SYNTHESIS OF 1,4-DISUBSTITUTED-1,2,3-TRIAZOLE COMPOUNDS CONTAINING TWO OR THREE TRIAZOLE RINGS WITH ANTICANCER ACTIVITY

Abstract

The invention specifically relates to the synthesis of novel 1,4-disubstituted-1,2,3-triazole compounds containing 2 or 3 triazole rings with anticancer activity using copper-containing magnetic heterogeneous catalysts. More specifically, the invention encompasses the obtaining of novel triazole compounds containing 2 or 3 triazole rings exhibiting high antiproliferative activity against cancerous cells and proliferative activity against normal cells via the CuAAC (Copper(I)-catalyzed Azide-Alkyne Cycloaddition) click reaction from benzyl halides, sodium azide, and terminal alkyne derivatives in the presence of copper-containing magnetic heterogeneous catalysts.

Description

1 TARIFF 1,4- CONTAINING TWO OR THREE TRIAZOLE RINGS WITH ANTICANCER ACTIVITY SYNTHESIS OF DISUBSTITUTIONED-1,2,3-TRIAZOLE COMPOUNDS Technical Area Specifically, the invention concerns the enhancement of anticancer activity using copper-containing magnetic heterogeneous catalysts. 1,4-disubstituted-1,2,3-triazole compounds containing two or three triazole rings synthesis of these compounds A549, MCF-7, HCT-116, L929, Pc-3, HAP39 and SH-SY5Y It is geared towards in vitro anticancer activity studies against cell lines such as these. More specifically The invention describes the use of copper-containing magnetic heterogeneous catalysts in the presence of benzyl halides and sodium azide. and terminal alkyne derivatives CuAAC (Copper(I)-catalyzed Azide-Alkyne Cycloaddition) 10 Containing 2 or 3 triazole rings that exhibit many biological activities via a click reaction. obtaining new compounds and testing these compounds against the aforementioned cell lines This includes their studies on anticancer activity. State of the Art The 1,2,3-triazole ring exhibits high chemical stability and can participate in hydrogen bonding interactions. organic due to its aromatic character and easy combination with different pharmacophore groups. It is known as an important heterocyclic structure in synthetic and medical chemistry. In the literature, it is referred to as 1,2,3- Triazole derivatives have particularly strong anticancer, antimicrobial, antiviral, anti-inflammatory, and enzyme properties. It is reported to be used in the design of compounds that can exhibit inhibitory properties. [Further details about the last paragraph are omitted here] In recent years, hybrid constructs containing 1,2,3-triazole have been developed as drug candidate molecules targeting cancer-related targets. It has been reported that its design has attracted attention. One of the most common methods for the synthesis of 1,4-disubstituted-1,2,3-triazoles is using sodium azide and It is the CuAAC reaction of terminal alkynes in the presence of a copper catalyst. CuAAC The reaction involves the selective association of terminal alkynes with azides to form 1,4-disubstituted-1,2,3- Click chemistry is one of the fundamental reactions in that it yields triazole products. It is accepted. In studies reported by researchers in the literature, terminal Different 1,4- alkynes are formed as a result of copper(I) catalyzed 1,3-dipolar cycloaddition reactions with azides. It has been shown that disubstituted-1,2,3-triazoles can be obtained using click chemistry and biogonals. The importance of chemistry was also highlighted by the 2022 Nobel Prize in Chemistry. The current literature contains 30 studies on the synthesis of 1,2,3-triazole derivatives via the CuAAC reaction. Although numerous studies exist, these studies mostly focus on a limited number of mono-triazoles. obtaining the derivative or using classical homogeneous copper catalyst systems 2 It is based on. However, biphenylnitrile, trifluoromethyl, trifluoromethoxy, nitro, methoxy, different pharmacobody groups such as carboxylic acids, quinoxaline, and trisubstituted aromatic nuclei new 1,4- containing two or three triazole rings in the same molecular skeleton Synthesis of disubstituted-1,2,3-triazole compounds in a broad product library Studies on this topic are limited, particularly regarding electron-withdrawing and electron-donating substituents. systematically modified, 1,4-disubstituted-1,2,3- containing two- or three-triazole rings This product is obtained with high purity and high yield using the same synthesis approach as triazole compounds. These series are quite important for medical chemistry and pharmaceutical chemistry. Therefore, the aforementioned novel triazole derivatives using practical, selective and recoverable catalyst systems Synthesis with high purity and yield, both increasing the product variety of existing synthesis methods 10 It is suitable for both development in terms of biological activity and antiproliferative activity studies. It emerged as a technical need in terms of creating new composite libraries. It is emerging. Brief Description of the Invention The main objective of this invention is to develop structural 15 new generation magnetic heterogeneous catalysts containing copper. Novel 1,4- containing two- or three-triazole rings with high antiproliferative properties and a high diversity of characteristics. The aim is to synthesize disubstituted-1,2,3-triazole compounds. The invention covers the following: Compounds containing two- or three-triazole rings; carboxylic acid on a benzene ring (-COOH), trifluoromethyl (-CF3), trifluoromethoxy (-OCF3), nitro (-NO2), methoxy (-OCH3), fluorine (- F) containing substituents such as quinoxaline or 2,4,6-trimethylbenzene aromatic groups 20 It consists of derivatives containing different functional groups. In this respect, the invention is relevant to medical chemistry. and a wide range of compounds containing two- or three-triazole rings that can be evaluated in the fields of pharmaceutical chemistry. This enables the creation of a new triazole compound library. Another objective of the invention is to create new triazoles containing two- or three-triazole rings. The compounds are reacted using magnetic catalysts via the CuAAC click reaction. The aim is to ensure that different benzyl groups are obtained selectively, practically, and efficiently at each stage. Electron-withdrawing or electron-donating groups, based on halide and terminal alkyne derivatives. a novel 1,4-disubstituted-1,2,3-triazole containing numerous two- or three-triazole rings The compound can be synthesized; the resulting products are used in the development of anticancer drug candidates and biological agents. They can be evaluated as suitable candidate molecules for activity studies. 30 Shapes Figure 1. 1H NMR (a) of 2,3-bis((4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (10) compound. and 13C NMR (b) spectra. 3 Figure 2. 19F NMR (a) of 2,3-bis((4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (10) compound. and FT-IR (b) spectra. Figure 3. Q-TOF-LC / MS for the compound 2,3-bis((4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (10) spectrum. Figure 4. 1H NMR (a) of 2,3-bis((4-(4-nitrophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (11) 5 and 13C NMR (b) spectra. Figure 5. FT-IR (a) of 2,3-bis((4-(4-nitrophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (11) compound and Q-TOF-LC / MS (b) spectra. Figure 6. 1H of the compound 2,3-bis((4-(4-(triflomethyloxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (12). NMR (a) and 13C NMR (b) spectra. 10 Figure 7. 2,3-bis((4-(4-(trifluromethyloxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (12) compound 19F NMR (a) and FT-IR (b) spectra. Figure 8. 2,3-bis((4-(4-(trifluoromethyloxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (12) compound Q-TOF-LC / MS spectrum. Figure 9. 1H 15 of the compound 2,3-bis((4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (13). NMR (a) and 13C NMR (b) spectra. Figure 10. 19F of the compound 2,3-bis((4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (13). NMR (a) and FT-IR (b) spectra. Figure 11. Q- of the compound 2,3-bis((4-(4-(trifluromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (13). TOF-LC / MS spectrum. 20 Figure 12. 2,3-bis((4-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (14) compound 1H NMR (a) and 13C NMR (b) spectra. Figure 13. 2,3-bis((4-(3,5-bis(trifluoromethyl)phenyll)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (14) compound 19F NMR (a) and FT-IR (b) spectra. Figure 14. 2,3-bis((4-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (14) compound 25 Q-TOF-LC / MS spectrum. Figure 15. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-phenyl-1H-1,2,3-triazole) (15) 1H NMR (a) and 13C NMR (b) spectra of the compound. Figure 16. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-phenyl-1H-1,2,3-triazole) (15) FT-IR (a) and Q-TOF-LC / MS (b) spectra of the compound. 30 Figure 17. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(p-tolyl)-1H-1,2,3-triazole) (16) 1H NMR (a) and 13C NMR (b) spectra of the compound. Figure 18. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(p-tolyl)-1H-1,2,3-triazole) (16) FT-IR (a) and Q-TOF-LC / MS (b) spectra of the compound. Figure 19. 4,4',4''-(((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(1H-1,2,3-triazole-1,4-dil))tribenzoic 35 1H NMR (a) and 13C NMR (b) spectra of compound acid (17). Figure 20. 4,4',4''-(((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(1H-1,2,3-triazole-1,4-dil))tribenzoic D2O-NMR (a) and FT-IR (b) spectra of compound acid (17). Figure 21. 4,4',4''-(((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(1H-1,2,3-triazole-1,4-dil))tribenzoic Q-TOF-LC / MS spectrum of compound acid (17). 40 Figure 22. 3,3',3''-(((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(1H-1,2,3-triazol-1,4- 1H NMR (a) and 13C NMR (b) spectra of the compound tribenzoic acid (18). Figure 23. 3,3',3''-(((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(1H-1,2,3-triazol-1,4- D2O-NMR (a) and FT-IR (b) spectra of the compound tribenzoic acid (18). Figure 24. 3,3',3''-(((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(1H-1,2,3-triazol-1,4-45 Q-TOF-LC / MS spectra of the compound tribenzoic acid (18). Figure 25. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-fluorophenyl)-1H-1,2,3-triazole) 1H NMR (a) and 13C NMR (b) spectra of compound (19). 4 Figure 26. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-fluorophenyl)-1H-1,2,3-triazole) 19F NMR (a) and FT-IR (b) spectra of compound (19). Figure 27. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-nitrophenyl)-1H-1,2,3-triazole) 1H NMR (a) and 13C NMR (b) spectra of compound (20). Figure 28. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-nitrophenyl)-1H-1,2,3-triazole) 5 FT-IR (a) and Q-TOF-LC / MS (b) spectra of compound (20). Figure 29. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-methoxyphenyl)-1H-1,2,3-triazole) 1H NMR (a) and 13C NMR (b) spectra of compound (21). Figure 30. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-methoxyphenyl)-1H-1,2,3-triazole) FT-IR (a) and Q-TOF-LC / MS (b) spectra of compound (21). 10 Detailed Description of the Invention The products obtained within the scope of this invention are quinoxaline or 2,4,6-trimethylbenzene aromatic groups. 1,4-disubstituted-1,2,3-triazole containing two or three triazole rings formed on it 15 They are heterocyclic compounds. These products are formed from various benzyl halide derivatives and terminal alkynes. CuAAC click reaction of its derivatives in the presence of copper-containing magnetic heterogeneous catalysts This is obtained as a result. With this method, quinoxaline or 2,4,6-trimethylbenzene groups 1,4-disubstituted-1,2,3-triazole containing two or three triazole rings built on it In its compounds, 4-trifluoromethylbenzyl, benzyl, 4-20 is located at position number four of the triazole ring. fluorobenzyl, 4-nitrobenzyl, 4-methoxybenzyl, 4-carboxybenzyl, 4-trifluoromethylbenzyl, 4- trifluoromethoxybenzyl or 3,5-bis(trifluoromethyl)benzyl groups are present while one of the triazole rings is present. In position number 2, it is 2,3-diethylquinoxaline or 1,3,5-triethyl-2,4,6-trimethylbenzene aromatic. New products carrying groups have been synthesized. Thus, the invention is not limited to a single type of triazole. Different cancers depend not on the synthesis of the compound, but on the substituents carried by the triazole ring. bis-triazole and tris-triazole structures exhibiting different anticancer activities against cells the preparation of a broad and structurally diverse new group of organic compounds It provides opportunities. Products obtained in preferred applications of the invention include functional benzoic acid. Triazole derivatives containing the group bis-30, which carries two triazole rings via the quinoxaline core. triazole compounds and tris- that carry three triazole rings via a 2,4,6-trimethylbenzene core. Triazole compounds are included. These products contain nitrile, carboxylic acid, nitro, methoxy, Functional groups such as fluorine, trifluoromethyl, and trifluoromethoxy contribute to the electronic properties of compounds. This contributes to the diversification of their characteristics and potential biological interactions. Therefore, the products obtained within the scope of this invention are related to medical chemistry, pharmaceutical chemistry, and anticancer. 35 in activity studies targeting biological targets such as drug candidate development These are important as new candidate molecules that can be evaluated. The findings obtained within the scope of the invention... The synthesis schemes, open structures, and names of the obtained compounds are given in Tables 1 and 2. Table 1. Bis-based structure built upon the 2,3-diethylquinoxaline group obtained within the scope of the invention. synthesis scheme, structure and names of triazole rings (Group 1). 5 + NaN3 CH3CN / H2O + Catalyst RX: Cl, Br R: -F, -NO2, -OCF3, -CF3 N N X X NN NN NN N N R R 10-14 NN NN NN N N FF 2,3-bis((4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline 11 NN NN NN NN O2N NO2 2,3-bis((4-(4-nitrophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline 12 NN NN NN NN F3CO OCF3 2,3-bis((4-(4-(triflomethyloxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline 13 NN NN NN NN F3C CF3 2,3-bis((4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline 6 14 NN NN NN NN CF3 F3C F3C CF3 2,3-bis((4-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline + NaN3 CH3CN / H2O + Catalyst RX: Cl, Br R: -F, -NO2, -OCF3, -CF3 N N X X NN NN NN N N R R 10-14 Scheme 1. Synthesis scheme of compounds 10-14 obtained within the scope of the invention. Synthesis flow for compounds 10-14: In the preferred practice, 5 is first added to the reaction vessel. 1 equivalent of substituted quinoxaline halide (1 mmol), 2.4 equivalents of sodium azide (2.4 mmol) and 2 An equivalent terminal alkyne derivative (2 mmol) is added. Then, the reaction medium to be used is added. Water / acetonitrile (2:1, v:v) (total 3 mL) mixture based on substituted quinoxaline halide. A solvent system consisting of combinations is added to the reaction mixture. Catalytic magnetic heterogeneous catalyst containing a certain amount (maximum 5-10 mg) of copper (CuO / CoO@NPC or 10 CuO / ZnO / Co3O4@NPC) is added. The prepared reaction mixture can be processed outdoors without requiring any inert reaction conditions. Temperature range: room temperature to 80 °C, depending on the type of substituted quinoxaline halide used. It is heated while stirring for 1–12 hours at intervals. During this process, sodium quinoxaline halide is removed. Benzylazide intermediates are formed in the presence of azides, and the resulting benzilazide intermediates interact with terminal alkynes. In the presence of copper-containing catalysts, the azide-alkyne undergoes a cycloaddition reaction to form new 1,4- It forms disubstituted-1,2,3-triazole compounds. After the reaction is complete, the mixture is cooled to room temperature. Then, the copper-containing mixture... A magnetic heterogeneous catalyst is a catalyst in which a magnet is brought close to the reaction vessel from the reaction medium. The solids are separated using a magnet, and the remaining solvent and solids are transferred to another container. Solvent 20 The remaining product is removed and purified by crystallization (Scheme-1). 7 Table 2. Structure built upon the 1,3,5-triethyl-2,4,6-trimethylbenzene group obtained within the scope of the invention. Synthesis scheme, structure, and names of induced tris-triazole compounds (Group 2). + NaN3 CH3CN / H2O + Catalyst RX: Cl, Br R: -H, -CH3, -COOH, -F, -NO2, -OCH3 X XX N N NN N N N N N R R R 15-21 N N N N N NN N N 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-phenyl-1H-1,2,3-triazole) 16 N N N N N NN N N 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(p-tolyl)-1H-1,2,3-triazole) 8 17 N N N N N NN N N OH HIGH OH HIGH OH HIGH 4,4',4''-(((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(1H-1,2,3-triazole-1,4- dil))tribenzoic acid 18 N N N N N NN N N HIGH OH HO HIGH HIGH OH 3,3',3''-(((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(1H-1,2,3-triazole-1,4- dil))tribenzoic acid 19 N N N N N NN N N F F F 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-fluorophenyl)-1H-1,2,3-triazole) 9 N N N N N NN N N O2N O2N NO2 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(4-(4-nitrophenyl)-1H-1,2,3-triazole) 21 N N N N N NN N N H3CO H3CO OCH3 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(4-(4-methoxyphenyl)-1H-1,2,3- triazole) + NaN3 CH3CN / H2O + Catalyst RX: Cl, Br R: -H, -CH3, -COOH, -F, -NO2, -OCH3 X XX N N NN N N N N N R R R 15-21 Scheme 2. Synthesis scheme of compounds 15-21 obtained within the scope of the invention. Synthesis flow for compounds 15-21: In the preferred practice, the reaction vessel is first filled with... 1 equivalent of substituted benzyl halide (1 mmol), 3.6 equivalents of sodium azide (3.6 mmol) and 3 An equivalent terminal alkyne derivative (3 mmol) is added. Then, the reaction medium to be used is added. Water / acetonitrile (2:1, v:v) (total 3 mL) mixture based on substituted benzyl halide. A solvent system consisting of combinations is added to the reaction mixture. Catalytic magnetic heterogeneous catalyst containing a certain amount (maximum 5-10 mg) of copper (CuO / CoO@NPC or CuO / ZnO / Co3O4@NPC) is added. The prepared reaction mixture can be subjected to any inert reaction conditions in the open air. without requiring, depending on the type of benzyl halide substituted used, between room temperature and 80 It is heated while stirring for 1–12 hours at temperature ranges of °C. During this process, benzyl Benzylazide intermediates are formed from the halide in the presence of sodium azide, and the resulting benzilazide intermediates Azide-alkyne cycloaddition of terminal alkynes in the presence of copper-containing catalysts. It reacts to form new 1,4-disubstituted-1,2,3-triazole compounds. After the reaction is complete, the mixture is cooled to room temperature. Then, the copper-containing mixture... A magnetic heterogeneous catalyst is a catalyst in which a magnet is brought close to the reaction vessel from the reaction medium. They are separated using a magnet, and the remaining solvent and solids are transferred to another container. The solvent... The remaining product is removed and purified by crystallization (Scheme-2). 11 Table 3. Characterization data of 1,4-disubstituted-1,2,3-triazole compounds. Compound No 2,3-bis((4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (10) en: <350°C, 1H NMR (400 MHz, DMSO-d6): δ 8.67 (s, 2H, Ar-H), 8.00-7.83 (m, 8H, Ar-H), 7.30 (t, 4H, Ar-H, J= 8 Hz), 5.70 (s, 2H, CH2N). 13C{1H} NMR (101 MHz, DMSO-d6): δ 163.49, 161.06, 149.39, 146.13, 140.96, 131.33, 129.15, 127.76, 127.72, 127.68, 123.16, 116.40, 116.19 (Ar-C), 52.46 (CH2N). 19F NMR (376 MHz, DMSO-d6) δ −114.05. ν(triazole halka): 3087 (cm−1), ν(CN): 1500 (cm−1). HRMS (ESI+, CH3CN, m / z): For C26H18F2N8, [M+H]+:481.17 is calculated, found to be 481.1682. 11 2,3-bis((4-(4-nitrophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (11) in: 251-253°C, 1H NMR (400 MHz, DMSO-d6): δ 8.89 (s, 2H, Ar-H), 8.30 (d, 4H, Ar- H, J= 9 Hz), 8.13 (d, 4H, Ar-H, J= 8 Hz), 8.01 (q, 2H, Ar-H, J= 4 Hz), 7.87 (q, 2H, Ar- H, J= 4 Hz), 6.34 (s, 4H, CH2N). 13C{1H} NMR (101 MHz, DMSO-d6): δ 149.18, 147.05, 145.02, 141.00, 137.51, 131.45, 129.18, 126.46, 125.31, 124.79 (Ar-C), 52.70 (CH2N). ν(triazole halka): 3105 (cm−1), ν(CN): 1514 (cm−1). HRMS (ESI+, CH3CN, m / z): For C26H18H10O4, the calculated [M+H]+:535.15, found at 535.1586. 12 2,3-bis((4-(4-(triflomethyloxy)phenyl)-1X-1,2,3-triazol-1-yl)methyl)quinoxaline (12) in: 260-262°C, 1H NMR (400 MHz, DMSO-d6): δ 8.72 (s, 2H, Ar-H), 8.02-7.98 (m, 6H, Ar-H), 7.85 (q, 2H, Ar-H, J= 4 Hz), 7.45 (d, 4H, Ar-H, J= 8 Hz), 6.30 (s, 4H, CH2N). 13C{1H} NMR (101 MHz, DMSO-d6): δ 149.34, 148.28, 145.71, 140.97, 131.37, 130.53, 129.16, 127.49, 123.73, 122.05 (Ar-C, OCF3), 52.52 (CH2N). 19F NMR (376 MHz, CDCl3) δ -56.79. ν(triazole halka): 3076 (cm−1), ν(CN): 1499 (cm−1). HRMS (ESI+, CH3CN, m / z): Calculated for C28H18F6N8O2 [M+H]+:613.15, found at 613.1529. 13 2,3-bis((4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (13) en: <350°C, 1H NMR (400 MHz, DMSO-d6): δ 8.80 (s, 2H, Ar-H), 8.08 (d, 4H, Ar-H, J= 8 Hz), 8.00 (s, 2H, Ar-H), 7.86 (s, 2H, Ar-H), 7.79 (d, 4H, Ar-H, J= 8 Hz), 6.32 (s, 4H, CH2N). 13C{1H} NMR (101 MHz, DMSO-d6): δ 149.28, 145.59, 141.02, 135.08, 131.44, 129.18, 126.19, 124.46 (Ar-C, CF3), 52.64 (CH2N). 19F NMR (376 MHz, CDCl3) δ -61.01. ν(triazol halkası): 3091 (cm−1), ν(CN): 1332 (cm−1). HRMS (ESI+, CH3CN, m / z): C28H18F6N8 için hesaplanan [M+H]+:581.16, bulunan 581.1632. 14 2,3-bis((4-(3,5-bis(triflorometil)fenill)-1H-1,2,3-triazol-1-il)metil)kinoxalin (14) en: 238-240°C, 1H NMR (400 MHz, DMSO-d6): δ 8.76 (s, 2H, Ar-H), 8.32 (s, 4H, Ar- H), 8.13 (q, 2H, Ar-H, J= 4 Hz), 7.96-7.93 (m, 4H, Ar-H), 6.29 (s, 4H, CH2N). 13C{1H} NMR (101 MHz, DMSO-d6): δ 149.10, 144.07, 141.25, 133.45, 131.72, 131.42, 131.09, 130.76, 129.32, 127.69, 125.52, 124.98, 124.58, 122.27, 121.42 (Ar-C, CF3), 53.37 (CH2N). 19F NMR (376 MHz, CDCl3) δ -61.65. ν(triazole halka): 2941 (cm−1), ν(CN): 1278 (cm−1). HRMS (ESI+, CH3CN, m / z): [M+H]+:717.13, calculated for C30H16F12H8, feathers 717.1378. 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-phenyl-1H-1,2,3-triazole) (15) in: 158-160°C, 1H NMR (400 MHz, DMSO-d6): δ 8.39 (s, 3H, Ar-H), 7.85 (d, 6H, Ar- H, J= 8 Hz), 7.42 (t, 6H, Ar-H, J= 8 Hz), 7.32 (t, 3H, Ar-H, J= 8 Hz), 5.79 (s, 6H, CH2N), 2.47 (s, 9H, CH3). 13C{1H} NMR (101 MHz, DMSO-d6): δ 146.68, 139.99, 131.25, 131.10, 129.27, 128.32, 125.69, 121.46 (Ar-C), 49.17 (CH2N), 16.91 (CH3). ν(triazole halka): 3109 (cm−1), ν(CN): 1509 (cm−1). HRMS (ESI+, CH3CN, m / z): for C36H33H9 hesaplanes [M+H]+:592.29, feathers 592.2946. 16 1,1',1''-((2,4,6-trimetilbenzen-1,3,5-tril)tris(metilen))tris(4-(p-tolil)-1H-1,2,3-triazol) (16) en: 259-261°C, 1H NMR (400 MHz, DMSO-d6): δ 8.30 (d, 3H, Ar-H, J= 8 Hz), 7.73 (d, (6H, Ar-H, J= 8 Hz), 7.22 (d, 6H, Ar-H, J= 8 Hz), 5.76 (s, 6H, CH2N), 2.46 (s, 9H, CH3), 2.32 (s, 9H, CH3). 13C{1H} NMR (101 MHz, DMSO-d6): δ 146.74, 139.93, 139.57, 139.37, 137.58, 131.59, 131.26, 131.12, 129.82, 128.34, 125.60, 120.98, 120.94 (Ar-C), 12 49.06 (CH2N), 21.29 (CH3), 16.76 (CH3). ν(triazol halkası): 3086 (cm−1), ν(CN): 2105 (cm−1), ν(CN): 1499 (cm−1). HRMS (ESI+, CH3CN, m / z): C39H39N9 in hesaplanan [M+H]+: 634.33620, bulunan 634.33978. 17 4,4',4''-(((2,4,6-trimetilbenzen-1,3,5-tril)tris(metilen))tris(1H-1,2,3-triazol-1,4- dil))tribenzoik asit (7) en: 298-300°C, 1H NMR (400 MHz, DMSO-d6): δ 13.01 (s,3H, COOH), 8.56 (s,3H, Ar-H), 7.99 (s, 12H, Ar-H), 5.81 (s, 6H, CH2N), 2.51 (s, 9H, CH3). 13C{1H} NMR (101 MHz, DMSO-d6): δ 167.50 (COOH), 145.81, 140.15, 135.20, 131.16, 130.42, 125.61, 122.65 (Ar-C), 49.27 (CH2N), 16.96 (CH3). ν(triazol halkası): 2977 (cm−1), ν(CO): 2098 (cm−1), ν(CN): 1682 (cm−1). HRMS (ESI+, CH3CN, m / z): C39H33N9O6 için hesaplanan [M+H]+: 725.26209, bulunan 724.26125. 18 3,3',3''-(((2,4,6-trimetilbenzene-1,3,5-tril)tris(metilen))tris(1H-1,2,3-triazol-1,4- dil))tribenzoik asit (18) en: 276-278°C, 1H NMR (400 MHz, DMSO-d6): δ 13.13 (s,3H, COOH), 8.57 (s, 3H, Ar-H), 8.44 (s, 3H, Ar-H), 8.10 (d, 3H, Ar-H, J= 8 Hz), 7.89 (d, 3H, Ar-H, J= 8 Hz), 7.55 (t, 3H, Ar-H, J= 6 Hz), 5.80 (s, 6H, CH2N), 2.51 (s, 9H, CH3). 13C{1H} NMR (101 MHz, DMSO-d6): δ 167.62 (COOH), 145.90, 140.14, 131.88, 131.52, 131.15, 129.96, 129.65, 129.05, 126.31, 122.07 (Ar-C), 49.27 (CH2N), 16.96 (CH3). ν(triazole halka): 3084 (cm−1), ν(CN): 1694 (cm−1). HRMS (ESI+, CH3CN, m / z): Calculated for C39H33H9O6 [M+H]+: 724.25873, feather 724.26173. 19 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-fluorophenyl)-1H-1,2,3- triazole) (19) in: 300-302°C, 1H NMR (400 MHz, DMSO-d6): δ 8.42 (s, 3H, Ar-H), 7.97 (d, 6H, Ar- H, J= 8 Hz), 7.42 (d, 6H, Ar-H, J= 8 Hz), 5.79 (s, 6H, CH2N), 2.47 (s, 9H, CH3). 13C{1H} NMR (101 MHz, DMSO-d6): δ 148.26, 145.43, 139.52, 131.03, 130.50, 127.54, 122.02 (Ar-C), 49.14 (CH2N), 16.14 (CH3). 19F NMR (376 MHz, CDCl3) δ -114.32. ν(triazole halka): 3095 (cm−1), ν(CF): 2109 (cm−1), ν(CN): 1498 (cm−1). 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-nitrophenyl)-1H-1,2,3- triazole) (20) en: 233-235°C, 1H NMR (400 MHz, DMSO-d6): δ 8.64 (s, 3H, Ar-H), 8.29 (d, 6H, Ar- H, J= 8 Hz), 8.13 (d, 6H, Ar-H, J= 8 Hz), 5.82 (s, 6H, CH2N), 2.48 (s, 9H, CH3). 13C{1H} NMR (101 MHz, DMSO-d6): δ 147.03, 144.81, 139.68, 139.59, 137.52, 131.75, 130.91, 126.47, 124.76, 123.57 (Ar-C), 49.34 (CH2N), 16.82 (CH3). ν(triazol halkası): 3083 (cm−1), ν(NO): 2107 (cm−1), ν(CN): 1516 (cm−1). HRMS (ESI+, CH3CN, m / z): C36H30N12O6 için hesaplanan [M+H]+: 727.24448, bulunan 727.24840. 21 1,1',1''-((2,4,6-trimetilbenzen-1,3,5-tril)tris(metilen))tris(4-(4-metoksifenil)-1H-1,2,3- triazol) (21) en: 239-241°C, 1H NMR (400 MHz, DMSO-d6): δ 8.23 ​​(s, 3H, Ar-H), 7.76 (d, 6H, Ar- H, J= 8 Hz), 6.98 (d, 6H, Ar-H, J= 9 Hz), 5.75 (s, 6H, CH2N), 3.78 (s, 9H, OCH3), 2.46 (s, 9H, CH3). 13C{1H} NMR (101 MHz, DMSO-d6): δ 159.43, 146.62, 139.90, 139.35, 131.58, 131.14, 127.03, 123.70, 120.40, 114.66 (Ar-C), 55.59 (OCH3), 49.04 (CH2N), 16.77 (CH3). ν(triazole ring): 3090 (cm−1), ν(CO): 2092 (cm−1), ν(CN): 1499 (cm−1). HRMS (ESI+, CH3CN, m / z): Calculated [M+H]+ for C39H39N9O3: 683.32430, found. 682.32330. FT-IR bending and strain frequencies of target 1,4-disubstituted-1,2,3-triazole compounds are given in Table 4. The most characteristic FT-IR stretching vibrations for 1,4-disubstituted-1,2,3-triazole compounds are given. The peaks belonging to the triazole ring are around 3000-3100 cm-1, and the Ar-CH peaks are around 2200 cm-1, C≡N. Aliphatic-CH peaks with stretching vibration, aromatic C=C stretching around 1400-1500 cm-1. 13 Vibrations are observed. In addition to these, specific compounds can be identified via FT-IR spectra. OH peaks are observed around 3000 cm-1, while CF, CO, and NO peaks are observed around 2200 cm-1. Table 4.FT-IR bending and strain frequencies of 1,4-disubstituted-1,2,3-triazole compounds. Compound FT-IR bending and strain frequencies (10) ν(triazole ring): 3087 (cm−1), ν(C=C-Ar): 1500 (cm−1). (11) ν(triazole ring): 3105 (cm−1), ν(C=C-Ar): 1514 (cm−1). (12) ν(triazole ring): 3076 (cm−1), ν(C=C-Ar): 1499 (cm−1). (13) ν(triazole ring): 3091 (cm−1), ν(C=C-Ar): 1332 (cm−1). (14) ν(triazole ring): 2941 (cm−1), ν(C=C-Ar): 1278 (cm−1). (15) ν(triazole ring): 3109 (cm−1), ν(C=C-Ar): 1509 (cm−1). (16) ν(triazole ring): 3086 (cm−1), ν(CN): 2105 (cm−1), ν(C=C-Ar): 1499 (cm−1). (17) ν(triazole ring): 2977 (cm−1), ν(CO): 2098 (cm−1), ν(C=C-Ar): 1682 (cm−1). (18) ν(triazole ring): 3084 (cm−1), ν(C=C-Ar): 1694 (cm−1). (19) ν(triazole ring): 3095 (cm−1), ν(CF): 2109 (cm−1), ν(C=C-Ar): 1498 (cm−1). (20) ν(triazole ring): 3083 (cm−1), ν(NO): 2107 (cm−1), ν(C=C-Ar): 1516 (cm−1). (21) ν(triazole ring): 3090 (cm−1), ν(CO): 2092 (cm−1), ν(C=C-Ar): 1499 (cm−1). Table 5. Half-maximal values ​​of compounds determined after 48 hours on different cell lines. inhibitory concentration (IC₅₀, μM) values Compounds Cell Line (48 hours) A549 MCF-7 HCT-116 L929 PC-3 HEP 3B SH-SY5Y Compound 10 785±1.61 8078±31.48 373.6±1.91 IC₅₀: NC IC₅₀: NC IC₅₀: NC 1209±11.89 Compound 11 IC₅₀: NC 774.5±3.14 253.8±1.84 IC₅₀: NC IC₅₀: NC 770.9±4.76 156.4±1.54 Compound 12 35.59±2.2 IC₅₀: NC IC₅₀: NC IC₅₀: NC IC₅₀: NC 638.2±29.38 66.85±1.76 Compound 13 7318±32.14 1218±1.72 1286±2 IC₅₀: NC IC₅₀: NC IC₅₀: NC 4350±60813, Compound 14 IC₅₀: NC 309.7±1.76 620.2±2.01 289.1±1.4 IC₅₀: NC IC₅₀: NC IC₅₀: NC Compound 15 IC₅₀: NC IC₅₀: NC 544±2.14 IC₅₀: NC IC₅₀: NC 3390±8.88 IC₅₀: NC Compound 16 337.6±1.81 3436±2.16 2327±1.28 702.6±1.9 IC₅₀: NC 927.7±5.09 145±2.39 Compound 17 64.61±1.56 15064±32.2 1 IC₅₀: NC IC₅₀: NC IC₅₀: NC 922.3±5.65 IC₅₀: NC Compound 18 34.79±1.81 1596±1.18 2592±1.5 4854±3 IC₅₀: NC IC₅₀: NC 107.9±1.59 Compound 19 50.35±2.18 9748±3.27 IC₅₀: NC IC₅₀: NC IC₅₀: NC IC₅₀: NC 511.7±6.7 Compound 20 IC₅₀: NC 1262±1.49 3716±2.92 175.9±1.28 395.7±3.7 19.36±1.49 495.2±3.87 Compound 21 46.44±1.7 IC₅₀: NC 113.5±1.28 66.69±1.4 3 IC₅₀: NC 426.5±4.59 151.5±1.72 Gefitinib 44.71±1.92 100.6±1.45 IC₅₀: NC 155.7±1.2 4 329.3±1.3 9 100.6±1.45 183.3±3.96 *Data are presented as mean ± standard deviation (SD) (n=4). IC₅₀ values ​​are derived from dose-response curves. It has been calculated. NC: Uncalculated value. 14 Table 6. Half-maximal values ​​of compounds determined after 24 hours on different cell lines. inhibitory concentration (IC₅₀, μM) values According to the results of the anticancer activity performed; 5 In the HCT116 (colon cancer) cell line, compounds coded 13 and 14 were present at 24 hours, respectively, at 50 and 100. At micromolar doses, they showed toxic activity of 50% and 35%, respectively. Reference The substance we use, gefinitib, is 60% selective at a dose of 100 micromolar. It has shown toxicity. We have 13 substances that show the same level of efficacy and can compete with gefinitib, and 14 are compounds. 10 In the A549 (lung cancer) cell line, compounds 12, 18, 17, 19, and 21, especially at 100 µM A high dose and a 48-hour period can reduce cell viability to below 60%, resulting in a strong toxic effect. has shown. Gefitinib has shown the most potent efficacy among known lung cancer drugs. Compounds 17 and 21 have shown toxic effects similar to gefitinib → These compounds are candidate drugs 15 it could be. Compound 12 has shown moderate toxicity. Other compounds generally show viability between 80–130%, therefore exhibiting antiproliferative effects. It is weak or negligible in that respect. Articles Cell Line (24 Hours) A549 MCF-7 HCT116 L929 PC3 HEP3B SHSY Compound 10 IC₅₀: NC 236.9±1.4 IC₅₀: NC 2358±34.2 IC₅₀: NC 66.8±1.56 221.6±1.89 Compound 11 IC₅₀: NC 618.8±1.43 IC₅₀: NC 328.4±1.66 IC₅₀: NC 49.51±1.53 96.18±1.33 Compound 12 74.16±1.34 94.03±1.36 412.7±1.61 IC₅₀: NC 2556±39.99 193.2±2.61 569.7±9.65 Compound 13 IC₅₀: NC 709.4±1.58 99.07±1.21 277.2±2.75 IC₅₀: NC 752.7±6.66 IC₅₀: NC Compound 14 IC₅₀: NC 490.9±1.64 137±1.46 252.9±2.67 IC₅₀: NC 200±3.1 312.9±5.43 Compound 15 IC₅₀: NC IC₅₀: NC 8332±587.49 456.2±1.39 IC₅₀: NC 379.5±3.7 IC₅₀: NC Compound 16 95.95±1.67 1171±1.53 IC₅₀: NC 272.3±1.26 306.2±2.37 IC₅₀: NC IC₅₀: NC Compound 17 81.45±1.65 IC₅₀: NC IC₅₀: NC 351.3±2.11 805.8±1.65 IC₅₀: NC 145.5±1.65 Compound 18 651±2.44 2365±1.89 IC₅₀: NC 212.8±1.33 IC₅₀: NC IC₅₀: NC IC₅₀: NC Compound 19 137±2.42 9168±94.84 IC₅₀: NC 262.8±1.25 IC₅₀: NC IC₅₀: NC 212.3±1.76 Compound 20 254.1±1.76 2275±2.32 IC₅₀: NC 55.97±1.66 137.8±1.3 212.9±3.15 IC₅₀: NC Compound 21 651.4±1.17 75.19±1.67 4297±6.58 96.63±1.06 IC₅₀: NC IC₅₀: NC IC₅₀: NC Gefitinip 45.78±1.47 66.89±1.36 770.3±1.88 110.8±1.74 IC₅₀: NC 1442±20.75 239.7±2.11 In the MCF-7 (breast cancer) cell line, compound number 21 was administered to the cells at a dose of 100 µM over a 24-hour period. It showed a high cytotoxic effect by reducing its viability to below 60%. Gefinitib at 48 hours. Ultimately, it showed a toxic effect in 60% of cases. Compound 21 caused significant loss of viability in MCF-7 cells. In this context, this Compounds can be potent chemotherapeutic candidates. 5 Gefitinib has proven effective as a reference drug in a breast cancer cell line. Since most other compounds show viability between 90–120%, in terms of antiproliferative effect... weak or negligible. Some compounds may have increased cell proliferation (>100%) → this is not antiproliferative, It means proliferative effect. 10 If a compound kills cancer cells while not harming healthy cells, that's ideal. It is an anticancer candidate. Accordingly, compound number 21 was 80% effective in A549 and MCF-7 cell lines. While exhibiting toxic effects at a certain rate, it showed a toxic effect of 40% on healthy cells. Effective and can be considered as a selective compound candidate. Compound number 17 showed 60% toxicity in the A549 (lung cancer) cell line, while compound number 15 It did not damage healthy cells. It was not effective in breast and colon cancer cell lines. Gefinitib has also shown a toxic effect profile in healthy cells. In conclusion, compound 17 is effective against cancer cells as well as healthy cells. They are preferred candidates because they exhibit lower toxicity compared to cells. It can be evaluated. Gefitinib, used as a reference drug, has a potent efficacy against cancer cell lines. It has shown some effect; however, it has also had significant toxic effects on healthy cells. In this context, compound code 17 is for the A549 cell line; and compound code 21 is for the MCF-7 cell line. They stand out as potential anticancer agents with high selectivity. For the PC-3 (Human Prostate Cancer) Cell Line: In this study, 12 unique compounds were synthesized and 25 compounds were used as positive controls. The antiproliferative effects of gefitinib on the PC-3 cell line were investigated at 5 different concentrations (5, 10, 25, 50 and 100 μM) were evaluated. The obtained data were compared with a negative control group (NK, 100%). Cell viability findings of the PC-3 cell line were normalized using (viability) as a reference. This is presented in Tables 5 and 6. 16 Preliminary screening analyses revealed no significant antiproliferative effect among the compounds. Candidate compounds exhibiting (reducing cell viability to 50% or below) are presented below: Compound 20: Significant antiproliferative effect in PC-3 cells with 52.41% cell viability at 48 hours. has shown. The findings indicate that some compounds have time- and dose-dependent antiproliferative effects. 5 It has been shown that it can demonstrate this, and the effect is particularly noticeable during the 48-hour incubation period. This indicates that it has become apparent. Positive Control (Gefitinip) Comparison: Gefitinib, at a dose of 100 μM, reduced cell viability to 55.31% at 24 hours, while at 48 hours this level... The effect was observed to decrease and then increase to 74.08%. 10 For the PC-3 cell line, Compound 20 stands out as a potential candidate. For HEP 3B (Liver Cancer) Cell Line: In the HEP 3B cell line, early (24-hour) resistance to compounds compared to the PC-3 cell line. Higher sensitivity has been observed. Many compounds show noticeable sensitivity even at low doses. It has been determined that it exhibits antiproliferative effects. Cell viability findings of HEP 3B cell line 15 This is presented in Tables 5 and 6. The following compounds have shown strong inhibition in liver cancer cells: Compound 20: Delayed antiproliferative effect with 28.04% cell viability at 100 µM at 48 hours. has shown. Positive Control (Gefitinib) Comparison: 20 Gefitinib showed limited antiproliferative effect in HEP ​​3B cells at 24 hours, while at 48 hours it reached 100%. At a dose of µM, it reduced cell viability to 40.81%. Compound 20's effect on HEP3B cells... its antiproliferative effects in the line were close to and higher than the positive control compound. It has been determined. The findings indicate that Compound 20, in particular, is potent in hepatocellular carcinoma cells and 25 Showing remarkable antiproliferative effect, suitable for further in vitro and mechanistic studies. This indicates that they could be considered among the priority candidates. For SH-SY5Y (Neuroblastoma) Cell Line: In the SH-SY5Y cell line, the antiproliferative effects of the compounds were generally more pronounced at 48 hours. it became apparent and the dose-response relationship was more consistent during this time period. 30 17 This has been observed. High cell viability values ​​observed in some compounds at 24 hours, It may be related to early adaptation mechanisms of neuroblastoma cells. SH-SY5Y Cell viability findings for the cell line are presented in Tables 2 and 3 (n:4). Prominent compounds in neuroblastoma cells: Compound 12: Showed an antiproliferative effect that increased over time. 5 Compound 17: Showed stable antiproliferative effect. Compounds 18 and 19: Showed moderate antiproliferative activity. Positive Control (Gefitinib) Comparison: Gefitinib, at a dose of 50 µM, increased cell viability to 46.62% in SH-SY5Y cells at 48 hours. It has lowered the levels of compounds 12 and 17 compared to the positive control compound at the same dose. It has been determined to exhibit antiproliferative activity. The findings indicate that Compound 17, in particular, has a potent and dose-dependent efficacy in neuroblastoma cells. It has been shown to emerge as a leading candidate compound based on its antiproliferative effects. 20 30 35 40

Claims

18 REQUESTS 1. It is a 1,4-disubstituted-1,2,3-triazole compound, and its characteristic feature is that it is selected from the following group; 2,3-bis((4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (10) 2,3-bis((4-(4-nitrophenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (11) 2,3-bis((4-(4-(trifluoromethyloxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (12) 2,3-bis((4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (13) 2,3-bis((4-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline (14) 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(4-phenyl-1H-1,2,3-triazole) (15) 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(4-(p-tolyl)-1H-1,2,3-triazole) (16) 4,4',4''-(((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(1H-1,2,3-triazole-1,4-dil))tribenzoic acid (17) 3,3',3''-(((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(1H-1,2,3-triazole-1,4-dil))tribenzoic acid (18) 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(4-(4-fluorophenyl)-1H-1,2,3-triazole) (19) 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(4-(4-nitrophenyl)-1H-1,2,3-triazole) (20) 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(4-(4-methoxyphenyl)-1H-1,2,3-triazole) (21) 2. A compound according to claim 1 for use in the treatment of cancer.

3. According to claim 2, it is a compound and its characteristic is that the cancer is lung cancer, breast cancer, colon cancer 5 The cancer may be prostate cancer, hepatocellular carcinoma, or neuroblastoma.

4. According to claim 3, it is a compound, and its characteristic is that the cancer is lung cancer and the compound is... It is selected from the following group: 2,3-bis((4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline, 4,4',4''-(((2,4,6-trimethylbenzene-1,3,5-triyl)tris(methylene))tris(1H-1,2,3-triazole-1,4-diyl))tribenzoic acid, 10 3,3',3''-((((2,4,6-trimethylbenzene-1,3,5-triyl)tris(methylene))tris(1H-1,2,3-triazole-1,4-diyl))tribenzoic acid, 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-fluorophenyl)-1H-1,2,3-triazole) or 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(4-(4-methoxyphenyl)-1H-1,2,3-triazole).

5. According to claim 4, it is a compound and its property is; the compound is 4,4',4''-(((2,4,6-trimethylbenzene-1,3,5-15 tril)tris(methylene))tris(1H-1,2,3-triazole-1,4-dil))tribenzoic acid.

6. Compound for use according to claim 4, and its property is; the compound is 1,1',1''-((2,4,6- trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-methoxyphenyl)-1H-1,2,3-triazole) It is the fact that.

7. It is a compound for use according to claim 3, and its characteristic feature is that the cancer is breast cancer and 20 the compound 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-methoxyphenyl)- It is 1H-1,2,3-triazole). 19 8. It is a compound for use according to claim 3, and its characteristic feature is that the cancer is colon cancer and the compound 2,3-bis((4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline or 2,3-bis((4-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline It is the fact that.

9. It is a compound for use according to claim 3, and its characteristic feature is that the cancer is prostate cancer and 5 the compound 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4-nitrophenyl)-1H- It is 1,2,3-triazole.

10. Compound for use according to claim 3, its characteristic is; cancer of hepatocellular carcinoma and the compound is 1,1',1''-((2,4,6-trimethylbenzene-1,3,5-tril)tris(methylene))tris(4-(4- It is nitrophenyl)-1H-1,2,3-triazole). 10 11. The compound is for use according to Claim 3, and its characteristic feature is that the cancer is neuroblastoma and the compound 2,3-bis((4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)methyl)quinoxaline or 4,4',4''-(((2,4,6-trimethylbenzene-1,3,5-trile)tris(methylene))tris(1H-1,2,3-triazole-1,4- (dil)) It is tribenzoic acid. 15 12. Compound for use according to claim 11, its characteristic is; the compound is 4,4',4''-(((2,4,6- trimethylbenzene-1,3,5-tril)tris(methylene))tris(1H-1,2,3-triazole-1,4-dil))tribenzoic acid It is the fact that.

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