KR101761767B1 - Composition for decreasing nephrotoxicity diseases comprising chalcone derivatives - Google Patents

Abstract

상기 화학식 1에서 A는

,

,

또는

이고,
상기 R₁ 내지 R₁₅ 는 각각 독립적으로 수소원자; C₁ 내지 C₆ 알콕시; C₁ 내지 C₆ 알킬; 페닐; 불소, 염소, 브롬 및 요오드로 구성되는 군으로부터 선택되는 할로겐; 니트로(-NO₂); 알릴옥시(allyloxy); 또는 디메틸아민(-N(CH₃)₂)일 수 있다.
본 명세서에 따른 조성물은 신장 독성을 나타내는 약물에 의한 신장 세포의 손상을 보호하고 신장 독성을 감소시켜 신장을 보호할 수 있으며, 따라서 약물성 신장 질환을 예방하거나 치료할 수 있는 효과를 나타낸다.The present invention relates to a novel chalcone derivative compound and a composition for reducing nephrotoxicity comprising the chalcone derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient. The chalcone derivative compound of the present specification may have a structure of the following formula (1).
[Chemical Formula 1]

In the above formula (1), A represents

,

,

or

ego,
Each of R ₁ to R ₁₅ independently represents a hydrogen atom; C ₁ to C ₆ alkoxy; C ₁ to C ₆ alkyl; Phenyl; Halogen selected from the group consisting of fluorine, chlorine, bromine and iodine; Nitro (-NO ₂ ); Allyloxy; Or may be a dimethylamino _{(-N (CH 3) 2)} .
The composition according to the present invention can protect the kidney by protecting the kidney cells from damage by the drug showing renal toxicity and reducing the renal toxicity, thus exhibiting the effect of preventing or treating drug-induced kidney disease.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for decreasing nephrotoxicity including chalcone derivatives,

The present disclosure relates to compositions for reducing nephrotoxicity.

Kidney is an important excretory organ that excretes urine in the body. Several medicines and environmental pollutants are toxic to the kidneys. Typical drugs causing renal toxicity include non-steroidal anti-inflammatory analgesics such as phenacetin, aspirin, and indomethacin; Anticancer agents such as puromycin, daunomycin, cyclophosphamide, penicillamine, adriamycin and cisplatin, immunosuppressants, amikacin, gentamycin, kanamycin, neomycin, sisomycin, streptomycin, tobramycin Aminoglycoside antibiotics; Cephalosporin antibiotics; Carbapenem antibiotics such as imipenem and melopenem; Heavy metals such as cadmium, lead, mercury, and chromium; And inorganic and organic heavy metal compounds, compounds such as chloroform, D-serine, sulfonamide, 2-bromoethylene and hydrobromide, or fungal toxins such as okara-toxin and citrinin. Renal diseases caused by nephrotoxicity to these drugs include nephritis, pyelonephritis, nephrotic syndrome, renal cancer, acute pyelonephritis, chronic pyelonephritis, renal tuberculosis, urinary tract infection, urinary stone, ureter stones, acute renal failure, chronic renal failure, Diabetic nephropathy, chronic glomerulonephritis, acute progressive nephritis, nephrotic syndrome, pancreatic glomerulosclerosis, membranous sinusitis, or membranous proliferative glomerulonephritis.

Chalcone (β-phenylacrylophenone) is a substance possessing an aromatic ketone. It is known as a kind of plant secondary metabolite. It is known as a substance having various effects such as antimicrobial, anti-cancer and anti-inflammation.

KR 10-2009-0073522 A KR 10-2008-0014365 A KR 10-2014-0005081 A

Accordingly, it is an object of the present invention to provide a composition for the prevention or treatment of nephrotoxic diseases which can effectively prevent or treat renal toxicity caused by a renal toxicity inducing substance to solve the above problems.

The present invention also aims to provide a novel chalcone derivative compound.

To achieve the above object, the present invention provides a novel chalcone derivative compound and a composition for reducing nephrotoxicity comprising the chalcone derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient.

The composition according to one aspect of the present invention exhibits an effect of protecting the kidney or kidney cells from the kidney toxic inducer, thereby enhancing the survival rate of kidney cells which can be reduced by the kidney toxicity inducer. Accordingly, the composition according to one aspect of the present invention has an effect of preventing or treating renal disease by reducing nephrotoxicity.

In one aspect, the present invention may relate to a novel chalcone derivative having a structure represented by the following formula (1) or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

,

,

또는

이고,A is

,

,

or

ego,

Each of R ₁ to R ₁₅ independently represents a hydrogen atom; C ₁ to C ₆ alkoxy; C ₁ to C ₆ alkyl; Phenyl; Halogen selected from the group consisting of fluorine, chlorine, bromine and iodine; Nitro (-NO ₂ ); Allyloxy; Or a dimethylamino _{(-N (CH 3) 2)} .

Specifically, in one aspect of the present invention, R ₁ , R _4, and R ₅ are hydrogen atoms; R ₂ and R ₃ are each independently a C ₁ to C ₆ alkoxy, nitro (-NO ₂ ), or a halogen selected from the group consisting of fluorine, chlorine, bromine and iodine; R ₆ to R ₉ are hydrogen atoms; R ₁₀ is a hydrogen atom; R ₁₁ to R ₁₄ are each independently selected from the group consisting of hydrogen, C ₁ to C ₆ alkoxy, C ₁ to C ₆ alkyl, phenyl, dimethylamine (-N (CH ₃ ) ₂ ), allyloxy or fluorine, Bromine, and iodine; R ₁₅ can be C ₁ to C ₆ alkyl.

Specifically, in one aspect of the invention, R ₂ and R ₃ are each independently a hydrogen atom, a methoxy, a nitro (-NO ₂ ), or a halogen selected from the group consisting of fluorine, chlorine, and bromine; R ₁₁ to R ₁₄ are each independently a hydrogen atom, methoxy, methyl, chlorine, bromine, phenyl, allyloxy or dimethylamine (-N (CH ₃ ) ₂ ); R ₁₅ may be ethyl.

In one aspect of the present invention, typical examples of the compound represented by Formula 1 are as follows:

1) E) -1- (4-chlorophenyl) -3- (1H-indol-3-yl) prop-

2) (E) -1- (4-chlorophenyl) -3- (3,4-dimethoxyphenyl) prop-

3) (E) -1- (4-chlorophenyl) -3- (4-dimethylamino) phenyl) prop-

4) (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-chlorophenyl) prop-

5) Synthesis of (E) -1- (4-chlorophenyl) -3- (para-tolyl)

6) (E) -3- (4-Chlorophenyl) -1- (3-methoxyphenyl) prop-

7) (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (3- methoxyphenyl) prop-

8) (E) -1- (4-bromophenyl) -3- (4- (dimethylamino) phenyl) prop-

 9) (E) -1- (4-Bromophenyl-3,5-dimethoxy) -1- (3,4- (dimethoxyphenyl)

10) (E) -1- (4-bromophenyl) -3- (1H-indol-3-yl) prop-

11) (E) -3- (4-dimedylamino) phenyl) -1- (4-fluorophenyl) prop-

12) (E) -3- (3,4-dimethoxy) phenyl) -1- (4-fluorophenyl) prop-

13) (E) -1- (4-bromophenyl) -3- (3,4-dimethoxyphenyl) prop-

14) (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-bromophenyl) prop-

      15) Synthesis of (E) -1- (4-fluorophenyl) -3- (3,4,5-trimethoxyphenyl) prop-

      16) (E) -3- (4- (dimethylamino) phenyl) -1- (4-nitrophenyl) prop-

      17) (E) -1- (4-fluorophenyl) -3- (1H-indol-3-yl) prop-

18) (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-fluorophenyl) prop-

19) (E) -1- (3,4-dimethoxyphenyl) -3- (4- (dimethoxyamino) phenyl) prop-

20) (E) -3- (4- (dimethoxyamino) phenyl) -1- (3-methoxyphenyl) prop-

21) (E) -1- (3,4-dimethoxyphenyl) -3- (naphthyl-2-yl) prop-

22) (E) -1- (3,4-dimethoxyphenyl) -3- (9-ethyl-9H-carbazolyl-

23) (E) -3 - ([1,1'-biphenyl] -4-yl) -1- (3,4-dimethoxyphenyl) prop-

24) (E) -3- (4-Bromo-3,5-dimethoxyphenyl) -1- (4-bromophenyl) prop-

25) (E) -1- (4-bromophenyl) -3- (naphthal-2-yl) prop-

26) (E) -3- (4-Bromo-3,5-dimethoxyphenyl) -1- (3- methoxyphenyl) prop-

27) (E) -1- (4-Chlorophenyl) -3- (9-ethyl-9H-carbamoyl-

28) (E) -3 - ([1,1'-biphenyl] -4-yl) -1- (4- chlorophenyl)

29) (E) -1- (4-Chlorophenyl) -3- (naphthal-2-yl) prop-

30) (E) -3- (4- (Allyloxy) phenyl) -1- (4-chlorophenyl) prop- 2-en-1-one.

The chalcone derivative represented by Formula 1 according to an aspect of the present invention may exist in the form of a pharmaceutically acceptable salt. Salts are useful as acid addition salts formed by pharmaceutically acceptable free acids. The term "pharmaceutically acceptable salt" of the present invention means a concentration that has a relatively non-toxic and harmless effective action in a patient, wherein the adverse effect due to the salt is an adverse effect of the compound &Quot; means all organic or inorganic addition salts.

The acid addition salt is prepared by a conventional method, for example, by dissolving the compound in an excess amount of an acid aqueous solution, and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. The same molar amount of the compound and the acid or alcohol (e.g., glycol monomethyl ether) in water may be heated and then the mixture may be evaporated to dryness, or the precipitated salt may be subjected to suction filtration.

As the free acid, organic acids and inorganic acids can be used. As the inorganic acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid and the like can be used. Examples of the organic acids include methanesulfonic acid, p- toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycollic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid and the like can be used , But are not limited to these.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal salt or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the non-soluble salt salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically acceptable to produce sodium, potassium, or calcium salt, but not limited thereto. The corresponding silver salt can also be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

The pharmaceutically acceptable salts of the compounds of formula (1) include, unless otherwise indicated, salts of acidic or basic groups which may be present in the compounds of formula (1). For example, pharmaceutically acceptable salts may include sodium, calcium and potassium salts of hydroxy groups, and the other pharmaceutically acceptable salts of amino groups include hydrobromides, sulphates, sulphates, phosphates, hydrogen phosphates (Hydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts and the like, ≪ / RTI >

In one aspect, the present invention may relate to a composition comprising the chalcone derivative compound having the structure of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

In one aspect of the present invention, the composition may be a composition for improving, preventing or treating a kidney disease, for reducing nephrotoxicity, or for protecting a kidney.

In one aspect of the present invention, the kidney disease may be a drug-induced kidney disease.

In one aspect of the invention, the medicament is a non-steroidal analgesic anti-inflammatory agent such as phenacetin, aspirin, indomethacin and the like; Anticancer drugs such as puromycin, daunomycin, cyclophosphamide, penicillamine, adriamycin and cisplatin, immunosuppressants, amikacin, gentamycin, kanamycin, neomycin, sisomycin, streptomycin, tobramycin Aminoglycoside antibiotics; Cephalosporin antibiotics; Carbapenem antibiotics such as imipenem and melopenem; Heavy metals such as cadmium, lead, mercury, and chromium; And inorganic or organic heavy metal compounds, compounds such as chloroform, D-serine, sulfonamide, 2-bromoethylene and hydrobromide, or fungal toxins such as okara-toxin and citrinin.

Specifically, in one aspect of the present invention, the drug-induced kidney disease is selected from the group consisting of nephritis, pyelonephritis, nephrotic syndrome, renal cancer, acute pyelonephritis, chronic pyelonephritis, renal tuberculosis, urinary tract infection, urinary stone, ureteral stones, But are not limited to, one or more selected from the group consisting of renal failure, diabetic nephropathy, chronic glomerulonephritis, acute advanced nephritis, nephrotic syndrome, pancreatic glomerulosclerosis, membranoproliferative glomerulonephritis, and membranoproliferative glomerulonephritis.

In one aspect of the invention, the composition may be a pharmaceutical composition, a cosmetic composition or a food composition.

In one aspect of the present invention, nephrotoxicity may be characterized by neurotoxicity due to a drug. Specifically, in one aspect of the invention, nephrotoxicity may be nephrotoxicity induced by cisplatin.

The pharmaceutical compositions according to the present disclosure may be of various oral or parenteral formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, soft or hard capsules, etc. These solid preparations may contain one or more excipients such as starch, calcium carbonate, sucrose, Or lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The pharmaceutical dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds as well as in suitable aggregates. The salt is not particularly limited as long as it is pharmaceutically acceptable so long as it is pharmaceutically acceptable and includes, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, , Benzenesulfonic acid, toluenesulfonic acid, and naphthalenesulfonic acid.

The composition of the present invention may be administered parenterally or orally, and may be administered in one to several divided doses so as to be administered in an amount of 0.1 to 500 mg, preferably 1 to 100 mg per kg of body weight per day have. The dosage for a particular patient may vary depending on the patient's body weight, age, sex, health condition, diet, time of administration, administration method, excretion rate, severity of disease, and the like.

The pharmaceutical composition according to the present invention can be administered orally or parenterally in the form of powders, granules, tablets, soft or hard capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations such as ointments and creams, Sterile injection solutions, and the like, and may be formulated in any form suitable for pharmaceutical preparations.

The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like by various routes such as parenteral, oral, and the like, and all manner of administration can be expected. For example, Or by intravenous, intramuscular, subcutaneous, intramural or intracerebroventricular injection.

Meanwhile, since the composition according to the present invention has no serious toxicity and side effects, it can be safely used for prolonged use for preventive purposes.

The formulation of the food composition according to the present specification is not particularly limited, but may be formulated into, for example, tablets, granules, powders, liquid preparations such as a drink, caramels, gels, bars and the like. The food composition of each formulation can be mixed with the ingredients commonly used in the field in addition to the chalcone derivative without difficulty by those skilled in the art depending on the purpose of formulation or use, and synergistic effect can be obtained when they are applied simultaneously with other ingredients.

In the food composition according to the present invention, the determination of the dose of the chalcone derivative is within the level of those skilled in the art, and its daily dose is, for example, from 0.1 mg / kg / day to 5000 mg / kg / day, mg / kg / day to 500 mg / kg / day, but it is not limited thereto, and may vary depending on various factors such as the age, health condition, and complication of the subject.

The food composition according to the present invention may be used as a food or beverage such as various foods such as chewing gum, caramel product, candy, ice cream, confectionery, beverage such as soft drink, mineral water, alcoholic beverage, healthful food including vitamins and minerals .

The beverage containing the chalcone derivative according to one aspect of the present invention is not particularly limited to the other ingredients other than the chalcone derivative as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates such as ordinary beverages, As shown in FIG.

In addition to the above, the health food composition of the present invention may further contain various additives such as various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate etc.), pectic acid and its salts, A salt thereof, an organic acid, a protective colloid thickener, a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, a carbonating agent used in a carbonated drink, and the like. In addition, the functional food compositions of the present invention may comprise natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally included in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

The cosmetic composition according to the present disclosure may contain a cosmetically or dermatologically acceptable medium or base. It may be any formulation suitable for topical application, for example, a solution, a gel, a solid, an anhydrous product of a paste, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing a water phase in an oil phase, a multi-emulsion, May be used in the form of an aerosol or patch further comprising a capsule, a microgranule, an ionic (liposome) and a non-ionic follicle dispersant, a foam, a compressed propellant. These compositions may be prepared according to conventional methods in the art.

The cosmetic composition may contain, in addition to the above-mentioned substances, other ingredients which can give synergy to the main effect, so long as it does not impair the main effect. In addition to the chalcone derivative according to one aspect of the present invention, The composition may be appropriately selected by the person skilled in the art without difficulty depending on the purpose of formulation or use of the other cosmetic composition. For example, the cosmetic composition of the present invention may contain other components that are usually combined with the chalcone derivative, if necessary, in the cosmetic composition. Examples of the component include moisturizers, emollients, surfactants, organic and inorganic pigments, Antioxidants, stabilizers, thickeners, glycerin, pH adjusters, alcohols, pigments, flavorings, blood circulation accelerators, coolants, antiperspirants and purified water. The other ingredients to be contained in the cosmetic composition are not limited thereto, and the amount of the ingredients may be within the range that does not impair the objects and effects of the present invention.

The formulation of the cosmetic composition is not particularly limited and may be appropriately selected according to the purpose. For example, suppositories such as suppositories, supplements, essences, nutritional creams, massage creams, packs, gels, makeup bases, foundation, powders, lipsticks, patches, sprays, eye creams, eye essences, cleansing creams, cleansing foams, One selected from the group consisting of cleanser, hair shampoo, hair conditioning, hair treatment, hair essence, hair lotion, scalp hair tonic, scalp essence, hair gel, hair spray, hair pack, body lotion, body cream, body oil and body essence But the present invention is not limited thereto.

Hereinafter, the method of the present invention will be described in detail by way of examples. However, the following examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

[Example 1] (E) -1- (4-Chlorophenyl) -3- (1H-indol-3-yl) prop-

4-Chloroacetophenone (77.4 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by addition of indole-3-aldehyde (72.6 mg, 0.5 mmol), 10% NaOH solution (5 mL) Respectively. The reaction mixture was stored in a refrigerator overnight. To the reaction mixture was added water (20 mL) and 1N hydrochloric acid solution (0.22 mL) to adjust the pH to 6-7. The solid was then filtered and recrystallized to give 73 mg, 51.8% of (E) -1- (4-chlorophenyl) -3- (lH- indol-3-yl) prop- .

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 8.7 (s, 1H), 8.11 (d, J = 15.6 Hz, 1H), 8.02-7.98 (m, 3H), 7.63 (d, J = 2.8 Hz, 1H), 7.54 (d, J = 15.6 Hz, 1H ), 7.50-7.47 (m, 2H), 7.46-7. 44 (m, 1H), 7.34-7.30 (m, 2H).

¹³ C-NMR (CDCl ₃ -d , 100 MHz) 隆; 189.50, 139.32, 138.59, 137.31, 137.23, 130.41, 129.77, 128.83, 125.33, 123.70, 120.72, 117.38, 114.55, 111.99.

_{LC-MS calcd for C 17 H} 12 ClNO [M + H] = 281.06, found: 282.1.

[Example 2] (E) -1- (4-Chlorophenyl) -3- (3,4-dimethoxyphenyl) prop-

4-Chloroacetophenone (77.4 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 3,4-dimethoxybenzaldehyde (83 mg, 0.5 mmol) Phenyl) -3- (3,4-dimethoxyphenyl) prop-2-en-1-one 112 mg, 74.0%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 7.96 (d, J = 8.4 Hz , 2H), 7.77 (d, J = 15.6 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 15.6 Hz, 1H), 7.24 ( dd, J = 8.4 Hz, 2 Hz, 1H), 7.16 (d, J = 2 Hz, 1H), 6.90 (d, J = 8.4 Hz, 1H), 3.96 (s, 3H), 3.94 (s, 3H) .

¹³ C-NMR (CDCl ₃ -d , 100 MHz) 隆; 189.26, 151.63, 149.29, 145.55, 138.97, 136.78, 129.86, 129.56, 128.89, 127.67, 123.34, 119.46, 111.13, 110.01, 56.03, 55.99.

_{LC-MS calcd for C 17 H} 12 ClNO [M + H] = 302.1, found: 303.1.

[Example 3] (E) -1- (4-Chlorophenyl) -3- (4-dimethylamino) phenyl) prop-

N-dimethyl-4-benzaldehyde (74.6 mg, 0.5 mmol) was added to a solution of 4-chloroacetophenone (77.4 mg, 0.5 mmol) -Chlorophenyl) -3- (3,4-dimethylamino) phenyl) prop-2-en-1-one 98.6 mg, 68.6%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 7.95 (d, J = 8.8, 2H), 7.79 (d, J = 15.6 Hz, 1H), 7.54 (d, J = 8.8Hz 2H), 7.45 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 15.6 Hz, 1H), 6.69 (d, J = 8.8 Hz, 2H), 3.08 (s, 6H).

¹³ C-NMR (CDCl ₃ -d , 100 MHz) 隆; 189.25, 152.16, 146.35, 138.42, 137.40, 130.54, 129.73, 128.73, 122.43, 116.22, 111.80, 40.13.

_{LC-MS calcd for C 17 H} 16 ClNO [M + H] = 285.09, found: 286.1.

[Example 4] (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-chlorophenyl) prop-

4-Chloroacetophenone (77.4 mg, 0.5 mmol) was dissolved in ethanol (5 mL), and then 2-bromo-4,5-dimethylbenzaldehyde (122.5 mg, 0.5 mmol) (2-bromo-4,5-dimethoxyphenyl) -1- (4-chlorophenyl) prop-2-en-1-one 126 mg, 66.0%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 8.07 (d, J = 16 Hz , 1H), 7.94 (d, J = 8.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.24 (d, J = 16 Hz, 1H), 7.18 ( s, 1 H), 7.08 (s, 1 H), 3.95 (s, 3 H), 3.92 (s, 3 H).

¹³ C-NMR (CDCl ₃ -d , 100 MHz) 隆; 189.54, 151.70, 148.72, 143.92, 139.16, 136.47, 130.03, 128.94, 126.69, 122.49, 118.26, 115.81, 109.44, 56.32, 56.23.

_{LC-MS calcd for C 17 H} 14 BrClO 3 [M + H] = 380.0, found: 381.0.

Example 5 Synthesis of (E) -1- (4-chlorophenyl) -3- (para-tolyl) prop-2-en-

4-Chloroacetophenone (77.4 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 4-methyldimethylbenzaldehyde (59 mg, 0.5 mmol) -3- (para-tolyl) prop-2-en-1-one 91 mg, 70.9%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 7.96 (d, J = 8.4 Hz 2H), 7.80 (d, J = 15.6 Hz, 1H), 7.54 (d, J = 8, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.45-7.41 ( m, 1 H), 7.26-7.21 (m, 2 H), 2.39 (s, 3 H).

¹³ C-NMR (CDCl ₃ -d , 100 MHz) 隆; 189.29, 145.47, 141.37, 139.09, 136.67, 131.98, 129.89, 129.77, 128.92, 128.57, 120.50, 21.57.

_{LC-MS calcd for C 16 H} 13 ClO [M + H] = 256.1, found: 257.1.

Example 6 Synthesis of (E) -3- (4-chlorophenyl) -1- (3-methoxyphenyl) prop-2-en-

(75 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 4-chlorobenzaldehyde (70.2 mg, 0.5 mmol) 4-chlorophenyl) -1- (3-methoxyphenyl) prop-2-en-1-one 90 mg, 66%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 7.76 (d, J = 15.6 Hz , 1H), 7.61-7.57 (m, 3H), 7.55 (m, 1H), 7.48 (d, J = 15.6 Hz, 1H), 7.47-7.39 (m, 3H), 7.14 (m, 1 H), 3.89 (s, 3 H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.94, 159.94, 143.33, 139.41, 136.46, 133.38, 129.64, 129.62, 129.27, 122.48, 121.05, 119.45, 112.86, 55.52.

_{LC-MS calcd for C 16 H} 13 ClO 2 [M + H] = 272.1, found: 273.1.

[Example 7] (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (3- methoxyphenyl) prop-

After dissolving 1- (3-methoxyphenyl) ethanone (75 mg, 0.5 mmol) in ethanol (5 mL), 2-bromo-4,5-dimethoxybenzaldehyde (122.5 mg, 0.5 mmol) 122 mg, 64.7% of (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (3-methoxyphenyl) prop-2-en-

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 8.07 (d, J = 15.6 Hz , 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.52-7.51 (m, 1H), 7.40 (t, J = 8, 1H), 7.28 (t, J = 1H), 7.19 (s, 1H), 7.13-7.10 (m, 1H), 7.07 (s, 1H), 3.95 (s, 3H), 3.91 (s, 3H), 3.88 (s,

¹³ C-NMR (CDCl3- d , 100 MHz)?; 190.58, 151.53, 143.49, 139.54, 129.58, 126.86, 123.02, 121.17, 119.22, 115.73, 113.03, 109.34, 56.32, 56.22, 55.54.

_{LC-MS calcd for C 18 H} 17 BrO 4 [M + H] = 376.0, found: 377.0.

[Example 8] (E) -1- (4-Bromophenyl) -3- (4- (dimethylamino) phenyl) prop-

(E) -1- (4-Bromo-4-methoxyphenyl) -4-bromoacetophenone (99.5 mg, 0.5 mmol) was dissolved in ethanol (5 mL) Bromophenyl) -3- (4- (dimethylamino) phenyl) prop-2-en-1-one 100 mg, 60.8%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 7.87 (d, J = 8.4, 2H), 7.79 (d, J = 15.6 Hz, 1H), 7.62 (d, J = 8.4, 2H), 7.54 (d, J = 6.8 Hz, 2H), 7.27 (d, J = 15.6, 1H), 6.69 (d, J = 8.8 Hz, 2H), 3.053 (s, 6H).

¹³ C-NMR (CDCl ₃ -d , 100 MHz) 隆; 189.45, 152.18, 146.44, 137.84, 131.72, 130.57, 129.89, 127.08, 122.43, 116.20, 111.82, 40.14.

_{LC-MS calcd for C 17 H} 16 BrNO [M + H] = 329.0, found: 330.0.

[Example 9] (E) -1- (4-Bromophenyl-3,5-dimethoxy) -1- (3,4- (dimethoxyphenyl) prop-

3,4-dimethoxyacetophenone (122.5 mg, 0.5 mmol) was dissolved in ethanol (5 mL), and then 4-bromo-3,5-dimethoxybenzaldehyde (122.5 mg, 0.5 mmol) ) -1- (4-bromophenyl-3,5-dimethoxy) -1- (3,4- (dimethoxyphenyl) prop-2-en-1-one 90.6 mg, 45.1%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 7.73 (d, J = 15.6 Hz , 1H), 7.69 (dd, J = 8.4 Hz, 2 Hz, 1H), 7.63 (d, J = 2, 1H) 7.52 (d, J = 15.6 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.82 (s, 2H), 3.98 (s, 3H), 3.97 (s, 3H), 3.91 (s, 6H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 188.46, 157.34, 153.43, 149.36, 143.50, 135.33, 131.12, 123.17, 122.37, 110.74, 109.87, 104.41, 103.56, 102.92, 56.60, 56.16, 56.13.

_{LC-MS calcd for C 19 H} 19 BrO 5 [M + H] = 406.0, found: 407.0.

[Example 10] (E) -1- (4-Bromophenyl) -3- (1H-indol-3-yl) prop-

After dissolving 4-bromoacetophenone (99.5 mg, 0.5 mmol) in ethanol (5 mL), 3-indolcarboxyaldehyde (72.6 mg, 0.5 mmol) Phenyl) -3- (lH-indol-3-yl) prop-2-en-l-one 89 mg, 54.6%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 8.75 (s, 1H), 8.12 (d, J = 15.2 Hz, 1H), 8.02-8.00 (m, 1H), 7.93 (d, J = 8.8 Hz, 2H), 7.66-7.64 (m, 1H), 7.54 (d, J = 15.6 Hz, 1H), 7.47-7.45 (m, 1H), 7.33-7.31 (m, 2H).

¹³ C-NMR (CDCl 3 -d , 100 MHz)?: 189.65, 139.42, 137.75, 137.26, 131.80, 130.54, 129.90, 127.20, 125.32, 123.67, 121.90, 120.70, 117.27, 114.50, 112.02.

_{LC-MS calcd for C 17 H} 12 BrNO [M + H] = 325.0, found: 326.0.

Example 11 Synthesis of (E) -3- (4-dimedylamino) phenyl) -1- (4-fluorophenyl) prop-

4- (dimethylamino) benzaldehyde (74.6 mg, 0.5 mmol) was added to a solution of 4-fluoroacetophenone (99.5 mg, 0.5 mmol) Dimethylamino) phenyl) -1- (4-fluorophenyl) prop-2-en-1-one 91 mg, 67.6%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 2H), 7.80 (d, J = 15.2 Hz, 1H), 7.63-7.53 (m, 2H), 7.30 (d, J = 15.6 Hz, 2H), 7.32-7.28 , 6.71 - 6.57 (m, 1H), 3.05 - 2.98 (s, 6H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.00, 152.10, 146.09, 132.49, 131.32, 131.22, 130.87, 130.78, 130.51, 122.47, 119.64, 116.28, 115.63, 115.42, 111.81, 111.17, 40.17.

_{LC-MS calcd for C 17 H} 16 FNO [M + H] = 269.1, found: 270.1.

Example 12 Synthesis of (E) -3- (3,4-dimethoxy) phenyl) -1- (4-fluorophenyl) prop-

(E) -3- (4-fluoroacetophenone, 99.5 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 3,4-dimethoxybenzaldehyde Dimethoxy) phenyl) -1- (4-fluorophenyl) prop-2-en-1-one 107 mg, 74.7%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 8.09-8.05 (m, 2H), 7.79 (d, J = 15.6 Hz, 1H), 7.38 (d, J = 15.2Hz, 1H), 7.26-7.21 (m, 1H), 7.27-7.16 (m, 3H) , 6.92 (d, J = 8.4 Hz, 1H), 3.99 (s, 3H), 3.96 (s, 3H).

¹³ C-NMR (CDCl3- d , 100 MHz)?; 188.96, 151.52, 149.24, 145.30, 134.76, 131.49, 131.08, 130.99, 127.71, 124.05, 119.48, 115.83, 115.61, 111.08, 109.96, 56.04, 55.98.

_{LC-MS calcd for C 17 H} 15 FO 3 [M + H] = 286.1, found: 287.1.

[Example 13] (E) -1- (4-bromophenyl) -3- (3,4-dimethoxyphenyl) prop-

(E) -1- (4-fluorophenyl) acetophenone (99.5 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 3,4-dimethoxybenzaldehyde (4-bromophenyl) -3- (3,4-dimethoxyphenyl) prop-2-en-1-one 130 mg, 74.9%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 7.89 (d, J = 8.8 Hz , 2H), 7.82-7.80 (m, 1H), 7.77 (d, J = 15.6 Hz, 1H), 7.66-7.63 (m, 2H), 7.61-7.58 (m, 1H) , 7.34 (d, J = 15.6 Hz, IH), 7.25-7.23 (m, IH), 3.96 (s, 3H), 3.94 (s, 3H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 197.71, 145.65, 131.95, 131.88, 130.00, 129.69, 127.65, 123.39, 119.41, 111.11, 110.04, 56.04, 56.00.

_{LC-MS calcd for C 17 H} 15 BrO 3 [M + H] = 346.0, found: 347.0.

[Example 14] (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-bromophenyl) prop-

4-Bromoacetophenone (99.5 mg, 0.5 mmol) was dissolved in ethanol (5 mL) and then bromo-4,5- (dimethoxy) benzaldehyde (122.5 mg, 0.5 mmol) 3- (3-bromo-4,5-dimethoxyphenyl) -1- (4-bromophenyl) prop-2-en-1-one 130 mg, 74.9%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; J = 8.8 Hz, 2H), 7.25 (s, 1H), 7.23 (d, J = 15.6 Hz, 1H), 7.18 (s, 1H), 7.09 (s, 1H), 3.95 (s, 3H), 3.93 (s, 3H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.77, 151.69, 148.68, 144.01, 136.88, 131.94, 131.87, 130.40, 130.17, 127.85, 126.64, 122.41, 118.32, 115.76, 109.33, 56.34, 56.23.

_{LC-MS calcd for C 17 H} 14 Br 2 O 3 [M + H] = 423.9, found: 424.9.

[Example 15] (E) -1- (4-fluorophenyl) -3- (3,4,5-trimethoxyphenyl) prop-

After dissolving 4-fluoroacetophenone (69.1 mg, 0.5 mmol) in ethanol (5 mL), 3,4,5-trimethoxybenzaldehyde (98.1 mg, 0.5 mmol) (4-fluorophenyl) -3- (3,4,5-trimethoxyphenyl) prop-2-en-1-one (96 mg, 60.7%).

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; (D, J = 8.8 Hz, 2H), 7.72 (d, J = 15.6 Hz, 1H), 7.37 6.87 (s, 2H), 3.93 (s, 6H), 3.91 (s, 3H).

_{LC-MS calcd for C 18 H} 17 FO 4 [M + H] = 317.1, found: 317.1.

[Example 16] (E) -3- (4- (dimethylamino) phenyl) -1- (4-nitrophenyl) prop-

4-Nitroacetophenone (82.6 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 4- (N, N-dimethylamino) -benzaldehyde (74.6 mg, Phenol) -1- (4-nitrophenyl) prop-2-en-1-one (108 mg, 72.9%).

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; J = 8.8 Hz, 2H), 7.26 (d, J = 6.8 Hz, 2H) d, J = 15.2 Hz, 1H), 6.70 (d, J = 9.2 Hz, 2H), 3.06 (s, 6H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 188.93, 152.48, 149.66, 147.89, 144.26, 130.94, 129.18, 123.72, 122.0, 115.88, 111.81, 110.99, 40.137.

_{LC-MS calcd for C 17 H} 16 N 2 O 3 [M + H] = 297.1, found: 297.1.

[Example 17] (E) -1- (4-Fluorophenyl) -3- (1H-indol-3-yl) prop-

After dissolving 4-fluoroacetophenone (69.1 mg, 0.5 mmol) in ethanol (5 mL), 2-naphthylaldehyde (72.6 mg, 0.5 mmol) Phenyl) -3- (lH-indol-3-yl) prop-2-en-l-one 74 mg, 55.8%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 8.68 (s, 1H), 8.13-8.08 (m, 2H), 8.03-8.01 (m, 1H), 7.61 (d, J = 2.8Hz, 1H), 7.55 (d, J = 15.6 Hz, 1H), 7.47 -7.45 (m, 1 H), 7.34-7.3 (m, 2 H), 7.16 (m, 2 H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.23, 164.09, 139.06, 137.26, 135.27, 130.89, 130.80, 130.33, 125.36, 123.64, 121.86, 120.69, 117.44, 115.71, 115.49, 114.53, 111.99.

_{LC-MS calcd for C 17 H} 12 FNO [M + H] = 265.1, found: 266.1.

[Example 18] (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-fluorophenyl) prop-

4-fluoroacetophenone (69.1 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 2-bromo-4,5-dimethoxybenzaldehyde (122.5 mg, 0.5 mmol) 133 mg, 72.8% of 3- (2-bromo-4,5-dimethoxyphenyl) -1- (4-fluorophenyl) prop- 2-en-1-one was obtained.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; (M, 2H), 7.27 (d, J = 15.6 Hz, 1H), 7.19 (m, 3H), 7.09 (s, 3 H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.17, 151.64, 148.72, 143.63, 134.51, 131.24, 131.15, 126.77, 122.59, 118.16, 115.86, 115.81, 115.64, 109.47, 56.32, 56.23. _{LC-MS calcd for C 17 H} 14 BrFO 3 [M + H] = 364.0, found: 365.0.

Example 19 Synthesis of (E) -1- (3,4-dimethoxyphenyl) -3- (4- (dimethoxyamino) phenyl) prop-

(74.6 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 4- (dimethylamino) benzaldehyde (74.6 mg, 0.5 mmol) (3,4-dimethoxyphenyl) -3- (4- (dimethoxyamino) phenyl) prop-2-en-1-one 112 mg, 71.9%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 7.80 (d, J = 15.2 Hz , 1H), 7.68-7.62 (m, 2H), 7.56 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 15.2 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 6.70 (d, J = 8.8 Hz, 2H), 3.97 (s, 3H), 3.96 (s, 3H), 3.04 (s, 6H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 188.80, 152.74, 151.92, 149.09, 144.98, 132.13, 130.29, 122.89, 122.55, 116.54, 111.87, 110.84, 109.94, 56.06, 56.05, 40.18.

_{LC-MS calcd for C 19 H} 21 NO 3 [M + H] = 311.2, found: 312.2.

Example 20 Synthesis of (E) -3- (4- (dimethylamino) phenyl) -1- (3-methoxyphenyl) prop-

After dissolving 3,4-dimethoxyacetophenone (75.1 mg) in ethanol (5 mL), 2-naphthylaldehyde (74.6 mg) was added thereto. Amino) phenyl) -1- (3-methoxyphenyl) prop-2-en-1-one (100 mg, 71.1%).

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 7.78 (d, J = 15.2 Hz , 1H), 7.60-7.53 (m, 4H), 7.39 (t, J = 8.0 Hz, 1H), 7.35 (d, J = 15.2 Hz, 1H), 7.1 (m, 1H ), 6.75 (m, 1 H), 3.88 (s, 3 H), 3.06 (s, 6 H).

_{LC-MS calcd for C 18 H} 19 NO 2 [M + H] = 282.1, found: 282.1.

[Example 21] (E) -1- (3,4-dimethoxyphenyl) -3- (naphthyl-2-yl) prop-

(E) -1- (3, 4-dimethoxyacetophenone, 90.1 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 2-naphthylaldehyde (78.1 mg, Dimethoxyphenyl) -3- (naphthyl-2-yl) prop-2-en-1-one 97 mg, 60.9%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; (M, 2H), 7.88-7.82 (m, 3H), 7.81-7.78 (m, 1H), 7.74-7.71 , 2H), 6.94-6.92 (d, J = 8.4 Hz, 1H) 3.98 (s, 3H), 3.97 (s, 3H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 188.55, 153.31, 149.30, 144.07, 134.31, 133.41, 132.59, 131.42, 130.47, 128.69, 128.62, 127.81, 127.29, 126.75, 123.72, 123.07, 121.81, 110.85, 110.01, 56.12, 56.08.

_{LC-MS calcd for C 21 H} 18 O 3 [M + H] = 318.1, found: 319.1.

Example 22 Synthesis of (E) -1- (3,4-dimethoxyphenyl) -3- (9-ethyl-9H-carbazolyl-

(74.6 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 9-ethyl-9H-carbazole-3-carboxyaldehyde (111.6 mg, 0.5 mmol) E) -1- (3,4-dimethoxyphenyl) -3- (9-ethyl-9H-carbazolyl-3-yl) prop- 2-en-1-one 119 mg, 61.7%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 8.38 (d, J = 1.2Hz, 1H), 7.8 (dd, J = 8.4 Hz, 1.6Hz, 1H), 7.75 (dd, J = 8.4 Hz, 2 Hz, 1H), 7.67 (m, 1H), 7.61 (d, J = 15.6 Hz, 1H), 7.52-7.48 (m, 1H), 7.44-7.40 (m, 2H), 7.30-7.26 (m, 1H), 6.95 (d, J = 8.4 Hz, 1H), 4.40-4.35 (q, J = 7.2 Hz , 2H), 3.99 (s, 3H), 3.97 (s, 3H), 1.46 (t, J = 7.2 Hz, 3H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 188.78, 153.00, 149.21, 145.67, 141.39, 140.50, 131.90, 126.33, 126.29, 126.14, 123.49, 122.89, 122.81, 121.53, 120.65, 119.69, 118.69, 110.91, 110.0, 108.91, 108.87, 56.10, 37.80, 13.86.

_{LC-MS calcd for C 25 H} 23 NO 3 [M + H] = 385.17, found: 386.2.

Example 23 Synthesis of (E) -3 - ([1,1'-biphenyl] -4-yl) -1- (3,4-dimethoxyphenyl) prop-

(74.6 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 4-biphenylbenzaldehyde (99.6 mg, 0.5 mmol) (Dimethylamino) phenyl) -1- (3- (methoxyphenyl) prop-2-en-1-one 120 mg, 69.7%.

¹ H-NMR (CDCl ₃ -d , 400 MHz) 隆; 2H), 7.43-7.39 (m, 1H), 6.95 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 15.6 Hz, 1H), 7.77-7.60 (m, 9H), 7.51-7.48 , 3.99 (s, 3H), 3.98 (s, 3H).

¹³ C-NMR (CDCl ₃ -d , 100 MHz) 隆; 188.56, 153.30, 149.30, 143.55, 143.14, 140.19, 134.06, 131.40, 128.93, 128.90, 127.89, 127.60, 127.07, 123.03, 121.54, 110.83, 110.00, 56.13, 56.09.

LC-MS calcd for C ₂₃ H ₂₀ O ₃ [M + H] = 345.1, found: 345.1.

[Example 24] (E) -3- (4-Bromo-3,5-dimethoxyphenyl) -1- (4-bromophenyl) prop-

Bromoacetophenone (99.5 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by addition of 4-bromo-3,5-dimethoxybenzaldehyde (122 mg, 0.5 mmol) ) - 3- (4-bromo-3,5-dimethoxyphenyl) -1- (4-propophenyl) prop-2-en-1-one 136 mg, 64.2%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 7.88 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 15.6 Hz, 1H) , ≪ / RTI > 2H), 3.96 (s, 6H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.30, 157.44, 144.90, 136.75, 134.91, 132.00, 131.9, 130.40, 130.06, 129.85, 128.10, 122.18, 104.53, 65.60.

_{LC-MS calcd for C 17 H} 14 Br 2 O 3 [M + H] = 424.9, found: 424.9.

[Example 25] (E) -1- (4-bromophenyl) -3- (naphthal-2-yl) prop-

After dissolving 4-bromoacetophenone (99.5 mg, 0.5 mmol) in ethanol (5 mL), 2-naphthylaldehyde (78.1 mg, 0.5 mmol) was added and the mixture was reacted with (E) -1- Phenyl) -3- (naphthal-2-yl) prop-2-en-1-one 97 mg, 57.5%.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 8.04-7.97 (m, 2H), 7.95-7.91 (m, 2H), 7.91-7.83 (m, 3H), 7.81-7.78 (m, 1H), 7.72 (d, J = 6.4 Hz, 1H), 7.59 ( d, J = 15.6 Hz, 1H), 3.95 (m, 2H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.37, 145.53, 137.03, 134.94, 133.40, 132.20, 132.0, 130.90, 130.06, 128.82, 128.70, 127.84, 127.53, 127.39, 126.86, 123.61, 121.59.

_{LC-MS calcd for C 19 H} 13 BrO [M + H] = 336.0, found: 337.0.

[Example 26] (E) -3- (4-Bromo-3,5-dimethoxyphenyl) -1- (3-methoxyphenyl) prop-

3-methoxyacetophenone (75.1 mg) was dissolved in ethanol (5 mL), followed by the addition of 4-bromo-3,5-dimethoxybenzaldehyde (122.5 mg) 3-methoxyphenyl) prop-2-en-1-one (122 mg, 64.7%).

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; J = 7.6, (m, 1H), 7.48 (d, J = 15.6 Hz, 1H) 1H), 7.16-7.13 (m, 1H), 6.8 (s, 2H), 3.95 (s, 6H), 3.89 (s, 3H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 190.02, 159.93, 157.35, 144.27, 139.40, 135.11, 129.63, 122.71, 121.07, 119.24, 113.06, 104.48, 56.56, 55.52.

_{LC-MS calcd for C 18 H} 17 BrO 4 [M + H] = 377.0, found: 377.0.

[Example 27] (E) -1- (4-Chlorophenyl) -3- (9-ethyl-9H-carbamoyl-

4-Chloroacetophenone (77.3 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 3- (9-ethyl-9H-kappa-3-yl) aldehyde (111.6 mg, 0.5 mmol) Yl) prop-2-en-1-one (113 mg, 62.6%) as a white solid.

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 2H), 7.78 (m, 1H), 7.54-7.47 (m, 4H), 7.42 (m, 2H), 8.13 (m, , 7.29 (m, IH), 4.38 (q, 2H), 1.45 (t, 3H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 118.96, 147.06, 141.60, 140.52, 138.77,

LC-MS calcd for C ₂₃ H ₁₈ ClNO [M + H] = 360.1, found: 360.1.

[Example 28] (E) -3 - ([1,1'-biphenyl] -4-yl) -1- (4-chlorophenyl)

(77.3 mg, 0.5 mmol) was dissolved in ethanol (5 mL), followed by the addition of 1,1'-biphenylaldehyde (91.1 mg, 0.5 mmol) , 1'-biphenyl] -4-yl) -1- (4-chlorophenyl) prop- 2-en-1 -one (113 mg, 70.9%).

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 7.98 (m, 2H), 7.86 (d, J = 16 Hz, 1H), 7.74-7.62 (m, 6H), 7.54-7.45 (m, 5H), 7.3 (m, 1H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.14, 114.92, 143.55, 140.07, 139.23, 136.58, 133.66, 129.93, 129.06, 128.98, 127.98, 127.66, 127.08, 121.31.

_{LC-MS calcd for C 21 H} 15 ClO [M + H] = 319.1, found: 319.1.

[Example 29] (E) -1- (4-Chlorophenyl) -3- (naphthal-2-yl) prop-

(E) -1- (4-chlorophenyl) -lH-pyrrolo [2,3-d] pyrimidine was obtained in the same manner as in [ 3- (naphthal-2-yl) prop-2-en-1-one (90 mg, 61.5%).

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; (M, 3H), 7.86 (m, 3H), 7.80 (m, 1H), 7.6 (d, J = 15.6 Hz, 1H), 7.55-7.48 (m, 4H).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.16, 145.46, 139.23, 136.61, 134.49, 133.37, 132.21, 130.87, 129.95, 128.98, 128.81, 127.84, 127.52, 126.86, 123.61, 121.61.

_{LC-MS calcd for C 19 H} 13 ClO [M + H] = 293.1, found: 293.1.

Example 30 Synthesis of (E) -3- (4- ((4-chlorophenyl) propyl) phenyl) -1- (4-chlorophenyl) prop-2-en-1-one)

(E) -3- (4- (Allyloxy) phenyl) -piperidine was obtained in the same manner as in 4- (allyloxy) benzaldehyde (81.1 mg) after dissolving 4-chloroacetophenone ) -1- (4-chlorophenyl) prop-2-en-1-one (86 mg, 57.6%).

¹ H-NMR (CDCl ₃ - d , 400 MHz) 隆; 7.95 (d, J = 6.8 Hz, 2H), 7.78 (d, J = 15.6 Hz, 1H), 7.59 (d, J = 15.6 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 6.1-6.01 (m, 1H), 5.45 ).

¹³ C-NMR (CDCl ₃ - d , 100 MHz) 隆; 189.18, 160.85, 145.17, 138.96, 136.81, 132.68, 131.97, 130.32, 129.84, 129.74, 128.88127.93, 127.56, 119.23, 118.13, 115.21, 115.01, 68.90

_{LC-MS calcd for C 18 H} 15 ClO 2 [M + H] = 299.1, found: 299.1.

[Experimental Example] Evaluation of protecting activity of kidney cells

Protection against renal toxicity using pig kidney cells (purchased from LLC-PK1, ATCC) with reference to the method reported in the literature (Yokozawa et al., J. Pharm. Pharmacol. , 51, pp1325-1331, 1999) The effects were evaluated as follows.

First, LLC-PK1 cells were incubated with 100 μg / ml of 10% fetal bovine serum (Gibco BRL Life Technologies), penicillin G 100 units / ml (Gibco BRL Life Technologies) and streptomycin (Gibco BRL Life Technologies) Were subcultured in a 95% air / 5% carbon dioxide incubator maintained at 37 ° C using a DMEM (Gibco life rechnology, USA) medium supplemented with DMEM. The cultured LLC-PK1 cells were introduced into 96-well culture plates at a rate of 10 ⁴ , and cultured for 2 hours under the same conditions as above to allow cells to adhere to the culture plate and stabilize. Examples 2 to 30 were treated according to the concentrations shown in Table 1, followed by addition of a radical generating reagent (25 μM cisplatin dissolved in the medium) for 2 hours, followed by culturing for 24 hours. 10 μl of EZ-Tox (WST- Daeil Lab Service, Korea) reagent was added to each well, followed by incubation at 37 ° C. After 1 hour, the viability of the cells was measured by measuring the absorbance using a 450 nm detection wavelength in a BIO-TEK (Winooski, VT, USA) microplate reader. The measurement results are shown in Table 1 below.

division Concentration (μM) Cell survival rate (%) Example-2 0 59.8 ± 3.9 2 60.0 + - 2.9 10 70.3 ± 2.8 ^a 25 76.8 ± 3.2 ^a Example-3 0 59.1 ± 2.6 2 61.4 ± 3.4 10 64.1 ± 2.9 25 65.4 ± 2.9 ^a 50 76.3 ± 4.3 ^a 125 82.3 ± 2.4 ^a 250 87.3 ± 1.5 ^a Example-4 0 57.6 ± 3.6 2 50.2 ± 2.8 10 66.0 + 4.0 ^a 25 76.7 ± 3.0 ^a 60 79.6 ± 4.3 ^a 125 81.7 ± 3.0 ^a 250 86.6 ± 2.2 ^a Example 5 0 64.2 ± 2.0 2 64.9 ± 2.5 10 65.7 ± 1.7 25 67.3 ± 1.5 50 77.6 + 0.8 ^a 125 89.2 ± 1.8 ^a Example-6 0 62.1 ± 1.6 2 64.7 ± 2.4 10 82.9 ± 4.1 ^a 25 83.3 ± 3.7 ^a Example-7 0 66.8 ± 2.0 2 73.6 ± 2.1 ^a 10 78.2 ± 1.5 ^a 25 78.3 ± 1.2 ^a Example-8 0 60.8 ± 0.2 2 64.9 ± 3.0 ^a 10 70.5 + 1.7 ^a 25 72.4 ± 1.1 ^a 50 82.7 ± 2.5 ^a 125 83.5 ± 2.6 ^a 250 83.6 ± 0.7 ^a Example-9 0 58.3 ± 0.2 2 69.9 ± 2.1 ^a 10 70.6 ± 3.2 ^a 25 64.9 ± 3.2 ^a Example-11 0 61.4 ± 1.3 2 61.6 ± 1.6 10 62.2 ± 3.5 25 68.8 ± 2.2 ^a 50 67.0 ± 2.3 ^a 125 69.8 ± 1.8 ^a 250 77.2 ± 0.6 ^a Example-12 0 62.2 ± 1.5 2 74.5 + 4.6 ^a 10 71.5 ± 3.9 ^a Example-13 0 65.1 ± 4.3 2 71.4 ± 3.1 10 73.6 ± 1.7 ^a 25 79.5 ± 2.2 ^a 50 82.3 ± 3.0 ^a 125 84.5 ± 3.0 ^a Example-14 0 58.3 ± 1.7 2 58.6 ± 2.6 10 79.8 ± 2.7 ^a 25 86.1 ± 0.7 ^a Example-15 0 60.96 + - 2.8 2 63.84 + - 3.5 10 64.67 + - 4.0 25 71.52 ± 1.6 ^a 50 77.47 ± 1.8 ^a 125 80.79 ± 1.3 ^a 250 88.03 + 4.0 ^a Example-16 0 58.7 ± 4.2 2 59.6 ± 2.6 10 61.5 ± 0.5 25 62.6 ± 1.5 50 64.7 ± 1.8 125 75.2 + 1.7 ^a 250 76.8 + 4.0 ^a Example -18 0 59.3 ± 1.9 2 61.9 ± 2.1 10 69.6 ± 1.3 ^a 25 90.6 ± 3.4 ^a Example-19 0 55.7 ± 4.0 2 57.4 ± 4.1 10 57.6 ± 4.4 25 57.7 ± 1.9 50 58.3 ± 1.8 125 70.5 ± 1.3 ^a 250 89.2 ± 2.2 ^a Example-20 0 56.3 ± 3.8 2 61.8 ± 1.0 10 64.0 ± 3.5 25 64.1 ± 1.9 ^a 50 65.4 ± 1.2 ^a 125 65.8 ± 4.2 ^a 250 69.6 ± 3.8 ^a Example -21 0 58.1 ± 2.7 2 58.4 ± 2.3 10 59.5 ± 1.7 25 66.7 ± 2.1 ^a 50 66.7 ± 1.5 ^a 125 73.6 ± 2.3 ^a 250 86.7 ± 2.1 ^a Example-22 0 63.8 ± 3.9 2 75.5 ± 3.9 ^a 10 84.9 ± 2.3 ^a 25 75.0 ± 3.6 ^a Example-23 0 58.6 ± 3.7 2 61.0 ± 2.2 10 63.6 ± 3.4 25 84.4 ± 3.1 ^a 50 87.1 ± 2.1 ^a 125 89.1 ± 0.6 ^a 250 92.2 + 4.2 ^a Example -24 0 65.9 ± 3.4 2 66.3 ± 3.7 10 74.8 ± 2.9 ^a Example-25 0 63.1 ± 3.2 2 68.1 ± 0.7 ^a 10 69.3 ± 1.5 ^a 25 69.5 ± 2.9 ^a 50 69.9 ± 1.1 ^a 125 73.4 ± 3.1 ^a 250 78.0 + 1.7 ^a Example-26 0 59.4 ± 2.5 2 65.0 ± 2.4 ^a 10 72.3 ± 2.6 ^a 25 74.6 ± 3.7 ^a Example-27 0 60.4 ± 3.0 2 67.7 ± 3.8 ^a 10 74.4 ± 2.4 ^a 25 77.4 ± 3.3 ^a 50 77.0 + 4.1 ^a 125 78.8 ± 2.8 ^a 250 96.3 ± 3.2 ^a Example-28 0 60.5 ± 4.9 2 63.3 ± 4.2 10 60.7 ± 1.2 25 66.1 ± 1.3 50 73.7 ± 3.2 ^a 125 72.9 ± 3.6 ^a 250 87.8 ± 4.8 ^a Example-29 0 60.4 ± 3.0 2 57.1 ± 3.9 10 61.8 ± 3.6 25 61.9 ± 4.1 50 64.8 ± 1.0 125 67.4 ± 4.2 250 82.0 ± 2.5 ^a Example-30 0 63.6 ± 1.2 2 67.7 ± 4.0 10 76.7 ± 1.3 ^a 25 80.4 + 1.8 ^a 50 92.0 ± 2.1 ^a 125 98.3 ± 1.2 ^a 250 98.2 ± 4.1 ^a

* a represents statistical significance, p <0.001 vs cisplatin treatment standard values.

Table 1 above shows the effect of chalcone derivatives on LLC-PK1 cells, kidney epithelial cells treated with cisplatin. The number of LLC-PK1 cells was reduced to less than 60% of the cisplatin-untreated group by treatment with 25 μM cisplatin. The chalcone derivatives according to one aspect of the present invention have been shown to inhibit such cell damage.

The chalcone derivative compound according to one aspect of the present invention significantly increased cell survival rate in a concentration-dependent manner by treatment with 25 μM cisplatin.

In particular, in Examples 6, 14, 18, and 23, cell viability exceeded 80% at a concentration of 25 μM, and furthermore, Example 18 showed cell viability at a concentration of 25 μM at about 90% It was confirmed that the cell damage was remarkably protected. In addition, the cells of Examples 23, 27, and 30 showed cell viability exceeding 90% at a concentration of 250 μM. As a result, it was found that the chalcone derivative compound according to one aspect of the present invention effectively protects kidney cell damage by cisplatin. These results imply that chalcone derivative compounds can protect kidney cell damage resulting from oxidative stress.

Hereinafter, a pharmaceutical composition for reducing nephrotoxicity comprising a chalcone derivative according to one aspect of the present invention as an active ingredient, or a formulation example of a food composition will be described in detail, but the pharmaceutical composition can be applied to various formulations, Rather than limiting the scope of the invention.

[Formulation Example 1] Soft capsule

8 mg of the composition containing 20 mg of the chalcone derivative of Examples 1 to 30, 9 mg of vitamin E, 9 mg of vitamin C, 2 mg of palm oil, 8 mg of vegetable hardening oil, 4 mg of yellow pearls and 9 mg of lecithin were mixed and mixed by a conventional method, Solution. 400 mg per capsule is filled to prepare a soft capsule. Separately from this, a soft capsule sheet was prepared in a ratio of 66 parts by weight of gelatin, 24 parts by weight of glycerin and 10 parts by weight of sorbitol, and filled with the filling solution to prepare a soft capsule containing 400 mg of the composition of the present invention.

[Formulation Example 2] Tablets

8 mg of the composition containing 20 mg of the chalcone derivative of Examples 1 to 30, 9 mg of vitamin E, 9 mg of vitamin C, 200 mg of galactooligosaccharide, 60 mg of lactose and 140 mg of maltose were mixed and granulated using a fluid bed drier, (sugar ester) is added. 500 mg of these compositions are tabletted by conventional methods to prepare tablets.

[Formulation Example 3] Drinking agent

After mixing 8 mg of the composition containing 20 mg of the chalcone derivative of Examples 1 to 30, 9 mg of vitamin E, 9 mg of vitamin C, 10 g of glucose, 0.6 g of citric acid and 25 g of liquid oligosaccharide, 300 ml of purified water was added, Fill in as much as possible. It is filled in a bottle and sterilized at 130 ° C for 4 to 5 seconds to prepare a drink.

[Formulation Example 4]

8 mg of the composition containing 20 μM of the chalcone derivative of Examples 1 to 30, 9 mg of vitamin E, 9 mg of vitamin C, 250 mg of anhydrous crystalline glucose and 550 mg of starch were mixed and granulated into granules using a fluidized bed granulator, To prepare a granule.

[Formulation Example 5]

Injection was prepared according to a conventional method according to the composition shown in Table 2 below.

Compounding ingredient content A composition comprising 20 μM of the chalcone derivative of Examples 1 to 30 10-50 mg Sterile sterilized water for injection Suitable amount pH adjusting agent Suitable amount

[Formulation Example 6] Health functional food

Health functional foods were prepared according to the compositions shown in Table 3 below by a conventional method.

Compounding ingredient content A composition comprising 20 μM of the chalcone derivative of Examples 1 to 30 20 mg Vitamin A acetate 70 μg Vitamin E 1.0 mg Vitamin B1 0.13 mg Vitamin B2 0.15 mg Vitamin B6 0.5 mg Vitamin B12 0.2 μg Vitamin C 10 mg Biotin 10 μg Nicotinic acid amide 1.7 mg Folate 1 50 μg Calcium pantothenate 0.5 mg Ferrous sulfate 1.75 mg Zinc oxide 0.82 mg Magnesium carbonate 25.3 mg Potassium monophosphate 15 mg Dicalcium phosphate 55 mg Potassium citrate 90 mg Calcium carbonate 100 mg Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a component suitable for a health functional food as a preferred embodiment, the compounding ratio may be arbitrarily modified.

[Formulation Example 7] Health drinks

Health drinks were prepared in a conventional manner according to the composition shown in Table 4 below.

Compounding ingredient content A composition comprising 20 μM of the chalcone derivative of Examples 1 to 30 1000 mg Citric acid 1000 mg oligosaccharide 100 g Taurine 1g Purified water Balance

The above components are mixed according to a conventional health drink manufacturing method, and the mixture is stirred and heated at 85 DEG C for about 1 hour, and then the solution is sterilized by filtration.

[Formulation Example 8] Flexible longevity (skin lotion)

The softening longevity was prepared by a conventional method according to the composition shown in Table 5 below.

Compounding ingredient Content (% by weight) A composition comprising 20 μM of the chalcone derivative of Examples 1 to 30 0.2 glycerin 3.0 Butylene glycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 Phage-12 nonylphenyl ether 0.2 Polysorbate 80 0.4 ethanol 10.0 Triethanolamine 0.1 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 9] Nutritional lotion (milk lotion)

Nutrition lotion was prepared according to a conventional method according to the composition shown in Table 6 below.

Compounding ingredient Content (% by weight) A composition comprising 20 μM of the chalcone derivative of Examples 1 to 30 1.0 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxyvinyl polymer 0.1 Wax 4.0 Polysorbate 60 1.5 Caprylic / capric triglyceride 5.0 Squalane 5.0 Sorbitacecequioleate 1.5 Liquid paraffin 0.5 Cetearyl alcohol 1.0 Triethanolamine 0.2 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 10] Nourishing cream

Nutritive creams were prepared according to the compositions listed in Table 7 below in a conventional manner.

Compounding ingredient Content (% by weight) A composition comprising 20 μM of the chalcone derivative of Examples 1 to 30 2.0 glycerin 3.0 Butylene glycol 3.0 Liquid paraffin 7.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / capric triglyceride 3.0 Squalane 5.0 Cetearyl glucoside 1.5 Sorbitan stearate 0.4 Polysorbate 60 1.2 Triethanolamine 0.1 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 11] Massage cream

Massage creams were prepared in a conventional manner according to the composition shown in Table 8 below.

Compounding ingredient Content (% by weight) A composition comprising 20 μM of the chalcone derivative of Examples 1 to 30 2.0 glycerin 8.0 Butylene glycol 4.0 Liquid paraffin 45.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / capric triglyceride 3.0 Wax 4.0 Cetearyl glucoside 1.5 Sesquioleic acid sorbitan 0.9 Vaseline 3.0 paraffin 1.5 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 12] Pack

Packs were prepared in a conventional manner according to the composition shown in Table 9 below.

Compounding ingredient Content (% by weight) A composition comprising 20 μM of the chalcone derivative of Examples 1 to 30 0.2 glycerin 4.0 Polyvinyl alcohol 15.0 Hyaluronic acid extract 5.0 Beta Glucan 7.0 Allantoin 0.1 Nonyl phenyl ether 0.4 Polysorbate 60 1.2 Ethanol preservative 6.0 Preservative, coloring, fragrance Suitable amount Purified water Balance

Claims (10)

1. A pharmaceutical composition comprising a chalcone derivative compound having a structure represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient,
[Chemical Formula 1]

A is

,

,

or

ego,
Each of R ₁ to R ₁₅ independently represents a hydrogen atom; C ₁ to C ₆ alkoxy; C ₁ to C ₆ alkyl; Phenyl; Halogen selected from the group consisting of fluorine, chlorine, bromine and iodine; Nitro (-NO ₂ ); Allyloxy; Or dimethylamine (-N (CH ₃ ) ₂ ), which is effective for preventing, treating or preventing renal diseases caused by cisplatin. delete The method according to claim 1,
R ₁ , R _4, and R ₅ are hydrogen atoms;
R ₂ and R ₃ are each independently a hydrogen atom, a C ₁ to C ₆ alkoxy, nitro (-NO ₂ ), or a halogen selected from the group consisting of fluorine, chlorine, bromine and iodine;
R ₆ to R ₉ are hydrogen atoms;
R ₁₀ is a hydrogen atom; R ₁₁ to R ₁₄ are each independently selected from the group consisting of hydrogen, C ₁ to C ₆ alkoxy, C ₁ to C ₆ alkyl, phenyl, dimethylamine (-N (CH ₃ ) ₂ ), allyloxy or fluorine, Bromine, and iodine;
R ₁₅ is C ₁ to C ₆ alkyl composition. The method of claim 3,
R ₂ and R ₃ are each independently a hydrogen atom, methoxy, nitro (-NO ₂ ), or a halogen selected from the group consisting of fluorine, chlorine, and bromine;
R ₁₁ to R ₁₄ are each independently a hydrogen atom, methoxy, methyl, chlorine, bromine, phenyl, allyloxy or dimethylamine (-N (CH ₃ ) ₂ );
And R &lt; ₁₅ &gt; is ethyl. 5. The method of claim 4,
The chalcone derivative compound having the structure of the above formula (1)
1) E) -1- (4-chlorophenyl) -3- (lH-indol-3-yl) prop-
2) (E) -1- (4-chlorophenyl) -3- (3,4-dimethoxyphenyl) prop-
3) (E) -1- (4-chlorophenyl) -3- (4-dimethylamino) phenyl) prop-
4) (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-chlorophenyl) prop-
5) Synthesis of (E) -1- (4-chlorophenyl) -3- (para-tolyl)
6) (E) -3- (4-Chlorophenyl) -1- (3-methoxyphenyl) prop-
7) (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (3- methoxyphenyl) prop-
8) (E) -1- (4-bromophenyl) -3- (4- (dimethylamino) phenyl) prop-
9) (E) -1- (4-Bromophenyl-3,5-dimethoxy) -1- (3,4- (dimethoxyphenyl)
10) (E) -1- (4-bromophenyl) -3- (1H-indol-3-yl) prop-
11) (E) -3- (4-dimedylamino) phenyl) -1- (4-fluorophenyl) prop-
12) (E) -3- (3,4-dimethoxy) phenyl) -1- (4-fluorophenyl) prop-
13) (E) -1- (4-bromophenyl) -3- (3,4-dimethoxyphenyl) prop-
14) (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-bromophenyl) prop-
15) Synthesis of (E) -1- (4-fluorophenyl) -3- (3,4,5-trimethoxyphenyl) prop-
16) (E) -3- (4- (dimethylamino) phenyl) -1- (4-nitrophenyl) prop-
17) (E) -1- (4-fluorophenyl) -3- (1H-indol-3-yl) prop-
18) (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (4-fluorophenyl) prop-
19) (E) -1- (3,4-dimethoxyphenyl) -3- (4- (dimethoxyamino) phenyl) prop-
20) (E) -3- (4- (dimethoxyamino) phenyl) -1- (3-methoxyphenyl) prop-
21) (E) -1- (3,4-dimethoxyphenyl) -3- (naphthyl-2-yl) prop-
22) (E) -1- (3,4-dimethoxyphenyl) -3- (9-ethyl-9H-carbazolyl-
23) (E) -3 - ([1,1'-biphenyl] -4-yl) -1- (3,4-dimethoxyphenyl) prop-
24) (E) -3- (4-Bromo-3,5-dimethoxyphenyl) -1- (4-bromophenyl) prop-
25) (E) -1- (4-bromophenyl) -3- (naphthal-2-yl) prop-
26) (E) -3- (4-Bromo-3,5-dimethoxyphenyl) -1- (3- methoxyphenyl) prop-
27) (E) -1- (4-Chlorophenyl) -3- (9-ethyl-9H-carbamoyl-
28) (E) -3 - ([1,1'-biphenyl] -4-yl) -1- (4- chlorophenyl)
29) (E) -1- (4-Chlorophenyl) -3- (naphthal-2-yl) prop-
30) a compound selected from the group consisting of (E) -3- (4- (allyloxy) phenyl) -1- (4-chlorophenyl) prop- 2-en-1-one. The method according to claim 1,
Wherein the chalcone derivative compound or a pharmaceutically acceptable salt thereof is in a concentration of from 0.001 to 500 μM based on the total volume of the composition. 1. A pharmaceutical composition comprising a chalcone derivative compound having a structure represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient,
[Chemical Formula 1]

A is

,

,

or

ego,
Each of R ₁ to R ₁₅ independently represents a hydrogen atom; C ₁ to C ₆ alkoxy; C ₁ to C ₆ alkyl; Phenyl; Halogen selected from the group consisting of fluorine, chlorine, bromine and iodine; Nitro (-NO ₂ ); Allyloxy; Or dimethyamine (-N (CH ₃ ) ₂ ), for reducing nephrotoxicity caused by cisplatin, or for inhibiting nephrotoxicity caused by cisplatin. delete delete delete