotonin that the compound or pharmaceutical composition of the present invention is intended to inhibit is particularly serotonin 2A (5-HT 2A ) may be.

[0137] Additionally, the disease related to serotonin activation to be prevented or treated in the present invention may be a metabolic disease or cancer.

[0138] At this time, the metabolic disease may be any one selected from the group consisting of obesity, diabetes, hyperlipidemia, arteriosclerosis, fatty liver, steatohepatitis, fibrosis, and hypertension. Here, the fatty liver and steatohepatitis include alcoholic fatty liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH).

[0139] Meanwhile, metabolic-associated fatty liver disease (MASLD) may also be referred to as non-alcoholic fatty liver disease (NAFLD). Metabolic-associated steatohepatitis (MASH) may also be referred to as non-alcoholic steatohepatitis (NASH).

[0140] Additionally, the cancer may be any one selected from the group consisting of colon cancer, breast cancer, and ovarian cancer.

[0141] The pharmaceutical composition of the present invention may contain, as an active ingredient, an aminoalcohol derivative represented by the above chemical formula 1, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, or a prodrug thereof, in an amount of 0.1 to 90 wt%, specifically 0.1 to 75 wt%, and more specifically 1 to 50 wt%, based on the total weight of the composition.

[0142] The composition of the present invention may further comprise, in addition to the compound of the present invention, conventional, non-toxic, pharmaceutically acceptable additives formulated into a formulation according to conventional methods as active ingredients. For example, the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier, diluent, or excipient.

[0143] Examples of additives used in the composition of the present invention may include sweeteners, binders, solvents, solubilizers, wetting agents, emulsifiers, isotonic agents, absorbents, disintegrants, antioxidants, preservatives, lubricants, fillers, flavoring agents, and the like. For example, the additives may include lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, silica, talc, stearic acid, stearin, magnesium stearate, magnesium aluminosilicate, starch, gelatin, gum tragacanth, alginic acid, sodium alginate, methylcellulose, sodium carboxymethylcellulose, agar, water, ethanol, polyethylene glycol, polyvinylpyrrolidone, sodium chloride, calcium chloride, orange essence, strawberry essence, vanilla flavoring, and the like.

[0144] The composition of the present invention can be formulated in various formulations for oral administration (e.g., tablets, pills, powders, capsules, syrups or emulsions) or parenteral administration (e.g., intramuscular, intravenous or subcutaneous injection).

[0145] Preferably, the composition of the present invention can be formulated as a preparation for oral administration, and the additives used in this case can include cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid, magnesium stearate, calcium stearate, gelatin, talc, surfactants, suspending agents, emulsifiers, diluents, etc.

[0146] Specifically, solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations can be formulated by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc., into the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used.

[0147] In addition, liquid preparations for oral administration may include suspensions, solutions, emulsions, syrups, etc., and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.

[0148] Additionally, preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include withepsol, macrogol, Tween 61, cacao butter, laurin, and glycerogelatin. Meanwhile, injections may include conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifiers, stabilizers, and preservatives.

[0149] The compound or composition of the present invention may be administered to a patient in a therapeutically effective amount or a pharmaceutically effective amount.

[0150] Here, the term "therapeutically effective amount" or "pharmaceutically effective amount" refers to an amount of a compound or composition that is effective in preventing or treating a target disease, and is sufficient to treat the disease at a reasonable benefit / risk ratio applicable to medical treatment, and does not cause side effects. The level of the effective amount may be determined based on factors including the patient's health condition, type and severity of the disease, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, drugs used in combination or concurrently, and other factors well known in the medical field.

[0151] The compound or composition of the present invention can be administered as an individual therapeutic agent or in combination with another therapeutic agent, sequentially or simultaneously with conventional therapeutic agents, or in single or multiple doses. Considering all of the above factors, it is important to administer an amount that achieves maximum effect with the minimum amount possible without causing side effects, and this can be readily determined by those skilled in the art.

[0152] Specifically, the effective amount of the compound in the composition of the present invention may vary depending on the patient's age, sex, and weight, and is generally 0.1 to 1000 mg per kg of body weight, preferably 5 to 200 mg, administered daily or every other day, or divided into 1 to 3 times a day. However, since the amount may increase or decrease depending on the route of administration, severity of the disease, sex, body weight, age, etc., the scope of the present invention is not limited thereto.

[0153] Preferably, the compounds or compositions of the present invention may be administered for tumor therapy in combination with chemotherapy, radiation therapy, immunotherapy, hormonal therapy, bone marrow transplantation, stem cell replacement therapy, other biological therapies, surgical intervention, or a combination thereof. For example, the compounds or compositions of the present invention may be used as adjuvant therapy in conjunction with other long-term treatment strategies, or to maintain the patient's condition after tumor regression or chemoprevention in critically ill patients.

[0154] Preferably, the pharmaceutical composition of the present invention may further comprise one or more active ingredients, wherein the additional active ingredients are anti-proliferative compounds, such as aromatase inhibitors, anti-estrogens, topoisomerase I inhibitors, topoisomerase II inhibitors, microtubule-activating compounds, alkylating compounds, histone deacetylase inhibitors, compounds inducing cell differentiation processes, cyclooxygenase inhibitors, MMP inhibitors, mTOR inhibitors, anti-neoplastic anti-metabolites, platinum compounds, compounds targeting / reducing protein or lipid kinase activity, anti-angiogenic compounds, compounds targeting, reducing or inhibiting the activity of protein or lipid phosphatases, gonadorelin agonists, anti-androgens, methionine aminopeptidase inhibitors, bisphosphonates, biological response modifiers, anti-proliferative antibodies, heparanase inhibitors, inhibitors of Ras oncogenic isoforms. inhibitors, telomerase inhibitors, proteasome inhibitors, compounds used in the treatment of hematological malignancies, compounds targeting, decreasing or inhibiting the activity of Flt-3, Hsp90 inhibitors, kinesin spindle protein inhibitors, MEK inhibitors, leucovorin, EDG binding agents, anti-leukemic compounds, ribonucleotide reductase inhibitors, S-adenosylmethionine decarboxylase inhibitors, hemostatic steroids, corticosteroids, other chemotherapeutic compounds, photosensitizing compounds, but are not limited thereto.

[0155] [Example]

[0156] Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are provided only to facilitate a better understanding of the present invention, and the scope of the present invention is not limited by the examples.

[0157] Preparation of 2-((2-(3-methoxyphenethyl)phenoxy)methyl)oxirane

[0158]

[0159] 2-(3-methoxyphenethyl)phenol (200 g, 876 mmol, 1.0 eq) and 2-(chloromethyl)oxirane (162 g, 1.752 mmol, 2.0 eq) were placed in a 50 L reactor and dissolved in 3 L of acetonitrile. Cesium carbonate (570 g, 1.752 mmol, 2.0 eq) was added at room temperature and refluxed for 24 hours. The completion of the reaction was confirmed by TLC. The reaction temperature was cooled to room temperature. The mixture was filtered and washed with ethyl acetate. The organic layer was concentrated, and the residue was purified by column chromatography to obtain the title compound (201 g, 81%) as a liquid.

[0160] Preparation of 1-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol

[0161]

[0162] (Reaction scale of 5 g or less) 6-Fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (2.3 g, 10.443 mmol) was dissolved in isopropanol (50 mL), and 2-((2-(3-methoxyphenethyl)phenoxy)methyl)oxirane (2.97, 10.443 mmol) was added thereto. The resulting mixture was warmed and refluxed with stirring at 0 °C for 60 minutes. The temperature of the reaction mixture was reached to room temperature, warmed, and refluxed for 5 hours. The reaction mixture was then concentrated, and the residue was purified by column chromatography to obtain the title compound (3.8 g, 72%) as a brown solid.

[0163] (Reaction scale of 100 g or more) 6-Fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride (90 g, 352 mmol, 1.0 eq) and potassium carbonate (116 g, 844 mmol, 2.4 eq) were added to a 50 L reactor and stirred in 8 L of isopropanol at room temperature for 10 minutes. At the same temperature, 2-((2-(3-methoxyphenethyl)phenoxy)methyl)oxirane (100 g, 352 mmol, 1.0 eq) dissolved in 2 L of isopropanol was added and refluxed for 24 hours. The completion of the reaction was confirmed by TLC. The reaction temperature was cooled to room temperature. The mixture was filtered and washed with ethyl acetate. The organic layer was concentrated, and the residue was purified by column chromatography to obtain the title compound (134 g, 75%) as a solid.

[0164] Preparation of 4-((1-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid hydrochloride

[0165]

[0166] (Reaction scale of 5 g or less) 1-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol (1.2 g, 2.378 mmol) and succinic anhydride (951.94 mg, 9.512 mmol) were added to acetone (50 mL) and refluxed for 12 h. The completion of the reaction was confirmed by thin layer chromatography (TLC). The reaction mixture was concentrated, and the residue was purified by column chromatography, dissolved in ethyl acetate, and purged with dry HCl gas to pH 2. The reaction mixture was stirred for 2 h and filtered to obtain the title compound (1.1 g, 72%) as a white solid.

[0167] (Reaction scale of 100 g or more) 1-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol (100 g, 198 mmol 1.0 eq) and succinic anhydride (79 mg, 793 mmol, 4.0 eq) were added to a 50 L reactor and refluxed for 12 h. The completion of the reaction was confirmed by TLC. The reaction mixture was concentrated, and the residue was purified by column chromatography, dissolved in ethyl acetate, and purged with dry HCl gas to pH 2. The reaction mixture was stirred for 2 h and filtered to obtain the title compound (89 g, 70%) as a white solid.

[0168] The example compounds shown in Table 1 below were synthesized by the above synthetic route and similar routes.

[0169] NoStructural formulaChemical nameNMR1 1-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.67 (dd, J = 8.86, 5.19 Hz, 1H), 7.29 - 7.11 (m, 4H), 7.06 (dt, J = 8.85, 2.14 Hz, 1H), 6.95 - 6.85 (m, 2H), 6.81 (d, J = 7.32 Hz, 1H), 6.79 - 6.70 (m, 2H), 4.21 - 4.11 (m, 1H), 4.11 - 3.95 (m, 2H), 3.78 (s, 3H), 3.19 (d, J = 11.29 Hz, 1H), 3.15 - 3.05 (m, 1H), 2.99 (d, J = 11.29 Hz, 1H), 2.96 - 2.82 (m, 4H), 2.72 - 2.60 (m, 2H), 2.49 (dt, J = 10.83, 3.97 Hz, 1H), 2.23 (dt, J = 10.38, 1H), 2.19 - 1.95 (m, 4H).2 3-((3R,4R)-1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-3,4-dimethylpiperidin-4-yl)phenol 1 H NMR (300 MHz, CDCl3): δ 7.30 - 7.00 (m, 4H), 6.98 - 6.50 (m, 8H), 4.24 - 3.87 (m, 3H), 3.78 (s, 3H), 3.04 - 2.14 (m, 11H), 2.09 - 1.80 (m, 1H), 1.65 - 1.41 (m, 1H), 1.31 (s, 3H), 0.78 (d, J = 4.88 Hz, 3H).3 1-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.90 (d, J = 7.93 Hz, 1H), 7.81 (d, J = 8.24 Hz, 1H), 7.47 (t, J = 7.02 Hz, 1H), 7.36 (t, J = 7.02 Hz, 1H), 7.23 - 7.11 (m, 3H), 6.96 - 6.68 (m, 5H), 4.23 - 4.14 (m, 1H), 4.11 - 3.98 (m, 2H), 3.76 (s, 3H), 3.64 - 3.54 (m, 4H), 2.98 - 2.82 (m, 6H), 2.74 - 2.65 (m, 4H).4 (4-fluorophenyl)(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-4-yl)methanone 1 H NMR (300 MHz, CDCl3): δ 7.97 (dd, J = 5.34. 9.86 Hz, 2H), 7.23 - 7.08 (m, 5H), 6.92 - 6.84 (m, 2H), 6.80 (d, J = 7.63 Hz, 1H), 6.77 - 6.64 (m, 2H), 4.21 - 3.93 (m, 3H), 3.76 (s, 3H), 3.26 - 2.95 (m, 2H), 2.93 - 2.73 (m, 4H), 2.63 - 2.54 (m, 2H), 2.49 - 2.38 (m, 1H), 2.27 - 2.01 (m, 2H), 1.89 - 1.73 (m, 4H).5 1-(4-((4-fluorophenyl)(hydroxy)methyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.29 - 7.07 (m, 5H), 7.01 (t, J = 8.47 Hz, 2H), 6.87 (t, J = 7.33 Hz, 1H), 6.79 (dd, J = 16.94, 8.01 Hz, 1H), 6.74 - 6.54 (m, 3H), 4.32 (d, J = 7.56 Hz, 1H), 4.19 - 3.81 (m, 3H), 3.72 (s, 3H), 3.19 - 2.67 (m, 6H), 2.66 - 2.40 (m, 2H), 2.34 - 2.08 (m, 1H), 2.06 - 1.76 (m, 2H), 1.63 - 1.09 (m, 4H).6 1-(4-(4-fluorobenzyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 8.02 - 7.84 (m, 1H), 7.39 - 7.08 (m, 4H), 7.03 (t, J = 8.70 Hz, 1H), 6.96 - 6.57 (m, 6H), 4.65 - 4.34 (m, 2H), 4.32 - 3.52 (m, 4H), 3.72 (s, 3H), 3.49 - 3.18 (m, 2H), 3.04 - 2.52 (m, 6H), 2.39 - 1.42 (m, 6H).7 1-((4-fluorobenzyl)(1-methylpiperidin-4-yl)amino)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.26 - 7.06 (m, 5H), 6.96 (t, J = 8.77 Hz, 2H), 6.86 (dt, J = 1.14, 7.25 Hz, 1H), 6.81 - 6.70 (m, 4H), 3.98 -3.91 (m, 1H), 3.90 - 3.78 (m, 2H), 3.75 (s, 3H), 3.70 (d, J = 13.73 Hz, 1H), 3.58 (d, J = 13.73 Hz, 1H), 2.98 - 2.74 (m, 7H), 2.70 - 2.62 (m, 1H), 2.53 (tt, J = 3.81, 11.44 Hz, 1H), 2.26 (s, 3H), 1.99 - 1.73 (m, 4H), 1.70 - 1.56 (m, 2H).8 1-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 7.22 - 7.07 (m, 3H), 6.94 - 6.66 (m, 5H), 4.20 - 3.90 (m, 3H), 3.75 (s, 3H), 3.16 - 3.01 (m, 2H), 2.99 - 2.78 (m, 6H), 2.67 - 2.53 (m, 2H), 2.41 (dt, J = 11.14, 2.14 Hz, 1H), 2.28 - 1.84 (m, 5H), 1.32 (d, J = 6.71 Hz, 6H).9 Ethyl 2-((3S)-1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetate 1H NMR (300 MHz, CDCl3): δ 7.23- 7.03 (m, 3H), 6.92 - 6.64 (m, 5 H), 4.17 - 3.86 (m, 5H), 3.77 (s, 3H), 2.99- 2.63 (m, 6H), 2.59 - 2.43 (m, 2H), 2.35 - 1.92 (m, 5H), 1.89 - 1.47 (m, 3H), 1.24 (t, J = 6.87 Hz, 3H), 1.11 - 0.91 (m, 1H).10 Ethyl 2-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetate 1 H NMR (300 MHz, DMSO-d6): δ 7.18 - 7.04 (m, 3H), 6.90 (d, J = 7.93 Hz, 1H), 6.83 - 6.72 (m, 3H), 6.70 (dd, J = 7.78, 2.24 Hz, 1H), 4.73 (s, 1H), 4.04 - 3.82 (m, 5H), 3.68 (s, 3H), 2.85 - 2.61 (m, 7H), 2.39 - 2.26 (m, 1H),2.22 - 2.06 (m, 2H), 2.03 - 1.68 (m, 3H), 1.65 - 1.31 (m, 3H), 1.15 - 1.03 (m, 3H), 0.99 -0.81 (m, 1H).11 t-Butyl 1'-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-[4,4'-bipiperidine]-1-carboxylate 1H NMR (300 MHz, CDCl3): δ 7.22 - 7.07 (m, 3H), 6.92 - 6.77 (m, 3H), 6.76 - 6.69 (m, 2H), 4.25 - 3.89 (m, 5H), 3.76 (s, 3H), 3.06 (d, J = 10.99 Hz, 1H), 2.96 - 2.78 (m, 5H), 2.74 - 2.46 (m, 4H), 2.22 (t, J = 10.07 Hz, 1H), 1.93 (t, J = 10.07 Hz, 1H), 1.75 - 1.59 (m, 4H), 1.45 (s, 9H), 1.40 - 1.0 (m, 6H).12 1-([4,4'-bipiperidin]-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol dihydrochloride 1 H NMR (300 MHz, DMSO-d6): δ 9.99 (s, 1H), 8.95 - 8.55 (m, 2H), 7.20 - 7.06 (m, 3H), 6.92 (d, J = 8.24 Hz, 1H), 6.88 - 6.66 (m, 4H), 5.93 (d, J = 4.58 Hz, 1H), 4.50 - 4.38 (m, 1H), 4.04 - 3.88 (m, 2H), 3.72 (s, 3H), 3.61 - 3.51 (m, 2H), 3.38 - 3.10 (m, 4H), 3.04 - 2.68 (m, 8H), 1.89 - 1.69 (m, 4H), 1.68 - 1.45 (m, 2H), 1.44 - 1.25 (m, 4H).13 1-(2-allylphenoxy)-3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.66 (dd, J = 11.14, 4.88 Hz, 1H), 7.27 - 7.10 (m, 3H), 7.05 (dt, J = 8.85, 2.14 Hz, 1H), 6.96 - 6.77 (m, 2H), 6.07 - 5.85 (m, 1H), 5.10 - 4.92 (m, 2H), 4.20 - 3.91 (m, 3H), 3.55 - 3.24 (m, 2H), 3.23 - 2.92 (m, 3H), 2.62 (d, J = 6.41 Hz, 2H), 2.48 (dt, J = 10.53, 3.66 Hz, 1H), 2.24 (dt, J = 10.68, 3.66 Hz, 1H), 2.18 - 1.93 (m, 4H).14 1-(2-allylphenoxy)-3-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 7.90 (d, J = 8.24 Hz, 1H), 7.80 (d, J = 8.24 Hz, 1H), 7.46 (t, J = 8.24 Hz, 1H), 7.35 (t, J = 7.93 Hz, 1H), 7.23 - 7.10 (m, 2H), 6.91 (t, J = 7.63 Hz, 1H), 6.86 (d, J = 7.93 Hz, 1H), 6.07 - 5.92 (m, 1H), 5.12 - 5.0 (m, 2H), 4.24 - 4.13 (m, 1H), 4.09 - 3.97 (m, 2H), 3.68 - 3.51 (m, 4H), 3.41 (d, J = 6.41 Hz, 2H), 2.97 - 2.83 (m, 2H), 2.77 - 2.61 (m, 4H).15 1'-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-N-isopropyl-[4,4'-bipiperidine]-1-carbothioamide 1H NMR (300 MHz, CDCl3): δ 7.22 - 7.04 (m, 3H), 6.92 - 6.65 (m, 5H), 5.21 (d, J = 7.63 Hz, 1H), 4.73 -4.50 (m, 3H), 4.15 - 3.87 (m, 3H), 3.76 (s, 3H), 3.06 (d, J = 10.92 Hz, 1H), 2.98 - 2.72 (m, 7H), 2.64 - 2.44 (m, 2H), 2.23 (t, J 11.29 Hz, 1H), 1.94 (t, J = 11.29 Hz, 1H), 1.76 (d, J = 12.51 Hz, 2H), 1.68 (d, J = 12.51 Hz, 2 H), 1.43 - 1.03 (m, 6H).16 3,3'-([4,4'-bipiperidine]-1,1'-diyl)bis(1-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol) 1 H NMR (300 MHz, DMSO-d6): δ 7.20 - 7.07 (m, 6H), 6.93 (d, J = 7.79 Hz, 2H), 6.88 - 6.65 (m, 8H), 5.91 (s, 2H), 4.50 - 4.22 (m, 2H), 4.01 - 3.84 (m, 4H), 3.69 (s, 6H), 3.60 - 3.45 (m, 2H), 3.36 - 2.70 (m, 23H), 1.86 - 1.24 (m, 5H).17 2-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetic acid 1 H NMR (300 MHz, DMSO-d6): δ 7.23 - 7.03 (m, 3H), 6.95 (d, J = 8.24 Hz, 1H), 6.89 - 6.63 (m, 4H), 4.27 - 3.83 (m, 3H), 3.72 (s, 3H), 3.20 - 1.40 (m, 17 H).18 (E)-1-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxystyryl)phenoxy)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.65 (dd, J = 4.96, 8.71 Hz, 1H), 7.57 (dd, J = 1.53, 7.63 Hz, 1H), 7.46 (d, J = 16.40 Hz, 1H), 7.33 -7.19 (m, 3H), 7.18 - 6.87 (m, 6H), 6.79 (dd, J = 1.91, 7.82 Hz, 1H), 4.26 - 3.96 (m, 3H), 3.82 (s, 3H), 3.19 (d, 11.44 Hz, 1H), 3.16 - 3.04 (m, 1H), 3.00 (d, J = 11.44 Hz, 1H), 2.73 - 2.61 (m, 2H), 2.49 (dt, J = 3.81, 10.87 Hz, 1H), 2.28 - 2.01 (m, 5H).19 (E)-1-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxystyryl)phenoxy)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 7.88 (d, J = 8.01 Hz, 1H), 7.79 (d, J = 8.01 Hz, 1H), 7.59 (d, J = 6.10 Hz, 1H), 7.55 - 7.42 (m, 2H), 7.35 (t, J = 8.01 Hz, 1H), 7.32 - 7.06 (m, 5H), 6.99 (t, J = 7.25 Hz, 1H), 6.92 (d, J = 8.01 Hz, 1H), 6.80 (dd, J = 2.29, 8.20 Hz, 1H), 4.28 - 4.19 (m,1H), 4.15 - 4.02 (m, 2H), 3.82 (s, 3H), 3.69 - 3.47 (m, 4H), 2.95 - 2.84 (m, 2H), 2.79 - 2.62 (m, 4H).20 4-((1-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid hydrochloride 1H NMR (300 MHz, DMSO-d6): δ 12.28 (s, 1H), 10. 88 (s, 1H), 8.26 - 8.14 (m, 1H), 7.73 (dd, J = 7.93, 1.83 Hz, 1H), 7.35 (t, J = 8.54 Hz, 1H), 7.24 - 7.08 (m, 3H), 6.97 (d, J = 8.24 Hz, 1H), 6.92 - 6.65 (m, 4H), 5.71 (s, 1H), 4.19 (s, 2H), 3.72 (s, 3H), 3.76 - 3.57 (m, 3H), 3.54 - 3.12 (m, 4H), 2.91 - 2.61 (m, 5H), 2.59 - 2.13 (m, 7H).21 4-((1-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid hydrochloride 1 H NMR (300 MHz, DMSO-d6): δ 11.68 (s, 1H), 8.13 - 8.01 (m, 2H), 7.62 - 7.37 (m, 2H), 7.19 - 7.03 (m, 3H), 6.97 - 6.88 (m, 1H), 6.87 - 6.61 (m, 4H), 5.77 - 5.63 (m, 1H), 4.16 (s, 2H), 4.10 - 3.92 (m, 2H), 3.66 (s, 3H), 3.74 - 3.26 (m, 7H), 2.91 - 2.39 (m, 10H).22 1-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.21 - 6.95 (m, 6H), 6.93 - 6.81 (m, 2H), 6.78 (d, J = 7.63 Hz, 1H), 6.75 - 6.66 (m, 2H), 4.15 - 3.92 (m, 3H), 3.73 (s, 3H), 3.56 - 2.32 (m, 13H), 1.36 - 1.20 (m, 3H).23 4-((1-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid 1 H NMR (300 MHz, DMSO-d6): δ 12.26 (s, 1H), 11.25 (s, 1H), 7.31 - 7.05 (m, 6H), 6.96 - 6.64 (m, 5H), 5.74 - 5.59 (m, 1H), 4.11 (s, 2H), 3.67 (s, 3H), 3.80 - 3.09 (m, 7H), 3.06 - 2.54 (m, 7H), 2.53 - 2.33 (m, 3H), 1.38 - 1.17 (m, 3H).24 1-(5-(4-chloro-2-fluorophenyl)-2-methyl-7,8-dihydro-[1,3,4]thiadiazolo[2',3':2,3]imidazo[4,5-c]pyridin-6(5H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1 H NMR (300 MHz, DMSO-d6): δ 7.42 - 7.30 (m, 1H), 7.15 - 7.0 (m, 4H), 6.96 - 6.84 (m, 2H), 6.82 - 6.64 (m, 4H), 4.85 (dt, J = 4.58, 2.14, 1H), 4.11 - 3.72 (m, 4H), 3.72 (s, 3H), 3.65 (t, J = 2.75 Hz, 2H), 3.25 - 2.40 (m, 8H), 2.48 (s, 3H).25 1-(2-(3-methoxyphenethyl)phenoxy)-3-((3R,4R)-4-(3-methoxyphenyl)-3,4-dimethylpiperidin-1-yl)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 7.29 - 7.07 (m, 4H), 6.95 - 6.67 (m, 8H), 4.19 - 3.91 (m, 3H), 3.80 (s, 3H), 3.77 (s, 3H), 3.05 - 2.23 (m, 11H), 2.09 - 1.98 (m, 1H), 1.62 (d, J = 12.97 Hz, 1H), 1.33 (s, 3H), 0.80 (dd, J = 2.67, 6.87 Hz, 3H).26 2-((1S,4S)-4-(4-(3-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid 1 H NMR (300 MHz, DMSO-d6): δ 11.88 (s, 1H), 8.01 (d, J = 6.10 Hz, 2H), 7.60 - 7.31 (m, 2H), 7.08 (d, J = 6.10 Hz, 2H), 6.81 (d, J = 5.49 Hz, 2H), 4.92 (s, 1H), 4.11 - 3.65 (m, 3H), 3.63 - 3.21 (m, 5H), 2.91 - 2.27 (m, 6H), 2.12 (d, J = 4.27 Hz, 2H), 1.89 - 1.60 (m, 5H), 1.52 - 0.98 (m, 4H).27 2-((1S,4S)-4-(4-(3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid 1H NMR (300 MHz, DMSO-d6): δ 12.05 (s, 1H), 8.13 (s, 1H), 7.69 (dd, J = 2.14, 9.00 Hz, 1H), 7.31 (t, J = 9.16 Hz, 1H), 7.11 (d, J = 8.54 Hz, 2H), 6.84 (d, J = 8.54 Hz, 2H), 6.08 - 5.70 (m, 1H), 4.46 - 4.25 (m, 1H), 3.97 - 3.81 (m, 2H), 3.80 - 2.85 (m, 7H), 2.41 - 2.12 (m, 5H), 2.09 (d, J = 6.71 Hz, 2H), 1.82 - 1.60 (m, 5H), 1.48 - 1.28 (m, 2H), 1.16 - 0.96 (m, 2H).28 2-((1S,4S)-4-(4-(3-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid 1 H NMR (300 MHz, DMSO-d6): δ 11.93 (s, 1H), 7.20 (d, J = 15.26 Hz, 3H), 7.09 (d, J = 8.54 Hz, 2H), 6.81 (d, J = 8.24 Hz, 2H), 5.92 (s, 1H), 4.46 - 4.18 (m, 1H), 3.95 - 2.76 (m, 11H), 2.41 - 2.27 (m, 1H), 2.09 (d, J = 6.71 Hz, 2H), 1.81 - 1.58 (m, 5H), 1.46 - 1.22 (m, 5H), 1.16 - 0.96 (m, 2H).29 1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.51 (d, J = 7.02 Hz, 1H), 7.39 (d, J = 7.63 Hz, 1H), 7.37 - 7.26 (m, 3H), 7.23 - 7.04 (m, 5H), 6.96 - 6.83 (m, 3H), 6.80 (d, J = 7.32 Hz, 1H), 6.77 - 6.67 (m, 2H), 4.21 - 3.94 (m, 3H), 3.75 (s, 3H), 3.27 - 3.22 (m, 4H), 3.05 - 2.41 (m, 10H).30 9-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)-7-methyl-7,9-dihydro-8H-purin-8-one 1 H NMR (300 MHz, CDCl3): δ 8.65 (s, 1H), 8.16 (s, 1H), 7.20 - 6.98 (m, 3H), 6.96 -6.58 (m, 5H), 4.69 - 4.50 (m, 1H), 4.18 - 3.88 (m, 3H), 3.73 (s, 3H), 3.43 (s, 3H), 3.27 - 2.75 (m, 7H), 2.74 - 2.32 (m, 3H), 2.25 - 1.61 (m, 4H).31 9-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)-7,9-dihydro-8H-purin-8-one 1 H NMR (300 MHz, CDCl3): δ 8.68 (s, 1H), 8.33 (s, 1H), 7.20 - 7.04 (m, 3H), 6.92 - 6.80 (m, 2H), 6.75 (dd, J = 4.27, 7.02 Hz, 1H), 6.72 - 6.60 (m, 2H), 4.69 - 4.54 (m, 1H), 4.21 -3.93 (m, 3H), 3.72 (s, 3H), 3.28 - 2.98 (m, 2H), 2.96 - 2.38 (m, 8H), 2.24 - 2.10 (m, 1H), 1.96 - 1.64 (m, 3H).32 1-((3R,4R)-3,4-dimethyl-4-(3-(2,2,2-trifluoroethoxy)phenyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 7.32 - 7.10 (m, 5H),6.98 (d, J = 7.79 Hz, 1H), 6.95 - 6.67 (m, 6H), 4.35 (dq, J = 2.29, 8.24 Hz, 2H), 4.25 - 3.93 (m, 3H), 3.78 (s, 3H), 3.08 - 2.24 (m, 11H), 2.11 - 1.97 (m, 1H), 1.63 (d, J = 13.28 Hz, 1H), 1.34 (s, 3H), 0.80 (d, J = 6.87 Hz, 3H).33 1-(4-(1H-Benzo[d]imidazol-1-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1 H NMR (300 MHz, DMSO-d6): δ 8.33 (s, 1H), 7.64 (dd, J = 2.75, 7.63 Hz, 2H), 7.30 - 7.10 (m, 5H), 6.93 (d, J = 8.24 Hz, 1H), 6.85 - 6.74 (m, 3H), 6.69 (d, J = 8.24 Hz, 1H), 4.86 (d, J = 4.27 Hz, 1H), 4.39 - 4.25 (m, 1H), 4.05 - 3.87 (m, 3H), 3.67 (s, 3H), 3.10 - 2.96 (m, 2H), 2.86 - 2.72 (m, 4H), 2.65 - 2.41 (m, 2H), 2.33 - 2.19 (m, 2H), 2.11 - 1.87 (m, 4H).34 1-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.29 - 7.07 (m, 4H), 6.97 - 6.70 (m, 6H), 4.27 - 4.15 (m, 1H), 4.13 - 3.98 (m, 2H), 3.78 (s, 3H), 3.72 - 3.32 (m, 2H), 3.12 - 2.73 (m, 10 H).35 1-(2,4-bis(trifluoromethyl)-5,8-dihydropyrido[3,4-d]pyrimidin-7(6H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1 H NMR (300 MHz, DMSO-d6): δ 7.21 - 7.09 (m, 3H), 6.94 (d, J = 7.32 Hz, 1H), 6.87 - 6.76 (m, 3H), 6.72 (d, J = 7.93 Hz, 1H), 5.06 (dd, J = 4.73, 2.14 Hz, 1H), 4.19 - 4.09 (m, 1H), 4.05 - 3.90 (m, 2H), 3.97 (s, 2H), 3.70 (s, 2H), 3.08 - 3.0 (m, 2H), 2.95 - 2.66 (m, 8H).36 1-(2-(3-methoxyphenethyl)phenoxy)-3-(4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-yl)propan-2-ol 1 H NMR (300 MHz, DMSO-d6): δ 7.60 (s, 1H), 7.22 - 7.1 0 (m, 3H), 6.95 (d, J = 8.24 Hz, 1H), 6.88 - 6.76 (m, 6H), 6.70 (dd, J = 17.85, 8.24 Hz, 2H), 6.32 (s, 1H), 4.88 (dd, J = 3.05, 1.53 Hz, 1H), 4.09 - 3.87 (m, 3H), 3.70 (s, 3H), 2.92 - 2.74 (ml 4H), 2.64 - 2.42 (m, 10 H), 2.26(s, 3H).37 1-(2-(3-methoxyphenethyl)phenoxy)-3-((S)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 7.45 -6.98 (m, 11H), 6.98 - 6.65 (m, 6H), 4.85 - 4.63 (m, 1H), 4.29 - 3.91 (m, 2H), 3.77 (s, 3H), 3.89 - 3.72 (m, 1H), 3.52 - 2.61 (m, 10 H).38 1-(2-(3-methoxyphenethyl)phenoxy)-3-(4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)-1,4-diazepan-1-yl)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 7.27 - 7.05 (m,4H), 7.04 - 6.65 (m, 8H), 6.61 (d, J = 7.63 Hz, 1H), 6.32 (s, 1H), 5.00 (s, 1H), 4.14 - 3.88 (m, 3H), 3.74 (s, 3H), 3.84 - 3.52 (m, 4H), 3.15 - 2.55 (m, 10 H), 2.30 (s, 3H), 2.07 - 1.82 (m, 2H).39 1-(4-(1H-Benzo[d]imidazol-2-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1 H NMR (300 MHz, CDCl3): δ 7.58 - 7.42 (m, 2H), 7.23 - 7.05 (m, 5H), 6.95 - 6.61 (m, 5H), 4.21 - 3.87 (m, 3H), 3.70 (s, 3H), 3.18 - 2.76 (m, 7H), 2.68 - 2.46 (m, 2H), 2.42 - 2.26 (m, 1H), 2.20 - 1.92 (m, 5H).40 1-(2-(3-methoxyphenethyl)phenoxy)-3-(1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)propan-2-ol 1H NMR (300 MHz, DMSO-d6): δ 10.68 (s, 1H), 7.34 (d, J = 6.10 Hz, 1H), 7.25 (dd, J = 7.93, 1.83 Hz, 1H), 7.21 - 7.10 (m, 3H), 7.03 - 6.89 (m, 3H), 6.87 - 6.78 (m, 3H), 6.73 (d, J = 8.24 Hz, 1H), 4.96 (t, J = 2.75 Hz, 1H), 4.18 - 4.06 (m, 1H), 4.06 - 3.92 (m, 2H), 3.75 - 3.69 (m, 2H), 3.70 (s, 3H), 2.93 - 2.77 (m, 7H), 2.75 - 2.63 (m, 3H).41 1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)-1,4-diazepan-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol 1 H NMR (300 MHz, DMSO-d6): δ 7.50 (s, 1H), 7.44 - 7.28 (m, 4H), 7.18 - 7.08 (m, 4H), 6.92 (d, J = 7.32 Hz, 2H), 6.86 - 6.66 (m, 5H), 4.77 (s, 1H), 4.20 - 3.83 (m, 3H), 3.68 (s, 3H), 3.64 - 3.16 (m, 4H), 3.05 - 2.55 (m, 10 H), 2.20 - 1.40 (m, 2H).42 1-(2-(3-methoxyphenethyl)phenoxy)-3-(1'-(methylsulfonyl)-[4,4'-bipiperidin]-1-yl)propan-2-ol 1H NMR (300 MHz, CDCl3): δ 7.22 - 7.04 (m, 3H), 6.92 - 6.64 (m, 5H), 4.15 - 3.89 (m, 3H), 3.82 (d, J = 11.90 Hz, 2H), 3.76 (s, 3H), 3.07 (d, J = 10.66 Hz, 1H), 2.96 - 2.78 (m, 5H), 2.75 (s, 3H), 2.64 - 2.46 (m, 4H), 2.23 (t, J = 11.23 Hz, 1H), 1.95 (t, J = 11.60 Hz, 1H), 1.81 (d, J = 12.82 Hz, 2H), 1.69 (d,12.21 Hz, 2H), 1.43 - 1.03 (m, 6H).

[0170]

[0171] Experimental example: Measurement of inhibitory activity against serotonin 2A

[0172] For the compounds synthesized in the above examples, serotonin 2A (5-HT 2A ) was measured for inhibitory activity (in vitro), and the results are shown in Table 2 below.

[0173] Example NoIC 50 (nM)10.231620.0949730.887142.48450.953882.4431117.53132.379180.6305190. 65472492.58250.32630.62275.82961.19300.2035310.0497325.0433239.63418.36

[0174] As shown in Table 2 above, the inhibitory activity of the compounds of the examples against serotonin was confirmed.

Claims

1. A compound which is an amino alcohol derivative represented by the following chemical formula 1, a pharmaceutically acceptable salt, stereoisomer or prodrug thereof: [Chemical Formula 1] In the above formula L 1 A 5 to 15 membered heterocycle having one or more heteroatoms including N, or and; R 1 A 5 to 15 membered heterocycle having one or more heteroatoms, phenyl, -L 2 -phenyl, or -L 2 -R A and; R 2 is H, C 1-10 Alkyl, or -L 2 -R A and; R 3 Is , , , , or And, The above heteroatom is selected from N, S and O; the heterocycle and phenyl are each R A and R B with or without one or more substituents selected from; R A and R B are each independently H, halogen, hydroxy, oxo, methylsulfonyl, C 1-6 Alkyl, C 1-6 Alkoxy, haloC 1-6 Alkyl, haloC 1-6 Alkoxy, C 1-6 Alkoxycarbonyl, -C 1-6 Alkylene-COOH, benzyl, halobenzyl, , or , and; L 2 is a single bond, -C(=O)-, -CH(-OH)-, or -CH2-.

2. In paragraph 1, L 1 silver , , , , , , , , , , , or and here R A is H, C 1-6 Alkyl, haloC 1-6 A compound which is alkyl, benzyl, or halobenzyl.

3. In paragraph 1, R 1 silver , , , , , , , , , , , , or -L 2 -R A and here R A and R B are each independently H, halogen, hydroxy, oxo, methylsulfonyl, C 1-6 Alkyl, C 1-6 Alkoxy, haloC 1-6 Alkyl, haloC 1-6 Alkoxy, C 1-6 Alkoxycarbonyl, -C 1-6 alkylene-COOH, , or , and L 2 is a compound having a single bond, -C(=O)-, -CH(-OH)-, or -CH2-.

4. In paragraph 1, R 2 is H or In, compound.

5. In paragraph 1, The above amino alcohol derivative is a compound represented by the following chemical formula 1a: [Chemical Formula 1a] In the above formula is a single bond or a double bond; L 1 silver , , , , , , , , , , , or And, R 1 silver , , , , , , , , , , , , or -L 2 -R A and; R 2 is H or and; R A and R B are each independently H, halogen, hydroxy, oxo, methylsulfonyl, C 1-6 Alkyl, C 1-6 Alkoxy, haloC 1-6 Alkyl, haloC 1-6 Alkoxy, C 1-6 Alkoxycarbonyl, -C 1-6 Alkylene-COOH, benzyl, halobenzyl, , or , and; L 2 is a single bond, -C(=O)-, -CH(-OH)-, or -CH2-.

6. In paragraph 1, The above amino alcohol derivative is a compound represented by the following chemical formula 1b: [Chemical Formula 1b] In the above formula L 1 silver , or and; R 1 Silver halogen, or and; R A is a halogen.

7. In paragraph 1, The above amino alcohol derivative is a compound represented by the following chemical formula 1c: [Chemical Formula 1c] In the above formula L 1 silver or and; R 1 Silver halogen, or and; R A is a halogen.

8. In paragraph 1, The above compound is one compound selected from the group below: 1) 1-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 2) 3-((3R,4R)-1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-3,4-dimethylpiperidin-4-yl)phenol; 3) 1-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 4) (4-fluorophenyl)(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-4-yl)methanone; 5) 1-(4-((4-fluorophenyl)(hydroxy)methyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 6) 1-(4-(4-fluorobenzyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 7) 1-((4-fluorobenzyl)(1-methylpiperidin-4-yl)amino)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 8) 1-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 9) Ethyl 2-((3S)-1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetate; 10) Ethyl 2-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetate; 11) t-Butyl 1'-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-[4,4'-bipiperidine]-1-carboxylate; 12) 1-([4,4'-bipiperidin]-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol dihydrochloride; 13) 1-(2-allylphenoxy)-3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)propan-2-ol; 14) 1-(2-allylphenoxy)-3-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)propan-2-ol; 15) 1'-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)-N-isopropyl-[4,4'-bipiperidine]-1-carbothioamide; 16) 3,3'-([4,4'-bipiperidine]-1,1'-diyl)bis(1-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol); 17) 2-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)acetic acid; 18) (E)-1-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxystyryl)phenoxy)propan-2-ol; 19) (E)-1-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxystyryl)phenoxy)propan-2-ol; 20) 4-((1-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid hydrochloride; 21) 4-((1-(4-(Benzo[d]isothiazol-3-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid hydrochloride; 22) 1-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 23) 4-((1-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-yl)oxy)-4-oxobutanoic acid; 24) 1-(5-(4-chloro-2-fluorophenyl)-2-methyl-7,8-dihydro-[1,3,4]thiadiazolo[2',3':2,3]imidazo[4,5-c]pyridin-6(5H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 25) 1-(2-(3-methoxyphenethyl)phenoxy)-3-((3R,4R)-4-(3-methoxyphenyl)-3,4-dimethylpiperidin-1-yl)propan-2-ol; 26) 2-((1S,4S)-4-(4-(3-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid; 27) 2-((1S,4S)-4-(4-(3-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid; 28) 2-((1S,4S)-4-(4-(3-((R)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-2-hydroxypropoxy)phenyl)cyclohexyl)acetic acid; 29) 1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 30) 9-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)-7-methyl-7,9-dihydro-8H-purin-8-one; 31) 9-(1-(2-hydroxy-3-(2-(3-methoxyphenethyl)phenoxy)propyl)piperidin-3-yl)-7,9-dihydro-8H-purin-8-one; 32) 1-((3R,4R)-3,4-dimethyl-4-(3-(2,2,2-trifluoroethoxy)phenyl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 33) 1-(4-(1H-Benzo[d]imidazol-1-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 34) 1-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 35) 1-(2,4-bis(trifluoromethyl)-5,8-dihydropyrido[3,4-d]pyrimidin-7(6H)-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 36) 1-(2-(3-methoxyphenethyl)phenoxy)-3-(4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-yl)propan-2-ol; 37) 1-(2-(3-methoxyphenethyl)phenoxy)-3-((S)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol; 38) 1-(2-(3-methoxyphenethyl)phenoxy)-3-(4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)-1,4-diazepan-1-yl)propan-2-ol; 39) 1-(4-(1H-Benzo[d]imidazol-2-yl)piperidin-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; 40) 1-(2-(3-methoxyphenethyl)phenoxy)-3-(1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)propan-2-ol; 41) 1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)-1,4-diazepan-1-yl)-3-(2-(3-methoxyphenethyl)phenoxy)propan-2-ol; and 42) 1-(2-(3-methoxyphenethyl)phenoxy)-3-(1'-(methylsulfonyl)-[4,4'-bipiperidin]-1-yl)propan-2-ol.

9. A pharmaceutical composition for preventing or treating a disease related to serotonin activation, comprising the compound of paragraph 1 as an active ingredient.

10. In paragraph 9, A pharmaceutical composition, wherein the disease associated with the above serotonin activation is a metabolic disease or cancer.

11. In paragraph 10, A pharmaceutical composition, wherein the metabolic disease is any one selected from the group consisting of obesity, diabetes, hyperlipidemia, arteriosclerosis, fatty liver, steatohepatitis, fibrosis, and hypertension.

12. In paragraph 10, A pharmaceutical composition, wherein the cancer is any one selected from the group consisting of colon cancer, breast cancer, and ovarian cancer.

13. A method for treating a disease associated with serotonin activation, comprising administering to a subject a compound of claim 1.

14. Use of the compound of claim 1 for the manufacture of a medicament for the prevention or treatment of a disease associated with serotonin activation.

15. Use of the compound of paragraph 1 for the prevention or treatment of diseases related to serotonin activation.

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