CN112574192B - Amino acid derivative bithiazole-tryptamine anticancer compound and application thereof - Google Patents
Amino acid derivative bithiazole-tryptamine anticancer compound and application thereof Download PDFInfo
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- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The invention discloses an amino acid derivative bithiazole-tryptamine compound and application thereof. The amino acid derivative bithiazole-tryptamine compound disclosed by the invention can inhibit the application of colon cancer cell strain HCT116, gastric cancer cell strain MKN45, non-small cell lung cancer cell strain A549 and drug-resistant oral cancer cell strain KBV drugs, namely the application of preparing anti-tumor drugs. The synthetic method has simple route and high product purity, and can meet the large-scale preparation requirement. The amino acid derivative bithiazole-tryptamine compound with anticancer activity has good anticancer effect, shows obvious inhibition effect on colon cancer, gastric cancer and lung cancer, particularly shows similar inhibition effect on drug-resistant oral cancer cell line KBV to that of a commercially available broad-spectrum anticancer drug adriamycin (DOX), and can be applied to the field of antitumor.
Description
Technical Field
The invention relates to an amino acid derivative bithiazole-tryptamine compound with anticancer activity, which comprises pharmaceutically acceptable salts, solvates and prodrugs thereof, and a preparation method and application of the compound, and belongs to the field of pharmaceutical chemistry.
Background
Tumor refers to a local lump formed by abnormal proliferation of cells of local tissues under the action of various tumorigenic factors. Benign tumors are easy to clean, generally do not transfer, do not recur, and only have extrusion and blocking effects on organs and tissues. However, malignant tumors can also destroy the structure and function of tissues and organs, causing necrosis, hemorrhage and infection, and patients may die due to exhaustion of organ functions. When a cell in the body mutates, it constantly divides and is not controlled by the body, and finally forms cancer. All organs in the human body are composed of cells. Cell growth and differentiation can meet the needs of the body, and the ordered process can keep people healthy. However, if the cells continue to divide, these additional large numbers of cells form tumors. Cells of malignant tumors can invade and destroy adjacent tissues and organs. Moreover, cancer cells can pass out of the tumor and into the blood or lymphatic system, which is how the cancer develops new tumors from the original site to other organs, a process called metastasis, and most cancers are named according to the organ or cell type from which they originate. In recent years, due to the special structural characteristics and physicochemical properties of the bithiazole compounds and the wide application in the development of new drugs, the bithiazole compounds are receiving more and more attention (chem.Sci.2014,5, 3929-containing materials 3935), and in structural view, the bithiazole compounds have more non-covalent bond recognition sites and more rigid molecular structures than the single-thiazole compounds. Therefore, the patent envisages obtaining the tryptamine compound with good anti-tumor effect and novel structure.
Disclosure of Invention
The invention aims to provide a novel amino acid derivative bithiazole-tryptamine compound, a preparation method thereof, and application of the compound in preparation of medicines for inhibiting colon cancer cell strains HCT116, gastric cancer cell strains MKN45, non-small cell lung cancer cell strains A549 and drug-resistant oral cancer cell strains KBV, namely application in preparation of antitumor medicines.
The technical scheme of the invention is as follows:
an amino acid derivative bithiazole-tryptamine compound with anticancer activity has the following general formula:
wherein: n is 0,1, 2;
r is selected from Boc-L-Ala or Boc-D-Ala;
the synthesis route of the amino acid derivative bithiazole-tryptamine compound with the anticancer activity comprises the following steps:
the preparation method of the amino acid derivative bithiazole-tryptamine compound with anticancer activity comprises the following steps:
(1) one-pot synthesis method of thiazole: dissolving protected amino acid and pentafluorophenyl diphenyl phosphate (FDPP) in an organic solvent, sequentially adding methyl dithioazide, triethylamine and triphenylphosphine, reacting at 20-100 ℃ until the reaction is finished, cooling, sequentially adding 1, 8-diazabicycloundecene-7-ene (DBU) and bromotrichloromethane into a reaction mixture, continuously stirring at room temperature for reacting for 0.5-4 h, adding an isovolumetric saturated ammonium chloride solution for quenching reaction, extracting with DCM, drying an organic layer with anhydrous sodium sulfate, spin-drying, and separating by column chromatography to obtain a thiazole compound;
further preferably, the solvent is dichloromethane, the reaction temperature is 50 ℃, and the reaction time is 5 hours or 3 hours; according to molar ratio, protected amino acid: methyl dithioazide: FDPP: triethylamine: triphenylphosphine: DBU: bromo-trichloromethane is 4-6: 1: 4-6: 6-10: 6-10: 5-15: 5-15;
(2) and (3) hydrolysis reaction: dissolving a thiazole compound in an organic solvent, adding a sodium hydroxide aqueous solution for hydrolysis, adjusting the pH value to 3-4 by using a dilute hydrochloric acid solution after reacting overnight, extracting with ethyl acetate, drying with anhydrous sodium sulfate, spin-drying, and performing column chromatography separation to obtain carboxylic acid;
further preferably, the solvent is a mixed solution of methanol and tetrahydrofuran, and the ratio of methanol: tetrahydrofuran: 1: 1:1, the concentration of the sodium hydroxide solution is 0.5-1.5 mmol/ml.
(3) Condensation reaction: dissolving carboxylic acid and tryptamine in an organic solvent, and sequentially adding a condensation reagent and diisopropylethylamine until the reaction is finished to obtain a target condensation product.
Further preferably, the solvent is dichloromethane or N, N-dimethylformamide; the condensation reagent is 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethyluronium Hexafluorophosphate (HATU) or pentafluorophenyl diphenyl phosphate (FDPP), and the molar ratio of carboxylic acid: tryptamine: condensation reagent: diisopropylethylamine ═ 1: 1-1.5: 1-3: 1-5;
advantageous effects
The invention provides an amino acid derivative bithiazole-tryptamine compound and an efficient synthetic route thereof.
The target compound of the invention has obvious inhibition effect on colon cancer cell strains HCT116, gastric cancer cell strains MKN45 and non-small cell lung cancer cell strains A549, especially has similar inhibition effect on drug-resistant oral cancer cell strains KBV to that of the market broad-spectrum anticancer drug adriamycin (DOX), and has wide market prospect and scientific value.
The synthetic method has simple route and high product purity, and can meet the large-scale preparation requirement. The amino acid derivative bithiazole-tryptamine compound with anticancer activity has good anticancer effect, shows obvious inhibition effect on colon cancer, gastric cancer and lung cancer, particularly shows similar inhibition effect on drug-resistant oral cancer cell line KBV to that of a commercially available broad-spectrum anticancer drug adriamycin (DOX), and can be applied to the field of antitumor.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of alanine-derived bitriazole-tryptamine (12).
FIG. 2 is a nuclear magnetic carbon spectrum of alanine-derived bitriazole tryptamine (12).
FIG. 3 shows the IC50 pattern of Compound 12 against colon cancer cell line HCT 116.
FIG. 4 is an IC50 chart of compound 12 against drug resistant oral cancer cell line KBV.
FIG. 5 shows the IC50 pattern of compound 12 against non-small cell lung cancer cell line A549.
FIG. 6 shows IC50 of Compound 12 against gastric cancer cell line MKN 45.
Detailed Description
The invention is further described below with reference to examples, but without limiting the scope of the invention in any way.
EXAMPLE 1 Compound (3)
The method comprises the following steps: 4mmol of Boc-L-Ala-COOH and 4mmol of pentafluorophenyl diphenyl phosphate were dissolved in 80ml of dichloromethane, and after stirring at room temperature for 10min, 10mmol of triethylamine, 8mmol of triphenylphosphine and 1mmol of dithioazide 2 were sequentially added to the reaction system, followed by heating and refluxing until the reaction was completed by TLC monitoring; cooling the reaction system to room temperature, slowly adding 10mmol of bromotrichloromethane and 12mmol of 1, 8-diazabicycloundecen-7-ene (DBU) into the system, continuing to react for 1 hour at room temperature, adding saturated ammonium chloride solution to quench the reaction, extracting with dichloromethane, combining organic phases, drying with anhydrous sodium sulfate, removing the solvent by rotary evaporation to obtain brown viscous liquid, and separating by column chromatography to obtain the target thiazole compound 3 with the yield of 78%. [ alpha ] to]D 20-36.4(c 0.5,MeOH)；m.p.86-89℃；1H NMR(400MHz,CDCl3)δ:1.44(s,9H),1.61(d,J＝6.4Hz,3H),3.93(s,3H),5.03-5.14(m,1H),5.20(s,br,1H),8.10(s,1H)；13C NMR(100MHz,CDCl3)δ:21.2,27.8,48.4,51.9,80.0,127.0,146.3,154.4,161.3,174.6；ESI-HRMS calcd for C12H18N2NaO4S([M+Na]+)309.0885,found 309.0848.
EXAMPLE 2 Compound (5)
The method comprises the following steps: dissolving 0.5mmol of compound 3 in 10ml of mixed solution (volume ratio is 1:1) of methanol and tetrahydrofuran, adding 5ml of 0.5N sodium hydroxide solution into the system under the condition of ice water, monitoring by TLC until the reaction is complete, carefully adding 0.5N hydrochloric acid solution into the system under the condition of ice water to adjust the pH value to 2-3, extracting by ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, and directly using for the next reaction after spin-drying. Dissolving the prepared carboxylic acid and 0.5mmol of pentafluorophenyl diphenyl phosphate in 10ml of dichloromethane, stirring at normal temperature for 10min, sequentially adding 1.5mmol of triethylamine, 1.5mmol of triphenylphosphine and 0.125mmol of dithioazide 2 into a reaction system, and heating and refluxing until the TLC monitoring reaction is finished; cooling the reaction system to room temperature, slowly adding 2.0mmol of bromotrichloromethane and 2.5mmol of 1, 8-diazabicycloundec-7-ene (DBU) into the system, continuing to react for 1 hour at normal temperature, adding saturated ammonium chloride solution to quench the reaction, extracting with ethyl acetate, combining organic phases, drying with anhydrous sodium sulfate, removing the solvent by rotary evaporation to obtain brown viscous liquid, and separating by column chromatography to obtain the target thiazole compound 5 with the yield of 65 percent in two steps. [ alpha ] to]D 20-98.4(c 0.5,CHCl3)；1H NMR(400MHz,CDCl3)δ8.15(s,1H),8.01(s,1H),5.26(s,1H),5.08(s,1H),3.93(s,3H),1.60(d,J＝6.8Hz,3H),1.42(s,9H)；13C NMR(100MHz,CDCl3)δ175.0,163.6,162.0,155.1,148.2,147.5,128.2,117.3,80.4,77.6,77.2,76.9,52.6,48.9,28.4,21.7；ESI-HRMS calcd for C15H19N3NaO4S2([M+Na]+)392.0709,found 392.0721；
EXAMPLE 3 Compound (7)
The method comprises the following steps: dissolving 0.5mmol of compound 5 in 10ml of mixed solution (1:1) of methanol and tetrahydrofuran, adding 5ml of 0.5N sodium hydroxide solution into the system under the condition of ice water, monitoring by TLC until the reaction is complete, carefully adding 0.5N hydrochloric acid solution into the system under the condition of ice water to adjust the pH value to 2-3, extracting by ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, and spin-drying to be directly used for the next reaction. Dissolving the prepared carboxylic acid and 0.5mmol of pentafluorophenyl diphenyl phosphate in 10ml of dichloromethane, stirring at normal temperature for 10min, sequentially adding 1.5mmol of triethylamine, 1.5mmol of triphenylphosphine and 0.125mmol of dithioazide 2 into a reaction system, and heating and refluxing until the TLC monitoring reaction is finished; cooling the reaction system to room temperature, slowly adding 2.0mmol of bromotrichloromethane and 2.5mmol of 1, 8-diazabicycloundec-7-ene (DBU) into the system, continuing to react for 1 hour at normal temperature, adding saturated ammonium chloride solution to quench the reaction, extracting with ethyl acetate, combining organic phases, drying with anhydrous sodium sulfate, removing the solvent by rotary evaporation to obtain brown viscous liquid, and separating by column chromatography to obtain the target thiazole compound 7 with the yield of 56% in two steps. [ alpha ] to]D 20-44(c 0.5,CHCl3)；1H NMR(400MHz,CDCl3)δ8.21(s,1H),8.15(s,1H),7.98(s,1H),5.20(s,1H),5.13(s,1H),3.98(s,3H),1.65(d,J＝6.4Hz,4H),1.47(s,9H)；13C NMR(100MHz,CDCl3):δ163.7,163.4,162.1,149.3,148.6,147.7,128.3,118.1,116.9,53.7,52.8,48.9,21.9；ESI-HRMS calcd for C18H20N4NaO4S3([M+Na]+)475.0539,found 475.0564；
EXAMPLE 4 Compound (10)
The method comprises the following steps: dissolving 0.5mmol of compound 3 in 10ml of mixed solution (1:1) of methanol and tetrahydrofuran, adding 5ml of 0.5N sodium hydroxide solution into the system under the condition of ice water, monitoring by TLC until the reaction is complete, carefully adding 0.5N hydrochloric acid solution into the system under the condition of ice water to adjust the pH value to 2-3, extracting by ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, and spin-drying to be directly used for the next reaction. The prepared carboxyl isDissolving acid, 1.0mmol of 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethylurea Hexafluorophosphate (HATU) and 1.2mmol of diisopropylethylamine in 15ml of dichloromethane, adding 0.5mmol of tryptamine into the system, reacting overnight, after TLC monitoring reaction is completed, adding saturated ammonium chloride solution into the system to quench the reaction, extracting with ethyl acetate for three times, combining organic phases, drying with anhydrous sodium sulfate, spin-drying to obtain a crude product, and separating by column chromatography to obtain the target compound 10, wherein the yield of the two steps is 78%. [ alpha ] to]D 20-59(c 0.6,MeOH)1H NMR(400MHz,CDCl3):δ1.55(d,J＝7.2Hz,3H),2.02(s,3H),3.09(t,J＝7.2Hz,2H),3.70-3.86(m,2H),5.36(dq,J＝7.2Hz,J＝8.0Hz,1H),6.04(d,J＝7.2Hz,1H),7.09(d,J＝2.4Hz,1H),7.13(t,J＝7.2Hz,1H),7.22(t,J＝7.2Hz,1H),7.39(d,J＝8.0Hz,1H),7.66(d,J＝7.2Hz,1H),8.00(s,1H)8.51(br,1H)；13C NMR(100MHz,CDCl3):δ21.4,23.2,25.4,39.7,46.9,111.2,1130,118.8,119.4,122.1,122.2,122.9,127.4,136.3,149.9,160.8,169.3,172.2；ESI-HRMS calcd for C21H26N4NaO3S([M+Na]+)437.1618,found 437.1633；
EXAMPLE 5 Compound (11)
The method comprises the following steps: dissolving 0.5mmol of compound 5 in 10ml of mixed solution (1:1) of methanol and tetrahydrofuran, adding 5ml of 0.5N sodium hydroxide solution into the system under the condition of ice water, monitoring by TLC until the reaction is complete, carefully adding 0.5N hydrochloric acid solution into the system under the condition of ice water to adjust the pH value to 2-3, extracting by ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, and spin-drying to be directly used for the next reaction. Dissolving the prepared carboxylic acid, 1.0mmol of 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethylurea Hexafluorophosphate (HATU) and 1.2mmol of diisopropylethylamine in 15ml of dichloromethane, adding 0.6mmol of tryptamine into the system, reacting overnight, after TLC monitoring reaction is completed, adding saturated ammonium chloride solution into the system to quench the reaction, extracting with ethyl acetate for three times, combining organic phases, drying with anhydrous sodium sulfate, spin-drying to obtain a crude product, and separating by column chromatography to obtain the target compound 11, wherein the yield of the two steps is 73%. [ alpha ] to]D 20-210(c 0.5,CHCl3)；1H NMR(400MHz,CDCl3):δ8.50(s,1H),8.08(s,1H),7.69(s,1H),7.66(d,J＝8.0Hz,1H),7.58(t,J＝5.4Hz,1H),7.38(d,J＝8.0Hz,1H),7.19(t,J＝7.2Hz,1H),7.11(t,J＝7.2Hz,1H),7.07(s,1H),5.31(s,1H),5.11(s,1H),3.79(dd,J＝12.8,6.8Hz,2H),3.10(t,J＝6.8Hz,2H),1.62(d,J＝6.8Hz,3H),1.48(s,9H).ESI-HRMS calcd for C24H27N5NaO3S2([M+Na]+)520.1448,found 520.1456；
EXAMPLE 6 Compound (12)
The method comprises the following steps: dissolving 0.5mmol of compound 7 in 10ml of mixed solution (1:1) of methanol and tetrahydrofuran, adding 5ml of 0.5N sodium hydroxide solution into the system under the condition of ice water, monitoring by TLC until the reaction is complete, carefully adding 0.5N hydrochloric acid solution into the system under the condition of ice water to adjust the pH value to 2-3, extracting by ethyl acetate for three times, combining organic phases, drying by anhydrous sodium sulfate, and spin-drying to be directly used for the next reaction. Dissolving the prepared carboxylic acid, 1.2mmol of 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethylurea Hexafluorophosphate (HATU) and 1.2mmol of diisopropylethylamine in 15ml of dichloromethane, adding 0.8mmol of tryptamine into the system, reacting overnight, after TLC monitoring reaction is completed, adding saturated ammonium chloride solution into the system to quench the reaction, extracting with ethyl acetate for three times, combining organic phases, drying with anhydrous sodium sulfate, spin-drying to obtain a crude product, and separating by column chromatography to obtain the target compound 12, wherein the yield of the two steps is 73%. [ alpha ] to]D 20-162.6(c 0.5,DMSO)；1H NMR(400MHz,CDCl3):δ8.20(s,1H),8.12(s,1H),7.98(s,1H),7.79(s,1H),7.69(d,J＝7.6Hz,1H),7.57(t,J＝5.4Hz,1H),7.40(d,J＝8.0Hz,1H),7.22(t,J＝7.6Hz,1H),7.16–7.09(m,2H),5.19(s,1H),5.13(s,1H),3.83(dd,J＝12.8,6.8Hz,2H),3.13(t,J＝6.8Hz,2H),1.65(d,J＝6.8Hz,3H),1.48(s,9H)；1H NMR(400MHz,d-DMSO):δ178.3,163.7,162.1,160.8,151.5,149.2,147.6,136.8,127.8,124.8,123.2,121.5,119.0,118.8,118.5,112.2,111.9,49.1,28.8,25.8,21.1；ESI-HRMS calcd for C27H28N6NaO3S3([M+Na]+)603.1277,found 603.1279；
The following are the pharmacological tests and data for some of the compounds of the invention.
EXAMPLE 7 pharmacological test
Inhibitory Activity of Compounds 10, 11 and 12 against human Colon cancer cell line HCT116, gastric cancer cell line MKN45, non-Small cell Lung cancer cell line A549 and drug-resistant oral cancer cell line KBV
The half Inhibition Concentration (IC) of aryl derivative bithiazole compound on HCT116, MKN45, KBV and other three cell strains is determined by adopting MTT (3- (4, 5-dimethylthiazole-2) -2, 5-diphenyl tetrazole bromide salt) method50). The detection principle is as follows: MTT can penetrate through cell membrane to enter into cell, amber dehydrogenase in mitochondria of living cell can reduce exogenous MTT into blue-purple needle formazan crystal which is difficult to dissolve in water and deposited in cell, the crystal can be dissolved by dimethyl sulfoxide (DMSO), and the absorbance is measured to reflect cell survival rate. Median Inhibitory Concentration (IC)50) The drug concentration was defined as the drug concentration at which 50% of tumor cells survived, a standard curve of the cell growth inhibition rate was prepared from the measured optical density (OD value), and the corresponding drug concentration was determined on the curve.
The measurement method is as follows:
1. cells were seeded at 2000 cells/well in 96-well plates in CO2Culturing in an incubator for 24 hours;
2. diluting the concentration of the substance to be tested (mother liquor 10mM) to 20-10-3.3-1-0.3. mu.M;
3. three groups of parallel holes are arranged at each concentration, a compound to be detected is added into the inoculated cells respectively, and the culture is continued for 72 hours;
4. taking out the 96-well plate, adding 20 mul MTT solution into each well, and incubating for 2 hours in an incubator;
5. discarding the upper layer liquid, adding 150. mu.l DMSO into each well, shaking for 15min, and allowing formazan to completely dissolve;
6. absorbance was measured at 570 nm.
Three parallel tests, taking the average value of the experimental results and measuring the IC50The values are shown in Table 1.
TABLE 1
Among them, Dox (doxorubicin) was used as a control.
Pharmacological tests show that the amino acid derivative bithiazole-tryptamine compound disclosed by the invention shows obvious antitumor activity, and particularly the compounds 10, 11 and 12 show inhibition activity on human colon cancer cell strains HCT116, gastric cancer cell strains MKN45, non-small cell lung cancer cell strains A549 and drug-resistant oral cancer cell strains KBV. According to the invention, DNA is damaged by introducing a bithiazole heterocyclic ring structure, G2/M cell cycle block and G2/M DNA damage check point activation are caused, so that cancer cell apoptosis is caused, namely, the number of thiazole heterocycles is changed to adjust the length, rigidity and heteroatom number of 'functional staples', and further adjust and control the conformation, stability and binding capacity with DNA of the synthetic molecules, so that the compounds 10, 11 and 12 of the invention show inhibitory activities on human colon cancer cell strains HCT116, gastric cancer cell strains MKN45, non-small cell lung cancer cell strains A549 and drug-resistant oral cancer cell strains KBV.
The above experimental results describe in detail the preferred embodiments of the present invention, but the present invention is not limited to the specific details in the above embodiments; within the scope of the collocation concept of the invention, various equivalent changes can be made to the technical scheme of the invention, and the changes all belong to the protection scope of the invention. In order to avoid unnecessary repetition, the invention does not separately describe the possible combination modes of various structures; the same should be considered as the disclosure of the present invention, as long as it does not depart from the gist of the present invention.
Claims (6)
1. An amino acid derivative bithiazole-tryptamine compound with anticancer activity is characterized in that: the structure is shown as general formula I:
wherein: n is 1, 2;
r is selected from
2. The use of a class of amino acid-derived bithiazole-tryptamine compounds according to claim 1 with anticancer activity for the preparation of anticancer drugs.
3. The application of the amino acid derivative bithiazole-tryptamine compound in the preparation of anticancer drugs according to claim 2, characterized in that the amino acid derivative bithiazole-tryptamine compound is applied in the preparation of anti-gastric cancer drugs.
4. The application of the amino acid derivative bithiazole-tryptamine compound in the preparation of anticancer drugs according to claim 2, characterized in that the amino acid derivative bithiazole-tryptamine compound is applied in the preparation of anti-intestinal cancer drugs.
5. The application of the amino acid derivative bithiazole-tryptamine compound in the preparation of anticancer drugs according to claim 2, characterized in that the amino acid derivative bithiazole-tryptamine compound is applied in the preparation of anti-lung cancer drugs.
6. The use of the amino acid-derived bithiazole-tryptamine compound according to claim 2 for preparing an anticancer drug, wherein the amino acid-derived bithiazole-tryptamine compound is used for preparing an anti-oral cancer drug.
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| CN103664932B (en) * | 2013-11-04 | 2016-08-17 | 南京大学 | One class indoles grafting thiazole hydrazone analog derivative and preparation method thereof and the inhibitory action to cancer cell tubulin polymerization |
| CN109666006B (en) * | 2018-12-07 | 2022-09-02 | 烟台大学 | Aryl derivative bithiazole compound and preparation method and application thereof |
| CN110204538B (en) * | 2019-06-04 | 2022-02-08 | 烟台大学 | Aryl thiazole-tryptamine ocean red tide algae algicide and preparation method and application thereof |
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